bromochloroacetic-acid and Adenocarcinoma

Adenoid basal carcinoma (ABC) is uncommon malignancy of the uterine cervix and it can be pure or combined with cervical intraepithelial lesions. There were less than 20 cases of ABC combined with invasive squamous carcinoma (mixed type) in English literature. These cases had similar properties as seen at postmenopausal women and diagnosed with abnormal cervical smear findings. Here we present a case of 37-year-old woman who suffered from spotting and received endocervical curettage. The pathological report revealed squamous cell carcinoma (SCC) of the cervix. The patient underwent type 3 radical hysterectomy and bilateral pelvic and para-aortic lymph node dissection. The final pathological report revealed SCC coexisting with ABC. Human papillomavirus (HPV) 16,18 and others (11 types) were negative in both components of the mixed tumor by in situ hybridization detection. Our case was cytokeratin 7 negative, cytokeratin 8 positive and p63 positive which supports the hypothesis that mixed type cervical carcinoma originates from endocervical reserve cells.

Topics: Adenocarcinoma; Adult; Biomarkers, Tumor; Carcinoma, Squamous Cell; Female; Humans; Keratins; Lymph Nodes; Neoplasm Invasiveness; Uterine Cervical Neoplasms

Topics: Adenocarcinoma; Aged; Biomarkers, Tumor; Carcinoma, Renal Cell; Diagnosis, Differential; Humans; Keratins; Kidney Neoplasms; Liver Neoplasms; Lung Neoplasms; Male; Neoplasm Proteins; Neoplasms, Second Primary; Neoplasms, Unknown Primary; Organ Specificity; Prostatic Neoplasms

The diagnosis of large cell carcinoma can only be made on a sampled resected tumor and should not be applied to biopsies or cytology. In the 2015 WHO classification, the definition of large cell carcinoma is restricted to carcinomas both lacking morphological signs of glandular, squamous or neuroendocrine differentiation and exhibiting a null or unclear phenotype (TTF1-/p40 ou p63 ou CK5/6+ focally). These carcinomas have an adenocarcinoma molecular profile because they harbor a significant number of KRAS and BRAF mutations, a profile that is more similar to adenocarcinoma than squamous cell carcinoma. They also have a worse prognosis than the other types of non-small cell lung carcinoma. Many large cell carcinomas previously classified on morphological data alone are now reclassified in the adenocarcinoma and squamous cell carcinoma types, including immunohistochemical features. The other large cell carcinoma subtypes from the 2004 WHO classification, i.e. large cell neuroendocrine carcinoma and basaloid carcinoma, are grouped respectively with the other neuroendocrine tumors and squamous cell carcinomas. Clear cell and rhabdoid features are now considered as cytological variants that can occur in any histopathological subtype and not as distinct subtypes. Lymphoepithelioma-like carcinoma is moved to the group of other and unclassified carcinomas as NUT carcinoma.

Topics: Adenocarcinoma; Biomarkers, Tumor; Carcinoma, Large Cell; Cell Differentiation; DNA-Binding Proteins; Genes, ras; Humans; Immunophenotyping; Keratins; Lung Neoplasms; Prognosis; Proto-Oncogene Proteins B-raf; Transcription Factors; Tumor Suppressor Proteins

Topics: Adenocarcinoma; Female; Humans; Keratins; Mesonephroma; Middle Aged; Neprilysin; Vaginal Neoplasms

Topics: Adenocarcinoma; Aged; Carcinoma, Adenosquamous; Diagnosis, Differential; Female; Humans; Keratins; Membrane Proteins; Tongue Neoplasms; Treatment Outcome

A relatively large number of broad-spectrum immunohistochemical epithelial markers that can be used as part of the screening panels employed in the recognition of the main cell lineages during the initial evaluation of a poorly differentiated tumor are currently available. Variations exist in the sensitivity and specificity of the individual markers that have traditionally been used for the demonstration of epithelial differentiation and in the pitfalls associated with these markers. This article reviews not only the reactivity of the various pan-keratin antibodies that are often used to assist in the demonstration of epithelial differentiation, but also that of those that have recently become available. A review of the non-keratin, broad-spectrum epithelial markers that have been recognized as being useful is also presented.

Topics: Adenocarcinoma; Biomarkers, Tumor; Clone Cells; Epithelial Cells; Female; Humans; Immunohistochemistry; Keratins; Male

We report a case of a prostatic adenocarcinoma that showed diffuse aberrant p63 expression in the secretory cells and review the literature and differential diagnosis. p63-positive prostatic adenocarcinoma is rare and is typically encountered when working up an atypical focus with basal markers and α-methylacyl coenzyme A racemase. These carcinomas have unusual morphologic features such as atrophic cytoplasm and basaloid morphology. The differential diagnosis includes basal cell hyperplasia and basal cell carcinoma; morphologic features such as the presence of small, infiltrative acini with nuclear atypia, lack of high-molecular-weight cytokeratin expression, and positive α-methylacyl coenzyme A racemase and prostate-specific antigen expression can help distinguish a p63-positive prostatic adenocarcinoma from atypical basal cell proliferations. Current controversies regarding the grading, prognosis, and molecular profile of p63-positive prostatic adenocarcinomas are also discussed.

Topics: Adenocarcinoma; Aged; Biomarkers, Tumor; Carcinoma, Basal Cell; Cell Proliferation; Diagnosis, Differential; Humans; Hyperplasia; Keratins; Male; Membrane Proteins; Neoplasm Grading; Prognosis; Prostate; Prostate-Specific Antigen; Prostatic Neoplasms; Racemases and Epimerases

The diagnosis of prostatic adenocarcinoma relies on a constellation of architectural, cytological, and immunohistochemical features. Although the diagnosis of prostatic adenocarcinoma is straightforward in most cases, due to earlier detection of the disease in the modern era, pathologists have become increasingly challenged in diagnosing small foci of cancer when only a few atypical glands are present in needle biopsies. Immunohistochemistry has therefore become an essential tool in the evaluation of such foci to confirm the absence of basal cells. In this context, the 2 most commonly used basal cell markers are anti-keratin 34BE12 and p63. Furthermore, α-methylacyl-CoA racemase, a marker found to be overexpressed in the cytoplasm of prostatic adenocarcinoma glands, is also commonly used in routine practice. Another diagnostic role of immunohistochemistry is to confirm the prostatic origin of the tumor in the primary or metastatic setting of high-grade prostatic adenocarcinoma, which may be confused with nonprostatic carcinomas. We herein review the utility as well as the limitations of immunohistochemistry in the diagnosis of prostatic adenocarcinoma, and we describe the most important pitfalls in the interpretation of various immunostains that pathologists should be aware of to minimize misdiagnoses.

Topics: Adenocarcinoma; Atrophy; Biomarkers, Tumor; Biopsy, Needle; Diagnosis, Differential; Diagnostic Errors; GATA3 Transcription Factor; Humans; Immunohistochemistry; Keratins; Male; Prostate; Prostatic Neoplasms; Racemases and Epimerases; Transcription Factors; Tumor Suppressor Proteins

Tumor 'budding', loosely defined by the presence of individual cells and small clusters of tumor cells at the invasive front of carcinomas, has received much recent attention, particularly in the setting of colorectal carcinoma. It has been postulated to represent an epithelial-mesenchymal transition. Tumor budding is a well-established independent adverse prognostic factor in colorectal carcinoma that may allow for stratification of patients into risk categories more meaningful than those defined by TNM staging, and also potentially guide treatment decisions, especially in T1 and T3 N0 (Stage II, Dukes' B) colorectal carcinoma. Unfortunately, its universal acceptance as a reportable factor has been held back by a lack of definitional uniformity with respect to both qualitative and quantitative aspects of tumor budding. The purpose of this review is fourfold: (1) to describe the morphology of tumor budding and its relationship to other potentially important features of the invasive front; (2) to summarize current knowledge regarding the prognostic significance and potential clinical implications of this histomorphological feature; (3) to highlight the challenges posed by a lack of data to allow standardization with respect to the qualitative and quantitative criteria used to define budding; and (4) to present a practical approach to the assessment of tumor budding in everyday practice.

Topics: Adenocarcinoma; Biomarkers, Tumor; Cell Movement; Colorectal Neoplasms; Epithelial-Mesenchymal Transition; Humans; Keratins; Neoplasm Invasiveness; Neoplasm Staging; Prognosis

Keratins are the intermediate filament (IF)-forming proteins of epithelial cells. Since their initial characterization almost 30 years ago, the total number of mammalian keratins has increased to 54, including 28 type I and 26 type II keratins. Keratins are obligate heteropolymers and, similarly to other IFs, they contain a dimeric central α-helical rod domain that is flanked by non-helical head and tail domains. The 10-nm keratin filaments participate in the formation of a proteinaceous structural framework within the cellular cytoplasm and, as such, serve an important role in epithelial cell protection from mechanical and non-mechanical stressors, a property extensively substantiated by the discovery of human keratin mutations predisposing to tissue-specific injury and by studies in keratin knockout and transgenic mice. More recently, keratins have also been recognized as regulators of other cellular properties and functions, including apico-basal polarization, motility, cell size, protein synthesis and membrane traffic and signaling. In cancer, keratins are extensively used as diagnostic tumor markers, as epithelial malignancies largely maintain the specific keratin patterns associated with their respective cells of origin, and, in many occasions, full-length or cleaved keratin expression (or lack there of) in tumors and/or peripheral blood carries prognostic significance for cancer patients. Quite intriguingly, several studies have provided evidence for active keratin involvement in cancer cell invasion and metastasis, as well as in treatment responsiveness, and have set the foundation for further exploration of the role of keratins as multifunctional regulators of epithelial tumorigenesis.

Topics: Adenocarcinoma; Animals; Biomarkers, Tumor; Cell Transformation, Neoplastic; Cytoplasm; Epithelial Cells; Female; Health; Humans; Intermediate Filaments; Keratins; Male; Mice; Protein Biosynthesis; Protein Interaction Domains and Motifs; Protein Processing, Post-Translational

To investigate the clinicopathological features, histogenesis and prognosis of mucinous tubular and spindle cell carcinoma (MTSCC).. Five MTSCCs were studied with histochemical, immunohistochemical staining, electron microscopy, and review of the related literatures.. Four cases of MTSCC were females and one was male. Three patients presented with flank discomfort and two were incidentally found with health examination. In gross examination, the tumors were circumscribed. The cut surface was solid, gray-white, yellow or red. Necrosis was present in one case of high-grade MTSCC. Microscopically, low-grade MTSCC was mainly consisted of tubular, spindle cell and mucinous stroma with relatively bland morphology, and mitoses were rare. While in the high-grade area of one case, the cells were spindle or polymorphic with severe atypia and high mitotic activity, without mucinous stroma and tubular structure. Mucin was positive for Alcian blue. The neoplastic cells were positive for vimentin (5/5), CKpan (5/5), CK7 (5/5), CK19 (5/5), 34betaE12 (1/5), EMA (5/5), E-cadherin (3/5), CD10 (1/5), P504S (5/5), and CAM5.2 (5/5). The Ki-67 index was low (< or = 5%) in the low-grade component, while it was high (15%) in the high-grade component. Ultrastructural study showed short microvilli along glandular lumens. The nuclear membrane was focally invaginated. Four cases were followed up for 3 to 52 months, and recurrence and metastasis were not found.. MTSCC occurs predominantly in females and it is a rare kidney neoplasm. Most of MTSCCs are low-grade and the prognosis is relatively good. However, the patients of high-grade MTSCC should be closely followed up.

Topics: Adenocarcinoma; Adenocarcinoma, Mucinous; Adult; Carcinoma; Carcinoma, Medullary; Carcinoma, Renal Cell; Diagnosis, Differential; Female; Humans; Keratins; Kidney Neoplasms; Leiomyosarcoma; Male; Middle Aged; Mucin-1; Nephrectomy; Racemases and Epimerases; Vimentin

Primary adenocarcinoma of urinary bladder is an uncommon neoplasm and is a source of diagnostic confusion with adenocarcinomas arising in adjacent organs, especially colon. These tumors show varied histologic picture and degree of differentiation. Clinical association with bladder exstrophy and schistosomiasis has been well documented. Primary bladder adenocarcinomas have overlapping histologic and immunohistochemical features with adenocarcinomas arising from other primary sites and the suggested immunohistochemical panel includes cytokeratins 7 and 20, 34βE12, thrombomodulin, CDX2, and β-catenin. Clinical, imaging, histologic, and immunohistochemical correlation should be done while rendering this diagnosis, as prognosis and therapeutic options for primary versus metastatic adenocarcinoma vary widely.

Topics: Adenocarcinoma; beta Catenin; CDX2 Transcription Factor; Homeodomain Proteins; Humans; Immunohistochemistry; Keratin-20; Keratin-7; Keratins; Microfilament Proteins; Thrombomodulin; Urinary Bladder Neoplasms

We report a case of a 27-year-old woman with a nonpigmented lesion on the right scalp. Histological examination showed a malignant nodular neoplasm with 2 distinct but intimately admixed components: a malignant melanoma with a spindle component and an unusual glandular component. Immunohistochemical studies demonstrated epithelial differentiation on the basis of cytokeratin (CAM5.2 and AE1/AE3) expression in the glandular component and melanocytic differentiation (HMB-45, PNL2, MITF, and S-100) of the spindle cell component. A single melanocytic marker (MITF) was expressed in both components, raising the possibility of dual differentiation in a single tumor, rather than the alternative considerations of a collision tumor or a reactive pseudoepitheliomatous hyperplasia with eccrine duct lumen formation within a melanoma. This unusual tumor with both melanocytic and epithelial components may represent a true melanocarcinoma, which becomes a plausible consideration, in view of melanoma plasticity and recent experimental evidence and speculation about the role of stem cells in melanoma.

Topics: Adenocarcinoma; Adult; Cell Differentiation; Epithelial Cells; Female; Humans; Immunohistochemistry; Keratins; Melanocytes; Melanoma, Amelanotic; Microphthalmia-Associated Transcription Factor; Neoplasms, Glandular and Epithelial; Neoplasms, Multiple Primary; Scalp; Skin Neoplasms

Breast metastases from gastric cancer are extremely rare. A case report of a 37-year-old female with breast inflammatory invasion and ascites is described. Breast biopsy revealed carcinomatous invasion of the lymphatics from adenocarcinoma cells with signet-ring features. Estrogen (ER) and progesterone receptors (PR) and c-erb-B2 were negative. Upper gastrointestinal endoscopy revealed a prepyloric ulcerative mass. Histopathologic examination of the lesion showed infiltration from a high-grade adenocarcinoma, identical with that of the breast. Immunostaining was positive for cytokeratins CK-7 and CK-20 and CEA and negative for ER and PR. Ascitic fluid cytology was positive for adenocarcinoma cells. Mammography was not diagnostic. Abdominal CT scanning revealed large ovarian masses suggestive of metastases (Krukenberg's tumor). A cisplatin-based regimen was given but no objective response was observed. The patient died six months after initial diagnosis. A review of the literature is performed.

Topics: Adenocarcinoma; Adult; Ascites; Breast Neoplasms; Carcinoembryonic Antigen; Carcinoma, Signet Ring Cell; Female; Humans; Immunohistochemistry; Keratin-20; Keratin-7; Keratins; Ovarian Neoplasms; Stomach Neoplasms

Topics: Adenocarcinoma; Biomarkers, Tumor; Brain Neoplasms; Breast Neoplasms; Carcinoma, Hepatocellular; Carcinoma, Neuroendocrine; Carcinoma, Small Cell; Carcinoma, Squamous Cell; Cell Differentiation; Cytogenetic Analysis; Head and Neck Neoplasms; Humans; Immunohistochemistry; Keratins; Liver Neoplasms; Lymphatic Metastasis; Magnetic Resonance Imaging; Mesothelioma; Neoplasm Metastasis; Neoplasms, Unknown Primary; Peritoneal Neoplasms; Positron-Emission Tomography; Prognosis; Rhabdomyosarcoma; Tomography, X-Ray Computed; Urinary Bladder Neoplasms

The ovary is a common site of metastatic tumour. In many cases of ovarian metastasis there is a known history of malignancy but in other cases the ovarian tumour is the first manifestation of disease. In this review metastatic colorectal, appendiceal, gastric, breast, pancreatic and biliary tract, hepatocellular, renal, transitional and cervical carcinomas and metastatic malignant melanoma involving the ovary are discussed, as is the issue of synchronous ovarian and endometrial carcinomas. Peritoneal tumours, including primary peritoneal carcinoma, mesothelioma and intra-abdominal desmoplastic small round cell tumour, involving the ovary are also discussed, together with a variety of other rare, metastatic ovarian neoplasms. Many metastatic adenocarcinomas involving the ovary, especially those exhibiting mucinous differentiation, closely mimic primary ovarian adenocarcinomas with morphologically bland areas simulating benign and borderline cystadenoma. This is referred to as a maturation phenomenon. In recent years immunohistochemistry, especially but not exclusively differential cytokeratin (CK7 and CK20) staining, has been widely used as an aid to distinguish between a primary and secondary ovarian adenocarcinoma. While immunohistochemistry undoubtedly has a valuable role to play and is paramount in diagnosis in some cases, the results must be interepreted with caution, especially in mucinous tumours, and within the relevant clinical context. We feel the significance of differential cytokeratin staining is not always understood by histopathologists and this can result in erroneous interpretation. We critically discuss the value of immunohistochemistry and associated pitfalls with each tumour type described.

Topics: Adenocarcinoma; Female; Humans; Immunohistochemistry; Intermediate Filament Proteins; Keratin-20; Keratin-7; Keratins; Ovarian Neoplasms; Ovary

Topics: Adenocarcinoma; Antigens, Neoplasm; Biomarkers, Tumor; Carcinoma, Large Cell; Carcinoma, Small Cell; Carcinoma, Squamous Cell; Electrochemistry; Humans; Immunoenzyme Techniques; Keratin-19; Keratins; Luminescent Measurements; Lung Neoplasms; Radioimmunoassay; Reference Values; Specimen Handling

Colonic carcinoma metastasis to the thyroid is rare. Here the authors present the case of an 81-year-old lady who presented with metastatic colonic adenocarcinoma in her thyroid gland. This case is unique as it is the first to demonstrate metastasis from the colon to the thyroid with no other site involvement. The use of cytokeratin immunohistochemical staining is reviewed along with the current perspectives on the concept of skip metastasis.

Topics: Adenocarcinoma; Aged, 80 and over; Biomarkers, Tumor; Colonic Neoplasms; Female; Humans; Keratins; Neoplasm Proteins; Thyroid Neoplasms

Most adenomas and carcinomas of the small intestine and extrahepatic bile ducts arise in the region of the papilla of Vater. In familial adenomatous polyposis (FAP) it is the main location for carcinomas after proctocolectomy. In many cases symptoms due to stenosis lead to diagnosis at an early tumor stage. In about 80%, curative intended resection is possible. Operability is the most relevant prognostic factor. Most ampullary carcinomas resp. carcinomas of the papilla of Vater develop from adenomatous or flat dysplastic precursor lesions. They can be sited in the ampulloduodenal part of the papilla of Vater, which is lined by intestinal mucosa. They also can develop in deeper parts of the ampulla, which are lined by pancreaticobiliary duct mucosa. Intestinal-type adenocarcinoma and pancreaticobiliary-type adenocarcinoma represent the main histological types of ampullary carcinoma. Furthermore, there exist unusual types and undifferentiated carcinomas. Many carcinomas of intestinal type express the immunohistochemical marker profile of intestinal mucosa (keratin 7-, keratin 20+, MUC2+). Carcinomas of pancreaticobiliary type usually show the immunohistochemical profile of pancreaticobiliary duct mucosa (keratin 7+, keratin 20-, MUC2-). Even poorly differentiated carcinomas, as well as unusual histological types, may conserve the marker profile of the mucosa they developed from. These findings underline the concept of histogenetically different carcinomas of the papilla of Vater which develop either from intestinal- or from pancreaticobiliary-type mucosa of the papilla of Vater. Molecular alterations in ampullary carcinomas are similar to those of colorectal as well as pancreatic carcinomas, although they appear at different frequencies. In future studies, molecular alterations in ampullary carcinomas should be correlated closely with the different histologic tumor types. Consequently, the histologic classification should reflect the histogenesis of ampullary tumors from the two different types of papillary mucosa.

Topics: Adenocarcinoma; Adenoma; Ampulla of Vater; Common Bile Duct Neoplasms; Gallbladder Neoplasms; Humans; Immunohistochemistry; Intermediate Filament Proteins; Keratin-20; Keratin-7; Keratins; Mucin 5AC; Mucin-2; Mucins; Prognosis

Primary sebaceous neoplasms of the salivary glands are extremely rare occurrences; furthermore, sebaceous lymphadenocarcinoma has only been reported in three patients. We report a case of sebaceous lymphadenocarcinoma arising in a lymphadenoma of the parotid gland. The patient was a 55-year-old man who presented with a parotid mass of 3 years' duration. Histologically, the lesion consisted of a sebaceous lymphadenoma with transition to a sebaceous carcinoma. The cytologic touch-preparation at the time of frozen section showed clusters of benign sebaceous cells in a rich lymphocytic background together with tridimensional clusters of malignant epithelial cells, strongly raising the suspicion of a malignant neoplasm arising in a benign sebaceous lesion. Malignant transformation of the sebaceous lymphadenoma, although rare, should be considered in enlarging, locally invasive parotid lesions, considering that clinical behavior and prognosis will be determined by the nature of the malignant component.

Topics: Adenocarcinoma; Adenolymphoma; Biomarkers, Tumor; Humans; Immunohistochemistry; Keratins; Male; Middle Aged; Parotid Neoplasms; Radiotherapy, Adjuvant; Sebaceous Gland Neoplasms; Sebaceous Glands; Treatment Outcome

Ovarian metastasis originating from bronchioloalveolar carcinoma (BAC) has not been reported previously. We report a 63-year-old Chinese woman who was diagnosed as BAC with pleural metastasis in 1997. Four years later, she complained of vaginal bleeding, and a pelvic mass was discovered by an abdominal computerized tomography scan. Tumor debulking and total hysterectomy with bilateral salpingo-oopherectomy were performed. Pathology disclosed well-differentiated adenocarcinoma, with abundant clear cytoplasm, in the ovaries. Furthermore, immunohistochemical staining revealed that the tumor cells from the ovary and pleura were reactive to thyroid transcription factor 1 (TTF-1) and cytokeratin-7 (CK-7) but were negative for cytokeratin-20 (CK-20). The results of immunohistochemical staining, clinical course, and pathological features were compatible with the diagnosis of BAC with ovarian metastasis. In conclusion, to investigate the primary site of a metastatic ovarian cancer, clinicians should not forget the lungs since the incidence of lung cancer in females is increasing. Moreover, a monoclonal antibody panel for TTF-1, CK-7, and CK-20 may facilitate discrimination between primary and metastasized ovarian adenocarcinomas and/or identifying tumors of pulmonary origin.

Topics: Adenocarcinoma; Adenocarcinoma, Bronchiolo-Alveolar; Biomarkers, Tumor; Fallopian Tubes; Female; Humans; Immunohistochemistry; Intermediate Filament Proteins; Keratin-20; Keratin-7; Keratins; Lung Neoplasms; Middle Aged; Nuclear Proteins; Ovarian Neoplasms; Ovariectomy; Thyroid Nuclear Factor 1; Transcription Factors

The normal prostate shows a high degree of cellular organization. The basal layer is populated by prostate epithelial stem cells and a population of transiently proliferating/amplifying (TP/A) cells intermediate to the stem cells and fully differentiated cells. The luminal layer is composed of fully differentiated prostate epithelial cells. Neuroendocrine cells are scattered throughout the gland. This organization is also seen in prostate cancer, where the tumor cell origin (cancer stem cells) can be traced to a normal cell type by characteristic keratin expression patterns. Basal cells showed strong expression of K-[keratin]5, but they were only weakly positive for K18. Luminal cells strongly expressed K18. A subpopulation of basal cells coexpressed K5 and K14. These keratin expression patterns changed with the degree of cell differentiation as well as location. The least differentiated stem cells in the basal layer were positive for K5 and K14, with weak expression for K18. Intermediate stages of differentiation were identified by expression of K5 and K18. Neuroendocrine cells also expressed K5 as well as typical neuroendocrine cell markers (eg, chromogranin A). Evidence supporting the hypothesis that prostate cancer arises from malignant transformation of intermediate stem cells included the presence in prostate cancers of keratin patterns associated with the intermediate stages of differentiation, androgen independence of both prostate cancers and intermediate stem cells, and expression of c-met by both the TP/A intermediate stem cells and tumor cells.

Topics: Adenocarcinoma; Androgens; Cell Differentiation; Cell Division; Cell Transformation, Neoplastic; Epithelial Cells; Humans; Immunophenotyping; Keratins; Male; Neoplasm Proteins; Neoplasms, Hormone-Dependent; Prostatic Neoplasms; Proto-Oncogene Proteins c-met; Stem Cells

Polymorphous low-grade adenocarcinoma (PLGA) and adenoid cystic carcinoma (ACC) have several overlapping histological patterns, including cribriform, tubular and solid patterns. The overlapping clinicopathological features of PLGA and ACC may result in a diagnostic pitfall. ACC has a much worse prognosis than PLGA, making differentiation important for therapeutic and prognostic purposes. Histopathological features remain the most reliable criteria to distinguish between these two tumours. Although PLGA and ACC have many features in common, PLGA is uncommon in the major salivary glands. Histopathological distinction is therefore mainly a problem in tumours of minor salivary gland origin where small biopsies often contribute to diagnostic difficulties. This paper reviews studies which have utilised several immunohistochemical markers in attempts to distinguish between PLGA and ACC, and also studies which have focussed on the two tumours individually. The potential discriminating value of immunohistochemistry between cases of PLGA and ACC still remains controversial.

Topics: Actins; Adenocarcinoma; Biomarkers, Tumor; Carcinoembryonic Antigen; Carcinoma, Adenoid Cystic; Diagnosis, Differential; Humans; Keratins; Mucin-1; Proliferating Cell Nuclear Antigen; S100 Proteins; Salivary Gland Neoplasms

Adenocarcinoma of the upper esophagus arising in heterotopic gastric mucosa is a rare tumor, with only 15 cases reported to date. We report a case in a 61-year-old man complaining of dysphagia. The upper endoscopy revealed that the tumor measured 3 cm and was 22 cm distant from the incisivors. A hiatal hernia with erosive esophagitis of the distal esophagus was present. On microscopic examination the tumor corresponded to a poorly differentiated adenocarcinoma immunoreactive for cytokeratin (CK) 7 and p53. The surrounding heterotopic gastric mucosa contained foci of intestinal metaplasia immunoreactive for CK7 in the surface epithelium and the entire glands and CK20 in the superficial epithelium and superficial glands. The CK7 and p53 positivity that we observed is very common in Barrett's adenocarcinomas. Moreover, intestinal metaplasia in heterotopic gastric mucosa shows the same CK7/CK20 pattern as specialized Barrett's mucosa. These common features shared by adenocarcinomas of the upper esophagus arising in heterotopic gastric mucosa and adenocarcinoma of the lower esophagus developing on Barrett's mucosa suggest that those two types of cancer have a common pathogenesis, related to gastroesophageal reflux disease.

Topics: Adenocarcinoma; Barrett Esophagus; Biomarkers, Tumor; Choristoma; Combined Modality Therapy; Esophageal Neoplasms; Fatal Outcome; Gastric Mucosa; Humans; Immunohistochemistry; Keratin-7; Keratins; Male; Middle Aged; Tumor Suppressor Protein p53

In diagnosing uterine cancers, cells and tissue samples can be directly obtained from the lesion. Cytologic and histologic investigation is the best method for screening and early detection of primary uterine cancers. Tumor markers may be useful for monitoring the clinical course of therapy and early detection of recurrence for which cytologic examination can not be done. Moreover, high levels of tumor markers may represent tumor invasiveness and metastasis to lymph nodes and/or other organs, and may indicate a poor prognosis for the patient. Strictly speaking, tumor markers are not tumor-specific but tumor-associated substances. They can be elevated in sera from healthy individuals under various conditions, and from patients with benign tumors. Squamous cell carcinoma-associated antigen (SCC) is relatively tumor-specific, and widely used for monitoring patients with squamous cell carcinoma not only of the uterine cervix. On the other hand, there is no specific tumor marker for uterine corpus carcinoma. Combination assay of several tumor markers including cancer antigen 125 (CA125) as a core marker may be of greater diagnostic value in cases of uterine corpus carcinoma.

Topics: Adenocarcinoma; Antigens, Neoplasm; Biomarkers, Tumor; CA-125 Antigen; CA-19-9 Antigen; Carcinoembryonic Antigen; Carcinoma, Squamous Cell; Female; Humans; Keratin-19; Keratins; Neoplasm Proteins; Serpins; Tissue Polypeptide Antigen; Uterine Cervical Neoplasms; Uterine Neoplasms

Several case reports have emphasized that esophageal carcinoid tumors are associated with a poor prognosis. To expand our knowledge about the pathology and biologic behavior of these rare tumors, we reviewed the clinicopathologic and immunohistochemical findings of four cases of primary esophageal carcinoid. The age of the patients ranged from 48 to 82 years (mean 63 years; median 61 years). The lower segment of the esophagus was involved in two cases and the mid segment was involved in one case. The sizes of the tumors ranged from 0.3 cm to 3.5 cm. Two tumors were confined to the lamina propria and two invaded into the muscular wall. Two tumors appeared polypoid, whereas the remaining two were incidental findings and associated with adenocarcinoma arising in a background of Barrett esophagus. The adenocarcinoma was superficially invasive in one case, whereas it penetrated the muscular wall in the other. All four carcinoid tumors were immunoreactive with chromogranin and synaptophysin. There was focal expression of serotonin in two cases, glucagon in one case, and pancreatic polypeptide in one case. Endocrine cell hyperplasia was noted in both the Barrett esophagus and the invasive adenocarcinoma. One patient died secondary to postoperative pneumonia. Three patients are alive and disease free at 1, 6, and 23 years status post therapy. None of the patients had metastatic disease. These findings show that esophageal carcinoids are associated with a favorable prognosis. They arise in two settings: (1) a single large polypoid tumor or (2) an incidental finding and in association with adenocarcinoma arising in the background of Barrett esophagus. The presence of endocrine cell hyperplasia in the Barrett mucosa and the adenocarcinoma supports the hypothesis that these lesions arise from a common stem cell.

Topics: Adenocarcinoma; Aged; Aged, 80 and over; Barrett Esophagus; Carcinoid Tumor; Chromogranins; Esophageal Neoplasms; Female; Gastrins; Glucagon; Humans; Immunohistochemistry; Keratins; Male; Middle Aged; Pancreatic Polypeptide; Polyps; Prognosis; Synaptophysin

Metastatic adenocarcinoma from an unknown primary site is a common clinical problem. The use of cytokeratins 20 (CK20) and 7 (CK7) was proposed to identify the primary sites in this situation. In this review, the results of 29 studies were summarised and the difficulties of data comparison described. Most tumours retained the CK20 phenotype during metastasis, but lung, non-mucinous ovarian, and gastric adenocarcinomas showed statistically significant differences in CK20 expression in the reported primary and metastatic cases. Ductal breast carcinomas, lung and non-mucinous ovarian adenocarcinomas showed significant differences in CK7 expression when primary and metastatic tumours were compared. CK20 positivity alone indicates metastatic spread of adenocarcinoma in several organs. CK7 negativity is consistent with metastases of adenocarcinomas in the lungs, ovaries, liver or serous membranes. CK20/7 phenotyping of adenocarcinomas is a useful diagnostic tool if based on algorithmic and probabilistic approaches and a detailed database.

Topics: Adenocarcinoma; Biomarkers, Tumor; Diagnosis, Differential; Humans; Intermediate Filament Proteins; Keratin-20; Keratin-7; Keratins; Neoplasms, Unknown Primary; Phenotype

A 1 cm polypoid lesion was encountered on the posterior vaginal wall in a 56-year-old woman with no history of diethylstilbestrol exposure that on microscopic examination was a moderately differentiated adenocarcinoma of intestinal type. The tumor was cytokeratin 20 and carcinoembryonic antigen positive and negative for cytokeratin 7. Mucin histochemistry demonstrated the presence of o-acetylated sialomucin, a specific marker of large intestinal differentiation. The initial interpretation favored a metastasis from a colonic adenocarcinoma, but clinical investigations showed no evidence of a primary gastrointestinal lesion. The morphology, histochemical, and differential cytokeratin profile led to the lesion being reinterpreted as a primary intestinal-type adenocarcinoma of the vagina arising from a tubular adenoma. Although a very rare tumor, awareness of this lesion is important as it must be distinguished from metastatic adenocarcinomas from other sites.

Topics: Adenocarcinoma; Adenoma; Carcinoembryonic Antigen; Fallopian Tubes; Female; Humans; Intestinal Neoplasms; Keratins; Middle Aged; Mucins; Omentum; Ovariectomy; Vaginal Neoplasms

Topics: Adenocarcinoma; Barrett Esophagus; Biomarkers; Cardia; Epithelium; Esophageal Neoplasms; Humans; Intermediate Filament Proteins; Keratin-20; Keratin-7; Keratins

The presence of colonic-type epithelium in the urinary tract is not an uncommon occurrence, but tumors derived from it are rare. Tumors arising from colonic-type epithelium, including villous adenoma and adenocarcinoma, have been reported in the renal pelvis, ureter, urinary bladder, and urethra. Villous adenomas of the urinary tract are rare, being most common in the urinary bladder, followed by the urethra. Morphologic features of these tumors are similar to those of the colonic adenomas. The largest published series of villous adenomas of the urinary tract was a study of 23 patients. This study is reviewed and other reports on villous adenomas of the urinary tract are discussed.

Topics: Adenocarcinoma; Adenoma, Villous; Aged; Aged, 80 and over; Biomarkers; Carcinoembryonic Antigen; Humans; Immunohistochemistry; Intermediate Filament Proteins; Keratin-20; Keratin-7; Keratins; Mucin-1; Neoplasms, Multiple Primary; Urologic Neoplasms

One of the major diagnostic challenges in prostate needle biopsy interpretation is definitive establishment of a malignant diagnosis based on a minimal or limited amount of carcinoma in needle biopsy tissue. Major and minor diagnostic criteria should be used for interpretation of small foci of carcinoma. The constellation of findings and a combination of the major and minor diagnostic criteria permit a definitive diagnosis of focal adenocarcinoma. The differential diagnosis of minimal prostatic adenocarcinoma in needle biopsy tissue is broad and includes many benign lesions. The benign entities most likelty to be misdiagnosed as minimal prostatic adenocarcinoma are atypical adenomatous hyperplasia (adenosis) and atrophy. High-grade prostatic intraepithelial neoplasia and a descriptive diagnosis of focal glandular atypia or atypical small acinar proliferation also should be considered before diagnosing minimal adenocarcinoma. The most valuable adjunctive study for the diagnosis of minimal adenocarcinoma is immunohistochemistry using antibody 34 beta E12, reactive against basal cell-specific high-molecular-weight cytokeratins. Most cases can be diagnosed based on H&E-stained sections without this immunostain. Most minimal carcinomas in prostate needle biopsy tissue are of intermediate histologic grade, and most are indicative of pathologically significant carcinoma in the whole prostate gland.

Topics: Adenocarcinoma; Atrophy; Biopsy, Needle; Diagnosis, Differential; Humans; Hyperplasia; Immunohistochemistry; Keratins; Male; Prostatic Neoplasms

Although it is generally accepted that immunohistochemistry can assist in distinguishing between epithelial mesotheliomas and metastatic adenocarcinomas to the serosal membranes, a great deal of controversy exists regarding not only the practical value of some of the markers currently used, but also which should be included as part of the routine diagnostic panel. Until recently, these panels consisted primarily of antibodies that stained adenocarcinomas but not mesotheliomas. Over the last few years, however, markers that are commonly expressed in mesotheliomas but not in adenocarcinomas have been recognized. The focus of this review is on those markers for which there is an indication that they have a practical use in the diagnosis of mesothelioma. Special emphasis is placed on those which have been most recently recognized.

Topics: Adenocarcinoma; Antibodies, Monoclonal; Biomarkers, Tumor; Cadherins; Calbindin 2; Carcinoembryonic Antigen; Diagnosis, Differential; DNA-Binding Proteins; Humans; Hyaluronan Receptors; Keratins; Lewis X Antigen; Mesothelioma; S100 Calcium Binding Protein G; Thrombomodulin; Transcription Factors; WT1 Proteins

Clinically evident metastases of carcinomas to the thyroid gland are rare, particularly from a colorectal primary tumor. We present a case of colonic adenocarcinoma metastatic to the thyroid gland with histopathologic and immunohistochemical findings. A 68-year-old woman with a history of Dukes' stage B colon carcinoma presented a mass in the thyroid gland. The tumor was confirmed to be metastatic adenocarcinoma from the colon. The immunohistochemical findings demonstrated positive staining for cytokeratin 20, low-molecular-weight cytokeratin, villin and carcinoembryonic antigen, but stains were negative for cytokeratin 7 and thyroglobulin.

Topics: Adenocarcinoma; Aged; Biomarkers, Tumor; Carcinoembryonic Antigen; Carrier Proteins; Colonic Neoplasms; Female; Humans; Immunoenzyme Techniques; Intermediate Filament Proteins; Keratin-20; Keratin-7; Keratins; Microfilament Proteins; Thyroid Neoplasms; Thyroid Nodule; Tomography, X-Ray Computed

Gastric adenocarcinoma is one of the most common gastrointestinal (GI) malignancies, especially among Japanese adults, but represents only 0.05% of all malignant pediatric GI tumors. We report a case of gastric adenocarcinoma arising at the esophageal gastric junction of an 11-year-old girl. The tumor was polypoid, measuring 3.0 x 3.0 x 1.2 cm and was light gray and partially red in color with a stalk. Light microscopic examination of the lesion demonstrated adenocarcinoma of variable degrees of both architectural and nuclear atypia with invasion into the submucosa. Immunohistochemical findings of cytokeratin subtypes revealed positive immunoreactivity for cytokeratin subtypes 8, 19 and 20 and negative for 5/6/18, 7, 13 and 14, which is consistent with those of gastric adenocarcinoma. The patient was alive and well 12 months postoperatively.

Topics: Adenocarcinoma; Antimetabolites, Antineoplastic; Child; Cisplatin; Esophagectomy; Esophagogastric Junction; Female; Fluorouracil; Gastrectomy; Humans; Immunohistochemistry; Keratins; Stomach Neoplasms

A variety of small acinar lesions of the prostate can mimic prostate cancer in punch biopsies and in transurethral resection material. The first part of this review deals with differential diagnostic problems of the central and transition zone, including atypical adenomatous hyperplasia of the prostate, atrophic processes, sclerosing adenosis, basal cell hyperplasia, and low-grade adenocarcinoma. The second part deals with differential diagnostic problems in the peripheral zone: prostatic intraepithelial neoplasia, postatrophic hyperplasia, Cowper's glands, seminal vesicles, and ductal and intraductal carcinoma. Finally, atypical and small acinar proliferations are described. Diagnostic perspectives are discussed. proliferations (ASAP) that cannot be integrated into any of the well-established diagnostic entities [1, 16, 22, 41]. The relevant glandular proliferations of the central, transitional and peripheral zones of the prostate are discussed here with reference to the related carcinomas.

Topics: Adenocarcinoma; Atrophy; Diagnosis, Differential; Humans; Keratins; Male; Precancerous Conditions; Prostate; Prostate-Specific Antigen; Prostatic Diseases; Prostatic Hyperplasia; Prostatic Intraepithelial Neoplasia; Prostatic Neoplasms

Adenocarcinomas account for up to 60% of all metastatic neoplasms of unknown primary origin. In general, adenocarcinomas are the most difficult metastatic tumor to accurately identify the primary site. Some metastatic adenocarcinomas have distinctive histological features that allow for their site determination (eg, colonic adenocarcinoma, bronchioloalveolar cell carcinoma), although the majority of metastatic adenocarcinomas have histological features that are not distinctive enough to allow for a specific diagnosis of their origin. For this reason, electron microscopy and immunohistochemistry have been used to help identify the exact type (origin) of metastatic adenocarcinomas. Relatively specific ultrastructural features used to diagnose metastatic adenocarcinomas of unknown primary origin include tubular myelin, intranuclear surfactant apoprotein tubular inclusions, Clara cell granules, uniform short microvilli with filamentous cores and core rootlets, Langerhans cells associated with neoplastic cells, cytoplasmic hyaline globules, lipid droplets, glycogen, and cytoplasmic crystals. Only a few of these ultrastructural features are absolutely specific. Relatively specific immunohistochemical tests used to diagnose metastatic adenocarcinomas of unknown primary origin include prostate-specific antigen, thyroglobulin, estrogen and progesterone receptor proteins, thyroid transcription factor-I, and surfactant apoproteins. Of these, prostate-specific antigen and thyroglobulin are the most specific. The purpose of this article is to discuss the use of electron microscopy and immunohistochemistry in the site-specific diagnosis of metastatic adenocarcinomas of unknown primary origin.

Topics: Adenocarcinoma; Biomarkers, Tumor; Female; Humans; Immunoenzyme Techniques; Keratins; Male; Microscopy, Electron; Neoplasms, Unknown Primary

Topics: Adenocarcinoma; Biomarkers, Tumor; Cadherins; Calbindin 2; Diagnosis, Differential; Humans; Hyaluronan Receptors; Immunohistochemistry; Keratins; Lung Neoplasms; Mesothelioma; Pleural Neoplasms; S100 Calcium Binding Protein G; Thrombomodulin

Topics: Adenocarcinoma; Biomarkers, Tumor; Breast Neoplasms; Carcinoma, Squamous Cell; Carcinoma, Transitional Cell; Cell Differentiation; Colorectal Neoplasms; Female; Humans; Keratins; Neoplasms, Glandular and Epithelial; Oropharyngeal Neoplasms; Pancreatic Neoplasms; Stomach Neoplasms; Urologic Neoplasms

Topics: Adenocarcinoma; Biomarkers, Tumor; Bone Marrow; Germany; Humans; Japan; Keratins; Lymphatic Metastasis; Neoplasm Staging; Prognosis; Stomach Neoplasms; Survival Rate; United States

Herein is a review of clear cell neoplasms of selected sites in the urinary tract and male reproductive system, including the kidney, the urinary bladder, testis, epididymis, and prostate. Clear cell cytoplasmic alteration in neoplasms at these sites is a relatively common light microscopic finding. Examples of such neoplasms with clear cell change include the clear cell type of renal cell carcinoma, clear cell adenocarcinoma of urethra and bladder, the classic type of seminoma, papillary cystadenoma of the epididymis, and well-differentiated adenocarcinoma of the prostate. Of importance, numerous non-neoplastic benign entities may also manifest cleared cytoplasm and therefore are presented in the differential in this review. Indeed, knowledge of the neoplastic and non-neoplastic entities displaying clear cell change at each anatomic site should enable the surgical pathologist to approach the differential diagnosis of these conditions in a more logical and rigorous fashion.

Topics: Adenocarcinoma; Alkaline Phosphatase; Biomarkers, Tumor; Carcinoma, Renal Cell; Diagnosis, Differential; Genital Neoplasms, Male; Humans; Immunohistochemistry; Keratins; Kidney Neoplasms; Male; Mucin-1; Prostatic Neoplasms; Testicular Neoplasms; Urinary Bladder Neoplasms; Urologic Neoplasms

We report a case of primary gastric choriocarcinoma with liver metastasis. The mixed histologic patterns included adenocarcinoma, undifferentiated carcinoma, and choriocarcinoma. Immunohistologic staining for the beta-subunit of human chorionic gonadotrophin (beta-HCG) showed positive results in the choriocarcinoma, adenocarcinoma, and normal mucosal gland. However, positive HCG cells were present at different intensities in the choriocarcinoma, adenocarcinoma, and normal mucosal gland. The level of HCG was significantly increased in serum. This unusual tumor probably resulted from dedifferentiation of a primary adenocarcinoma or developed directly from the mucosal glands.

Topics: Adenocarcinoma; Aged; alpha-Fetoproteins; Choriocarcinoma; Chorionic Gonadotropin, beta Subunit, Human; Fatal Outcome; Humans; Immunohistochemistry; Keratins; Liver Neoplasms; Male; Mucin-1; Neoplasms, Multiple Primary; Stomach Neoplasms

We report a case of adenocarcinoma of the rectum with foci of metaplastic shadow cells. The patient was a 65 year old man with anemia. Macroscopically the tumor was an ordinary rectal cancer. Microscopically, in addition to the features of moderately differentiated adenocarcinoma invading the subserosa, islands of shadow cells in tumor nests were detected in both primary and one of three pericolic metastatic lymph node lesions. Neoplastic glandular cells showed gradual transition to shadow cells. An antibody specific for high-molecular-weight cytokeratins reacted with the shadow cells and intermediate zone epithelial cells surrounding them, but no CEA, low-molecular-weight cytokeratins or cyclin D1 was detectable in them. Cytokeratin 14 was expressed only in the transitional zone epithelial cells. The intermediate zone epithelial cells were regarded as metaplastic squamous cells, from which the shadow cells were derived. The patient died of multiple liver metastases nine and a half months after surgery. To our knowledge, this is the first report of an immunohistochemical study of rectal adenocarcinoma containing shadow cells not only in the primary lesion but also in a metastatic lymph node.

Topics: Adenocarcinoma; Aged; Carcinoembryonic Antigen; Cyclin D1; Epithelial Cells; Humans; Immunohistochemistry; Keratins; Lymph Nodes; Lymphatic Metastasis; Male; Metaplasia; Rectal Neoplasms; Rectum; Tumor Suppressor Protein p53

Pleural cancers are tumours which are frequently refractory to all treatment. Faithful animal models (experimentally reproducing the human disease) are necessary to study the natural history of this disease and to test standard or experimental treatments. The athymic bald mouse is currently used for the construction of experimental models because it avoids immunological rejection. Initially murine models were constructed following subcutaneous injection of cloned cells then implantation of tumour fragments. The tumours obtained are not superimposable on the human disease in terms of local, regional or metastatic development and the results from these studies, using such models, are difficult to transpose to humans. It is possible to implant fragments of histologically intact human tumour into the pleura of bald mice. This orthoptic (site for site) transplantation enables one to obtain in the mouse a tumour which tends to conserve the biological characteristics of the original tumour and to develop locally, regionally and at distance in a fashion which is similar to the human disease. In spite of the inherent limits of immunotolerance of the host and thus difficulties of extrapolation to man, this review attempts to point out the place for these models and for an understanding of the therapy of pleural cancers.

Topics: Adenocarcinoma; Animals; Antineoplastic Agents; Autopsy; Carcinoembryonic Antigen; Humans; Immunohistochemistry; Interferon-gamma; Keratins; Mesothelioma; Mice; Mice, Nude; Mucin-1; Neoplasm Transplantation; Neoplasms, Experimental; Pleura; Pleural Neoplasms; Recombinant Proteins; Vimentin

There has been relatively little written on the diagnosis and reporting of adenocarcinoma of the prostate diagnosed in core needle biopsy specimens.. This article reviews issues concerning diagnosing, grading, and quantification of prostate carcinoma in core needle biopsy specimens.. The diagnosis of prostate carcinoma in core needle biopsy specimens is discussed, including the relative frequency and utility of various architecture, cytologic, and ancillary features. Grading of prostate carcinoma in core needle biopsy specimens is evaluated along with the relationship of core needle biopsy grade to corresponding radical prostatectomy grade. The relationship between the extent of carcinoma in core needle biopsy specimens to extent of tumor in the radical prostatectomy is summarized. Finally, this article summarizes articles supporting the use of high molecular weight cytokeratin in the diagnosis of adenocarcinoma of the prostate in core needle biopsy specimens.. Pathologists are not only called upon to diagnose limited cancer in core needle biopsy specimens, but also to quantify and grade these cancers accurately. Issues relating to this pathologic evaluation are critical for physicians treating men with adenocarcinoma of the prostate.

Topics: Adenocarcinoma; Biomarkers, Tumor; Biopsy, Needle; Carcinoma; Humans; Immunohistochemistry; Keratins; Male; Molecular Weight; Prostatectomy; Prostatic Neoplasms

The light microscopic, immunohistochemical, and ultrastructural features of a case of apocrine carcinoma of the upper lip of a 54-year-old white man are described. The neoplasm had a cribriform intraductal component resembling apocrine carcinoma of the breast. The tumor had irregular borders and infiltrated skeletal muscle. The neoplastic cells had abundant eosinophilic granular cytoplasm and showed apical decapitation secretion characteristic of apocrine differentiation. The differential diagnosis is discussed with particular reference to distinction of the tumor from oncocytic carcinoma and ductal carcinoma of minor salivary gland.

Topics: Adenocarcinoma; Antibodies, Neoplasm; Apocrine Glands; Apolipoproteins; Apolipoproteins D; Carcinoembryonic Antigen; Carcinoma; Carrier Proteins; Diagnosis, Differential; Glycoproteins; Humans; Immunoenzyme Techniques; Keratins; Lip Neoplasms; Male; Membrane Transport Proteins; Middle Aged; Salivary Gland Neoplasms

Two cases of tumors of the posterior portion of the petrous bone are presented. Both resulted in significant loss of hearing and caused extensive bone destruction. Microscopically, they corresponded to papillary adenomatous tumors with few histologically aggressive features. Immunohistochemical studies were done, and a positive reaction was obtained with the antibodies against the cytokeratins, Leu-7 and neuronal-specific enolase. A diagnosis of adenocarcinoma of the endolymphatic sac was made. These are rare tumors known for their long clinical prodrome and their local aggressiveness. Increased awareness will allow for earlier diagnosis and treatment.

Topics: Adenocarcinoma; Adenoma; Adolescent; Adult; Bone Neoplasms; CD57 Antigens; Endolymphatic Sac; Female; Humans; Immunohistochemistry; Keratins; Phosphopyruvate Hydratase; Temporal Bone; Tomography, X-Ray Computed

A tumor mass resected from the anterior bladder wall of a 68-year-old woman displayed unusual histologic features: sheets of hepatoid cells merging focally with a secondary glandular pattern of adenocarcinoma. Intracytoplasmic hyaline globules and bile production within the solid areas supported the impression of hepatocytic differentiation. Immunoreactivity for alpha-fetoprotein (AFP) and alpha-1-antitrypsin and a striking canalicular immunostaining pattern for carcinoembryonic antigen and epithelial membrane antigen all indicate hepatocellular differentiation within this bladder tumor. This represents a case of a hepatoid adenocarcinoma located in the urinary bladder. The use of the term "hepatoid" in the literature is reviewed and the reported cases are grouped into two distinct categories of tumors: (1) germ cell tumors with focal hepatoid areas and (2) true hepatoid adenocarcinomas that meet histologic and immunohistochemical criteria for hepatocellular differentiation. AFP-producing tumors without any other feature of hepatocellular differentiation should not be considered as hepatoid tumors. This classification of hepatoid tumors is likely to be important in elucidating the histogenesis and clinicopathologic features of these unusual neoplasms.

Topics: Adenocarcinoma; Aged; alpha 1-Antitrypsin; alpha-Fetoproteins; Antigens, Neoplasm; Carcinoembryonic Antigen; Carcinoma, Endometrioid; Carcinoma, Transitional Cell; Cell Nucleus; Cytoplasm; Female; Humans; Keratins; Liver; Membrane Glycoproteins; Mucin-1; Ureteral Neoplasms; Urinary Bladder Neoplasms; Uterine Neoplasms

Sixteen cases of small-cell carcinoma of the endometrium were encountered in patients who ranged in age from 30 to 78 (mean, 57.4) years. Of the 12 patients whose presenting features are known, eight had abnormal vaginal bleeding, three had pain related to metastatic tumor, and one patient had both symptoms. On pelvic examination, adnexal masses were palpable in three patients, and vaginal involvement was evident in two; one patient had a large palpable periumbilical mass. Thirteen patients underwent total abdominal hysterectomy and bilateral salpingo-oophorectomy. Extrauterine spread was documented intraoperatively in eight cases, including widespread intraabdominal and ovarian metastases in four cases, vaginal involvement in the two cases noted previously, paraaortic lymph node involvement in one case, and tubal involvement in one case. Three tumors were International Federation of Gynecology and Obstetrics (FIGO) stage I, four were stage II, two were stage III, and six were stage IV; in one case, there was insufficient information to allow staging. On gross examination, the tumors were usually described as bulky, ill-defined, and invasive of the myometrium; four were polypoid. Microscopic examination revealed sheets, cords, and nests of small or intermediate-sized cells with scanty cytoplasm, hyperchromatic nuclei, and a high mitotic rate. Single-cell and zonal necrosis and vascular invasion were typically present. Synchronous grade 1 or grade 2 endometrial endometrioid adenocarcinoma was present in eight cases, and complex atypical endometrial hyperplasia, in two others. In three cases, the adenocarcinoma merged almost imperceptibly with the small-cell component. None of the tumors contained argyrophil or argentaffin cells, although nine of 11 tumors were immunoreactive for neuron-specific enolase (one of these was also Leu-7 positive), and another was chromogranin positive. Of the 11 cases with follow-up information, seven patients died of disease (at least four with distant metastases) with a median survival of 12 months, and another patient was alive with distant metastases at 18 months. The remaining patients were clinically free of disease at postoperative intervals of < or = 1 year (two cases) and 4.5 years (one case). This study confirms that small-cell carcinomas of the endometrium are a histologically distinctive subtype of endometrial carcinoma, which, like their counterparts in the uterine cervix, are aggressive tumors with a propensity for

Topics: Adenocarcinoma; Adult; Aged; Carcinoma, Small Cell; Endometrial Neoplasms; Female; Histocytochemistry; Humans; Immunohistochemistry; Keratins; Middle Aged; Neoplasm Invasiveness; Neoplasm Staging; Neoplasms, Multiple Primary; Phosphopyruvate Hydratase

We report a case of spindle-cell adenosquamous carcinoma of the esophagus. This represents the third case in the worldwide literature in which an esophageal polypoid tumor contains adenosquamous carcinoma rather than the usual squamous cell carcinoma in addition to a prominent spindle-cell element. The spindle-cell component displayed positive immunoreaction for both keratin and vimentin, as expression of bidirectional differentiation within a single neoplasm.

Topics: Adenocarcinoma; alpha 1-Antichymotrypsin; alpha 1-Antitrypsin; Carcinoma, Squamous Cell; Esophageal Neoplasms; Humans; Immunohistochemistry; Keratins; Male; Microscopy, Electron; Middle Aged; Vimentin

This is a report of a fatal case of a primary and solid adenosquamous carcinoma (ASC) of the liver in a 58-year-old Japanese woman. There was no association with biliary cysts. Histochemistry and immunohistochemistry support the contention that the neoplasm arose from squamous metaplasia of a mucus-secreting adenocarcinoma (MSA) of intrahepatic biliary duct epithelium.

Topics: Adenocarcinoma; Aged; Aged, 80 and over; alpha-Fetoproteins; Carcinoembryonic Antigen; Carcinoma, Squamous Cell; Female; Humans; Immunohistochemistry; Keratins; Liver Neoplasms; Male; Microscopy, Electron; Middle Aged

Topics: Adenocarcinoma; Adenoma, Islet Cell; Animals; Antibodies, Monoclonal; Breast Neoplasms; Carcinoma, Small Cell; Carcinoma, Squamous Cell; Cytoskeletal Proteins; Desmoplakins; Desmosomes; Electrophoresis, Polyacrylamide Gel; Granulosa Cell Tumor; Humans; Immunosorbent Techniques; Intermediate Filament Proteins; Intermediate Filaments; Keratins; Kidney Neoplasms; Lung Neoplasms; Melanoma; Membrane Proteins; Meningioma; Mesothelioma; Microscopy, Electron; Microscopy, Fluorescence; Neoplasms; Neurosecretory Systems; Skin Neoplasms

This diagnostic seminar discusses the current status of the principles and problems of cytology as it is applied to the diagnosis of lung cancer. This discussion is divided into four major parts. Part I presents a discussion of cytopreparatory techniques and cytology of the lung in the absence of cancer. The cytology of benign proliferations which may mimic cancer is emphasized. The role of cytology in the diagnosis of pulmonary infectious organisms is noted. Part II discusses lung cancer as manifested in specimens of sputum, bronchial washings, and bronchial brushings. Part III presents some data on the validity of cytology with respect to role of specimen number and type in lung cancer diagnosis and cell typing in lung cancer. The continued usefulness and importance of multiple specimens of sputum for lung cancer diagnosis are documented. Part IV presents a brief synopsis of fine needle aspiration biopsy of lung cancer.

Topics: Adenocarcinoma; Aspergillus; Biopsy, Needle; Blastomyces; Bronchi; Carcinoma; Carcinoma, Small Cell; Carcinoma, Squamous Cell; Cell Nucleus; Coccidioides; Cryptococcus neoformans; Cytodiagnosis; Cytological Techniques; Cytoplasm; Epithelium; Histoplasma; Humans; Keratins; Lung Diseases; Lung Diseases, Fungal; Lung Diseases, Parasitic; Lung Neoplasms; Macrophages; Metaplasia; Pneumocystis; Sputum; Strongyloides; Suction; Virus Diseases

Topics: Adenocarcinoma; Carcinoma; Diagnosis, Differential; Endocrine System Diseases; Humans; Immunoenzyme Techniques; Keratins; Lymphoma; Melanoma; Neoplasm Invasiveness; Neoplasms, Germ Cell and Embryonal; Skin Neoplasms; Sweat Gland Neoplasms

Immunohistochemistry of intermediate filaments (IF) is a new and important way to evaluate the epithelial, mesenchymal, muscular, glial, or neural differentiation in tumors. This is based on the stable cell-type-specific expression of IF proteins in normal and neoplastic tissues. Immunohistochemical studies with antibodies to intermediate filaments have also given new perspectives in the histogenesis and biologic nature of many tumors. This article reviews both the recent findings and the authors' experience in the use of intermediate filament antibodies in tumor diagnosis and classification.

Topics: Adenocarcinoma; Antibodies, Neoplasm; Carcinoma, Squamous Cell; Desmin; Diagnosis, Differential; Glial Fibrillary Acidic Protein; Histocytochemistry; Humans; Immunochemistry; Keratins; Melanoma; Mesothelioma; Microfilament Proteins; Microscopy, Electron; Neoplasm Proteins; Neoplasms; Nervous System Neoplasms; Sarcoma; Soft Tissue Neoplasms; Thyroid Neoplasms; Urinary Bladder Neoplasms; Vimentin

Topics: Adenocarcinoma; Carcinoma, Basal Cell; Carcinoma, Squamous Cell; Cell Differentiation; Cells, Cultured; Digestive System Neoplasms; Epithelium; Female; Histocytochemistry; Humans; Keratins; Molecular Weight; Neoplasms

Currently, the diagnostic sensitivity of malignant liver mass biopsies is an important problem in the definitive diagnosis. In this study, we aimed to investigate the role of selective peripheral approach to lesion biopsies for diagnostic sensitivity of liver masses.. Between June 2007 and March 2011, totally 88 patients (50 male, 38 female), referred to our Interventional Radiology Department for sonographically guided Tru-cut biopsies for liver lesions, were examined.All biopsies were performed by an experienced radiologist with an 18-gauge Tru-cut biopsy needle with a spring-loaded biopsy gun under sonographic guidance. We describe two locations (peripheral and central) for liver lesions, with the inner 2/3 part of the mass as central and the outer 1/3 part as peripheral. We obtained biopsy from both of these locations, and samples were transferred to the Pathology Department separately.. According to pathological and immunohistochemistry studies, there were 42 hepatocellular carcinomas and 46 metastases. All of the metastatic tumors were stained by cytokeratin (10 lung adenocarcinoma, 15 breast adenocarcinoma, 16 gastrointestinal tract, 4 prostate, and 1 malignant melanoma of these 46 metastases were reported as primary). According to histopathological results, diagnostic sensitivity was 97.7% in peripherally located biopsies and 86.3% in biopsies taken from the center of the masses (p=0.0063).. Selective peripheral biopsy approach in Tru-cut biopsies of liver lesions has better sensitivity rates for histopathologic diagnosis compared to the centrally located and random biopsies.

Topics: Adenocarcinoma; Adult; Aged; Biomarkers, Tumor; Biopsy, Needle; Breast Neoplasms; Carcinoma, Hepatocellular; Creatine Kinase; Diagnosis, Differential; Female; Gastrointestinal Neoplasms; Humans; Keratins; Liver Cirrhosis; Liver Neoplasms; Lung Neoplasms; Male; Melanoma; Middle Aged; Prostatic Neoplasms; Sensitivity and Specificity; Skin Neoplasms

Recent surgical concepts for primary rectal cancer include the combination of surgery and short-term neoadjuvant radiotherapy (STNR). This is usually given in a dose of 25 Gy over five days in order to reduce local recurrence rates. Clinical studies have shown that local recurrence is found in some patients despite STNR. We identified molecular patterns of the Wnt- and apoptosis pathways as well as expression of junction-associated molecules in rectal cancer specimens of patients who received STNR and in those who did not. Expression patterns were examined by immunohistochemistry and molecular techniques such as LightCycler RT-PCR and Western blot analysis in 25 sporadic rectal adenocarcinoma specimens derived from STNR-patients or non-pretreated donors, respectively. The molecular pattern in response to STNR was heterogeneous and was reflected by responders who show activation of apoptosis and cellular remodeling, whereas the group of non-responders from STNR did not show such reaction and was very similar to untreated controls. Enhanced expression of beta-catenin was generally mediated by STNR, but exclusively in the responder group impaired expression of c-Myc and junction-associated molecules as well as cleavage of poly-ADP-ribose polymerase and of the caspase substrate cytokeratin 19 were found. The molecular profile suggests that STNR interferes with Wnt-signaling and c-Myc expression. STNR in its present form is not suitable to fully complete the sequence of apoptosis in all rectal adenocarcinomas.

Topics: Adenocarcinoma; Adult; Aged; Apoptosis; beta Catenin; Blotting, Western; Cytoskeletal Proteins; Dose Fractionation, Radiation; Female; Gene Expression Regulation, Neoplastic; Humans; Immunohistochemistry; Intercellular Signaling Peptides and Proteins; Keratins; Male; Middle Aged; Neoadjuvant Therapy; Proto-Oncogene Proteins c-myc; Rectal Neoplasms; Reverse Transcriptase Polymerase Chain Reaction; Signal Transduction; Trans-Activators; Wnt Proteins

The DNA content of oesophageal tumour cells is a prognostic factor in untreated patients. To investigate whether DNA ploidy is useful to select patients for neoadjuvant therapy it is of interest to develop a method allowing reliable flow cytometric analysis of the DNA content of tumour cells obtained by forceps biopsy during endoscopy before start of therapy.. Freshly frozen forceps biopsy samples from 30 patients with oesophageal cancer were disaggregated. DNA was stained with propidium iodide and ploidy was determined by flow cytometry. To enhance sensitivity epithelial cells were simultaneously labelled with anti-cytokeratin antibodies. Results were compared with image analysis. To evaluate the sampling error, parallel measurements were done in 10 patients by image analysis on forceps biopsies obtained during endoscopy before surgery and on the resected tumour.. The sensitivity to detect aneuploidy was lower for standard flow cytometry than for image analysis (13 versus 33%). The overall sensitivities were identical using a double labelling technique with additional cytokeratin-staining of the epithelial cells, but divergent results were obtained in 2 cases, where detection of aneuploidy was either possible with image analysis or with double labelling flow cytometry only. DNA content of samples gained by forceps biopsies and surgically resected tumours was concordant in 8 of 10 cases. In 2 patients, aneuploidy was detected only in the surgically resected tumour but not in the pre-operatively obtained forceps biopsies.. A flow cytometric method for routine determination of the DNA ploidy of cells obtained by forceps biopsies from patients with oesophageal cancer was developed and evaluated against image analysis. The technique allows the prediction of DNA content before tumour resection, and might be used for optimising therapy and the patient's quality of live.

Topics: Adenocarcinoma; Aneuploidy; Carcinoma, Squamous Cell; Cell Death; Diploidy; DNA, Neoplasm; Endoscopy, Digestive System; Epithelial Cells; Esophageal Neoplasms; Esophagectomy; Flow Cytometry; Gene Expression Regulation, Neoplastic; Humans; Image Processing, Computer-Assisted; Keratins; Mathematical Computing; Microscopy, Fluorescence; Ploidies; Predictive Value of Tests; Prognosis

Micrometastatic disease in bone marrow is of prognostic significance in colorectal cancer patients. However, detection rates of standard immunocytology are relatively low. We used magnetic activated cell sorting (MACS), a highly sensitive method, to increase detection rates and correlated the presence of cytokeratin (CK)-expressing cells with clinical parameters.. Bone marrow was obtained from 51 consecutive patients with newly diagnosed colorectal adenocarcinoma who underwent primary surgery and 18 control subjects. International Union Against Cancer (UICC) stage I disease was diagnosed in 11 patients, stage II disease was diagnosed in 14 patients, stage III disease was diagnosed in 12 patients, and stage IV disease was diagnosed in 14 patients. CK-positive cells were enriched and stained with magnetically labeled CAM 5.2 antibodies directed to CK 7 and 8.. CK-positive cells were found in 33 (65%) patients and were absent in 18 (35%). Four of 11 (36%) patients with UICC stage I disease, nine of 14 (64%) with stage II diease, eight of 12 (67%) with stage III disease, and 12 of 14 (86%) with stage IV disease were CK-positive. Epithelial cells were more frequently found in pT3/4 (72%) than in pT1/2 (36%) tumors (P =.026), but there was no difference for lymph node status. CK-positive patients had a higher chance for elevated carcinoembryonic antigen (85% v 15%, P = NS) and CA 19-9 levels (92% v 8%, P =.019). There were no significant differences in CA 72-4, sex, age, tumor grading, or tumor localization regarding the presence of CK-positive cells. All control subjects were CK-negative.. In searching for micrometastases in colorectal cancer patients, we have achieved high detection rates by using MACS. The presence of these cells correlated significantly with tumor stage, tumor extension, and the tumor marker CA 19-9.

Topics: Adenocarcinoma; Aged; Aged, 80 and over; Bone Marrow Neoplasms; Colorectal Neoplasms; Female; Humans; Immunomagnetic Separation; Keratins; Male; Middle Aged; Neoplasm Metastasis; Neoplasm Staging; Sensitivity and Specificity

Chromophobe renal cell carcinoma is a relatively uncommon variant of renal carcinoma described in 1985. The main differential diagnosis is renal oncocytoma. Hale's colloidal iron staining is a powerful adjunct to morphological interpretation but it is not specific and is sometimes difficult to interpret. We studied the immunohistochemical expression of cytokeratin 7 to determine its value in distinguishing chromophobe renal cell carcinoma from renal oncocytoma.. Immunostaining was performed on paraffin-embedded tumor tissue of 6 chromophobe renal cell carcinomas and 11 oncocytomas with an antibody to cytokeratin 7 (clone OV-TL 12/30, Dako, France) using a streptavidin-biotin method.. All chromophobe renal cell carcinomas showed strong cytoplasmic staining with peripheral cell accentuation. In contrast, 8 of 11 oncocytomas were entirely negative and 3 showed only weak and focal staining in less than 5% of the tumor cells.. Immunohistochemical staining for cytokeratin 7 may be useful for the differential diagnosis of renal oncocytomas and chromophobe renal cell carcinomas when Hale's colloidal iron staining is uncertain.

Topics: Adenocarcinoma; Adenoma, Oxyphilic; Adult; Aged; Aged, 80 and over; Biopsy, Needle; Carcinoma, Renal Cell; Diagnosis, Differential; Female; Humans; Immunohistochemistry; Keratin-7; Keratins; Kidney Neoplasms; Male; Middle Aged; Sensitivity and Specificity

The presence of cytokeratin 18-positive cells in bone marrow correlates with conventional risk factors in many tumors. We examined whether this was also valid for localized or lymphatically spread prostate cancer.. Immediately before radical prostatectomy, bone marrow aspirates from both sides of the iliac crest were taken from 287 patients. The presence of cells containing cytokeratin 18 was interpreted as micrometastasis.. In patients with negative lymph nodes (n = 219), conventional risk factors (Gleason score, pathologic stage, ploidy, and preoperative prostate-specific antigen) did not correlate with the preoperative detection of cells containing cytokeratin 18. There was also no correlation with lymph node metastases. Furthermore, there was no interdependency between the preoperatively detected number of cells and the established risk factors.. We assume the presence of epithelial cells in bone marrow to be an independent parameter, the clinical importance of which must be substantiated by further studies.

Topics: Adenocarcinoma; Aged; Bone Marrow Neoplasms; Flow Cytometry; Humans; Keratins; Male; Middle Aged; Ploidies; Prognosis; Prostatectomy; Prostatic Neoplasms; Risk Factors

Recently, tissue polypeptide-specific antigen (TPS), a cytokeratin 18 marker, was described to be discriminative between cancer of the prostate (CaP) and benign prostatic hyperplasia (BPH). Cyfra 8/18, a marker which recognizes both cytokeratin 8 and 18 fragments, is discussed to improve sensitivity and specificity of TPS. We investigated whether Cyfra 8/18 serum concentration discriminates between patients with clinically localized CaP and BPH.. Serum Cyfra 8/18 levels were determined in patients with untreated CaP before radical prostatectomy (pT1-3pNoMo; n = 11) and with histologically confirmed BPH (n = 22). Cyfra 8/18 concentration was correlated to the prostate-specific antigen (PSA) concentration.. Median Cyfra 8/18 level was 0.64 ng/ml in CaP patients and 0.57 ng/ml in BPH patients. This difference is statistically not significant (p = 0.91). Furthermore, no correlation to PSA levels could be established (CaP: r = 0.036; BPH: r = 0.09).. In contrast to a recent report we found the Cyfra 8/18 serum concentration to be a nondiscriminative parameter between CaP and BPH.

Topics: Adenocarcinoma; Aged; Biomarkers, Tumor; Humans; Keratins; Male; Middle Aged; Prognosis; Prostate-Specific Antigen; Prostatic Hyperplasia; Prostatic Neoplasms; Sensitivity and Specificity; Statistics, Nonparametric

After curative resection for pancreatic cancer, only 10% of patients survive disease for 5 years. These dismal results suggest the presence of occult tumor at the time of initial operation. This phase I/II study was conducted to compare traditional exploratory laparotomy with radioimmunoguided surgery (RIGS) in the assessment of disseminated pancreatic cancer.. Ten patients with the diagnosis of adenocarcinoma of the pancreas were injected intravenously with 1 mg CC49 monoclonal antibody radiolabeled with 2 mCi iodine 125. All patients were evaluated by a standard abdominal exploration followed by RIGS. Tumor identified by each technique was documented and categorized as neoplasm disseminated to viscera or lymphatics.. There were 25 visceral sites of disease that were traditionally discovered at the time of exploration including pancreas, omentum, small bowel, pelvis, liver, and other. All 25 sites of disease were positive by RIGS plus an additional four sites of visceral tumor for a total of 29 RIGS positive sites of disease. Six lymphatic sites of disease were discovered by traditional examination; however, 44 sites of lymphatic sites were documented by RIGS (p < 0.001). In addition, nine traditionally and pathologically negative/RIGS positive nodes were subjected to cytokeratin and MOC 31 immunohistochemistry. Six of nine nodes were positive by cytokeratin immunohistochemistry, and five of the six cytokeratin positive nodes were MOC 31 positive.. These data suggest that the RIGS technique detected significantly more foci of visceral spread of tumor than traditional exploratory laparotomy and significantly more sites of lymphatic dissemination were identified by RIGS than by standard exploration.

Topics: Adenocarcinoma; Antibodies, Monoclonal; Antigens, Neoplasm; Humans; Immunohistochemistry; Iodine Radioisotopes; Keratins; Laparoscopy; Liver Neoplasms; Lymphatic Metastasis; Neoplasm Metastasis; Pancreatic Neoplasms; Radioimmunodetection; Survival Rate; Time Factors

The micrometastatic spread of tumour cells is usually missed by conventional diagnostic techniques, although this spread largely determines the prognosis of patients with primary epithelial cancers. By use of the monoclonal antibody, CK2, to epithelial cytokeratin component number 18 (CK18), individual disseminated carcinoma cells present in bone marrow of cancer patients can now be identified. In the present study, this approach has been applied to patients with virginal stage C adenocarcinoma of the prostate. Double-sided aspirates of iliac bone marrow from 24 of 44 evaluable patients (54.4%) exhibited between one and 38 CK18-positive cells per sample of 2 x 10(6) mononuclear cells. In 13 of these 24 positive patients, CK-positive cells were only detected in one of the two aspirates analysed. There was no statistically significant correlation between this finding and established risk factors, such as the volume and histological grade of the primary tumour or the concentration of prostate specific antigen and prostatic acid phosphatase in serum. The follow-up time is too short to provide meaningful data on the prognostic significance of isolated CK18-positive cells in bone marrow, which, however, has been recently demonstrated in other types of primary epithelial cancers. In conclusion, the presence of prostatic tumour cells in bone marrow might be interpreted as an indicator of the metastatic capacity of an individual primary tumour. The immunocytochemical detection of these cells may, therefore, be useful for increasing the precision of current tumour staging, and to monitor minimal residual cancer in an individual patient.

Topics: Adenocarcinoma; Antibodies, Monoclonal; Biomarkers, Tumor; Bone Marrow Neoplasms; Humans; Immunoenzyme Techniques; Keratins; Male; Prostatic Neoplasms; Risk Factors

Cytokeratins, the intermediate filaments, are expressed by many epithelial cells. Immunohistochemistry revealed the presence of cytokeratin-19 both in bronchial epithelium and in lung cancer cells. The aim of our study was to establish the value of serum cytokeratin-19 estimation by immunoenzymatic assay (Enzymun Cyfra 21-1, Boehringer Mannheim) in the patients (pts) with lung cancer (Ic). 153 pts (104 men, 49 women, median age 50 years) entered this study. The group consisted of 37 pts with benign lung diseases (control group), 56 pts with squamous cell Ic, 37 pts with small cell Ic and 23 with adenocarcinoma. Cut off value was determined at 4 ng/ml, with 96% of specificity. Elevated cytokeratin-19 values were found in 41% of pts with lung cancer (45% of squamous cell Ic, 39% of adenocarcinoma and 35% of small cell Ic). Median cytokeratin-19 values were 2.2 ng/ml in the control group, 3.4 ng/ml in squamous cell Ic, 3.3 ng/ml adenocarcinoma and 2.9 in small cell Ic. Cytokeratin-19 elevation was observed more often in non small cell Ic pts with advanced disease, stage III--46%, stage IV--50% than in early stages (I + II)--34%. In small cell Ic pts the frequency of cytokeratin-19 elevation was 20% in limited disease versus 45% in extensive disease. We conclude that cytokeratin estimation is not valuable in the recognition of histologic type of lung cancer, although elevated levels are seen more often in squamous cell Ic. Cytokeratin-19 estimation may be also helpful in lung cancer staging.

Topics: Adenocarcinoma; Adolescent; Adult; Aged; Biomarkers, Tumor; Carcinoma, Small Cell; Carcinoma, Squamous Cell; Female; Humans; Keratins; Lung Neoplasms; Male; Middle Aged; Peptide Fragments

To evaluate the efficiency of pan-keratin immunostaining, tissue microarrays of 13,501 tumor samples from 121 different tumor types and subtypes as well as 608 samples of 76 different normal tissue types were analyzed by immunohistochemistry. In normal tissues, strong pan-keratin immunostaining was seen in epithelial cells. Staining intensity was lower in hepatocytes, islets of Langerhans, and pneumocytes but markedly reduced in the adrenal cortex. Pan-keratin was positive in ≥98% of samples in 62 (83%) of 75 epithelial tumor entities, including almost all adenocarcinomas, squamous cell and urothelial carcinomas. Only 17 of 121 tumor entities (13%) had a pan-keratin positivity rate between 25% and 98%, including tumors with mixed differentiation, endocrine/neuroendocrine tumors, renal cell carcinomas, adrenocortical tumors, and particularly poorly differentiated carcinoma subtypes. The 15 entities with pan-keratin positivity in 0.9%-25% were mostly of mesenchymal origin. Reduced/absent pan-keratin immunostaining was associated with high UICC stage (p = 0.0001), high Thoenes grade (p = 0.0183), high Fuhrman grade (p = 0.0049), advanced tumor stage (p < 0.0001) and lymph node metastasis (p = 0.0114) in clear cell renal cell carcinoma, advanced pT stage (p = 0.0007) in papillary renal cell carcinoma, and with advanced stage (p = 0.0023), high grade (p = 0.0005) as well as loss of ER and PR expression (each p < 0.0001) in invasive breast carcinoma of no special type (NST). In summary, pan-keratin can consistently be detected in the vast majority of epithelial tumors, although pan-keratin can be negative a fraction of renal cell, adrenocortical and neuroendocrine neoplasms. The data also link reduced pan-keratin immunostaining to unfavorable tumor phenotype in in epithelial neoplasms.

Topics: Adenocarcinoma; Biomarkers, Tumor; Carcinoma; Carcinoma, Renal Cell; Humans; Keratins; Kidney Neoplasms

The aim of this study is to envisage a streamlined pathological workup to rule out CUPs in patients presenting with MUOs. Sixty-four MUOs were classified using standard histopathology. Clinical data, immunocytochemical markers, and results of molecular analysis were recorded. MUOs were histologically subdivided in clear-cut carcinomas (40 adenocarcinomas, 11 squamous, and 3 neuroendocrine carcinomas) and unclear-carcinoma features (5 undifferentiated and 5 sarcomatoid tumors). Cytohistology of 7/40 adenocarcinomas suggested an early metastatic cancer per se. In 33/40 adenocarcinomas, CK7/CK20 expression pattern, gender, and metastasis sites influenced tissue-specific marker selection. In 23/40 adenocarcinomas, a "putative-immunophenotype" of tissue of origin addressed clinical-diagnostic examinations, identifying 9 early metastatic cancers. Cell lineage markers were used to confirm squamous and neuroendocrine differentiation. Pan-cytokeratins were used to confirm the epithelial nature of poorly differentiated tumors, followed by tissue and cell lineage markers, which identified one melanoma. In total, 47/64 MUOs (73.4%) were confirmed CUP. Molecular analysis, feasible in 37/47 CUPs (78.7%), had no diagnostic impact. Twenty CUP patients, mainly with squamous carcinomas and adenocarcinomas with putative-gynecologic-immunophenotypes, presented with only lymph node metastases and had longer median time to progression and overall survival (< 0.001), compared with patients with other metastatic patterns. We propose a simplified histology-driven workup which could efficiently rule out CUPs and identify early metastatic cancer.

Topics: Adenocarcinoma; Biomarkers, Tumor; Carcinoma, Squamous Cell; Female; Humans; Immunohistochemistry; Keratins; Neoplasms, Unknown Primary

Growing teratoma syndrome (GTS) is a rare clinical entity that can occur in patients with a history of treatment for germ cell tumors (GCTs) and normalized serum tumor markers. Owing to the assortment of tissue types found in teratomas that may exhibit atypical features, distinguishing GTS from metastatic cancer in extragonadal masses can be challenging. Fine-needle aspiration biopsy (FNAB) can be useful for the rapid diagnosis of metastatic masses and has been effective in distinguishing GCTs from one another. However, discrepancies in cytologic and histologic diagnoses have been reported in the evaluation of GCTs by FNAB. The potential incomplete sampling of metastatic teratomas in GTS by FNAB along with features of cellular atypia commonly found in teratomas can lead to a misdiagnosis of metastatic carcinoma and drastically affect treatment. Correlation of cytologic, histologic, clinical, and radiographic findings are essential in evaluating metastatic masses in patients with a history of GCT. We report a case of a 46-year-old man with GTS originally diagnosed on FNAB as metastatic adenocarcinoma compatible with a colorectal primary tumor.

Topics: Adenocarcinoma; Biopsy, Fine-Needle; Diagnosis, Differential; Humans; Keratins; Male; Middle Aged; Neoplasm Metastasis; Rectum; Teratoma; Tomography, X-Ray Computed

Plasmacytoid urothelial carcinoma (PUC) is a rare but clinically aggressive variant of high-grade urothelial carcinoma (HGUC). Cytological features include single plasmacytoid neoplastic cells with N:C ratio around 0.5, eccentric nuclei, nuclear hyperchromasia, irregular nuclear membrane, and vacuolated cytoplasm. Micropapillary urothelial carcinoma (MPUC) is another clinically aggressive variant of HGUC that shares some overlapping features of PUC. The diagnosis of these two aggressive variants in pleural effusions can be challenging due to features mimicking adenocarcinoma, unusual immunochemistry profile, and confusion with differential diagnoses, especially when pertinent clinical information is unavailable. We present report on one case each of pleural fluid metastasis of PUC and MPUC respectively, and compare the findings with that of a metastatic conventional HGUC originally thought to be metastatic adenocarcinoma. The diagnosis of PUC was confirmed with immunohistochemical studies showing expression for cytokeratin, GATA-3, uroplakin II, and CD138, diminished or loss of E-cadherin membranous expression, negative expression for p63, p53, Epicam-BerEP4, Epicam-MOC31, and p120. The diagnosis of MPUC was confirmed with immunostain profile similar to that of PUC except positive stain for E-cadherin, p120, and p53. The diagnosis of HGUC was confirmed with immunohistochemical studies showing expression for cytokeratin, GATA-3, uroplakin II, p63, Epicam-BerEP4 (focal weak), and Epicam-MOC31. Our cases of metastatic urothelial carcinoma showed features mimicking adenocarcinoma and others, especially the MPUC and HGUC were diagnosed without prior tissue diagnosis of urothelial carcinoma. This report emphasizes the cytohistological and immunohistochemical details of urothelial carcinoma involving effusion fluid and discusses potential pitfalls in diagnosis.

Topics: Adenocarcinoma; Cadherins; Carcinoma, Papillary; Carcinoma, Transitional Cell; Humans; Keratins; Tumor Suppressor Protein p53; Urinary Bladder Neoplasms; Uroplakin II; Urothelium

Hepatoid carcinoma (HC) encompasses epithelial extrahepatic tumors exhibiting features of hepatocellular carcinoma (HCC) both by morphology and immunohistochemistry. Distinguishing metastatic HCC from HC may be challenging, particularly when limited material, such as a cytologic specimen, is available. HC from prostatic origin is unusual and has only rarely been characterized by cytology. Herein we present an 86-year-old male with history of castration-resistant prostate cancer developing a left adrenal gland nodule. Fine needle aspiration revealed a poorly differentiated malignant neoplasm diagnosed as metastatic hepatoid prostatic adenocarcinoma based on immunohistochemistry (positive for HepPar1, AFP, NKX3.1, PSMA, and Racemase; and negative for CK7, CK20, cytokeratin 34betaE12, p63, and Arg-1). Because prostatic carcinoma with hepatoid features is rare, and the patient had failed standard therapy, next generation sequencing was performed in an attempt to identify druggable molecular targets. Well-known prostate carcinoma-related alterations were found in three genes (CDK12, AR, and SPOP). In addition, three variants of uncertain significance (DDR2 R128C, SRC P428L, and HNRNPU K574Sfs*32) were identified, which to the best of our knowledge have not been previously reported. Our results support the power of an immunohistochemistry panel including Arg-1 and HepPar1 when HC is suspected, and highlight the value of cytology for comprehensive diagnostic evaluation.

Topics: Adenocarcinoma; Aged, 80 and over; alpha-Fetoproteins; Biomarkers, Tumor; Carcinoma, Hepatocellular; Humans; Keratins; Liver Neoplasms; Male; Nuclear Proteins; Prostate; Prostatic Neoplasms; Racemases and Epimerases; Repressor Proteins

Intercalated duct lesions (IDLs) are usually asymptomatic. We report a case of IDL, in which a palpable mass formed. The patient was a 45-year-old Japanese male, who noticed a mass in the left parotid region. The nodular lesion was well-circumscribed, but did not have a fibrous capsule or exhibit infiltrative growth. It contained a small cystic space and consisted of basaloid cells arranged in a cribriform pattern and inner ductal cells. It had some solid areas of nest-like proliferation displaying mild cellular atypia. Immunohistochemically, the luminal cells were positive for cytokeratin (CK)7 and epithelial membrane antigen, and the abluminal cells were positive for CK5/6, p63, and DOG1. S-100 protein-positive stromal cells were also seen. The lesion's cells were all positive for SOX10, and the nuclei of some basaloid cells were positive for β-catenin. The Ki-67 labeling index was 3.8%. The ductal cells contained diastase-digestion-resistant, Periodic acid Schiff-positive zymogen granules. Genetically, the lesion harbored a missense mutation in the CTNNB1 gene. We diagnosed the lesion as an IDL. As IDLs are usually small non-neoplastic lesions, symptomatic cases are rare. Based on its common immunohistochemical and genetic features, IDL may be a precursor of basal cell adenoma/adenocarcinoma, such as intercalated duct adenoma.

Topics: Adenocarcinoma; Adenoma; Amylases; beta Catenin; Humans; Keratins; Ki-67 Antigen; Male; Middle Aged; Mucin-1; Parotid Gland; Periodic Acid; S100 Proteins; Salivary Gland Neoplasms

The aim of this study was to investigate the relationship between tumor budding (TB) and clinicopathologic prognostic criteria in colorectal adenocarcinomas and to discuss the inclusion of the fourth group in the scoring system. A total of 131 cases were included in the study. TB was scored according to the classical 3-tiered scoring system and our proposed 4-tiered scoring system: BD0 (no buds), BD1* (1-4 buds), BD2 (5-9 buds), and BD3 (≥10 buds). Cytokeratin staining was applied to 80 randomly selected cases and TB scoring was re-evaluated. TB was not observed in 31 (23.7%) of 131 cases and was categorized as BD0. Patients with BD0 budding had lower pT category, AJCC stage, tumor grade, less lymph node metastasis, lymphovascular invasion, tumor deposits (p < 0.05), and longer overall survival than BD1* patients (log-Rank p: 0.018). There was significant compatibility between the evaluation of TB with H&E and cytokeratin (kappa: 0.727, p < 0.001). In conclusion, we think it is valuable to add the "BD0" category to the International Tumor Budding Consensus Conference (ITBCC) scores. However, more research with larger cohorts is needed for clinical applicability. H&E staining is sufficient for the assessment of budding, except in conditions such as increased inflammation where the tumor-stroma interface may be obscured.

Topics: Adenocarcinoma; Colorectal Neoplasms; Humans; Keratins; Lymphatic Metastasis; Neoplasm Staging; Prognosis

The role of c-KIT receptor in anal sac gland adenocarcinoma (ASGAC) is unclear despite its importance in the development of tumours. In this preliminary study, the expression of c-KIT was investigated in rarely observed canine ASGAC. The potential use of CAM5.2 in distinguishing ASGAC from perianal gland tumours was also evaluated. ASGAC was diagnosed in five out of 25 examined perianal tumours. By immunohistochemistry, cytosolic (abnormal) c-KIT expression was seen in four of the five cases. CAM5.2 immunoreactivity was detected in neoplastic cells of all ASGAC cases examined, whereas it was not evident in any case of perianal gland tumour. The findings suggest that c-KIT expression and its cellular localization may be important in the oncogenesis of ASGAC and CAM5.2 can be used to distinguish between ASGAC and perianal gland tumours.

Topics: Adenocarcinoma; Anal Gland Neoplasms; Anal Sacs; Animals; Biomarkers; Dog Diseases; Dogs; Keratins; Proto-Oncogene Proteins c-kit

Mucoepidermoid carcinoma (MEC) arising in pleomorphic adenoma (PA) is an extremely rare entity. Involvement of minor salivary glands by this entity has only being described twice previously. We report on a diagnostically challenging case in an 18 year old male with a large mass in the junction of the hard and soft palates that has been present for 12 months. Both cytology and incisional biopsy were inconclusive and indicated benign mixed tumour. Upon excision of the tumour with a 5 mm clear margin, histology demonstrated PA that has been replaced by small nests and cribriform islands of high-grade MEC with 13 mm of invasion beyond the original PA capsule. The tumour was composed of mostly intermediate-type cells with up to 7 mitoses per 10 high power fields. The tumour cells were positive for cytokeratin (CAM 5.2) and S100. Due to the high-grade nature and focal positive posterior margin of the resected specimen, adjuvant radiotherapy was administered. In conclusion, this case highlights the need to consider rare entities such as mucoepidermoid carcinoma ex pleomorphic adenoma in atypical cytological and histological findings. Moreover, it underlines the need to manage lesions with unconfirmed histological diagnosis with wide excision margins to avoid having involved margins post resection.

Topics: Adenocarcinoma; Adenoma, Pleomorphic; Adolescent; Carcinoma, Mucoepidermoid; Humans; Keratins; Male; Salivary Gland Neoplasms; Salivary Glands, Minor

Colorectal carcinoma (CRC) is associated with significant morbidity and mortality worldwide. Cytokeratins (CKs) are widely expressed in various types of carcinomas, whereas in CRC it is usually CK7 - and CK20 + . A subset of CRCs is CK7 + . This study aims to determine the prevalence of CK7 expression in CRC and its impact on overall survival. We analyzed 300 randomly selected surgically treated CRC cases using paraffin embedded tumor tissue samples and evaluated CK7 and CK20 expression using the tissue microarray method. Tumors with positivity > 10% and > 25% of tumor cells were considered CK7 and CK20 positive, respectively. Expression of both CKs and several clinical-pathological variables (stage, grade, laterality, mismatch-repair/MMR status) were evaluated using patient follow up data (Kaplan-Meier analysis of cancer-specific survival (CSS)). Significant results include shorter CSS (restricted mean 4.98 vs. 7.74 years, P = 0.007) and 5-year survival (29.4% vs. 64.6%, P = 0.0221) in CK7 + tumors compared to CK7 - tumors, respectively; without significant association with grade, stage or right-sided location. These results were significant in a multivariate analysis. CK20 + tumors are more frequently MMR-proficient and left-sided. MMR-deficient tumors are more frequently right-sided and had longer survival. CK7 expression, right-sided location (rmean CSS 6.83 vs. 8.0 years, P = 0.043), MMR-proficiency (rmean CSS 7.41 vs. 9.32 years, P = 0.012), and UICC stages III + IV (rmean CSS 6.03 vs. 8.92 years, P < 0.001) of the tumor correlated with negative prognostic outcomes, whereas the most significant results concern stage and CK7 positivity. The result concerning negative prognostic role of CK7 differs from those obtained by several previous studies focused on this topic.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Biomarkers, Tumor; Colorectal Neoplasms; Diagnosis, Differential; Female; Humans; Intermediate Filament Proteins; Keratin-7; Keratins; Male; Middle Aged; Prognosis

Only few studies examined the prognostic effect of tumor budding in esophageal adenocarcinomas so far. However, different quantification approaches were used, so results cannot be directly compared. Recently, the International Tumor Budding Consensus Conference (ITBCC) published consensus criteria for the evaluation of tumor budding in colorectal cancer, which we applied in our study. Hematoxylin and eosin (H&E) and cytokeratin (AE1/AE3) stained whole tissue slides of 104 resected esophageal adenocarcinomas were evaluated. The mean count of tumor buds was analyzed in one high power field according to the ITBCC criteria and assigned to budding groups Bd1-3. Tumor budding was significantly associated with a worse overall survival. Regardless of the quantification approach, an increased number of tumor buds was significantly associated with reduced overall survival (OS) (H&E: HR = 1.05 (95% CI 1.029-1.073), p < 0.001; cytokeratin: HR = 1.073 (95% CI 1.045-1.101), p < 0.001). In multivariable analysis tumor budding according to ITBCC criteria on H&E stained slides was an independent prognostic factor. Tumor budding, according to ITBCC criteria, is an independent prognostic factor in resected esophageal adenocarcinoma. Prospective studies using ITBCC criteria are useful in the near future to validate our results.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Biomarkers, Tumor; Cell Movement; Esophageal Neoplasms; Esophagectomy; Female; Humans; Immunohistochemistry; Keratins; Male; Middle Aged; Neoplasm Invasiveness; Predictive Value of Tests; Retrospective Studies; Risk Assessment; Risk Factors; Treatment Outcome

Somatostatin receptor 2a (SSTR2a) is an important diagnostic marker of meningioma and neuroendocrine tumours and is frequently expressed in primary and metastatic non-keratinising nasopharyngeal carcinoma (NK-NPC). Since NK-NPC cases are considered a kind of lymphoepithelioma-like carcinoma (LELCs) which originate from the nasopharynx, information on the expression profile of SSTR2a in LELC in other sites with squamous and glandular differentiations is still lacking. This study aimed to assess the expression of SSTR2a in LELC of various organs and clarify its expression profile.. Expression of SSTR2a in 164 cases of LELC was retrospectively analysed by immunohistochemistry in paraffin-embedded tissues, including 146 cases of LELC with squamous differentiation (120 cases of the nasopharynx, 21 cases of the lung and 5 cases of the parotid gland) and 18 cases of LELC with glandular differentiation (15 cases of the stomach and 3 cases of the liver).. We found that all (100%) cases of LELC of the lung (21/21) and parotid gland (5/5), and 93.3% (112/120) cases of LELC of the nasopharynx showed a diffused and strong expression of SSTR2a, while cases of gastric (0/15) and biliary (0/3) showed no SSTR2a expression.. SSTR2a is constantly expressed in LELC with squamous differentiation, but not expressed in LELC with glandular differentiation. However, the selective expression mechanism of SSTR2a remains unknown, which needs further investigation. Our novel findings might provide potential therapeutic approaches for the treatment of LELC with squamous cell differentiation.

Topics: Adenocarcinoma; Adolescent; Adult; Aged; Aged, 80 and over; Carcinoma, Squamous Cell; Cell Differentiation; Female; Herpesvirus 4, Human; Humans; Immunohistochemistry; Keratins; Male; Middle Aged; Receptors, Somatostatin; Retrospective Studies

The transition zones of the squamous and columnar epithelia constitute hotspots for the emergence of cancer, often preceded by metaplasia, in which one epithelial type is replaced by another. It remains unclear how the epithelial spatial organization is maintained and how the transition zone niche is remodelled during metaplasia. Here we used single-cell RNA sequencing to characterize epithelial subpopulations and the underlying stromal compartment of endo- and ectocervix, encompassing the transition zone. Mouse lineage tracing, organoid culture and single-molecule RNA in situ hybridizations revealed that the two epithelia derive from separate cervix-resident lineage-specific stem cell populations regulated by opposing Wnt signals from the stroma. Using a mouse model of cervical metaplasia, we further show that the endocervical stroma undergoes remodelling and increases expression of the Wnt inhibitor Dickkopf-2 (DKK2), promoting the outgrowth of ectocervical stem cells. Our data indicate that homeostasis at the transition zone results from divergent stromal signals, driving the differential proliferation of resident epithelial lineages.

Topics: Adenocarcinoma; Animals; Biomarkers, Tumor; Carcinoma, Squamous Cell; Cell Differentiation; Cell Lineage; Cellular Microenvironment; Cervix Uteri; Epithelium; ErbB Receptors; Female; Gene Expression Regulation, Neoplastic; Homeostasis; Humans; Keratins; Metaplasia; Mice, Inbred C57BL; Organoids; Receptors, Notch; Stem Cells; Stromal Cells; Transcription, Genetic; Uterine Cervical Neoplasms; Wnt Signaling Pathway

Liquid biopsy analyzes the current status of primary tumors and their metastatic regions. We aimed to develop an optimized protocol for single-cell sequencing of floating tumor cells (FTCs) in pleural effusion as a laboratory test. FTCs were enriched using a negative selection of white blood cells by a magnetic-activated cell sorting system, and CD45-negative and cytokeratin-positive selection using a microfluidic cell separation system with a dielectrophoretic array. The enriched tumor cells were subjected to whole-genome amplification (WGA) followed by genome sequencing. The FTC analysis detected an EGFR exon 19 deletion in Case 1 (12/19 cells, 63.2%), and EML4-ALK fusion (17/20 cells, 85%) with an alectinib-resistant mutation of ALK (p.G1202R) in Case 2. To eliminate WGA-associated errors and increase the uniformity of the WGA product, the protocol was revised to sequence multiple single FTCs individually. An analytical pipeline, accurate single-cell mutation detector (ASMD), was developed to identify somatic mutations of FTCs. The large numbers of WGA-associated errors were cleaned up, and the somatic mutations detected in FTCs by ASMD were concordant with those found in tissue specimens. This protocol is applicable to circulating tumor cells analysis of peripheral blood and expands the possibility of utilizing molecular profiling of cancers.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Anaplastic Lymphoma Kinase; Antineoplastic Agents; Carbazoles; Cell Separation; Crizotinib; DNA; Drug Resistance, Neoplasm; Exons; Female; Gene Amplification; Gene Deletion; Gene Expression Profiling; Genes, erbB-1; High-Throughput Nucleotide Sequencing; Humans; Immunomagnetic Separation; Keratins; Leukocyte Common Antigens; Liquid Biopsy; Lung Neoplasms; Male; Middle Aged; Mutation; Neoplastic Cells, Circulating; Oncogene Proteins, Fusion; Piperidines; Pleural Effusion, Malignant; Protein Kinase Inhibitors

Alpha-methylacyl-coenzyme A-racemase (AMACR), also known as p504s, is overexpressed in prostatic adenocarcinoma and is frequently used in combination with basal cell markers to aid in diagnosing difficult prostate adenocarcinoma cases. In this retrospective method comparison study, we examined the sensitivity and specificity of the ready-to-use anti-p504s (SP116) Rabbit Monoclonal Primary Antibody compared to the monoclonal rabbit anti-human AMACR clone 13H4 in prostatic adenocarcinoma samples. De-identified prostatic adenocarcinoma tissue samples were stained with either the SP116 or 13H4 antibody clone in combination with the VENTANA Basal Cell Cocktail (34βE12+p63) and scored as positive or negative for prostatic adenocarcinoma. The scoring pathologist was blinded to the known historical diagnosis of each sample. The scoring pathologist correctly diagnosed each sample regardless of which p504s clone was used. Both assays using either clone were 100% concordant in their sensitivity and specificity. This study demonstrates that the ready-to-use anti-p504s (SP116) Rabbit Monoclonal Primary Antibody is equivalent to clone 13H4 concentrate when used according to package insert instructions in combination with the VENTANA Basal Cell Cocktail (34βE12+p63) to aid pathologists in the diagnosis of prostatic adenocarcinoma.

Topics: Adenocarcinoma; Animals; Antibodies, Monoclonal; Antibody Specificity; Biomarkers, Tumor; Humans; Immunohistochemistry; Keratins; Male; Predictive Value of Tests; Prostatic Neoplasms; Rabbits; Racemases and Epimerases; Reproducibility of Results; Retrospective Studies

Pancreatic ductal adenocarcinoma (PDAC) has dismal 5-year survival (<9%). We hypothesize that exposure of tumors to conventional therapies may preferentially modulate immune biomarkers in the tumor microenvironment in PDAC. PDAC patients who underwent upfront surgical resection or who received neoadjuvant FOLFIRINOX with or without neoadjuvant radiotherapy followed by surgical resection were selected for study. Total expression of immunologically relevant transcripts and spatially resolved expression of immunologically relevant proteins was quantitated using multiplexed methods (NanoString nCounter and GeoMX platforms). This analysis identified numerous differentially expressed transcripts associated with the type of neoadjuvant therapy received. Moreover, we identified significant alterations in the expression and/or spatial distribution of immunologically relevant proteins in different regions (tumor cell rich, immune cell rich, stromal cell rich) of the tumor microenvironment. These data provide insight into the immunological effects of clinically relevant neoadjuvant therapy for resectable/borderline-resectable PDAC by describing significant differences in the expression of key immunologic biomarkers within the PDAC microenvironment that were associated with the type of treatment patients received prior to surgical resection. This represents a comprehensive analysis of numerous biomarkers conducted on the PDAC microenvironment. This work may guide strategic new combination therapies for pancreatic cancer.

Topics: Adenocarcinoma; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Pancreatic Ductal; Combined Modality Therapy; Female; Fluorouracil; Gene Expression; Humans; Irinotecan; Keratins; Leucovorin; Male; Middle Aged; Neoadjuvant Therapy; Oxaliplatin; Pancreas; Pancreatic Neoplasms; Radiotherapy; Transcriptome; Tumor Microenvironment

Pancreatic and periampullary carcinoma are aggressive tumours where preoperative assessment is challenging. Disseminated tumour cells (DTC) in the bone marrow (BM) are associated with impaired prognosis in a variety of epithelial cancers. In a cohort of patients with presumed resectable pancreatic and periampullary carcinoma, we evaluated the frequency and the potential prognostic impact of the preoperative presence of DTC, defined as cytokeratin-positive cells detected by immunocytochemistry (ICC).. Preoperative BM samples from 242 patients selected for surgical resection of presumed resectable pancreatic and periampullary carcinoma from 09/2009 to 12/2014, were analysed for presence of CK-positive cells by ICC. The median observation time was 21.5 months. Overall survival (OS) and disease-free survival (DFS) were calculated by Kaplan-Meier and Cox regression analysis.. Successful resections of malignant tumours were performed in 179 of the cases, 30 patients resected had benign pancreatic disease based on postoperative histology, and 33 were deemed inoperable intraoperatively due to advanced disease. Overall survival for patients with resected carcinoma was 21.1 months (95% CI: 18.0-24.1), for those with benign disease OS was 101 months (95% CI: 69.4-132) and for those with advanced disease OS was 8.8 months (95% CI: 4.3-13.3). The proportion of patients with detected CK-positive cells was 6/168 (3.6%) in resected malignant cases, 2/31 (6.5%) in advanced disease and 4/29 (13.8%) in benign disease. The presence of CK-positive cells was not correlated to OS or DFS, neither in the entire cohort nor in the subgroup negative for circulating tumour cells (CTC).. The results indicate that CK-positive cells may be present in both patients with malignant and benign diseases of the pancreas. Detection of CK-positive cells was not associated with differences in prognosis for the entire cohort or any of the subgroups analysed.. clinicaltrials.gov ( NCT01919151 ).

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Ampulla of Vater; Biomarkers, Tumor; Common Bile Duct Neoplasms; Duodenal Neoplasms; Female; Follow-Up Studies; Humans; Keratins; Male; Middle Aged; Pancreatic Neoplasms; Prognosis; Survival Rate

Regional lymph node metastases in patients with carcinoma of the esophagogastric junction (EGJ) are an important prognostic factor. According to the tumor, node, and metastasis classification, isolated tumor cells (ITCs) are single tumor cells or small clusters of tumor cells not exceeding 0.2 mm. Tumor clusters >0.2 mm are classified as metastases. The significance of lymph nodes with ITCs is unclear, although not contributing to the pN category. The aim of this study was to determine the prevalence of regional lymph nodes with ITCs on the primary hematoxylin and eosin-stained slide and to examine how often deeper sections reveal a true metastasis. The study included surgical specimens of 126 patients with adenocarcinoma of the EGJ. Lymph nodes with ITCs were identified. Additional sections were cut and stained with hematoxylin and eosin and with cytokeratin. All slides were evaluated for the presence of tumor cells, and it was determined whether the criteria for a metastasis were met on the additional sections. ITCs were detected in 59 (1.7%) of 3454 lymph nodes and in 41 (32.5%) of 126 patients. In 29 (49.2%) lymph nodes with ITCs on the primary slide, further sections resulted in a changed status from ITCs to a metastasis. In 7 (17.1%) of 41 patients, the pN category was changed. In patients with adenocarcinoma of the EGJ, the presence of ITCs in regional lymph nodes is a common observation. ITCs often represent part of a real metastasis. To obtain a pN category as accurate as possible, we strongly recommend thorough examination of regional lymph nodes with additional sections when ITCs are observed.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Esophageal Neoplasms; Esophagogastric Junction; Female; Humans; Keratins; Lymph Nodes; Lymphatic Metastasis; Male; Middle Aged; Stomach Neoplasms

Rectal squamous cell carcinoma (SCC) is a rare tumor with unresolved etiology. Human immunodeficiency virus-infected individuals and solid organ transplant recipients experience >30-fold and approximately 3-fold elevated rates of rectal SCC, respectively, suggesting immunosuppression plays a role.

Topics: Adenocarcinoma; Anus Neoplasms; Biomarkers; Carcinoma, Squamous Cell; Case-Control Studies; DNA-Binding Proteins; DNA, Viral; Human papillomavirus 16; Humans; In Situ Hybridization; Keratins; Oncogene Proteins, Viral; Papillomavirus Infections; Rectal Neoplasms; Repressor Proteins; Transcription Factors; Tumor Suppressor Proteins; Viral Envelope Proteins

Histone deacetylases, HDACs, have been demonstrated to play a critical role in epigenetic signaling and were found to be overexpressed in several type of cancers; therefore, they represent valuable targets for anticancer therapy. 9-Hydroxystearic acid has been shown to bind the catalytic site of HDAC1, inducing G0/G1 phase cell cycle arrest and activation of the p21

Topics: Adenocarcinoma; Albumins; Cell Membrane; Cell Proliferation; Cell Survival; Chemistry Techniques, Synthetic; Colonic Neoplasms; Drug Discovery; HCT116 Cells; Histone Deacetylase 1; HT29 Cells; Humans; Keratins; Nanoparticles; Reactive Oxygen Species; S Phase Cell Cycle Checkpoints; Signal Transduction; Solubility; Stearic Acids

A 12-year-old, male miniature dachshund has an ulcer on the footpad of the right hind limb. Despite treatment for longer than 6 months, the ulcer did not heal. Biopsy of the lesion was done to make a definitive diagnosis. Histologically, there were lumens containing weakly eosinophilic fluid surrounded by tumor cells with a similar circular pale nucleus and distinct nucleoli that showed some variation in size. Immunohistochemically, the tumor cells were positive for cytokeratin (AE1/AE3) and vimentin, were negative for S100 and p63. A poorly differentiated eccrine adenocarcinoma was diagnosed. Treatment was started with toceranib, an anti-angiogenic agent, and enlargement of the lesion was not observed during the administration period.

Topics: Adenocarcinoma; Angiogenesis Inhibitors; Animals; Biopsy; Dog Diseases; Dogs; Hindlimb; Immunohistochemistry; Indoles; Keratins; Male; Pyrroles; Sweat Gland Neoplasms; Vimentin

Prostate cancer (PCa) is a major cause of cancer death among men. The histopathological examination of post-surgical prostate specimens and manual annotation of PCa not only allow for detailed assessment of disease characteristics and extent, but also supply the ground truth for developing of computer-aided diagnosis (CAD) systems for PCa detection before definitive treatment. As manual cancer annotation is tedious and subjective, there have been a number of publications describing methods for automating the procedure via the analysis of digitized whole-slide images (WSIs). However, these studies have focused only on the analysis of WSIs stained with hematoxylin and eosin (H&E), even though there is additional information that could be obtained from immunohistochemical (IHC) staining. In this work, we propose a framework for automating the annotation of PCa that is based on automated colorimetric analysis of both H&E and IHC WSIs stained with a triple-antibody cocktail against high-molecular weight cytokeratin (HMWCK), p63, and α-methylacyl CoA racemase (AMACR). The analysis outputs were then used to train a regression model to estimate the distribution of cancerous epithelium within slides. The approach yielded an AUC of 0.951, sensitivity of 87.1%, and specificity of 90.7% as compared to slide-level annotations, and generalized well to cancers of all grades.

Topics: Adenocarcinoma; Area Under Curve; Biomarkers, Tumor; Biopsy, Needle; Cohort Studies; Colorimetry; Eosine Yellowish-(YS); Hematoxylin; Humans; Image Interpretation, Computer-Assisted; Immunohistochemistry; Keratins; Male; Neoplasm Staging; Prostate; Prostatic Neoplasms; Racemases and Epimerases; Sensitivity and Specificity; Transcription Factors; Tumor Suppressor Proteins

Primary thymic adenocarcinoma is an extremely rare tumor, and thymic enteric type adenocarcinoma has recently been proposed as a distinct pathological entity. Herein, we report the first cytological description of thymic enteric type adenocarcinoma. A 29-year-old Japanese female without a significant past medical history was found to have an abnormal chest shadow. Chest computed tomography demonstrated a well-circumscribed tumor in the anterior mediastinum, and thymectomy was performed. The Papanicolaou staining of the touch smear of the resected tumor demonstrated tightly cohesive epithelial cell clusters in a necrotic background. These cells were cuboidal to columnar in shape and had large round to oval nuclei with conspicuous nucleoli. Some of these neoplastic cells had intracytoplasmic mucin. Immunocytochemically, the neoplastic cells were positive for cytokeratin 20 and CDX-2. Histopathological study revealed tubular and papillotubular neoplastic growth composed of cuboidal to columnar neoplastic cells that contained large round to oval nuclei. Some of the neoplastic cells had intracytoplasmic mucin. Immunohistochemical study confirmed the expression of cytokeratin 20 and CDX-2. The final diagnosis of thymic enteric type adenocarcinoma was made. The cytological and immunocytochemical features of this case led to a diagnosis of enteric type adenocarcinoma. However, these features alone cannot be differentiated from a metastatic adenocarcinoma arising from the gastrointestinal tract. Cytological examination of a fine-needle aspiration of the mediastinal tumor has been reported to be useful in making a diagnosis. Therefore, an awareness of this new pathological entity is important for differentiating a thymic tumor from a metastatic carcinoma in the thymus.

Topics: Adenocarcinoma; Adult; CDX2 Transcription Factor; Diagnosis, Differential; Female; Gastrointestinal Neoplasms; Humans; Keratins; Papanicolaou Test; Thymus Neoplasms

The aim of this study was to verify if positive results yielded with conventional cytology and immunocytochemical analysis of peritoneal washes correlate with established prognostic factors and overall survival (OS) in gastric cancer patients.. The study included the data of 271 gastrectomized patients. Peritoneal washes of 131 (48.3%) patients were examined by means of conventional cytology, and material from 140 (51.7%) subjects treated surgically after this date was subjected to immunocytochemical analysis.. Free cancer cells (FCCs) were detected significantly less often in patients from conventional cytology group than in those from immunocytochemistry group (4.6% vs. 12.1%). Positive result of immunocytochemical analysis was significantly more often associated with presence of pT3/4 tumor (94.1% vs. 60.2%), lymph node ratio ≥0.2 (82.4% vs. 43.1%) and involvement of blood vessels (64.7% vs. 28.5%). Median OS in patients with immunocytochemical evidence of FCCs in peritoneal washes was significantly shorter than in those without (11 vs. 45 months). Moreover, the two groups differed significantly in terms of 5- (0% vs. 43.1%) and 10-year OS rates (0.0% vs. 29.3%).. In contrast to conventional cytology, immunocytochemically documented presence of FCCs in peritoneal washes correlates with established prognostic factors and OS in gastric cancer patients.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Biomarkers, Tumor; Cytological Techniques; Female; Gastrectomy; Humans; Immunohistochemistry; Kaplan-Meier Estimate; Keratins; Lymph Node Excision; Male; Middle Aged; Neoplasm Proteins; Neoplasm Staging; Peritoneal Lavage; Peritoneal Neoplasms; Proportional Hazards Models; Stomach Neoplasms

We report a case of vimentin-positive early gastric adenocarcinoma arising in a hyperplastic polyp (HP). A 72-year-old Japanese man was admitted for the detailed examination of a gastric polyp. He had a subtotal gastrectomy due to acute abdomen 12 years ago. Upper endoscopy revealed a pedunculated polyp measuring approximately 2 cm on the greater curvature of upper body of the remnant stomach. Magnifying endoscopy revealed that the microsurface pattern was irregular and partially absent accompanied with irregular microvessels at the upper end of the polyp. We speculated that the lesion was an adenocarcinoma arising in the HP. Endoscopic submucosal dissection (ESD) was performed. Histological examination of the ESD specimen revealed that the lesion consisted of well- to poorly differentiated adenocarcinoma at the protruding lesion and foveolar hyperplastic epithelia at the base of the polyp. Immunohistochemically, most of tumor cells that comprised poorly-differentiated adenocarcinoma were positive for both cytokeratin and vimentin. Although carcinomas have occasionally been found in HPs, the histological features of the present case are considered extremely unusual. To the best of our knowledge, this is the first case of vimentin-positive early gastric carcinoma arising in a HP.

Topics: Adenocarcinoma; Aged; Endoscopic Mucosal Resection; Humans; Hyperplasia; Keratins; Male; Polyps; Stomach Diseases; Stomach Neoplasms; Vimentin

To investigate immunohistochemical predictors for intestinal and pancreatobiliary types of adenocarcinoma of ampulla of Vater and identify clinicopathological characteristics associated with the histological types and patient survival.. Immunohistochemical markers included MUC1, MUC2, MUC5AC, CDX2, CK7, and CK20. The data were analyzed by univariate and multivariate methods. The two-step cluster method was used to determine the best immunohistochemical markers to discriminate the intestinal from the pancreatobiliary type.. This study identified 9 (33.3%) intestinal and 21 (66.7%) pancreatobiliary tumors. CK7 and CDX2 achieved the highest value (= 1) as predictor markers, while CK20, MUC1, and MUC2 showed degrees of importance equal to 0.77, 0.71, and 0.68, respectively. MUC5AC did not reach 0.50 of importance. In the univariate analysis, lymph node involvement, staging (TNM), and angiolymphatic and perineural invasions were associated with histological types. The independent clinicopathological variable in the multivariate model to predict the histological type was angiolymphatic invasion (p = 0.005), OR = 17 (95% CI 2.33 to 123.83). The final model showed positive nodes (N1) associated with shorter survival (HR = 9.5; p = 0.006). Overall survival at 12, 36, and 60 months was 88.5, 67.0, and 47.6%, respectively.. CDX2 and CK7 were the immunohistochemical markers that best discriminated the intestinal from the pancreatobiliary type. Lymph node involvement had a high impact on survival and proved to be more frequent in the pancreatobiliary type.

Topics: Adenocarcinoma; Adult; Aged; Ampulla of Vater; Bile Duct Neoplasms; Bile Ducts, Intrahepatic; Biomarkers, Tumor; CDX2 Transcription Factor; Common Bile Duct Neoplasms; Female; Follow-Up Studies; Humans; Immunohistochemistry; Keratins; Male; Middle Aged; Mucins; Neoplasm Proteins; Prognosis

This study aimed to investigate the significance of lymph node micrometastasis (LNMM) in the lung cancer nodal categories.. Between 1 January 2009 and 31 December 2013, 589 patients with suspected c-stage 1 and p-T1-2aN0-1M0 lung adenocarcinoma were enrolled in this study. The study evaluated LNMM with cytokeratin (AE1/AE3) and transcription factor-1 (TTF1) (8G7G3/1) expression by immunohistochemistry. Recurrence-free survival (RFS) and overall survival (OS) were compared among the T1-2aN0-1M0 patients stratified by the new N categories.. From 589 patients, 7892 removed lymph nodes were examined, and LNMM was observed in 55 (9.3%) of the patients. The patients without LNMM or N1 had the best RFS (5-year rate: 80% vs 25%; P < 0.001) and OS (5-year rate: 87% vs 43%; P < 0.001), followed by the patients with LNMM, compared with those in the N1 category (RFS: 5-year rate, 25% vs 8%; P = 0.010; OS: 5-year rate, 43% vs 20%; P = 0.009). Similarly, this trend was observed when patients were subdivided into the T1 and T2a categories. Multivariate analysis showed that the new N categories with the addition of LNMM were an independent prognostic factor. This result also was noticed in all subgroups.. The findings showed LNMM to be clinically significant as a risk factor for lung cancer. Clinicians should consider LNMM when estimating N categories to determine prognosis and the best treatment strategy.

Topics: Adenocarcinoma; Aged; Disease-Free Survival; Female; Humans; Keratins; Lung Neoplasms; Lymph Nodes; Lymphatic Metastasis; Male; Middle Aged; Neoplasm Micrometastasis; Neoplasm Staging; Survival Rate; Thyroid Nuclear Factor 1

Primary poorly differentiated lacrimal gland adenocarcinoma in the orbital region is an extremely rare type of neoplasm with only 1 related case in the literature. Its high grade of malignancy makes the timely data reported necessary. Hence, we present an extremely rare disease with biopsy results and recommendations on clinical treatment in an elderly male with Chinese descent.. A 66-year-old Chinese man presented with swelling in the left ocular region and eyeball proptosis. On physical examination, the patient had redness, tenderness, and swelling of the left eye. A surgical incision was noted on the left orbital region. Left eye movements were restricted.. Immunohistochemical examination revealed pan-cytokeratin (PCK, +), p63 (partial, +), cytokeratin 7 (CK7, +), cytokeratin 14 (CK14, +), epithelial membrane antigen (EMA, +), protein expressed by erythroblast transformation-specific related gene (ERG, -), S-100 (, -), Epstein-Barr virus-encoded small RNA (EBER, -), smooth muscle actin (SMA, -), and Ki-67 (with a proliferation index approximately 40%). After carefully reviewed the manifestations, imaging findings, and immunohistochemical evidences, a diagnosis of poorly differentiated adenocarcinoma of lacrimal gland was made.. Based on the gene sequencing results, we started the patient with an intensive PF chemotherapy including a combination of cisplatine, fluorouracil, and epirubicin. Two months later, radiotherapy was introduced to the therapy regimen.. The patient responded well to the treatment without severe adverse events. MRI scan showed remarkable remission.. This rare case report will help raise the awareness of high grade lacrimal gland cancer, and subsequently aid the diagnosis in future cases. Positive immunohistochemical markers of CK7, CK14, EMA, p63, and high proliferation index of Ki-67 can help establishing a diagnosis, and cisplatine-fluorouracil program is proved feasible. We share the difficulties we have encountered, hoping to improve patient care in the future.

Topics: Adenocarcinoma; Aged; Antineoplastic Combined Chemotherapy Protocols; Biomarkers, Tumor; Eye Neoplasms; Humans; Keratins; Lacrimal Apparatus Diseases; Male

Topics: Adenocarcinoma; Aged, 80 and over; Humans; Keratins; Male; Prostatic Neoplasms

Aquaporin-5 (AQP5) and -3 (AQP3) are protein channels that showed to be up-regulated in a variety of tumors. Our goal was to investigate the expression pattern of AQP5 and AQP3 in pancreatic ductal adenocarcinomas (PDA) and correlate with cell proliferation, tumor stage and progression, and clinical significance.. 35 PDA samples in different stages of differentiation and locations were analyzed by immunohistochemistry for expression of AQP5, AQP3 and several markers of cell proliferation and tumorigenesis.. In PDA samples AQP5 was overexpressed in the apical membrane of intercalated and intralobular ductal cells while AQP3 was expressed at the plasma membrane of ductal cells. AQP5 was also found in infiltrative cancer cells in duodenum. Simultaneous overexpression of EGFR, Ki-67, and CK7, with decreased E-cad and increased Vim that characterize epithelial mesenchymal transition, tumor formation and invasion, strongly suggest AQP3 and AQP5 involvement in cell proliferation and transformation. AQP3 overexpression is reinforced in late and more aggressive PDA stages whereas AQP5 is related with tumor differentiation, suggesting it may represent a novel marker for PDA aggressiveness and intestinal infiltration.. These findings suggest AQP3 and AQP5 involvement in PDA development and the usefulness of AQP5 in early PDA diagnosis.

Topics: Adenocarcinoma; Adult; Aged; Aquaporin 3; Aquaporin 5; Cadherins; Case-Control Studies; ErbB Receptors; Female; Humans; Keratins; Ki-67 Antigen; Male; Middle Aged; Neoplasm Proteins; Pancreatic Ducts; Pancreatic Neoplasms

To efficiently replicate the biology and pathogenesis of human esophageal adenocarcinoma (EAC) using the modified Levrat model of end-to-side esophagojejunostomy.. End-to-side esophagojejunostomy was performed on rats to induce gastroduodenoesophageal reflux to develop EAC. Animals were randomly selected and serially euthanized at 10 (n = 6), 17 (n = 8), 24 (n = 9), 31 (n = 6), 38 (n = 6), and 40 (n = 6) wk postoperatively. The esophagi were harvested for downstream histopathology and gene expression. Histological evaluation was completed to determine respective rates of carcinogenic development. Quantitative reverse transcription-polymerase chain reaction was performed to determine gene expression levels of. The overall study mortality was 15%. Causes of mortality included anastomotic leak, gastrointestinal hemorrhage, stomach ulcer perforation, respiratory infection secondary to aspiration, and obstruction due to tumor or late anastomotic stricture. 10 wk following surgery, 100% of animals presented with esophagitis. Barrett's esophagus (BE) was first observed at 10 wk, and was present in 100% of animals by 17 wk. Dysplasia was confirmed in 87.5% of animals at 17 wk, and increased to 100% by 31 wk. EAC was first observed in 44.4% of animals at 24 wk and increased to 100% by 40 wk. In addition, two animals at 38-40 wk post-surgery had confirmed macro-metastases in the lung/liver and small intestine, respectively.. Esophagojejunostomy was successfully replicated in rats with low mortality and a high tumor burden, which may facilitate broader adoption to study EAC development, progression, and therapeutics.

Topics: Adenocarcinoma; Anastomosis, Surgical; Animals; Barrett Esophagus; Biomarkers, Tumor; Carcinogenesis; Disease Models, Animal; Disease Progression; Esophageal Neoplasms; Esophagus; Gastroesophageal Reflux; Humans; Jejunum; Keratin-19; Keratins; Male; Mucin-2; Rats; Rats, Sprague-Dawley; Real-Time Polymerase Chain Reaction

Topics: AC133 Antigen; Adenocarcinoma; Adult; Aged; Aged, 80 and over; Aldehyde Dehydrogenase; Biomarkers, Tumor; Carcinoma, Pancreatic Ductal; Disease-Free Survival; Female; Gene Expression Regulation, Neoplastic; Humans; Hyaluronan Receptors; Keratins; Male; Middle Aged; Neoplastic Cells, Circulating; Neoplastic Stem Cells; Prognosis

Primary thymic adenocarcinoma is an extraordinarily rare malignancy; only 49 cases have been reported in the medical literature to date. Because of its rarity, clinical and pathologic characteristics of thymic adenocarcinoma are unclear. We present nine cases of primary thymic adenocarcinoma and discuss clinicopathologic findings in the context of the existing literature. Two-hundred twenty-six thymic carcinoma cases were diagnosed at Samsung Medical Center in Korea, from January, 2001 to July, 2016. Nine of these 226 cases were primary thymic adenocarcinomas. The mean age of primary thymic adenocarcinoma patients was 53.6 years, slightly younger than the mean age of patients with thymic squamous cell carcinomas. The male to female ratio was 2:1. Symptoms, if present, were usually due to compression by the tumor. Tumors showed an extra- or intra-cellular mucin and tubular growth pattern, with CK20- and CDX2-immunoreactivity, similar to adenocarcinomas of the lower intestinal tract. Twenty-five previously reported cases, classified as mucinous adenocarcinoma and adenocarcinoma, not otherwise specified, also had similar characteristics to enteric-type adenocarcinoma and generally expressed CK20, CDX2, CEA, and/or MUC2. Some of these cases had a thymic cyst. These characteristics are different from those of papillary thymic carcinomas, which are morphologically similar to papillary thyroid carcinomas, express CK7 but not CK20, and are often associated with thymoma. The prognosis of thymic adenocarcinoma, enteric type appeared to be worse than the prognosis of papillary thymic carcinoma or carcinoma with adenoid cystic carcinoma-like features. In summary, we demonstrated that common primary thymic adenocarcinomas show enteric-type differentiation with mucin. This tumor type has distinct clinical, pathological, immunohistochemical and prognostic characteristics and is different from other subtypes of thymic adenocarcinoma, papillary thymic carcinoma, and carcinoma with adenoid cystic carcinoma-like features.

Topics: Adenocarcinoma; Adult; Aged; Biomarkers, Tumor; Carcinoembryonic Antigen; Carcinoma, Squamous Cell; Female; Humans; Keratins; Male; Middle Aged; Mucins; Thymus Neoplasms

Cervical cancer remains one of the leading causes of cancer-related deaths worldwide. Here we report the extensive molecular characterization of 228 primary cervical cancers, one of the largest comprehensive genomic studies of cervical cancer to date. We observed notable APOBEC mutagenesis patterns and identified SHKBP1, ERBB3, CASP8, HLA-A and TGFBR2 as novel significantly mutated genes in cervical cancer. We also discovered amplifications in immune targets CD274 (also known as PD-L1) and PDCD1LG2 (also known as PD-L2), and the BCAR4 long non-coding RNA, which has been associated with response to lapatinib. Integration of human papilloma virus (HPV) was observed in all HPV18-related samples and 76% of HPV16-related samples, and was associated with structural aberrations and increased target-gene expression. We identified a unique set of endometrial-like cervical cancers, comprised predominantly of HPV-negative tumours with relatively high frequencies of KRAS, ARID1A and PTEN mutations. Integrative clustering of 178 samples identified keratin-low squamous, keratin-high squamous and adenocarcinoma-rich subgroups. These molecular analyses reveal new potential therapeutic targets for cervical cancers.

Topics: Adenocarcinoma; APOBEC-1 Deaminase; B7-H1 Antigen; Carcinoma, Squamous Cell; Caspase 8; DNA-Binding Proteins; Female; Genomics; HLA-A Antigens; Human papillomavirus 16; Humans; Keratins; Mitogen-Activated Protein Kinase Kinases; Molecular Targeted Therapy; Mutation; Nuclear Proteins; Phosphatidylinositol 3-Kinases; Programmed Cell Death 1 Ligand 2 Protein; Protein Serine-Threonine Kinases; Proteomics; Proto-Oncogene Proteins p21(ras); PTEN Phosphohydrolase; Receptor, ErbB-3; Receptor, Transforming Growth Factor-beta Type II; Receptors, Transforming Growth Factor beta; RNA, Long Noncoding; Signal Transduction; Transcription Factors; Uterine Cervical Neoplasms; Virus Integration

Carcinoma ex pleomorphic adenoma (Ca ex PA) is a malignant neoplasm arising from primary or recurrent benign pleomorphic adenoma. It is rare with an annual incidence rate of 0.17 tumors per million. Histopathology remains the gold standard for the diagnosis of Ca ex PA, with only a handful of cases reported on cytology. In our case a 66-year-old male presented with the right parotid mass for 5 years rapidly increasing for the last 3 months. Fine needle aspiration cytology (FNAC) smears showed malignant tumor cells in clusters along with benign myoepithelial cells in chondromyxoid background. Histopathologically, highly pleomorphic malignant epithelial cells in sheets along with foci of comedonecrosis and areas corresponding to benign pleomorphic adenoma were observed on careful scrutiny. Immunohistochemistry revealed positivity for cytokeratin (CK 7) and gross cystic disease fluid protein 15 (GCDFP-15) while CK5/6 and high molecular weight CK (34 βE12) were negative in the malignant tumor cells. So, the final impression was Ca ex PA with salivary duct carcinoma as malignant component. We hereby report this case to highlight the significance of FNAC in the diagnosis of Ca ex PA which can be easily missed on cytopathology. However, it is important to corroborate the cytological findings with clinical suspicion of malignancy as well as radiology. Diagn. Cytopathol. 2017;45:651-654. © 2017 Wiley Periodicals, Inc.

Topics: Adenocarcinoma; Adenoma, Pleomorphic; Aged; Biomarkers; Biomarkers, Tumor; Biopsy, Fine-Needle; Carrier Proteins; Diagnosis, Differential; Epithelial Cells; Gene Expression; Glycoproteins; Humans; Immunohistochemistry; Keratin-7; Keratins; Male; Membrane Transport Proteins; Parotid Gland; Parotid Neoplasms; Salivary Gland Neoplasms

Metastatic pituitary carcinoma to bone is rare. In this report, we present a case of a 59-year-old female with recurrent pituitary adenoma of the sparsely granulated somatotroph subtype with metastasis to a few bony sites 10 years later. Needle core biopsy (NCB) with touch preparations was performed on a 5 mm lesion in left ilium. Diff-Quik stained NCB touch preparation slides showed a few loosely cohesive epithelial polygonal cells that were arranged in nests or acini, or singly, had scant vacuolated cytoplasm and eccentrically located round nuclei (plasmacytoid) with slight nuclear pleomorphism, fine granular chromatin, conspicuous nucleoli, and smooth nuclear membrane. Trilineage hematopoietic cells of bone marrow were also appreciated in the background. H&E stained core sections showed fragments of bone and bone marrow with nests of bland epithelial cells with similar cytomorphology as seen in NCB touch preparation slides. The tumor cells were immunoreactive for juxtanuclear dot-like staining of pan-cytokeratin (CAM 5.2 and AE1/AE3) (a specific feature), neuroendocrine markers (CD56, synaptophysin, and chromogranin. Additionally, scattered cells were immunoreactive for growth hormone. Molecular test showed that tumor cells were negative for the promoter methylation of O-6-Methylguanine-DNA Methyltransferase (MGMT). Final diagnosis of metastatic pituitary carcinoma was rendered. Morphology of metastatic pituitary carcinoma, its differential, clinical presentation and treatment were discussed. Diagn. Cytopathol. 2017;45:645-650. © 2017 Wiley Periodicals, Inc.

Topics: Adenocarcinoma; Anion Exchange Protein 1, Erythrocyte; Biomarkers; Biomarkers, Tumor; Biopsy, Large-Core Needle; Bone Neoplasms; CD56 Antigen; Chromogranin A; Female; Gene Expression; Growth Hormone; Humans; Ilium; Keratins; Middle Aged; Pituitary Neoplasms; Synaptophysin

The diagnosis of polymorphous low-grade adenocarcinoma (PLGA) remains difficult for general pathologists, particularly in cases of small biopsy samples. We aimed to characterize the histopathological spectrum and immunohistochemical aspects by using an accessible immunohistochemical panel of cytoskeletal proteins in limited samples of PLGA.. Forty-six patients diagnosed with PLGA in incisional biopsies were identified retrospectively. Seventy-two per cent of patients were women and 28% were men, with a mean age of 55 years. The palate was the most affected site. Grossly, the mean size of the samples was 0.8 cm and 74% of specimens were fragmented. All tumours characteristically displayed the microscopic features of architecturally diverse patterns, infiltrative areas and low-grade cytology. Neoplastic cells were diffusely positive to cytokeratin (CK) 7, vimentin and S100 protein, but only focally positive to CK14 and negative to α-smooth muscle actin (α-SMA), thus lacking myoepithelial differentiation.. Microscopic recognition of PLGA is facilitated by a characteristic combination of multiple architectural patterns of growth, infiltration of adjacent tissues and cytological aspects. These features are present even in small biopsy samples. The association of histopathological aspects with CK7, CK14, vimentin, S100 and α-SMA immunoexpression is helpful in reaching the diagnosis of doubtful cases.

Topics: Actins; Adenocarcinoma; Adult; Aged; Algorithms; Biomarkers, Tumor; Biopsy; Female; Humans; Immunohistochemistry; Keratin-14; Keratin-7; Keratins; Male; Middle Aged; Retrospective Studies; S100 Proteins; Salivary Gland Neoplasms; Vimentin

We assessed circulating tumor cells (CTCs) with epithelial and mesenchymal phenotypes as a potential prognostic biomarker for patients with pancreatic adenocarcinoma (PDAC).. PDAC is the fourth leading cause of cancer death in the United States. There is an urgent need to develop biomarkers that predict patient prognosis and allow for better treatment stratification.. Peripheral and portal blood samples were obtained from 50 patients with PDAC before surgical resection and filtered using the Isolation by Size of Epithelial Tumor cells method. CTCs were identified by immunofluorescence using commercially available antibodies to cytokeratin, vimentin, and CD45.. Thirty-nine patients (78%) had epithelial CTCs that expressed cytokeratin but not CD45. Twenty-six (67%) of the 39 patients had CTCs which also expressed vimentin, a mesenchymal marker. No patients had cytokeratin-negative and vimentin-positive CTCs. The presence of cytokeratin-positive CTCs (P < 0.01), but not mesenchymal-like CTCs (P = 0.39), was associated with poorer survival. The presence of cytokeratin-positive CTCs remained a significant independent predictor of survival by multivariable analysis after accounting for other prognostic factors (P < 0.01). The detection of CTCs expressing both vimentin and cytokeratin was predictive of recurrence (P = 0.01). Among patients with cancer recurrence, those with vimentin-positive and cytokeratin-expressing CTCs had decreased median time to recurrence compared with patients without CTCs (P = 0.02).. CTCs are an exciting potential strategy for understanding the biology of metastases, and provide prognostic utility for PDAC patients. CTCs exist as heterogeneous populations, and assessment should include phenotypic identification tailored to characterize cells based on epithelial and mesenchymal markers.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Biomarkers, Tumor; Female; Fluorescent Antibody Technique; Humans; Immunohistochemistry; Keratins; Leukocyte Common Antigens; Male; Middle Aged; Neoplasm Recurrence, Local; Neoplastic Cells, Circulating; Pancreatic Neoplasms; Phenotype; Prognosis; Survival Rate; Vimentin

Previously, we generated a preclinical mouse prostate tumor model based on PSA-Cre driven inactivation of Pten. In this model homogeneous hyperplastic prostates (4-5m) developed at older age (>10m) into tumors. Here, we describe the molecular and histological characterization of the tumors in order to better understand the processes that are associated with prostate tumorigenesis in this targeted mouse Pten knockout model. The morphologies of the tumors that developed were very heterogeneous. Different histopathological growth patterns could be identified, including intraductal carcinoma (IDC), adenocarcinoma and undifferentiated carcinoma, all strongly positive for the epithelial cell marker Cytokeratin (CK), and carcinosarcomas, which were negative for CK. IDC pattern was already detected in prostates of 7-8 month old mice, indicating that it could be a precursor stage. At more than 10 months IDC and carcinosarcoma were most frequently observed. Gene expression profiling discriminated essentially two molecular subtypes, denoted tumor class 1 (TC1) and tumor class 2 (TC2). TC1 tumors were characterized by high expression of epithelial markers like Cytokeratin 8 and E-Cadherin whereas TC2 tumors showed high expression of mesenchyme/stroma markers such as Snail and Fibronectin. These molecular subtypes corresponded with histological growth patterns: where TC1 tumors mainly represented adenocarcinoma/intraductal carcinoma, in TC2 tumors carcinosarcoma was the dominant growth pattern. Further molecular characterization of the prostate tumors revealed an increased expression of genes associated with the inflammatory response. Moreover, functional markers for senescence, proliferation, angiogenesis and apoptosis were higher expressed in tumors compared to hyperplasia. The highest expression of proliferation and angiogenesis markers was detected in TC2 tumors. Our data clearly showed that in the genetically well-defined PSA-Cre;Pten-loxP/loxP prostate tumor model, histopathological, molecular and biological heterogeneity occurred during later stages of tumor development.

Topics: Adenocarcinoma; Animals; Apoptosis; Biomarkers; Biomarkers, Tumor; Cadherins; Carcinoma; Carcinosarcoma; Cellular Senescence; Disease Progression; Epithelial Cells; Gene Expression Profiling; Gene Expression Regulation, Neoplastic; Inflammation; Keratins; Male; Mesoderm; Mice; Mice, Inbred Strains; Mice, Knockout; Neoplasm Proteins; Neovascularization, Pathologic; Prostatic Hyperplasia; Prostatic Neoplasms; PTEN Phosphohydrolase; RNA, Messenger; RNA, Neoplasm; Stromal Cells

Endometrial cancer (EC) is one of the most frequent causes of cancer death among women in developed countries. Histopathological diagnosis and imaging techniques for EC are limited, thus new prognostic markers are needed to offer patients the best treatment and follow-up.In the present paper we showed that the level of mitochondrial ribosomal protein MRPS18-2 (S18-2) increased in EC compared with the normal endometrium and hyperplasia, based on a study of 42 patient biopsies. Importantly, high expression of free E2F1 in EC correlates well with high S18-2 expression. The EC cell line HEC-1-A, which overexpresses S18-2 constitutively, showed an increased proliferation capacity in vitro and in vivo (in SCID mice). Moreover, pan-keratin, beta-catenin and E-cadherin signals are diminished in these cells, compared to the parental HEC-1-A line, in contrast to vimentin signal that is increased. This may be associated with epithelial-mesenchymal cell transition (EMT).We conclude that high expression of S18-2 and free E2F1, and low pan-keratin, beta-catenin, and E-cadherin signals might be a good set of prognostic markers for EC.

Topics: Adenocarcinoma; Animals; Antigens, CD; beta Catenin; Biomarkers, Tumor; Cadherins; E2F1 Transcription Factor; Endometrial Neoplasms; Female; Heterografts; Humans; Keratins; Mice; Mice, SCID; Ribosomal Proteins

Müllerianosis is the term used to designate lesions composed of an admixture of two or three types of müllerian-derivation glands in heterotopic location. In this report, we describe a case of incidental vaginal müllerianosis in a 59-year-old woman who underwent rectosigmoidectomy for rectal adenocarcinoma. In the vaginal cuff removed for neoplastic invasion, a separate multilocular mass measuring 1.5cm was found. The microscopic examination of the vaginal wall revealed endosalpingeal, endocervical and endometrial dilated or cystic glands with predominance of the endosalpingeal epithelium. Müllerian epithelium showed positivity for cytokeratins 7 and 8/18, high molecular weight cytokeratin, estrogen receptor alpha, and androgen receptor. The periglandular stroma was condensed and reactive for smooth-muscle actin, h-caldesmon, and CD10. To the best of our knowledge, a case of vaginal müllerianosis has not been previously reported. This lesion should be differentiated form vaginal adenosis and primary well-differentiated vaginal adenocarcinoma. The vagina should be added to the list of locations in which müllerianosis can be observed.

Topics: Adenocarcinoma; Cervix Uteri; Choristoma; Endometrium; Fallopian Tubes; Female; Humans; Incidental Findings; Keratins; Middle Aged; Rectal Neoplasms; Vaginal Diseases

Tumor budding has prognostic significance in many carcinomas and is defined as the presence of detached isolated single cells or small cell clusters up to 5 cells at the invasion front (peritumoral budding [PTB]) or within the tumor (intratumoral budding [ITB]). For esophageal adenocarcinomas (EACs), there are currently only few data about the impact of this morphological feature. We investigated tumor budding in a large collective of 200 primarily resected EACs. Pancytokeratin staining was demonstrated to be superior to hematoxylin and eosin staining for the detection of buds with substantial to excellent interobserver agreement and used for subsequent analysis. PTB and ITB were scored across 10 high-power fields (HPFs). The median count of tumor buds was 130/10 HPFs for PTB (range, 2-593) and 80/10 HPFs for ITB (range, 1-656). PTB and ITB correlated significantly with each other (r = 0.9; P < .001). High PTB and ITB rates were seen in more advanced tumor categories (P < .001 each); tumors with lymph node metastases (P < .001/P = .002); and lymphatic, vascular, and perineural invasion and higher tumor grading (P < .001 each). Survival analysis showed an association with worse survival for high-grade ITB (P = .029) but not PTB (P = .385). However, in multivariate analysis, lymph node and resection status, but not ITB, were independent prognostic parameters. In conclusion, PTB and ITB can be observed in EAC to various degrees. High-grade budding is associated with aggressive tumor phenotype. Assessment of tumor budding, especially ITB, may provide additional prognostic information about tumor behavior and may be useful in specific cases for risk stratification of EAC patients.

Topics: Adenocarcinoma; Biomarkers, Tumor; Biopsy; Chi-Square Distribution; Coloring Agents; Eosine Yellowish-(YS); Esophageal Neoplasms; Germany; Hematoxylin; Humans; Immunohistochemistry; Kaplan-Meier Estimate; Keratins; Logistic Models; Lymphatic Metastasis; Multivariate Analysis; Neoplasm Grading; Neoplasm Invasiveness; Observer Variation; Odds Ratio; Phenotype; Predictive Value of Tests; Proportional Hazards Models; Reproducibility of Results; Staining and Labeling; Switzerland

Tumor budding is recognized as an important risk factor for lymph node metastasis in pT1 colorectal cancer. Immunohistochemical staining for cytokeratin has the potential to improve the objective diagnosis of tumor budding over detection based on hematoxylin and eosin staining. However, it remains unclear whether tumor budding detected by immunohistochemical staining is a significant predictor of lymph node metastasis in pT1 colorectal cancer.. The purpose of this study was to clarify the clinical significance of tumor budding detected by immunohistochemical staining in comparison with that detected by hematoxylin and eosin staining.. This was a retrospective study.. The study was conducted at Niigata University Medical & Dental Hospital.. We enrolled 265 patients with pT1 colorectal cancer who underwent surgery with lymph node dissection.. Tumor budding was evaluated by both hematoxylin and eosin and immunohistochemical staining with the use of CAM5.2 antibody. Receiver operating characteristic curve analyses were conducted to determine the optimal cutoff values for tumor budding detected by hematoxylin and eosin and CAM5.2 staining. Univariate and multivariate analyses were performed to identify the significant factors for predicting lymph node metastasis.. Receiver operating characteristic curve analyses revealed that the cutoff values for tumor budding detected by hematoxylin and eosin and CAM5.2 staining for predicting lymph node metastases were 5 and 8. On multivariate analysis, histopathological differentiation (OR, 6.21; 95% CI, 1.16-33.33; p = 0.03) and tumor budding detected by hematoxylin and eosin staining (OR, 4.91; 95% CI, 1.64-14.66; p = 0.004) were significant predictors for lymph node metastasis; however, tumor budding detected by CAM5.2 staining was not a significant predictor.. This study was limited by potential selection bias because surgically resected specimens were collected instead of endoscopically resected specimens.. Tumor budding detected by CAM5.2 staining was not superior to hematoxylin and eosin staining for predicting lymph node metastasis in pT1 colorectal cancer.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Biomarkers; Biomarkers, Tumor; Colorectal Neoplasms; Coloring Agents; Eosine Yellowish-(YS); Female; Hematoxylin; Humans; Immunohistochemistry; Keratins; Logistic Models; Lymph Node Excision; Lymphatic Metastasis; Male; Middle Aged; Multivariate Analysis; Neoplasm Staging; Retrospective Studies; ROC Curve

Circulating tumor cells (CTC) have become an important tool in the monitoring of patients with advanced prostate cancer (PC). The role of CTC in localized disease has been addressed by only few studies. However, results of CTC analyses are strongly dependent on the platform used for CTC enrichment and detection. In the present study, a microfluidic platform allowing for antigen-independent enrichment of CTC was investigated for its ability to detect CTC in patients with clinically localized PC.. Blood (2ml) was collected preoperatively from 50 consecutive patients undergoing radical prostatectomy for clinically localized PC. CTC were enriched using a microfluidic ratchet mechanism allowing separation of CTC from white blood cells based on differences in size and deformability. Enriched cells were stained for immunofluorescence with antibodies targeting pancytokeratin, epithelial cell adhesion molecule, and CD45. In 21 patients, we performed staining for the androgen receptor. CTC counts were correlated with clinical and pathological parameters using the Wilcoxon-Mann-Whitney test for continuous parameters and Chi-square test for categorical parameters.. CTC were detected in 25 (50%) patients. The median number of CTC in CTC-positive patients was 9 CTC/2ml (range: 1-417). Pancytokeratin positive CTC showed expression of androgen the receptor. We observed no correlation between CTC counts and prostate-specific antigen concentration, tumor stage, lymph node stage, or Gleason grade.. In a representative cohort of patients with clinically localized PC, CTC can be detected in a considerable proportion of patients when using a new microfluidic ratchet mechanism. This encourages further studies assessing the prognostic effect of antigen-independent enriched CTC in patients with PC.

Topics: Adenocarcinoma; Aged; Biomarkers, Tumor; Cell Count; Cell Separation; Cell Shape; Epithelial Cell Adhesion Molecule; Equipment Design; Humans; Keratins; Lab-On-A-Chip Devices; Male; Middle Aged; Neoplasm Proteins; Neoplastic Cells, Circulating; Observer Variation; Preoperative Care; Prostatectomy; Prostatic Neoplasms; Receptors, Androgen

Subclassification of ampullary adenocarcinomas into intestinal and pancreatobiliary type has prognostic and therapeutic implications. Immunohistochemical staining against specific biomarkers has been proven to be a useful adjunct in determining the exact histotype. Furthermore the immunohistochemical profile is suggestive of the molecular pathogenic mechanisms through which the tumor evolved. The aim of this study was to correlate p53, MDM2, CK7, CK20, MUC1, MUC2 and CDX2 expression in ampullary adenocarcinomas with the type of differentiation and patients' survival.. Forty-seven radically resected ampullary adenocarcinomas were included in this study. Thirty-eight of them were eligible for survival analysis. Patients' data were retrospectively collected. All tumors were classified as intestinal or pancreatobiliary type, according to histologic criteria, and immunohistochemically stained against the aforementioned markers.. There were 18 intestinal and 29 pancreatobiliary type ampullary adenocarcinomas. A trend was found between intestinal type tumors and large tumor size. CK20, MUC2 and CDX2 expression was more prevalent in intestinal type tumors, while MUC1 was more frequently expressed in pancreatobiliary type tumors. Neither p53 nor MDM2 differential expression between the two histotypes reached statistical significance. Multivariate analysis indicated CK20 and MUC1 as independent predictors of the histotype. Mean and median survival was 90.3 and 55 months respectively. Overall 5-year survival rate was 48%. Survival analysis indicated TNM stage as the only independent prognostic factor. Although significant difference in survival rates among the two histotypes was implied based on survival plots, this difference could not gain statistical significance.. Immunoreactivity against CK20 and MUC1 in ampullary carcinomas is a useful adjunct to histologic examination in determining histotype. None of the immunohistochemical markers studied has prognostic significance. Future studies focused on other signaling pathways should seek further evidence of distinct tumorigenic mechanisms between histotypes of ampullary adenocarcinoma.

Topics: Adenocarcinoma; Adolescent; Adult; Aged; Aged, 80 and over; Ampulla of Vater; Biomarkers, Tumor; CDX2 Transcription Factor; Cell Differentiation; Common Bile Duct Neoplasms; Female; Humans; Immunohistochemistry; Kaplan-Meier Estimate; Keratins; Male; Middle Aged; Mucins; Prognosis; Proportional Hazards Models; Proto-Oncogene Proteins c-mdm2; Tumor Suppressor Protein p53; Young Adult

To characterize the immunophenotypic relationship between the squamous and the glandular compartments in the oesophagus of patients with columnar-lined oesophagus (CLO).. Eight tissue blocks from three oesophageal resection specimens from patients who underwent oesophagectomy for adenocarcinoma of the oesophagus were selected for immunohistochemical analysis. The markers of intestinal differentiation [CK20, CDX2 and MUC2] were all expressed in the expected pattern, solely in the glandular compartment of the resection specimens. CK4, CK17 and lysozyme were expressed in both the glandular and the squamous compartments. In addition, CK17 expression was found on both the squamous and glandular margins of the squamocolumnar transformation zones and in the submucosal gland (SMG) intraglandular and excretory ducts.. There is an immunophenotypic relationship between the squamous and the glandular compartments of the CLO, with expression of lysozyme, CK4 and CK17 in both squamous and columnar cells. These overlapping immunophenotypes indicate similar differentiation paths, and link the SMG unit with the columnar metaplasia and the neosquamous islands in CLO. Our findings support the theory of a cellular origin of CLO and neosquamous islands from the SMG unit.

Topics: Adenocarcinoma; CDX2 Transcription Factor; Esophageal Neoplasms; Esophagus; Homeodomain Proteins; Humans; Immunohistochemistry; Keratins; Metaplasia; Mucin-2; Mucous Membrane

Mammary tumors that spontaneously occurred in domestic Djungarian hamsters (Phodopus sungorus) were histologically examined. Forty-five mammary tumors included 14 adenomas, 18 adenocarcinomas, 1 lipid-rich carcinoma, 2 adenoacanthomas, 2 malignant adenomyoepitheliomas, 1 benign mixed tumor, and 7 "balloon cell" carcinosarcomas. The latter 4 types were newly recognized neoplasms in Djungarian hamsters. The relatively high incidence of spontaneous mammary carcinosarcomas in domestic Djungarian hamsters is intriguing. Carcinosarcomas exhibited anomalous histological features made up of a mixture of glandular cells, polygonal cells (including "balloon cells"), and sarcomatous spindle cells in varying proportions. Transitional features from glandular cells to polygonal cells and subsequently to sarcomatous spindle cells were observed. Using immunohistochemistry, we observed that glandular cells exhibited an epithelial phenotype (cytokeratin(+)/vimentin(-)), spindle cells exhibited a mesenchymal phenotype (cytokeratin(-)/vimentin(+)), and polygonal cells exhibited an intermediate phenotype (cytokeratin(+)/vimentin(+)). Reduction or loss of β-catenin expression and gain of S100A4 expression were observed in polygonal and spindle cells. The polygonal cell population included a varying number of characteristic cells that were expanded by large intracytoplasmic vacuoles. Electron microscopy revealed that these "balloon cells" had large cytoplasmic lumens lined by microvilli. These observations suggest that epithelial-mesenchymal transition may account for the pathogenesis of mammary carcinosarcomas in Djungarian hamsters.

Topics: Adenocarcinoma; Animals; beta Catenin; Carcinoma; Cricetinae; Epithelial-Mesenchymal Transition; Female; Immunohistochemistry; Keratins; Mammary Neoplasms, Animal; Phodopus; Rodent Diseases; Vimentin

Diagnosis of prostatic diseases with Immunohistochemistry still faces challenges because of the peculiar histology of the prostate and difference(s) in reactivity of Monoclonal antibodies (MoAb) to benign and malignant changes.. Thirty (30) archived paraffin embedded tissue samples from primary prostate tumors (15 Benign Prostatic Hyperplasia (BPH) and 15 Cancer of the prostate (CaP)) were sectioned at thickness of 5 µm and confirmed as BPH or CaP. Sections from each sample were stained by Immunohistochemistry using the Streptavidin-biotin method and using CK5/6, CK7, CK8,CK20 and Ki67 antibodies (Zymed Antibody products). Appropriate positive and negative controls for each antibody were setup alongside the test slides.. BPH samples were reactive to Ck5/6 (93.3%), Ck7 (80%) and Ck8 (100%). Only 13.3% of BPH samples were reactive to Ki67. The reactivity of Ck5/6, 7, 8 in CaP is a contrast with only 3(20%) of samples positive with Ck5/6, 2(13.3%) positive with Ck7 and 14(93.3%) with Ck8. While reactivity of Ck 8 is similar in BPH and CaP, no reaction was recorded in Ck 20 in both BPH and CaP. Ki67 was only reactive in 2(13.3) of BPH samples and 15(100%) of CaP. Only Ck 8 was expressed in both BPH and CaP. There was co-expression of Ck5/6, 7,8 and Ki67 in 13.3%; Ck7 and Ki67 in 13.3% in both BPH and CaP.. The various cytokeratins are individually expressed in both BPH and CaP. Ck5/6 and Ck7 are co-expressed and may be used in the diagnosis of BPH, Ck5/6,7,8 and Ki67 are co-expressed in Prostatic adenocarcinoma and squamous cell carcinoma of the prostate while Ck8 and Ki67 are co-expressed and may be used for diagnosis of Prostatic adenocarcinoma alone.

Topics: Adenocarcinoma; Biomarkers, Tumor; Carcinoma, Squamous Cell; Humans; Immunohistochemistry; Keratins; Ki-67 Antigen; Male; Prostatic Hyperplasia; Prostatic Neoplasms

Sentinel lymph node biopsy is the current standard procedure used to stage patients with breast cancer. The best histological method in evaluating sentinel nodes is highly debated among institutions and is thus not standardized. The optimal histological analysis is a balance between comprehensive evaluation of the sentinel nodes and cost effectiveness. One commonly used approach is serial sectioning and alternately staining with hemotoxylin and eosin and AE1/AE3 cytokeratin immunohistochemistry analysis. We report 2 cases of metastatic carcinoma demonstrating negative staining for AE1/AE3. This observation highlights a rare but potential pitfall to this commonly used strategy in assessing sentinel lymph node biopsies in breast cancer.

Topics: Adenocarcinoma; Breast Neoplasms; Carcinoma, Ductal, Breast; Female; Humans; Keratins; Lymph Nodes; Lymphatic Metastasis; Middle Aged; Neoplasm Staging; Sentinel Lymph Node Biopsy

Primary small bowel adenocarcinoma is rare. Although generally similar to colonic adenocarcinoma, some small bowel adenocarcinomas exhibit unique morphologic features, particularly those arising in association with Crohn disease. In this study, 15 sporadic small bowel adenocarcinomas and 11 Crohn enteritis-associated small bowel adenocarcinomas were examined for histology and immunohistochemical profile including cytokeratins (CK) 7 and 20, intestinal markers CDX2 and MUC2, and gastric epithelial markers MUC5AC and MUC6. We found that Crohn enteritis-associated small bowel adenocarcinomas frequently resemble gastric tubular adenocarcinoma histologically. In addition, when compared to sporadic small bowel adenocarcinoma, the former expressed MUC5AC and MUC6 with much higher frequency (82% vs. 7% and 73% vs. 0%, respectively). Ten of 11 Crohn enteritis-associated small bowel adenocarcinomas (91%) were positive for at least one gastric-type marker (MUC5AC or MUC6). Expression of CK7 was also more frequent in Crohn enteritis-associated small bowel adenocarcinoma (73% versus 27%) while expression of CK20 was less frequent (64% vs. 100%). There was no difference between sporadic and Crohn enteritis-associated small bowel adenocarcinoma in expression of CDX2 (100% vs. 91%) and MUC2 (93% vs. 73%). These observations suggest that there is a difference in the morphologic and immunohistochemical characteristics of sporadic versus Crohn enteritis-associated small bowel adenocarcinoma, particularly in their expression of gastric-type mucin. The findings also suggest that gastric differentiation in Crohn enteritis-associated small bowel adenocarcinoma is related to gastric metaplasia, a common phenomenon in Crohn disease.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Crohn Disease; Duodenal Neoplasms; Female; Humans; Ileal Neoplasms; Jejunal Neoplasms; Keratins; Male; Metaplasia; Middle Aged; Mucins; Stomach Neoplasms

To describe the morphology of focal prostatic atrophy and propose a comprehensive histologic classification for a proper diagnostic recognition.. A broad immunohistochemical study was performed as an adjunct to its recognition as well as a contribution to pathogenesis.. A morphologic continuum was seen on needle biopsies. Chronic inflammation was present only in complete atrophy. Immunohistochemical findings in partial atrophy are similar to normal acini. Luminal compartment in complete atrophy shows aberrant expression of 34betaE12 favoring an intermediate phenotype. ERG negativity in all variants of atrophy may have value in the identification of the lesion.. The morphologic findings favor a continuum probably partially preceding complete atrophy. Chronic inflammation may be a secondary phenomenon seen only in complete atrophy. Overexpression in complete atrophy of glutathione S-transferase pi relates to oxidative stress possibly related to chronic ischemia, of c-Met favors the concept that intermediate cells may be target for carcinogenesis, and of CD44 may be related to the recruitment of inflammatory cells.

Topics: Adenocarcinoma; Aged; Aged, 80 and over; Atrophy; Biopsy, Needle; Diagnosis, Differential; Humans; Hyaluronan Receptors; Immunohistochemistry; Kallikreins; Keratins; Male; Middle Aged; Prostate; Prostate-Specific Antigen; Prostatic Diseases; Prostatic Intraepithelial Neoplasia; Prostatic Neoplasms; Sclerosis

The workup of a malignant effusion usually requires immunostaining with a panel of markers. Although nuclear Wilms tumor 1 (WT1) expression is widely used to detect tumors of ovarian and mesothelial origin, it is less well known that WT1 is also expressed in the cytoplasm of melanomas and mesenchymal tumors. Because to the authors' knowledge the diagnostic utility of cytoplasmic WT1 expression has not been explored to date, the usefulness of a WT1/AE1/AE3 dual-color immunostain in the workup of malignant effusions was evaluated.. A total of 86 pleural effusions, including 17 metastatic melanomas, 31 metastatic adenocarcinomas, 10 malignant mesotheliomas, 10 lymphoproliferative disorders, 5 metastatic sarcomas, and 13 benign specimens, were immunostained using a peroxidase-based brown chromogen for WT1 and an alkaline phosphatase-based red chromogen for AE1/AE3 on cell block sections.. The majority of malignant effusions stained in 1 of 4 distinctive patterns: 1) all lung and breast adenocarcinomas demonstrated cytoplasmic AE1/AE3 expression without nuclear or cytoplasmic WT1 expression; 2) serous carcinomas of Müllerian origin, mesotheliomas, and benign mesothelial cells were positive for cytoplasmic AE1/AE3 as well as nuclear WT1; 3) melanomas, sarcomas, and a subset of plasma cell neoplasms were positive for cytoplasmic expression of WT1 but negative for AE1/AE3; and 4) large B-cell lymphomas and a subset of plasma cell neoplasms were negative for both markers.. A WT1/AE1/AE3 dual-color immunostain can reliably identify malignancy in pleural effusions and group malignant cells into discrete subsets, thereby narrowing the differential diagnosis. This simple double stain can be a cost-effective, first-line test in the workup of patients with malignant effusions.

Topics: Adenocarcinoma; Biomarkers, Tumor; Carcinoma; Coloring Agents; Epithelium; Humans; Immunohistochemistry; Keratins; Lymphoproliferative Disorders; Melanoma; Mesothelioma; Neoplasm Metastasis; Pleural Effusion, Malignant; Sarcoma; WT1 Proteins

This study aimed at evaluating the utility of a panel of antibodies, consisting of cytokeratins (CK) 5/6, CK34βE12, p63, thyroid transcription factor-1 (TTF-1), and CK7 for distinguishing between squamous cell carcinoma (SCC) and adenocarcinomas (Ad), as well as their expression with clinicopathological parameters and prognosis in SCC and Ad. 111 SCC of small biopsy specimens and 99 cases of Ad were stained by immunohistochemistry, among which 76 SCC and 64 Ad had complete follow-up data. Most of SCC displayed CK5/6 (91/99, 91.92%), CK34βE12 (83/99, 83.84%), p63 (96/99, 96.97%), and most of Ad showed expression of CK7 (89/111, 80.18%) and TTF-1 (105/111, 94.59%). The combination of CK5/6/CK34βE12/p63 seems to be useful for differentiating SCC from Ad with 100% sensitivity and 97.30% specificity, and TTF-1 was a useful biomarker for Ad with 94.59% sensitivity and 100% specificity. There were differences between CK5/6, p63, and TTF-1 expression with tumor differentiation (p<0.05) in SCC or Ad. Univariate analysis indicated that patients with high TTF-1 expression predicted better prognosis in Ad patients. Multivariate analysis showed that TTF-1 expression (HR=0.340, 95% CI 0.143-0.811, p=0.015) was a good independent predictor of Ad patient survival.

Topics: Adenocarcinoma; Adolescent; Adult; Aged; Aged, 80 and over; Biopsy; Diagnosis, Differential; DNA-Binding Proteins; Female; Humans; Immunohistochemistry; Keratin-5; Keratin-6; Keratin-7; Keratins; Lung Neoplasms; Male; Membrane Proteins; Middle Aged; Transcription Factors; Young Adult

Since circulating tumor cells (CTCs) have metastatic potential, their genetic and phenotypic characteristics could provide crucial information to establish the most effective therapy. We assessed the clinical utility of a methodology that allows the simultaneous analysis of CTC phenotype and genotype in colon cancer patients and, in addition, whether this methodology could provide complementary information to that obtained by the primary tumor biopsy. Thirty-three non-metastatic (stages 0-III) colon cancer patients and 9 healthy donor samples were evaluated. All peripheral blood samples (10 ml) were analyzed by cytokeratin immunomagnetic enrichment. Eight samples were analyzed by immunocytochemistry and 25 samples were analyzed by FICTION technique for simultaneous cytokeratin expression and chromosome 17 and ERBB2 gene status. A further study was carried out in one patient who showed CTC heterogeneity in chromosomal abnormalities. We analyzed HER2 protein expression on CTCs and FISH and HER2 protein expression in primary tumor of this patient. Our results show that 9.09% of patients had cytokeratin-positive CTCs (CK+/CTCs in peripheral blood). One of the patients showed heterogeneity in chromosomal 17 abnormalities and two different CK expression patterns on CTCs: one CK+/CTCs and one CK-/CTCs. Furthermore, 63.33% of these CTCs overexpressed HER2 protein while the primary tumor of this patient was diploid and did not express HER2 protein. We describe a methodology that allows the simultaneous genetic and phenotypic analysis of CTCs in colon cancer patients, which may provide essential information to select patients who might benefit from specific therapy.

Topics: Adenocarcinoma; Cell Separation; Chromosomes, Human, Pair 17; Colonic Neoplasms; Female; Flow Cytometry; Gene Expression Regulation, Neoplastic; Genes, erbB-2; Genotype; Humans; Immunohistochemistry; Immunophenotyping; In Situ Hybridization, Fluorescence; Keratins; Male; Neoplasm Grading; Neoplasm Staging; Neoplastic Cells, Circulating; Phenotype

Epithelial-mesenchymal transition (EMT) is defined as switching of polarized epithelial cells to a migratory fibroblastoid phenotype. EMT is known to be involved in the progression and metastasis of various cancers. The aim was to evaluate that whether EMT-related proteins' alterations are associated with clinicopathological features and prognosis in lung adenocarcinoma.. The expression of EMT-related proteins including cytokeratin, E-cadherin, TTF-1, β-catenin, vimentin, Snail, Twist, CD44 was evaluated by immunohistochemistry using a tissue array method in the lung adenocarcinoma tissues of 95 patients. In addition, clinicopathological characteristics and survival were compared with the expression of EMT-related proteins.. Loss of epithelial proteins and/or acquisition of the expression of mesenchymal proteins were observed in lung adenocarcinoma. These proteins' alteration was associated with poor cell differentiation and poor patients' outcome, respectively. Subjects were divided into two groups according to the number of EMT-related proteins' alteration. A higher number of EMT-related proteins' alteration was found to be significantly associated with unfavorable outcome. Multivariate analysis showed that a higher number of EMT-related proteins' alteration was independently associated with poor prognosis.. The number of EMT-related proteins' alteration is a significant prognostic marker to predict overall survival in patients with lung adenocarcinoma. The information generated will be valuable for the prognosis of patients with lung adenocarcinoma.. The virtual slides for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1007838329872974.

Topics: Adenocarcinoma; Adenocarcinoma of Lung; Adult; Aged; beta Catenin; Cadherins; Epithelial-Mesenchymal Transition; Female; Gene Expression Regulation, Neoplastic; Humans; Keratins; Lung Neoplasms; Male; Middle Aged; Nuclear Proteins; Prognosis; Thyroid Nuclear Factor 1; Transcription Factors; Vimentin

Receptor Activator of NF-kappa B (RANK) pathway controls mammary gland development in mice but its role in mammary stem cell fate remains undefined. We show that constitutive RANK signaling expands luminal and basal mammary compartments including mammary stem and luminal progenitor cell pools and interferes with the generation of CD61+ and Sca1+ luminal cells and Elf5 expression. Impaired mammary cell commitment upon RANK overexpression leads to the accumulation of progenitors including K14+K8+ bipotent cells and the formation of heterogeneous tumors containing hyperplastic basal, luminal, and progenitor cells. RANK expression increases in wild-type mammary epithelia with age and parity, and spontaneous preneoplastic lesions express RANK and accumulate K14+K8+ cells. In human breast tumors, high RANK expression levels are also associated with altered mammary differentiation. These results suggest that increased RANK signaling interferes with mammary cell commitment, contributing to breast carcinogenesis.

Topics: Adenocarcinoma; Aging; Animals; Breast Neoplasms; Carcinogenesis; Cell Compartmentation; Cell Differentiation; Cell Lineage; Cell Shape; Epithelium; Female; Gene Expression Regulation, Neoplastic; Humans; Keratins; Mammary Glands, Animal; Mammary Neoplasms, Experimental; Mammary Tumor Virus, Mouse; Mice; Models, Biological; Parity; Precancerous Conditions; Pregnancy; Receptor Activator of Nuclear Factor-kappa B; Stem Cells

Trefoil factor 3 (TFF3) is associated with various cancers and overexpressed in a subset of prostate cancers. Functional studies suggest that v-ets erythroblastosis virus E26 oncogene homolog (avian) (ERG) down-regulates TFF3 expression in hormone-naïve prostate cancer. To characterize this inverse relationship, we developed a triple immunostain encompassing ERG, TFF3, and high-molecular-weight cytokeratin. Triple stain was performed on 96 tumors and 52 benign cases represented in tissue microarrays. Distinct ERG and TFF3 protein was expressed in 45% (43/96) and 36% (35/96) of prostate cancers, respectively. Coexpression was observed in 5% (5/96) of tumor cases, and 24% (23/96) did not express ERG or TFF3. The inverse expression of ERG and TFF3 was significant (P < .0001), with 57% (30/53) of ERG-negative tumors demonstrating TFF3 expression. Sensitivity and specificity of combined ERG and TFF3 expression in detecting prostate cancer were 76% and 96%, respectively. The feasibility of triple immunostain protocol was validated in a set of 76 needle biopsies. The application of this multiplex in situ biomarker for molecular characterization of prostate cancer and as a supplemental diagnostic and prognostic tool in prostate needle biopsies should be further explored.

Topics: Adenocarcinoma; Adult; Aged; Biomarkers, Tumor; Humans; Keratins; Male; Middle Aged; Molecular Weight; Peptides; Prostatic Neoplasms; Tissue Array Analysis; Trans-Activators; Transcriptional Regulator ERG; Trefoil Factor-3

Spinal chordomas are more often located on the midline and are associated with marked destruction of the vertebral bodies. We report a rare case of large cervical (C2-C3) right lateral paravertebral chordoma extending into the spinal canal through a very enlarged intervertebral foramen. The tumor was initially diagnosed as a mucous adenocarcinoma on a percutaneous needle biopsy. However, the neuroradiological features, including the well-defined tumor margins, the regular and sclerosing lytic bone changes with regular enlargement of the intervertebral C2-C3 foramen, were in favor of a more slowly growing lesion, such as schwannoma or neurofibroma. At surgery a well-demarcated capsulated tumor involving the nerve root was partially resected. Histology was in favor of a low-grade chordoma (Ki-67/MIB-1<1%). Postoperative proton beam therapy was also performed. The differential neuroradiological diagnosis is discussed.

Topics: Adenocarcinoma; Aged; Cervical Vertebrae; Chordoma; Cone-Beam Computed Tomography; Female; Humans; Keratins; Magnetic Resonance Imaging; Spinal Neoplasms

When adenocarcinomas arise within the esophagus, particularly when located away from the gastroesophageal junction, it may be important in some patients to differentiate between a primary esophageal adenocarcinoma and metastasis from another site. Lung adenocarcinoma is one tumor that has been reported to frequently metastasize to the esophagus.. To create a panel of immunohistochemical markers that can reliably distinguish between an esophageal and pulmonary primary; within the gastrointestinal pathology literature, including published articles and textbooks, common lung immunohistochemical markers, such as TTF-1, are assumed to be negative in esophageal adenocarcinoma, yet, to our knowledge, no study has yet investigated the veracity of that presumption.. In this study, 24 cases each of pulmonary and esophageal adenocarcinomas were stained with TTF-1, napsin A, CDX2, 34βE12, N-cadherin, and IMP3 in an attempt to define an optimal panel for differentiation. Esophageal adenocarcinomas occurring at the gastroesophageal junction were excluded in this study because a gastric primary tumor cannot be excluded in those cases.. Surprisingly, TTF-1 and napsin A were positive in similar proportions of tumors from both sites. Those markers that differentiated statistically between esophageal and pulmonary adenocarcinoma were IMP3, CDX2, and N-cadherin.. When differentiating the origin of a tumor as either esophageal or pulmonary, an immunohistochemical panel consisting of IMP3, CDX2, and N-cadherin is superior to either TTF-1 or napsin A.

Topics: Adenocarcinoma; Antigens, CD; Aspartic Acid Endopeptidases; Biomarkers, Tumor; Cadherins; CDX2 Transcription Factor; Diagnosis, Differential; Esophageal Neoplasms; Homeodomain Proteins; Humans; Immunohistochemistry; Keratins; Lung Neoplasms; Nuclear Proteins; RNA-Binding Proteins; Staining and Labeling; Thyroid Nuclear Factor 1; Transcription Factors

Sarcomatoid carcinoma is an uncommon biphasic malignant tumor of the stomach. The histogenesis remains unknown, and a definitive diagnosis is obtained with immunohistochemical staining. Since prognosis is poor after surgery, more effective diagnostic tools are needed in order to select the optimal therapeutic approach. We report the case of an old female patient presenting with an endophytic tumor in the gastric fundus who underwent partial resection of the stomach. Histology revealed a poorly differentiated adenocarcinoma component mixed with sarcomatoid component. Immunohistochemically, the carcinoma components exhibited a positive reaction to pan-cytokeratin, whereas fusiform cells showed positive reactions to vimentin.

Topics: Adenocarcinoma; Aged, 80 and over; Female; Gastrectomy; Humans; Keratins; Stomach Neoplasms; Vimentin

Topics: Adenocarcinoma; Adenomatoid Tumor; Adenomyoma; Adult; Antibodies, Monoclonal, Murine-Derived; Biomarkers, Tumor; Calbindin 2; Diagnosis, Differential; Female; Follow-Up Studies; Humans; Keratins; Leiomyoma; Lymphatic Vessel Tumors; Middle Aged; Uterine Neoplasms; Young Adult

Primary cancer of the fallopian tube is a very rare tumor nowadays, accounting for approximately 0.14-0.3% of all tumors of the female genital tract. From these, bilateral primary cancer is found in less than 25% of all cases. We report here a case of bilateral primary cancer of the fallopian tube in a 48-year-old woman, associating uterine fibromatosis.

Topics: Adenocarcinoma; Cell Differentiation; Estrogens; Fallopian Tube Neoplasms; Female; Humans; Immunohistochemistry; Keratins; Middle Aged; Progesterone; Proliferating Cell Nuclear Antigen; Tumor Suppressor Protein p53

Single cell analysis and cell sorting has enabled the study of development, growth, differentiation, repair and maintenance of "liquid" tissues and their cancers. The application of these methods to solid tissues is equally promising, but several unique technical challenges must be addressed. This report illustrates the application of multidimensional flow cytometry to the identification of candidate stem/progenitor populations in non-small cell lung cancer and paired normal lung tissue. Seventeen paired tumor/normal lung samples were collected at the time of surgical excision and processed immediately. Tissues were mechanically and enzymatically dissociated into single cell suspension and stained with a panel of antibodies used for negative gating (CD45, CD14, CD33, glycophorin A), identification of epithelial cells (intracellular cytokeratin), and detection of stem/progenitor markers (CD44, CD90, CD117, CD133). DAPI was added to measure DNA content. Formalin fixed paraffin embedded tissue samples were stained with key markers (cytokeratin, CD117, DAPI) for immunofluorescent tissue localization of populations detected by flow cytometry. Disaggregated tumor and lung preparations contained a high proportion of events that would interfere with analysis, were they not eliminated by logical gating. We demonstrate how inclusion of doublets, events with hypodiploid DNA, and cytokeratin+ events also staining for hematopoietic markers reduces the ability to quantify epithelial cells and their precursors. Using the lung cancer/normal lung data set, we present an approach to multidimensional data analysis that consists of artifact removal, identification of classes of cells to be studied further (classifiers) and the measurement of outcome variables on these cell classes. The results of bivariate analysis show a striking similarity between the expression of stem/progenitor markers on lung tumor and adjacent tumor-free lung.

Topics: Adenocarcinoma; Biomarkers; Biomarkers, Tumor; Carcinoma, Non-Small-Cell Lung; DNA; DNA, Neoplasm; Epithelial Cells; Flow Cytometry; Humans; Keratins; Lung; Lung Neoplasms; Proto-Oncogene Proteins c-kit; Stem Cells

The use of supervised classification to extract markers from primary flow cytometry data is an emerging field that has made significant progress, spurred by the growing complexity of multidimensional flow cytometry. Whether the markers are extracted without supervision or by conventional gate and region methods, the number of candidate variables identified is typically larger than the number of specimens (p > n) and many variables are highly intercorrelated. Thus, comparison across groups or treatments to determine which markers are significant is challenging. Here, we utilized a data set in which 86 variables were created by conventional manual analysis of individual listmode data files, and compared the application of five multivariate classification methods to discern subtle differences between the stem/progenitor content of 35 nonsmall cell lung cancer and adjacent normal lung specimens. The methods compared include elastic-net, lasso, random forest, diagonal linear discriminant analysis, and best single variable (best-1). We described a broadly applicable methodology consisting of: 1) variable transformation and standardization; 2) visualization and assessment of correlation between variables; 3) selection of significant variables and modeling; and 4) characterization of the quality and stability of the model. The analysis yielded both validating results (tumors are aneuploid and have higher light scatter properties than normal lung), as well as leads that require followup: Cytokeratin+ CD133+ progenitors are present in normal lung but reduced in lung cancer; diploid (or pseudo-diploid) CD117+CD44+ cells are more prevalent in tumor. We anticipate that the methods described here will be broadly applicable to a variety of multidimensional cytometry problems.

Topics: AC133 Antigen; Adenocarcinoma; Antigens, CD; Biomarkers; Biomarkers, Tumor; Carcinoma, Non-Small-Cell Lung; Epithelial Cells; Flow Cytometry; Glycoproteins; Humans; Hyaluronan Receptors; Keratins; Lung; Lung Neoplasms; Peptides; Proto-Oncogene Proteins c-kit; Sensitivity and Specificity; Stem Cells

This report describes the clinical and pathological aspects of an apocrine sweat gland carcinoma with distant metastasis in an aged dog. A 7-year-old male terrier dog was referred to small animal hospital of Shahid Bahonar University of Kerman with a 5.5×3.5 centimeter pedunculated mass on its head near left auricular region which had been progressively growing since three months ago. The radiography showed no local and distant metastasis. Surgical excision and histological evaluation was done. Histologically, the mass was composed of epithelial cells arranged in glandular and solid patterns. The morphologic findings suggested either a primary or metastatic apocrine-gland carcinoma. Immunohistochemically, the tumor cells were intensely positive for cytokeratin 7 and 20 and negative for S100 protein. On the basis of histopathological and clinical findings, the tumor was diagnosed as a malignant apocrine gland tumor, arising from apocrine sweat glands of the skin. Local tumor recurrence with anorexia and weight loss was reported by the owner nine month later. Severe submandibular and prescapular lymphadenomegaly was noted in clinical examination. Several large pulmonary nodules were noted in chest radiographs resembling mediastinal lymph node metastasis. Second surgery and chemotherapy was rejected by the owner due to grave prognosis of the patient. The animal was died 45 days later due to respiratory complications. Tumors of apocrine sweat glands are relatively uncommon in dogs whereas apocrine gland adenocarcinoma with distant metastasis is extremely rare.

Topics: Adenocarcinoma; Animals; Biomarkers, Tumor; Dog Diseases; Dogs; Histocytochemistry; Immunohistochemistry; Keratins; Male; Microscopy; Neoplasm Metastasis; S100 Proteins; Sweat Gland Neoplasms; Sweat Glands

Molecular subtyping of breast cancer by gene expression has proven its significance in females. Immunohistochemical surrogates have been used for this classification, because gene expression profiling is not yet routinely feasible. Male breast cancer is rare and large series are lacking. In this study, we used immunohistochemistry for molecular subtyping of male breast cancer. A total of 134 cases of male breast cancer were immunohistochemically stained on tissue microarrays for estrogen receptor (ER), progesterone receptor (PR), HER2 and epidermal growth factor receptor (EGFR), as well as for CK5/6, CK14, and Ki67. HER2 was also assessed by chromogen in situ hybridization. Cases were classified as luminal A (ER+ and/or PR+, and HER2- and Ki67 low), luminal B (ER+ and/or PR+, and HER2+ or Ki67 high), HER2 driven (ER-, PR-, HER2+), basal-like (ER-, PR-, HER2-, CK5/6+ and/or CK14+ and/or EGFR+), or unclassifiable triple-negative (negative for all six markers). Luminal type A was by far the most encountered type of male breast cancers, representing 75% of the cases. Luminal type B was seen in 21% and the remaining 4% of cases were classified as basal-like (n=4) and unclassifiable triple-negative (n=1). No HER2 driven cases were identified. Patients with basal-like cancer were significantly younger (P=0.034). Luminal B type cancers showed significantly higher histological grade (P<0.001), mitotic index (P<0.001), and PR negativity (P=0.005) compared with luminal type A cancers. In conclusion, most male breast cancers are luminal A and luminal B types, whereas basal-like, unclassifiable triple-negative, and HER2 driven male breast cancers are rare. Luminal type B seem to represent a subtype with an aggressive phenotype. This distribution of molecular subtypes in male breast cancer is clearly different compared with female breast cancers, pointing to possible important differences in carcinogenesis.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Biomarkers, Tumor; Breast Neoplasms, Male; ErbB Receptors; Humans; Immunohistochemistry; In Situ Hybridization; In Situ Hybridization, Fluorescence; Keratins; Ki-67 Antigen; Male; Middle Aged; Neoplasm Proteins; Neoplasm Staging; Protein Array Analysis; Receptor, ErbB-2; Receptors, Steroid

Triple antibody cocktail immunohistochemical staining is routinely used as an ancillary method to establish a diagnosis of prostate cancer in biopsies with small foci of atypical glands. Crush artefact can distort surgical margins in radical prostatectomy specimens, occasionally making it difficult to diagnose a positive margin.. To investigate the ability of a cocktail stain to distinguish carcinoma from benign prostatic glands at the edge of crushed margins in prostatectomy specimens.. 10 radical prostatectomy specimens with crushed benign glands at the surgical margins, and 20 with crushed margins positive for carcinoma were retrieved from the pathology archives. The latter included 16 (80%) with positive apical margins, 2 (10%) incised intraprostatic margins, and 1 (5%) soft tissue margin. Two-colour triple antibody stain using a cocktail of antibodies against α-methylacyl coenzyme A racemase (AMACR), high molecular weight keratin and p63 was performed on all the selected cases.. In 10/10 specimens with crushed benign glands, basal cell staining continued to be detectable, while AMACR staining was negative in all cases (0/10). In the positive margin cases, none of the crushed glands expressed basal cell marker staining (0/20), whereas 14/20 (70%) of the cases showed variable levels of AMACR positivity at the inked margin.. Two-colour triple antibody cocktail stain is useful in the assessment of most, but not all, surgical margins with crushed artefact in prostatectomy specimens by helping to establish whether glands are malignant or benign.

Topics: Adenocarcinoma; Antibodies, Monoclonal; Biomarkers, Tumor; Humans; Immunohistochemistry; Keratins; Male; Prostatectomy; Prostatic Neoplasms; Racemases and Epimerases; Transcription Factors; Tumor Suppressor Proteins

Plectin, a member of the plakin family proteins, is a high molecular weight protein that is ubiquitously expressed. It acts as a cytolinker for the three major components of the cyotoskeleton, namely actin microfilaments, microtubules and intermediate filaments.. The aim of our experiments was to identify new binding sites for intermediate filaments on plectin and to specify these sites.. We introduced truncated forms of plectin into several cell lines and observe interaction between plectin and intermediate filaments.. We found that a linker region in the COOH-terminal end of plectin was required for the association of the protein with intermediate filaments. In addition, we also demonstrated that a serine residue at position 4645 of plectin may have a role on binding of plectin to intermediate filaments.. A linker region in the COOH-terminal end and serine residue at position 4645 may be important for the binding of plectin to intermediate filaments.

Topics: Actin Cytoskeleton; Adenocarcinoma; Adrenal Gland Neoplasms; Animals; Cell Line, Tumor; Chlorocebus aethiops; COS Cells; Cross-Linking Reagents; Gene Deletion; Intermediate Filaments; Keratinocytes; Keratins; Plectin; Protein Binding; Protein Structure, Tertiary; Vimentin

Distinguishing adenocarcinoma and squamous cell carcinoma of the esophagus is often based on morphological criteria and can be difficult in small biopsies. We analyzed commonly used immunohistochemical markers (p63, cytokeratin 5/6, cytokeratin 7, CDX2, MUC2, and MUC5AC) and 2 new markers, anterior gradient homolog 2 and SOX2, in esophageal carcinomas to establish the best panel to distinguish these tumors. Tissue microarrays with 69 esophageal adenocarcinomas and 41 whole sections of esophageal squamous cell carcinomas were stained for these markers and semiquantitatively scored. Sensitivities and specificities were calculated for individual markers and select combinations using the morphological diagnosis as a gold standard. All squamous cell carcinomas expressed p63 with 38 of 41 demonstrating reactivity in more than 75% of tumor cells. Cytokeratin 5/6 expression was seen in 40 of 41 squamous cell carcinomas with 39 of 41 demonstrating reactivity in more than 75% of tumor cells. SOX2 expression was present in 35 of 41 of squamous cell carcinomas but also in 24 of 69 of adenocarcinomas, frequently demonstrating extensive reactivity in adenocarcinomas. Anterior gradient homolog 2 was highly sensitive for adenocarcinoma and present in 68 of 69 of cases, but anterior gradient homolog 2 reactivity was also identified in 15 of 41 of squamous cell carcinomas, typically demonstrating focal reactivity in squamous cell carcinoma. MUC5AC expression was seen almost exclusively in adenocarcinomas with only a single squamous cell carcinoma demonstrating focal MUC5AC staining. Overall, the dual expression of both p63 and cytokeratin 5/6 was 99% specific and 98% sensitive for squamous cell carcinoma. In addition, anterior gradient homolog 2 and MUC5AC are useful positive markers of adenocarcinoma in the setting of absent or diminished p63 and cytokeratin 5/6 staining.

Topics: Adenocarcinoma; Biomarkers, Tumor; Carcinoma, Squamous Cell; Diagnosis, Differential; Esophageal Neoplasms; Esophagogastric Junction; Humans; Keratins; Mucin 5AC; Mucoproteins; Oncogene Proteins; Proteins; Sensitivity and Specificity; Tissue Array Analysis; Transcription Factors; Tumor Suppressor Proteins

Adenosquamous carcinoma originating in the stomach is an unusual neoplasm with few existing histological studies. This study was aimed to gain insight into the histogenetic and clinicopathological characteristics of gastric cancer with squamous cell carcinoma (SCC) components.. From January 2001 to June 2010 a total of 1735 patients underwent a resection of gastric cancer. Histopathologically, eight patients had adenocarcinoma containing SCC components, in which the proportion of SCC components was above 25% of the total tumor mass in four patients. The immunohistochemical and clinicopathological characteristics of these eight patients were analyzed.. The median survival duration was 22 months. Adenocarcinoma was present at the superficial layer of all tumors and SCC was primarily present at sites with deep invasion. Immunohistochemically, adenocarcinoma components were positive for cytokeratin (CK) 8/18/19 and CK7 in all cases. SCC components were positive for carcinoembryonic antigen and CK7 in more than 60% of patients. Expression patterns of p53 product were identical in both components. SCC components were positive for 34βE12 and adenocarcinoma components were negative for 34βE12 in all patients.. SCC components are derived from squamous metaplasia in a pre-existing adenocarcinoma. A gastric adenocarcinoma with SCC components is associated with various patterns of metastasis and both SCC and adenocarcinoma components have the potential for metastasis. Gastric cancer with SCC components is a clinically aggressive tumor.

Topics: Adenocarcinoma; Aged; Aged, 80 and over; Cadherins; Carcinoembryonic Antigen; Carcinoma, Adenosquamous; Carcinoma, Squamous Cell; Female; Humans; Immunohistochemistry; Keratin-18; Keratin-19; Keratin-7; Keratin-8; Keratins; Ki-67 Antigen; Male; Middle Aged; Retrospective Studies; Stomach Neoplasms; Survival Analysis; Tumor Suppressor Protein p53

Cytokeratin (CK) immunohistochemistry can play an important role in breast carcinoma evaluation. We evaluated the expression of a panel of commonly used CKs in a large cohort of breast cancers and assessed its correlation with other biomarkers and breast cancer subtypes. Expression of CK7, CK8, CK18 and CK19 was observed in more than 90 % of all breast carcinomas in this study, confirming their efficacy in immunohistochemical identification of breast cancer. A combination of CK8 and CK7 gave the highest sensitivity for detection of a minute number of breast cancer cells. Expression of other CKs, including CK5/6, CK14 and CK20, correlated positively with high tumour grade. The expression of CK5/6 and CK14 in a significant number of high-grade tumours raised concern regarding the use of absence of their expression to identify breast carcinoma. For identification of the basal subtype, CK5/6 gave a higher detection rate than CK14. CK20 expression was found more frequently than reported in previous studies, might constitute an indicator of poor prognosis and may be associated with the molecular apocrine subtype. This study highlights the diagnostic and prognostic relevance of the unique CK expression patterns in breast cancer.

Topics: Adenocarcinoma; Adenocarcinoma, Mucinous; Adult; Aged; Aged, 80 and over; Biomarkers, Tumor; Breast Neoplasms; Carcinoma, Ductal, Breast; Carcinoma, Lobular; Carcinoma, Medullary; Cohort Studies; Female; Humans; Immunohistochemistry; Keratins; Lymphatic Metastasis; Middle Aged; Neoplasm Staging; Prognosis; Tissue Array Analysis; Young Adult

To establish and characterize a lung adenocarcinoma cell line from a female patient in Xuanwei, Yunnan province.. Surgical specimen of the lung adenocarcinoma was obtained and cultured immediately in RPMI 1640 medium with 10% fetal bovine serum and 10(5) U/L penicillin and 100 mg/L streptomycin. When stable proliferation of the cells was achieved after over 40 passages in culture, the biological features of the cell line were investigated by cell morphology, karyotyping, protein marker expression [cytokeratins (CKs), epithelial membrane antigen (EMA) and CD proteins], growth kinetics, cell cycle phase distribution, mitotic index, colony formation in soft agar, cell invasion and tumorigenicity in Balb/c nude mice.. The established cell line was stably cultured for over 80 passages during a one-year period as an anchorage-dependent monolayer of short spindle, polygonal to epithelioid cells under phase contrast microscope. Microglandular cavities and disordered microfilaments were observed under transmission electron microscope. The growth curve presented in an "S" shape with the cell population doubled every 46.7 hours. The mitotic index was 1.5% and the colony formation rate was 8.3%. The cell cycle distribution included 76.9% in G(0)/G(1), 15.1% in S and 8.0% in G(2)/M. The cell line displayed a hypotriploid karyotype with a mode of 66 chromosomes and a median of 64 chromosomes. The cells expressed CK7, CK8, CK (Pan) and EMA by immunohistochemistry. A high level of cell surface expression of CD13 and CD59 was evident by flow cytometry. The cells were able to penetrate Matrigel in vitro but failed to form a stable xenograft in nude mice.. A new human lung adenocarcinoma cell line, designated as XLA-07, is successfully established from a Xuanwei lung cancer patient.

Topics: Adenocarcinoma; Adenocarcinoma of Lung; Animals; CD13 Antigens; CD59 Antigens; Cell Culture Techniques; Cell Cycle; Cell Line, Tumor; Cell Proliferation; Female; Humans; Karyotyping; Keratins; Lung Neoplasms; Mice; Mice, Inbred BALB C; Mice, Nude; Mucin-1; Neoplasm Transplantation; Polyploidy; Tumor Stem Cell Assay

The occurrence of adenocarcinoma after ileal pouch-anal anastomosis for ulcerative colitis (UC) is an infrequent but potentially lethal complication. Neither histomorphologic nor molecular features of pouch adenocarcinoma after ileal pouch-anal anastomosis have been fully investigated. We report the largest series of 12 pouch and peripouch adenocarcinomas and compared them with 58 randomly selected UC-associated adenocarcinomas. The mean age of patients with pouch/peripouch adenocarcinoma was 55.2 years (SD 14.8), which was not significantly different from that of controls (P=0.52). Pouch/peripouch adenocarcinoma and UC-associated adenocarcinoma had a comparable frequency of tumor-infiltrating lymphocytes, lack of dirty necrosis, mucin differentiation, signet ring cell differentiation, heterogeneity, and well differentiation (P>0.05 for all). Pouch/peripouch adenocarcinoma was more likely to show Crohn-like reaction compared with UC-associated adenocarcinoma (P=0.047). Loss of at least 1 mismatch repair protein was noted in 9% of pouch/peripouch adenocarcinomas and 9.6% of UC-related adenocarcinomas (P=1.0). There was no significant difference in the frequency of p53 overexpression (36.4% vs. 61.1%, P=0.184) or nuclear immunoreactivity for β-catenin (9% vs. 7.4%, P=0.99) in pouch/peripouch versus UC-associated adenocarcinomas, respectively. Pouch/peripouch and UC-associated adenocarcinoma had a comparable positive rate for CK7 (54.5% vs. 55.5%, P=0.99), CK20 (100% vs. 98.1%, P=0.99), and CDX2 (72.8% vs. 72.2%, P=0.99) by immunohistochemistry. In summary, pouch and peripouch adenocarcinoma can occur in patients without colorectal neoplasia and in those with idiopathic inflammatory bowel disease, can be potentially lethal, and has histomorphologic and molecular features similar to those of UC-associated adenocarcinoma.

Topics: Adenocarcinoma; Biomarkers, Tumor; CDX2 Transcription Factor; Colectomy; Colitis, Ulcerative; Colonic Pouches; Colorectal Neoplasms; DNA-Binding Proteins; Female; Homeodomain Proteins; Humans; Keratins; Lymphocytes, Tumor-Infiltrating; Male; Middle Aged; MutS Homolog 3 Protein; Neoplasm Staging; Postoperative Complications; Proctocolectomy, Restorative; Tissue Array Analysis

Topics: Adenocarcinoma; Adenocarcinoma, Clear Cell; Biomarkers; Carcinoma; Diagnosis, Differential; Female; Humans; Keratins; Membrane Proteins; Middle Aged; Mucin-1; Myoepithelioma; Neoplasm Recurrence, Local; Parotid Gland; Parotid Neoplasms; S100 Proteins

A 6-year-old Girolando dairy cow was presented for evaluation of a large subcutaneous facial mass. Fine-needle aspirates of the mass contained many neoplastic cells with high nuclear:cytoplasmic ratios arranged in sheets and loosely cohesive clusters with streaming erythrocytes and neutrophils in the background. Neoplastic cells were 13-25 μm in diameter and were round to cuboidal with variably distinct borders. Based on the signalment, anatomic location, and cytologic findings, differential diagnoses included salivary adenocarcinoma, squamous cell carcinoma, and mucoepidermoid carcinoma. The cow was euthanized and a necropsy was performed. The primary neoplasm arose from the left parotid salivary gland and meastatic tumor was found in the regional lymph nodes and lung. Histologically, the tumor was composed of anastomosing and irregular solid islets surrounded by scant stroma. Cells were negative for periodic acid-Schiff (PAS), PAS-diastase, and Alcian blue pH 2.5 stains, used to detect mucin. On immunohistochemical analysis, neoplastic luminal salivary gland cells expressed cytokeratin, but not S100, α-smooth muscle actin, or vimentin. Peripheral cells of neoplastic islets were immunoreactive for p63. The final diagnosis was nonsecretory adenocarcinoma of the parotid salivary gland.

Topics: Adenocarcinoma; Animals; Biopsy, Fine-Needle; Cattle; Cattle Diseases; Diagnosis, Differential; Face; Fatal Outcome; Female; Keratins; Lung; Lung Neoplasms; Lymph Nodes; Lymphatic Metastasis; Parotid Gland; Parotid Neoplasms

Myelosarcomas are, due to their rarity, a difficult differential diagnosis. Not infrequently, extensive immunohistochemical staining for characterization of the tumor is performed, if one does not directly think of myelosarcoma. In the present case, there was a positivity of the myeloid blasts for cytokeratin. This may complicate the discrimination of myelosarcoma from carcinoma, in particular small cell carcinoma, not only in the mediastinum, but also in the skin, e.g., Merkel cell carcinoma.

Topics: Adenocarcinoma; Biomarkers, Tumor; Cell Transformation, Neoplastic; Diagnosis, Differential; Female; Humans; Keratins; Leukemia, Myeloid, Acute; Lung Neoplasms; Lymph Node Excision; Lymph Nodes; Lymphatic Metastasis; Mediastinum; Middle Aged; Myeloid Cells; Neoplasms, Multiple Primary

Presentation of the Case A 37-year-old woman presented at 35 weeks of gestation with her third child with failure to adequately gain weight and was noted by her obstetrician to have delay in the growth of her baby. Ultrasound of the abdomen incidentally revealed the presence of a liver lesion. After additional evaluation, she ultimately delivered her daughter at 36 weeks uneventfully. She subsequently underwent additional evaluation. Liver magnetic resonance imaging (MRI) revealed a 5-cm solitary solid mass in segment 4A of the liver, concerning for malignancy. Serum α-fetoprotein, carcinoembryonic antigen, cancer antigen (CA)19-9, CA15-3, and CA125 were all normal. Liver biopsy was positive for adenocarcinoma. The tumor cells demonstrated a phenotype suggesting a possible breast primary, although the immunohistochemistry did not support that diagnosis and the tumor was negative for mammaglobin, gross cystic disease fluid protein (GCDFP)-15, estrogen receptor (ER), and progesterone receptor (PR) (Table 1). The tumor was also CDX2 and cardiotrophin-1 negative, but cytokeratin (CK) 19 positive. Her endoscopic retrograde cholangiopancreatography, upper endoscopy, colonoscopy, breast mammogram, and breast MRI were completely normal. A positron emission tomography-computed tomography scan showed a fluorodeoxyglucose-avid 5.8-cm × 6.0-cm hypoattenuating lesion with peripheral enhancement involving segment 4 and segment 8 at the dome. In addition, central necrosis within the lesion was noted. The left main portal vein was mildly attenuated by the mass. She eventually underwent a left hepatectomy en bloc with caudate resection, portal lymphadenectomy, cholecystectomy, and omental pedicle flap. On exploration of the abdomen, no additional disease was noted. The final pathology revealed a 9.4-cm moderately to poorly differentiated adenocarcinoma of the intrahepatic bile ducts. Venous invasion was present. Perineural invasion was absent. The margins were negative. Thirteen lymph nodes were obtained, all of which were negative, consistent with a stage T2, N0, MX intrahepatic cholangiocarcinoma. The tumor was positive for CK7, CK19, and CA19-9 and negative for CK20, CDX2, CA125, ER, PR, GCDFP-15, synaptophysin, and chromogranin (Table 1). The uninvolved liver was unremarkable and a trichrome stain showed no fibrosis. Following an uneventful postoperative recovery, she was referred for consideration of adjuvant therapy.

Topics: Adenocarcinoma; Adult; alpha-Fetoproteins; Bile Duct Neoplasms; Bile Ducts, Intrahepatic; Biomarkers; Biopsy; CA-125 Antigen; Capecitabine; Carcinoembryonic Antigen; Carrier Proteins; CDX2 Transcription Factor; Chemotherapy, Adjuvant; Cholangiocarcinoma; Cholangiopancreatography, Endoscopic Retrograde; Cytokines; Deoxycytidine; Female; Fluorodeoxyglucose F18; Fluorouracil; Gemcitabine; Glycoproteins; Hepatectomy; Homeodomain Proteins; Humans; Immunohistochemistry; Keratin-20; Keratins; Liver; Liver Neoplasms; Lymph Node Excision; Magnetic Resonance Imaging; Membrane Transport Proteins; Phenotype; Portal Vein; Pregnancy; Receptors, Estrogen; Receptors, Progesterone

Circulating tumour cells (CTCs) are cells that have detached from a primary tumour, circulate in the peripheral blood, and are considered to be the main root of distant metastases. We present a method for the detection of CTCs by real-time PCR on different cytokeratin markers.. Blood samples of a healthy donor were mixed with specific numbers of cells from different breast carcinoma cell line cells. RNA was isolated from the samples and transcribed into cDNA. TaqMan real-time PCR for cytokeratins 8, 18 and 19 was carried out and was correlated to that of 18S.. Cytokeratin gene expression increased in all samples, when as few as 10 tumour cells were added. In the CAMA-1 cell line, the increase was even greater the more cells were added.. By this methodology, cells from mammary carcinoma cell lines can be detected in blood samples. Its benefit will be validated in samples from patients with breast cancer.

Topics: Adenocarcinoma; Breast Neoplasms; Carcinoma, Ductal, Breast; Female; Humans; Keratins; MCF-7 Cells; Neoplastic Cells, Circulating; Real-Time Polymerase Chain Reaction

Infundibulocystic basal cell carcinoma (IBCC) is a variant of basal cell carcinoma. Sporadic cases usually represent a solitary tumor and multiple IBCC is rare. There have been no reports in which the tumor differentiation is characterized immunohistochemically. We report a case of multiple IBCC which developed on a patient's scalp by performing histopathological and immunohistochemical examinations, using monoclonal antibodies against cytokeratins (CKs). A 76-year-old female had noticed multiple small papules on her scalp. She noticed that the tumors were growing when she underwent systemic chemotherapy for metastatic lung cancer. Routine histopathological specimens from skin biopsies revealed findings typical of IBCC. The tumor cells expressed CK14 and CK17. However, CK1 and CK10 were expressed only in a few cells in the inner area of the tumors. The present case is unique in two points. First, multiple tumors developed on the patient's scalp during the systemic chemotherapy for the lung cancer. Second, the tumor showed CK expression patterns characteristic to infundibular and trichilemmal epithelia.

Topics: Adenocarcinoma; Aged; Antineoplastic Combined Chemotherapy Protocols; Biomarkers, Tumor; Camptothecin; Carboplatin; Carcinoma, Basal Cell; Docetaxel; Female; Humans; Immunohistochemistry; Irinotecan; Keratins; Lung Neoplasms; Neoplasms, Second Primary; Skin Neoplasms; Taxoids

Nonsmall cell lung carcinoma (NSCLC) accounts for 80% of lung cancers. The most prevalent subtypes of NSCLC are adenocarcinoma (ADC) and squamous cell carcinoma (SCC), which combined account for approximately 90%. Ten resected NSCLC patient tumors (5 ADC and 5 SCC) were directly introduced into severely immune deficient (NOD-SCID) mice, and the resulting xenograft tumors were analyzed by standard histology and immunohistochemistry (IHC) and by proteomics profiling. Mass spectrometry (MS) methods involving 1- and 2-dimensional LC-MS/MS, and multiplexed selective reaction monitoring (SRM, or MRM), were applied to identify and quantify the xenograft proteomes. Hierarchical clustering of protein profiles distinguished between the ADC and SCC subtypes. The differential expression of 178 proteins, including a comprehensive panel of intermediate filament keratin proteins, was found to constitute a distinctive proteomic signature associated with the NSCLC subtypes. Epidermal growth factor receptor (EGFR) was expressed in ADC and SCC xenografts, and EGFR network activation was assessed by phosphotyrosine profiling by Western blot analysis and SRM measurement of EGFR levels, and mutation analysis. A multiplexed SRM/MRM method provided relative quantification of several keratin proteins, EGFR and plakophilin-1 in single LC-MS/MS runs. The protein quantifications by SRM and MS/MS spectral counting were associated with superior dynamic range and reproducibility but were otherwise consistent with orthogonal methods including IHC and Western immuno blotting. These findings illustrate the potential to develop a comprehensive MS-based platform in oncologic pathology for better classification and potentially treatment of NSCLC patients.

Topics: Adenocarcinoma; Animals; Blotting, Western; Carcinoma, Non-Small-Cell Lung; Carcinoma, Squamous Cell; Chromatography, Liquid; Cluster Analysis; ErbB Receptors; Humans; Immunohistochemistry; Keratin-7; Keratins; Mice; Mice, Inbred NOD; Neoplasm Transplantation; Proteome; Reproducibility of Results; Statistics, Nonparametric; Tandem Mass Spectrometry; Transplantation, Heterologous

Behaviors of esophageal cancer are different according to the geographic distribution. The prevalence of bone marrow involvement in patients with esophageal cancer has been shown to be between 40% and 90%, but clinical correlation is unknown. The aim of this study is to determine the rate of bone marrow involvement in patients with esophageal cancer in the northeast of Iran and its relationship with clinicopathologic findings of the tumors.. A total of 43 patients with esophageal cancer, who were candidates for esophagectomy (without neo-adjuvant chemotherapy), were enrolled in this study from 2007 to 2009. Bone marrow samples derived from rib bone were stained with hematoxylin and eosin (H&E) to distinguish tumoral cells, and cytokeratin immunohistochemistry (CKIHC) was used to determine micrometastasis. The correlation of the results was studied with the histopathologic indices of primary tumor (T (tumor), N (node) and length of tumoral involvement and grading) as well as characteristics of the patients (sex and age).. The mean age was 64 (57-70) years and the M/F ratio was 2.9. As many as 38 patients (88.4%) had squamous cell carcinoma and five patients (11.6%) had adenocarcinoma. In nine cases (20.9%), the H&E test, and, in 13 cases (30.2%), the CKIHC evaluation was positive. Statistically, there was no relationship between the pathologic type and the stage of T with the H&E study and CKIHC test, respectively. On the other hand, a significant meaningful correlation was found between microscopic bone marrow involvement as well as mediastinal lymph node involvement and grade of the tumor.. Bone marrow involvement incidence was low in our geographic area. According to our study, bone marrow involvement in esophageal cancer is related to differentiation grade and mediastinal lymph node involvement.

Topics: Adenocarcinoma; Aged; Biomarkers, Tumor; Bone Marrow Neoplasms; Carcinoma, Squamous Cell; Cross-Sectional Studies; Esophageal Neoplasms; Esophagectomy; Female; Humans; Keratins; Lymphatic Metastasis; Male; Middle Aged; Neoplasm Grading; Neoplasm Micrometastasis; Neoplasm Proteins; Neoplasm Staging

Topics: Adenocarcinoma; Aged; Colonic Neoplasms; Head; Histocytochemistry; Humans; Immunohistochemistry; Keratins; Magnetic Resonance Imaging; Male; Microscopy; Orbital Neoplasms; Tomography, X-Ray Computed; Whole Body Imaging

Pseudohyperplastic carcinoma (PHPC) is a prostatic neoplasm that can be easily mistaken for nodular hyperplasia or atypical adenomatous hyperplasia. To determine the frequency and clinicopathologic characteristics of PHPC, we reviewed 200 simple prostatectomy specimens. We found 3 cases (1.5%) of PHPC. The tumors were small and ranged in size from 4 to 6 mm. Two of them were erroneously diagnosed as benign glandular proliferations in the original interpretation. Their histologic aspect at low magnification showed nodules of well-differentiated medium-sized glands with cystic dilation in a tight arrangement that imparted a benign appearance. Corpora amylacea were found in 2 cases. However, the lining cells showed nucleomegaly and prominent nuclei in most of the neoplastic glands, and the high-molecular-weight keratin (34BE12) immunostain revealed absence of basal cells. α-Methylacyl-CoA-racemase was positive in 2 cases. In one case, a small focus of moderated acinar adenocarcinoma was found adjacent to the pseudohyperplastic glands facilitating the diagnosis. The 3 patients are disease-free 3 and 4 years after surgery probably because of the small size of the tumors; however, it must be emphasized that most PHPC are considered moderately differentiated and potentially aggressive neoplasms.

Topics: Adenocarcinoma; Aged; Biomarkers, Tumor; Cell Nucleus; Humans; Keratins; Male; Middle Aged; Prostatectomy; Prostatic Hyperplasia; Prostatic Neoplasms; Racemases and Epimerases; Treatment Outcome

Topics: Adenocarcinoma; Carcinoid Tumor; Child; Chromogranin A; Common Bile Duct; Common Bile Duct Neoplasms; Diagnosis, Differential; Duodenum; Gallbladder; Humans; Keratins; Lymphoma; Male; Mucin-1; Neoplasm Invasiveness; Rhabdomyosarcoma; Stomach; Synaptophysin

We performed dual-color immunostaining with a 3-antibody cocktail (α-methylacyl coenzyme-A racemase, CK34betaE12, and p63) on prostate biopsies from 200 patients. Current practice (hematoxylin and eosin staining followed by dual-color immunostaining on selected cases) was compared with a protocol in which routine dual-color immunostaining was provided in all cases. In the original pathology reports, adenocarcinoma was diagnosed in 87/200 (43%) patients. Small foci interpreted as putative cancers were detected with dual-color immunostaining in 14/113 patients who were originally diagnosed with a nonmalignant lesion. All of the suggested cancerous foci were independently reevaluated by 5 pathologists. A diagnosis of adenocarcinoma was assessed by consensus in 8 cases, and atypical small acinar proliferation was diagnosed in 1 case. Consensus was not reached in 5 cases. Six of the foci reclassified as cancer were of Gleason score 3 + 3 = 6, while 2 were graded as Gleason score 4 + 4 = 8. The feasibility of routine dual-color immunostaining was also tested by analyzing the time spent on microscopic assessment. Because small, atypical lesions expressing α-methylacyl coenzyme-A racemase (blue chromogen) were easy to detect using dual-color immunostaining, the microscopic analysis of dual-color immunostaining and hematoxylin-eosin staining was faster than that of hematoxylin-eosin staining alone that was later followed by dual-color immunostaining in selected cases (median 251 seconds versus 299 seconds, P < .0001). We concluded that routine dual-color immunostaining of all prostate biopsies would produce better diagnostic sensitivity with a smaller microscopy workload for the pathologist. However, minute foci interpreted as cancer with dual-color immunostaining need to be confirmed with hematoxylin-eosin staining, and minimal criteria for a definitive diagnosis of cancer are still lacking.

Topics: Adenocarcinoma; Biopsy, Needle; Humans; Immunohistochemistry; Keratins; Male; Membrane Proteins; Prostate; Prostatic Neoplasms; Racemases and Epimerases; Staining and Labeling

Mesonephric remnant hyperplasia is a very rare benign mimicker of prostate adenocarcinoma. As most reported cases are from transurethral resection specimens, the anatomic location and histologic spectrum of this entity have not been fully elucidated. Its immunohistochemical profile using current prostatic diagnostic markers has also not been well studied. In this study, we retrospectively characterized 10 cases of mesonephric remnant hyperplasia involving the prostate and periprostatic tissue, including 8 cases seen in radical prostatectomy specimens, with emphasis on the histopathologic and immunohistochemical features. Patients ranged in age from 48 to 70 years (average, 60 y). Seven of them had concurrent prostatic adenocarcinoma and underwent radical prostatectomy; one patient underwent prostatectomy because of the misdiagnosis of mesonephric remnant hyperplasia on transurethral resection as carcinoma; 2 patients had transurethral resection for urinary obstruction. The distribution of prostatic mesonephric hyperplasia was concentrated in 2 areas: one was in the anterior fibromuscular stroma and adjacent anterolateral periprostatic tissue (n=6 of 8); the other was located toward the base posteriorly and posterolaterally either within or exterior to the prostate and around the seminal vesicle (n=4 of 8). Histologic patterns observed included the following: small-to-medium-sized acini or tubules with a lobular distribution (n=10 of 10); cysts either in clusters or scattered containing secretions (n=8 of 10); small or ill-formed glands with an infiltrative growth (n=7 of 10); glands with papillary infoldings or micropapillary tufts (n=4 of 10); and 2 cases exceptionally displayed nodules of ill-formed small glands intermixed with spindle cells, mimicking sclerosing adenosis or Gleason pattern 5 prostate cancer. Most cases (7 of 10) had florid hyperplasia and harbored 3 or more growth patterns. All cases were negative for prostate-specific antigen. Cytokeratin 34βE12 was diffusely positive in 4 of 9 cases, and showed focal immunoreactivity in the remaining 5 cases. Except for focal positivity seen in 4 of 7 cases, p63 was largely negative. Racemase was focally positive in 4 of 7 cases. Small glands with an infiltrative growth pattern, the most difficult to distinguish from cancer, were negative (n=3 of 6) or only focally positive (n=3 of 6) for 34βE12, negative for p63 (n=6 of 6), and focally positive for racemase (n=4 of 6). All cases examined in the stud

Topics: Adenocarcinoma; Aged; Biomarkers, Tumor; Diagnosis, Differential; Diagnostic Errors; Humans; Keratins; Male; Middle Aged; Paired Box Transcription Factors; PAX8 Transcription Factor; Prostate; Prostate-Specific Antigen; Prostatectomy; Prostatic Hyperplasia; Prostatic Neoplasms; Retrospective Studies; Wolffian Ducts

Immunohistochemistry is increasingly utilized to differentiate lung adenocarcinoma and squamous cell carcinoma. However, detailed analysis of coexpression profiles of commonly used markers in large series of whole-tissue sections is lacking. Furthermore, the optimal diagnostic algorithm, particularly the minimal-marker combination, is not firmly established. We therefore studied whole-tissue sections of resected adenocarcinoma and squamous cell carcinoma (n=315) with markers commonly used to identify adenocarcinoma (TTF-1) and squamous cell carcinoma (p63, CK5/6, 34βE12), and prospectively validated the devised algorithm in morphologically unclassifiable small biopsy/cytology specimens (n=38). Analysis of whole-tissue sections showed that squamous cell carcinoma had a highly consistent immunoprofile (TTF-1-negative and p63/CK5/6/34βE12-diffuse) with only rare variation. In contrast, adenocarcinoma showed significant immunoheterogenetity for all 'squamous markers' (p63 (32%), CK5/6 (18%), 34βE12 (82%)) and TTF-1 (89%). As a single marker, only diffuse TTF-1 was specific for adenocarcinoma whereas none of the 'squamous markers,' even if diffuse, were entirely specific for squamous cell carcinoma. In contrast, coexpression profiles of TTF-1/p63 had only minimal overlap between adenocarcinoma and squamous cell carcinoma, and there was no overlap if CK5/6 was added as a third marker. An algorithm was devised in which TTF-1/p63 were used as the first-line panel, and CK5/6 was added for rare indeterminate cases. Prospective validation of this algorithm in small specimens showed 100% accuracy of adenocarcinoma vs squamous cell carcinoma prediction as determined by subsequent resection. In conclusion, although reactivity for 'squamous markers' is common in lung adenocarcinoma, a two-marker panel of TTF-1/p63 is sufficient for subtyping of the majority of tumors as adenocarcinomas vs squamous cell carcinoma, and addition of CK5/6 is needed in only a small subset of cases. This simple algorithm achieves excellent accuracy in small specimens while conserving the tissue for potential predictive marker testing, which is now an essential consideration in advanced lung cancer specimens.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Algorithms; Biomarkers, Tumor; Biopsy; Carcinoma, Squamous Cell; Diagnosis, Differential; DNA-Binding Proteins; Female; Humans; Immunohistochemistry; Keratin-5; Keratin-6; Keratins; Lung Neoplasms; Male; Middle Aged; Predictive Value of Tests; Prospective Studies; Reproducibility of Results; Sensitivity and Specificity; Transcription Factors; Tumor Suppressor Proteins

The expression patterns of cytokeratin (CK) filaments in human epithelial neoplasms are complex and distinctive. The aims of this study were to analyze CK expression and to evaluate the diagnostic application of CKs in human non-small cell lung cancer (NSCLC).. mRNA expression of CK5, CK6, CK14, CK15, CK17, and CK19 was analyzed by Northern blotting. Protein expression of CK5/6, CK7, CK14, CK17, and CK18 was evaluated by immunohistochemistry on tissue microarrays.. Northern blotting showed that CKs were highly expressed in human bronchial epithelial cells and/or small airway epithelial cells. In NSCLC cell lines, the expression pattern of CKs was heterogeneous. Regarding protein expression of CKs in 95 primary lung tumors, expression of CK5/6, CK14, and CK17 proteins was increased in squamous cell carcinomas compared to adenocarcinomas (ADC; p = 0.001, p = 0.030, and p = 0.001, respectively), and higher expression was significantly associated with lower grading (p = 0.006, p = 0.002, and p = 0.001, respectively), while increased expression of CK7 and CK18 was observed in ADC (p = 0.001, respectively).. Our data suggest that CK5/6, CK7, CK14, CK17, and CK18 have diagnostic value in the subclassification of NSCLC.

Topics: Adenocarcinoma; Biomarkers, Tumor; Blotting, Northern; Carcinoma, Non-Small-Cell Lung; Carcinoma, Squamous Cell; Cell Line, Tumor; Gene Expression Regulation, Neoplastic; Humans; Immunohistochemistry; Keratin-14; Keratin-17; Keratin-18; Keratin-5; Keratin-6; Keratin-7; Keratins; Lung Neoplasms; Protein Array Analysis; RNA, Messenger

Metastatic pulmonary tumors secondary to breast cancer detected either before or after surgery are predominantly multiple and bilateral. However, in cases detected to have a solitary pulmonary nodule (SPN), determining whether the lesion represents a primary cancer, metastasis, or a benign pulmonary lesion can be difficult.. Between January 2000 and December 2009, we performed breast cancer surgery on 1,226 patients, of which 49 cases (3.9%) were detected to have pulmonary lesions before or after the surgery. In 14 of these patients, video-assisted thoracoscopic surgery was performed to remove a SPN.. Pathological examination of the resected specimens in these 14 cases revealed metastatic pulmonary tumor in 8 cases, primary lung cancer in 3 cases, and benign disease in 3 cases. While lobectomy was performed in one of these patients with metastatic pulmonary tumor, the remaining 7 underwent partial resection of the lung. The primary lung cancer was an adenocarcinoma in all 3 patients, and lobectomy plus mediastinal lymph node dissection was performed in these patients. The tumor grading based on pathological diagnosis was T1N0M0, p-Stage 1A in all 3 patients. The prognosis was good in the breast cancer patients in whom the metastatic lung tumor was a SPN.. Evaluating the immunohistochemical cytokeratin profile and levels of the TTF-1 and GCDFP-15 of the lesion was useful when distinguishing between pulmonary cancer and metastatic pulmonary tumor. In addition, some patients exhibited changes in the biological properties of the metastatic tumor, and delete tumor resection by video-assisted thoracoscopic surgery can be useful for deciding the drug treatment strategy in some cases.

Topics: Adenocarcinoma; Adult; Aged; Breast Neoplasms; Female; Follow-Up Studies; Humans; Keratins; Lung Neoplasms; Lymph Node Excision; Mastectomy; Middle Aged; Neoplasm Grading; Prognosis; Solitary Pulmonary Nodule; Tomography, X-Ray Computed

Tumor budding (TB) is showing increasing promise as a colorectal cancer (CRC) prognosticator that is independent of TNM staging. β-Catenin is a component of the Wingless/Wnt signaling pathway that is bound to membrane-associated E-cadherin and is essential for its correct position and function.. This study was designed to detect TB in 44 resected primary CRC cases and also to compare β-catenin expression in the tumor budding sites (TBS) and in the tumor center. Tumor budding was assessed in both H&E and pankeratin immunostained sections. Agreement between TB scoring using pancytokeratin and H&E was tested. Also, typing of the tumor margin and determination of degree of cytoplasmic pseudo-fragmentation was done. Tumor budding, cytoplasmic pseudofragments and β-catenin expression were related to known CRC prognosticators.. Ten tumors (22.7%) showed low grade (LG) budding and 34 tumors (77.3%) showed high grade (HG) budding. The 34 HG budding tumors were further subdivided into moderate and severe (n=13, n=21, respectively) budding cancers. Twenty nine tumors (65.9%) showed LG cytoplasmic pseudofragments and 15 tumors (34.1%) showed HG pseudofragments. Scoring of TB on H&E and pankeratin stained sections revealed moderate agreement (Kappa=.558; p=<.000). A significant relation between TB and cytoplasmic pseudofragments was observed (p=.009). Both TB and cytoplasmic pseudofragments did not significantly associate with clinicopathologic parameters. Immunoreactivity of nuclear and cytoplasmic β-catenin was significantly higher at TBS compared to tumor center (p=.005, p=.000, respectively). In opposition, membranous β-catenin expression was significantly higher in the tumor center than in TBS (p=.001). Although, nuclear β-catenin accumulation at TBS was noted, yet, it did not relate significantly with both TB and cytoplasmic pseudofragments around TBS (p=.649; p=.675, respectively). Also, nuclear β-catenin immunoreactivity did not relate significantly with the various clinicopathological variables.. Pankeratin immunostaining facilitates typing of CRC invasive margin, and determination of the degree of TB and cytoplasmic pseudo-fragmentation. β-Catenin expression differs significantly between tumor center and TBS in CRC. Cut-offs for TB assessment should be unified and further studies are recommended to allow a better understanding of this process before establishing TB as a prognostic factor beyond the TNM staging in CRC.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; beta Catenin; Cell Nucleus; Colorectal Neoplasms; Female; Humans; Keratins; Male; Middle Aged; Neoplasm Invasiveness; Tumor Burden

A 53-year-old woman had a tumor in the ascending colon. CT revealed tumor invasion to the surrounding tissue and also showed multiple swollen lymph nodes, liver metastases and ascites. Colonic tumor with severe stenosis was diagnosed by colonoscopy and the obtained biopsy specimen revealed poorly differentiated adenocarcinoma. Immunohistochemically, the tumor was positive for CEA, CK7, MUC2, MUC5AC·MUC6 (spotty) and negative for CK20, CDX2, TTF-1, GCDFP-15. Cytology of ascites also showed malignant cells. Although these protein expressions were specific for not primary colonic cancer but metastasis from ovarian cancer, the case was clinically and pathologically diagnosed as poorly differentiated adenocarcinoma of the colon with peritoneal metastases composed of micropapillary carcinoma. MLH1 and MSH2 protein expressions were normal. Even though modified FOLFOX6 chemotherapy was administered, the patient rapidly worsened due to pulmonary carcinomatous lymphangiosis and died a month after diagnosis. To determine the high-risk group of metastases, it seems necessary to require the accumulation of further cases evaluated by a precise immunohistochemistrical approach.

Topics: Adenocarcinoma; Colonic Neoplasms; Female; Humans; Immunohistochemistry; Keratins; Middle Aged; Peritoneal Neoplasms

Canine endometrial carcinomas are rare, and mostly occur in geriatric bitches. In this work, the uterus of a 10-year-old female Boxer evidencing an endometrial carcinoma on the body of the uterus was used to describe the histopathological features of the tumour and to study its immunophenotype. In this work, a panel of immunomarkers (cytokeratins AE1/AE3 and 14, vimentin, CD10 and Ki-67) was applied to the endometrial carcinoma to establish the staining patterns indicative of the tumour agressiveness and cellular differentiation. Additionally DNA ploidy was also performed. In this case, the tumour showed papillar pattern, with large pleomorphic, anaplastic cells and also some aberrant multinucleated and giant cells. In some areas of the tumour, it was also observed cytotrophoblastic-like cells outlining the papillae. Cytokeratin AE1/AE3 expression was detected in the luminal neoplasic cells. Cytokeratin 14 positivity was sporadic and irregular, and was observed mainly in the luminal epithelium. Only stromal and aberrant cells showed a positive staining to vimentin. Positive membranous staining to CD10 was evidenced by clear epithelial, cytotrophoblastic-like cells at the tumour surface but not by the stromal cells. The mitotic and Ki-67 indices were low, suggestive of a weak aggressiveness of the tumour. The multinucleated and giant cells evidenced a positive immunostaining to CK AE1/AE3, and CD 10; its positivity to vimentin was sporadic. This study aims to contribute to the advancement of the knowledge in canine endometrial carcinoma immunophenotype.

Topics: Adenocarcinoma; Animals; Biomarkers, Tumor; Dog Diseases; Dogs; Endometrial Neoplasms; Female; Immunohistochemistry; Keratins; Ki-67 Antigen; Neprilysin; Vimentin

The transcription functions of oestrogen receptors (ER) are influenced by several coregulators such as PELP1 (proline, glutamate and leucine rich protein 1). The aim of the present study, which uses tissue microarrays and immunohistochemistry, is to explore the clinical and biological relevance of PELP1 protein expression in a large series of consecutive patients (1,162 patients) with invasive breast cancers with particular emphasis on its role in the ER-positive/luminal-like class of tumours. Our results showed that increased PELP1 expression is associated with tumours of larger size, higher histological grade, higher mitotic count, and with positive expression of basal cytokeratins (CK) (CK14; P = 0.018 and CK5/6; P = 0.029), P-cadherin (P = 0.002), p53 and MIB1 (P = 0.018). There was an inverse association between PELP1 expression and ER (P = 0.002), progesterone (PgR) (P = 0.004), androgen (AR) receptor (P < 0.001), and luminal CK (CK18; P = 0.027) expression. A significant association between PELP1 expression and shorter breast cancer specific survival (BCSS) (P = 0.002) and disease-free survival (DFI) (P = 0.006) was found. Multivariate Cox hazard analysis showed that PELP1 expression was an independent predictor of shorter BCSS (Hazard ratio (HR) = 1.349, P = 0.006) and shorter DFI (HR = 1.255, P = 0.011). In the ER-positive/luminal-like group (n = 768), PELP1 expression showed similar association with other clinicopathological variables and was an independent predictor of shorter DFI (HR = 1.256, P = 0.036). In conclusion, PELP1 protein expression is an independent prognostic predictor of shorter BCSS and DFI in breast cancer and its elevated expression is positively associated with markers of poor outcome. PELP1 appears to have a potential application in assessing the clinical outcome of patients with ER-positive breast cancer.

Topics: Adenocarcinoma; Adult; Aged; Breast Neoplasms; Cadherins; Co-Repressor Proteins; Disease-Free Survival; Estrogens; Female; Humans; Kaplan-Meier Estimate; Keratins; Middle Aged; Mitotic Index; Neoplasm Invasiveness; Neoplasm Proteins; Neoplasms, Hormone-Dependent; Oligonucleotide Array Sequence Analysis; Prognosis; Receptors, Androgen; Receptors, Estrogen; Receptors, Progesterone; Trans-Activators; Transcription Factors; Tumor Burden; Tumor Suppressor Protein p53; Ubiquitin-Protein Ligases

Despite having a dramatically larger surface area than the large intestine, the small intestine is an infrequent site for the development of adenocarcinoma. To better understand the molecular abnormalities in small bowel adenocarcinoma (SBA), we characterised a number of candidate oncogenic pathways and the immunophenotype of this rare cancer.. Tissue microarrays were constructed from tumour samples from 54 patients with all stages of the disease. Immunohistochemistry and microsatellite instability (MSI) testing were conducted.. The profile of cytokeratin 20 and 7 coexpression was variable, but expression of caudal type homeobox transcription factor 2 (CDX2) was present in 70% of cases. In this young population (median age 54 years), loss of mismatch repair (MMR) proteins occurred in 35% of patients, with confirmed MSI in 100% of tested cases. Expression of vascular endothelial growth factor-A (VEGF-A) and epidermal growth factor receptor (EGFR) was common, occurring in 96 and 71% of patients, respectively. Only one case showed HER2 expression and none showed loss of phosphatase and tensin homologue mutated on chromosome 10 (PTEN).. These results suggest that alterations in DNA MMR pathways are common in SBAs, similar to what is observed in large bowel adenocarcinomas. Furthermore, the high percentage of tumours expressing both EGFR and VEGF suggests that patients with this rare cancer may benefit from therapeutic strategies targeting EGFR and VEGF receptor (VEGFR).

Topics: Adenocarcinoma; Adult; Aged; CDX2 Transcription Factor; DNA Mismatch Repair; Duodenal Neoplasms; ErbB Receptors; Female; Gene Expression Profiling; Genes, erbB-1; Genes, erbB-2; Homeodomain Proteins; Humans; Ileal Neoplasms; Immunophenotyping; Jejunal Neoplasms; Kaplan-Meier Estimate; Keratins; Male; Microsatellite Instability; Middle Aged; Neoplasm Proteins; Oligonucleotide Array Sequence Analysis; Oncogenes; PTEN Phosphohydrolase; Receptor, ErbB-2; Receptors, Vascular Endothelial Growth Factor

High intensity focused ultrasound (HIFU) is an emerging alternative for the treatment of prostate adenocarcinoma. Alpha-methylacyl-CoA racemase (AMACR) has been shown to be a sensitive immunomarker for prostate cancer, however, there is no information available concerning its utility and that of other immunomarkers for the detection of malignancy after HIFU therapy.. AMACR expression was examined in 11 cases of prostatic carcinoma treated by HIFU, with histological evidence of residual carcinoma. In seven cases tumour was examined from thin core biopsies and in four cases from tissue fragments obtained by transurethral resection of prostate (TURP). In addition to AMACR, immunostaining was also undertaken for p63, cytokeratin 34betaE12, cytokeratin 5, cytokeratin 8-18, prostate specific alkaline phosphatase (PSAP), prostate specific antigen (PSA), chromogranin and CD56.. In two of the cases foci of tumour were cut out in serial sections. AMACR was expressed in eight of nine evaluable cases (4/5 biopsies and 4/4 TURP specimens). Cytokeratin 8-18 and PSAP were positive in all cases, whereas PSA was positive in five of nine cases. Cytokeratin 34betaE12, cytokeratin 5, and p63 marked the basal layer in normal prostatic glands, but were negative in neoplastic glands. In four cases we found tumour cells with positive staining for CD56 and chromogranin.. A panel with positive markers for AMACR, and negative markers for p63/cytokeratin 5/cytokeratin 34betaE12 confirms the neoplastic nature of the residual glands on biopsies or TURP fragments sampled after HIFU therapy.

Topics: Ablation Techniques; Adenocarcinoma; Biomarkers, Tumor; Combined Modality Therapy; Fluorescent Antibody Technique, Direct; Humans; Immunoenzyme Techniques; Keratin-5; Keratins; Male; Necrosis; Prostatic Neoplasms; Racemases and Epimerases; Transurethral Resection of Prostate; Ultrasonic Therapy; Ultrasonography

We investigated the staining pattern of commonly used basal cell/myoepithelial markers, such as p63 (a p53-homologous nuclear protein), basal cell-specific cytokeratin antibody (34betaE12, K903), and smooth muscle myosin heavy chain (SMMHC) in benign and malignant bronchioloalveolar proliferations of the lung. We studied 85 lung lesions consisting of 35 bronchioloalveolar carcinoma, 30 well-differentiated adenocarcinoma, and 20 cases of benign lung lesions. In normal lung, p63, K903, and SMMHC decorated the basal cells of large and small airways and occasional cells of terminal bronchioles. In reactive processes, a distinctive staining pattern was present in 19/20 (95%) of the cases characterized by staining of basal cells of the airways and bronchiolar epithelium and squamous metaplastic epithelium for p63 and K903, whereas 12/20 (60%) stained with SMMHC. Respiratory ciliated cells, alveolar epithelial cells, and nonepithelial cells were negative. In bronchioloalveolar carcinoma, a discontinuous peripheral rim of p63-immunoreactive cells was retained surrounding and intermingled with the malignant bronchioloalveolar proliferation in 31/35 (88.5%) cases, SMMHC in 28/35 (80%) cases, and K903 in 20/35 (57%) cases. For adenocarcinoma, a majority of the cases (28/30, 93%) were negative for p63 and K903; however, SMMHC showed artifactual staining in the desmoplastic stroma in 6/30 (20%) cases. Our results highlighted the differential expression of basal cell markers across various bronchioloalveolar lesions. The staining pattern of basal cells in bronchioloalveolar carcinoma supports that these neoplasms may actually be carcinoma in-situ.

Topics: Adenocarcinoma; Adenocarcinoma, Bronchiolo-Alveolar; Adult; Aged; Aged, 80 and over; Biomarkers, Tumor; Carcinoma, Basal Cell; Diagnosis, Differential; Female; Humans; Immunohistochemistry; Keratins; Lung Neoplasms; Male; Membrane Proteins; Middle Aged; Predictive Value of Tests; Prognosis; Sensitivity and Specificity; Smooth Muscle Myosins

Uterine tumors resembling ovarian sex cord tumors (UTROSCT) are tumors of unclear histogenesis. The authors analyzed the ultrastructural features of 13 UTROSCT and correlated the findings with their immunohistochemical profile. Features included cells with frequent organoid, nested or cord-like arrangement (8), lumen formation (2; one of which showed surface microvilli), nuclei with irregular indentations (8), intermediate filaments (13), prominent paranuclear aggregates (5), cell junctions (9), desmosome-like junctions (2), tonofilaments (2), basal lamina (1), and cytoplasmic lipid droplets (7; prominent in 3). No dense bodies, subplasmalemmal densities or pinocytotic vesicles were seen. Ultrastructural epithelial differentiation was present in 2 tumors (positive for keratin or epithelial membrane antigen). Prominent lipid droplets correlated with sex cord markers positivity in 2 tumors. Ultrastructural features of smooth muscle differentiation were lacking and abundant paranuclear filaments did not correlate with myoid markers. UTROSCT are polyphenotypic neoplasms ultrastructurally with focal epithelial and variable sex cord-like differentiation. These findings suggest that UTROSCT may result from divergent differentiation in endometrial stromal tumors or represent a distinct group of uterine tumors with sex cord-like differentiation that are closer in histogenesis to ovarian sex cord stromal tumors.

Topics: Adenocarcinoma; Biomarkers, Tumor; Calbindin 2; Cell Nucleus; Cytoplasmic Structures; Desmosomes; Diagnosis, Differential; Female; Humans; Intermediate Filaments; Keratins; Microscopy, Electron, Transmission; Ovarian Neoplasms; S100 Calcium Binding Protein G; Sex Cord-Gonadal Stromal Tumors; Uterine Neoplasms

The molecular mechanism underlying epithelial metaplasia in Barrett's esophagus remains unknown. Recognizing that Hedgehog signaling is required for early esophageal development, we sought to determine if the Hedgehog pathway is reactivated in Barrett's esophagus, and if genes downstream of the pathway could promote columnar differentiation of esophageal epithelium.. Immunohistochemistry, immunofluorescence, and quantitative real-time polymerase chain reaction were used to analyze clinical specimens, human esophageal cell lines, and mouse esophagi. Human esophageal squamous epithelial (HET-1A) and adenocarcinoma (OE33) cells were subjected to acid treatment and used in transfection experiments. Swiss Webster mice were used in a surgical model of bile reflux injury. An in vivo transplant culture system was created using esophageal epithelium from Sonic hedgehog transgenic mice.. Marked up-regulation of Hedgehog ligand expression, which can be induced by acid or bile exposure, occurs frequently in Barrett's epithelium and is associated with stromal expression of the Hedgehog target genes PTCH1 and BMP4. BMP4 signaling induces expression of SOX9, an intestinal crypt transcription factor, which is highly expressed in Barrett's epithelium. We further show that expression of Deleted in Malignant Brain Tumors 1, the human homologue of the columnar cell factor Hensin, occurs in Barrett's epithelium and is induced by SOX9. Finally, transgenic expression of Sonic hedgehog in mouse esophageal epithelium induces expression of stromal Bmp4, epithelial Sox9, and columnar cytokeratins.. Epithelial Hedgehog ligand expression may contribute to the initiation of Barrett's esophagus through induction of stromal BMP4, which triggers reprogramming of esophageal epithelium in favor of a columnar phenotype.

Topics: Adenocarcinoma; Animals; Barrett Esophagus; Bile; Bile Reflux; Bone Morphogenetic Protein 4; Calcium-Binding Proteins; Cell Communication; Cell Differentiation; Cell Line; Disease Models, Animal; DNA-Binding Proteins; Epithelial Cells; Esophageal Neoplasms; Esophagus; Gastroesophageal Reflux; Hedgehog Proteins; Humans; Hydrogen-Ion Concentration; Keratins; Mesoderm; Metaplasia; Mice; Mice, Transgenic; Patched Receptors; Patched-1 Receptor; Phenotype; Precancerous Conditions; Receptors, Cell Surface; RNA Interference; Signal Transduction; SOX9 Transcription Factor; Transfection; Tumor Suppressor Proteins

Topics: Adenocarcinoma; Biomarkers, Tumor; Biopsy; Diagnostic Imaging; Female; Genes, ras; Humans; Incidence; Keratins; Male; Mass Screening; Neoplasm Proteins; Neoplasm Staging; Pancreatectomy; Pancreatic Neoplasms; Prognosis; Risk Factors

To investigate the pathological diagnostic features and the differential diagnosis of radial sclerosing lesions of the breast.. Morphological observation and immunohistochemistry were applied to forty-four cases of radial sclerosing lesions of the breast.. All forty-four patients were females, the mean age was 40.3 years (range 17 to 54 years). In the 31 consultation cases, 13 were misdiagnosed as carcinoma. The lesions had a radiating outline, and a central scar area where squeezed or pressed irregular shaped tubules were frequently seen. Dilated tubules and proliferated ducts or lobules were seen radically arranged at the periphery accompanied sometimes with the apocrine glands or columnar cell metaplasia and hyperplasia. Aside, there were 14 cases displaying necroses and 8 cases showing atypical ductal hyperplasia. Immunostaining showed myoepithelial cells around the pseudo-infiltrating tubules, and the florid proliferating epithelial cells were positive for CK5/6.. Radial sclerosing lesions of the breast possess characteristic histological features, and may be misdiagnosed as carcinoma. The lesions should be differentiated from ductal carcinoma in situ, lobular neoplasia, tubular carcinoma and invasive ductal carcinoma.

Topics: Adenocarcinoma; Adolescent; Adult; Breast; Breast Diseases; Breast Neoplasms; Carcinoma in Situ; Carcinoma, Ductal, Breast; Carcinoma, Lobular; Diagnosis, Differential; Diagnostic Errors; Female; Humans; Hyperplasia; Keratin-14; Keratin-5; Keratins; Middle Aged; Sclerosis; Young Adult

The size of lymph node (LN) metastases in prostate cancer patients represents an important prognosticator, but histological work-up may not reflect the true extent of tumor invasion. We present a novel technique (1) to detect early tumor cell dissemination and (2) to quantify the true tumor burden.. Prospectively 232 LN of 20 consecutive patients with prostate cancer after lymph node dissection were longitudinally bisected, one half was subjected to single cell immunocytochemistry for pancytokeratine (CK), the other half underwent routine histopathological work-up and step section analysis. In immunocytochemistry, tumor cell density (TCD) was quantified by calculating the number of CK-positive cells/million leucocytes and compared to routine histopathology and step section analysis.. Eight of 20 patients were positive in histopathology and step sectioning, but 14 of 20 patients were positive in single cell analysis. Twenty-five of 232 LN were positive in routine histopathology, whereas 52 of 232 LN were positive in single cell analysis. Median TCD in histopathologically positive LN was 3060.0 x 10(-6) and 9.9 x 10(-6) in histopathologically negative LN (P < 0.0001). Mean TCD of histopathologically negative LN of pN1 patients was significantly higher than the mean TCD of pN0 patients (P < 0.003). Mean TCD per patient correlated with serum-PSA (r(2) = 0.48, P < 0.006).. Single cell analysis has an increased detection rate compared to routine histopathology and even to serial step section analysis. The method can detect early tumor dissemination and enables quantification of the tumor burden. The subgroup of histopathologically negative LN with CK-positive cells represents tumor cell dissemination not depicted histologically.

Topics: Adenocarcinoma; Aged; Humans; Immunohistochemistry; Keratins; Linear Models; Lymph Node Excision; Lymph Nodes; Lymphatic Metastasis; Male; Middle Aged; Prospective Studies; Prostatic Neoplasms

A variety of markers have been proposed to identify breast cancer stem cells. Here, we used immunohistostaining and flow cytometry to analyze their interrelationships and to sort cells for tumorigenicity studies.. Cytokeratin, CD44, and CD90 were localized to primary breast cancer and normal breast (NB) tissue by immunohistostaining and related to CD117 and CD133 expression by flow cytometry. Immunodeficient NOD.CB17-Prkdc(scid) /J and NOD.Cg-Prkdc(scid) Il2rg(tm1Wjl) /SzJ mice were used to test tumorigenicity of sorted CD90+ low-light scatter, CD90+ high-light scatter, and CD90(neg) tumor cells.. NB basal cells coexpressed CD44 and CD90. As cells transited luminally, CD44 was retained and downmodulated, and CD90 was lost and cytokeratin increased. In breast tumors, basal-like CD44+/CD90+ cells were localized to the tumor periphery, adjacent to CD90+ stroma. Like normal luminal cells, interior tumor cells were CD44+/CD90-. Immunophenotyping (CD44/CD90/CD117/CD133) of cytokeratin+ cells revealed no significant difference in expression between tumors and tumor-free breast. In both, CD133 was distributed approximately equally among CD44/CD90 subsets, whereas CD117 expression was highest in the basal-associated CD44+/CD90+ subset. Sorted CD90+ pleural effusion cells with lymphoid light scatter, 49% of which were CD44+, were uniquely tumorigenic in immunodeficient mice (100 cells/injection).. Our data demonstrate that all tumors contain a small population of CD44+/CD90+ cells, mimicking the phenotype of ductal-basal cells. These are localized to the tumor periphery, adjacent to CD90+ stroma. Among the nonhematopoietic, nonmesothelial cells found in metastatic pleural effusions, low-light scatter CD90+ cells are most potently tumorigenic, compared to high-scatter CD90+ cells and CD90- cells. © 2010 International Clinical Cytometry Society.

Topics: AC133 Antigen; Adenocarcinoma; Animals; Antigens, CD; Biomarkers, Tumor; Breast Neoplasms; Female; Flow Cytometry; Glycoproteins; Humans; Hyaluronan Receptors; Keratins; Mice; Mice, Inbred NOD; Neoplasm Invasiveness; Neoplastic Stem Cells; Peptides; Pleural Effusion, Malignant; Proto-Oncogene Proteins c-kit; Thy-1 Antigens; Xenograft Model Antitumor Assays

In order of frequency, cervical intraepithelial neoplasia (CIN), combined adenocarcinoma in situ (AIS)/CIN lesions, and solitary AIS are the most prevalent premalignant lesions of the uterine cervix. As the morphologic distinction of these subtypes is not always straightforward, we performed an immunophenotyping analysis to establish distinguishing profiles for each of these squamous and glandular progenitor lesions of cervical carcinoma. A series of 26 premalignant cervical lesions, comprising 13 cases of AIS, of which 7 represented solitary AIS and 6 were combined with CIN (combined AIS/CIN), as well as 13 solitary high-grade CIN lesions, were immunophenotypically analyzed using antibodies directed against p16, p63, bcl-2, and cytokeratins (CK) 5, 7, 8, 13, 17, 18, and 19. Adjacent normal epithelia were also investigated. CIN lesions expressed the full panel of antibodies. Combined AIS/CIN lesions also expressed the full complement of markers in both the AIS and CIN compartments. However, the expression of p63, bcl-2, CK5, and CK17 was lower in AIS compared with CIN. The solitary AIS lesions could be subdivided into 2 subgroups, 1 expressing the full complement of markers and a second group in which no expression of p63, bcl-2, CK5, and a sporadically CK17 expression was observed. We conclude that 2 phenotypically distinct types of AIS can be identified, that is, AIS with a reserve cell marker phenotype and AIS with an endocervical glandular phenotype. These observations support the view that reserve cells are capable of bidirectional premalignant transformation, that is, into CIN and reserve cell-type AIS, as well as combined AIS/CIN. The endocervical type of AIS is probably a result of the unidirectional transformation of progenitor cells within the glandular cell compartment.

Topics: Adenocarcinoma; Biomarkers, Tumor; Female; Humans; Immunohistochemistry; Keratins; Proto-Oncogene Proteins c-bcl-2; Retrospective Studies; Tumor Suppressor Proteins; Uterine Cervical Dysplasia; Uterine Cervical Neoplasms

Met, the hepatocyte growth factor receptor, is important in transducing signals for tumour growth and metastasis. The aim of this study was to examine the pattern of Met expression and its value as a prognostic factor in oral squamous cell carcinomas (OSCCs). The material consisted of 53 OSCCs and five healthy controls from normal oral mucosa supplied with cell lines, 10 organotypic models supplied with oral cancer cells, and three organotypic models supplied with normal keratinocytes. Met protein expression was assessed by immunohistochemistry and western blotting. Met expression was scarce and limited to the basal layer in normal oral mucosa, but was more extensive in the tumours. Cytoplasmic expression of Met was found in the majority of the tumours, and nuclear expression was found in 72%, including a high fraction of the cells located at the invasive front. Organotypic models with normal or malignant oral cells yielded principally similar results as in the mucosa and the cancers, respectively. A smaller amount of Met immunoreactivity was detected, by western blotting, in the nuclear fraction of cultured oral cancer cells. In conclusion, Met was upregulated in OSCCs and was also found in the nucleus. However, Met was not a marker for prognosis in this study.

Topics: Adenocarcinoma; Biomarkers, Tumor; Breast Neoplasms; Carcinoma; Carcinoma, Squamous Cell; Cell Culture Techniques; Cell Line; Cell Nucleus; Cells, Cultured; Coculture Techniques; Cytoplasm; Female; Fibroblasts; Gingiva; Humans; Keratinocytes; Keratins; Male; Middle Aged; Mouth Mucosa; Mouth Neoplasms; Neoplasm Invasiveness; Prognosis; Proto-Oncogene Proteins c-met; Skin Neoplasms; Tissue Scaffolds; Tongue Neoplasms; Up-Regulation

Both endoscopic and surgical treatments are recommended for m3- or sm1-adenocarcinomas of the esophagus, depending on patients' lymph nodal status. Lymphatic dissemination is related to tumor infiltration depth, but varying incidences have been reported in m3- and sm1-adenocarcinomas. The study aim was to investigate whether the presence of occult tumor cells in lymph nodes could explain this variation.. Sixty-three node-negative (N0) patients with early esophageal adenocarcinoma (m2/m3/sm1-tumors) were included. Multilevel-sectioning of lymph nodes was performed; sections were stained by means of immunohistochemistry with cytokeratin marker CAM5.2. Two pathologists searched for micrometastases (0.2-2.0  mm) and isolated tumor cells (ITCs, <0.2  mm).. Positive CAM5.2 staining in lymph nodes was not seen in any of the 18 m2-patients. In 2/25 m3-tumors (8.0%) an ITC was found, but no micrometastases. Tumor cells were identified in 4/20 sm1-tumors (20.0%): three micrometastases and one ITC. Median follow-up was 121 months. Two m3-patients (3.2%) died due to disease recurrence, including one patient in whom an ITC was detected.. Lymphatic migration of tumor cells was found in node-negative m3- and sm1-adenocarcinomas of the esophagus (8.0% and 20.0%, respectively). However, the clinical relevance of these occult tumor cells should become apparent from large series of endoscopically treated patients.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Barrett Esophagus; Biomarkers; Esophageal Neoplasms; Female; Follow-Up Studies; Humans; Immunoenzyme Techniques; Keratins; Lymph Nodes; Lymphatic Metastasis; Male; Middle Aged; Neoplasm Recurrence, Local; Neoplasm Staging; Prognosis; Survival Rate

Topics: Adenocarcinoma; Aged; Female; Gastrectomy; Gastrointestinal Stromal Tumors; Humans; Keratins; Neoplasms, Multiple Primary; Proto-Oncogene Proteins c-kit; Stomach Neoplasms

Pancreatic cancer still remains a challenge for its biological complexity and lack of effective therapeutic strategies. Establishing new pancreatic cancer cell lines is therefore of paramount importance to clarify its biology.. We established and characterized 4 new pancreatic cancer cell lines (PP78, PP109, PP117, and PP161) according to their genetic (K-Ras, TP53, CDKN2A, and MADH4; DNA fingerprinting; karyotype), cytostructural (cytokeratins 7, 8, 18, and 19 vimentin, and ezrin), and functional profiles (doubling time; migration assay).. K-Ras, TP53, and CDKN2A gene alterations were detected in all 4 of them. Each cell line had a unique DNA profile revealed by DNA fingerprinting. A complex karyotype with numerous structural and numeric chromosomal abnormalities was present in each cell line. All 4 cell lines showed positivity for cytokeratins 7, 8, and 18. All but PP78 expressed cytokeratin 19, whereas vimentin was expressed only in PP117 and PP78 cells. A different ezrin cellular distribution was noticed in PP78 and PP117, being mostly located at membrane ruffles. This peculiar distribution was associated with the strongest migratory capability.. Our results seem to confirm the pancreatic ductal adenocarcinoma heterogeneity; in fact, the same genetic abnormalities (K-Ras, TP53, and CDKN2A) may have different effects on tumor biology depending on cellular differentiation.

Topics: Adenocarcinoma; Aged; Aged, 80 and over; Carcinoma, Pancreatic Ductal; Cell Line, Tumor; Cell Movement; Cell Proliferation; DNA Fingerprinting; Female; Genes, p16; Genes, p53; Genes, ras; Humans; Immunohistochemistry; In Situ Hybridization, Fluorescence; Karyotyping; Keratins; Male; Middle Aged; Pancreatic Neoplasms; Phenotype; Smad4 Protein; Vimentin

To assess the role of immunohistochemically detectable nodal microinvolvement of patients with "curatively" resected esophageal carcinoma.. In 73 patients with resectable esophageal carcinoma [squamous cell carcinoma (SCC), n = 45 (61.6%); adenocarcinoma (AC), n = 28 (38.4%)] a total of 2174 lymph nodes (LN) were removed. In each of the 1958 LN classified as negative on conventional histopathology, immunohistochemistry was performed using the anticytokeratin antibody AE1/AE3. To determine the role of the amount of residual tumor load, the patients were grouped according to the percentage of LN affected with micrometastasis (0%, <11%, and > or =11%).. Tumor cells were immunohistochemically detected in 47 LN (2.4%) from 25 (34.2%) patients. Five-year overall survival probability (5-YSP) of 30% in pN(0 )patients with detected occult tumor cells in LN was significantly worse than that in those without nodal microinvolvement (76%, P = 0.021), hereby resembling that of pN1-patients (24%, P = 0.84). Median overall survival in patients with no (0%), low (<11%), and high (>11%) micrometastatic tumor load was 43, 27, and 11 months, respectively. Substratification according to histological type showed that, in patients with AC, the presence of nodal microinvolvement had a significant impact on 5-YSP (0% versus 65%; P = 0.03), whereas in patients with SCC, differences of 5-YSP were only of borderline significance (24% versus 53%; P = 0.081).. Minimal tumor cell load as assessed by the ratio of micrometastatically affected LN is a complementary tool for better risk stratification of patients with esophageal carcinoma.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Biomarkers, Tumor; Carcinoma, Squamous Cell; Case-Control Studies; Disease Progression; Esophageal Neoplasms; Esophagectomy; Female; Follow-Up Studies; Humans; Immunoenzyme Techniques; Keratins; Lymph Nodes; Lymphatic Metastasis; Male; Middle Aged; Neoplasm Invasiveness; Neoplasm Recurrence, Local; Neoplasm Staging; Prognosis; Survival Rate

The clinical significance of immunohistochemically detected isolated tumor cells (ITC) in lymph nodes of gastric cancer patients is controversial. This study examined the prognostic impact of ITC on patients with early-stage gastric cancer in two large volume centers in the United States and Japan.. Fifty-seven patients with T2N0M0 gastric carcinoma who underwent gastric resection between January 1987 and January 1997 at Memorial Sloan-Kettering Cancer Center (MSKCC) in New York and 107 patients resected at National Cancer Center Hospital (NCCH) in Tokyo between January 1984 and December 1990 were studied. The sections were newly prepared from each lymph node for immunohistochemical staining for cytokeratin. Lymph nodes and original specimens from MSKCC were examined by pathologists in NCCH. The prognostic significance of the presence of ITC in lymph nodes was investigated in patients of both institutions.. ITC were identified in 30 of 57 patients (52.6%) at MSKCC and in 38 of 107 patients (35.5%) at NCCH. In both institutions, there was no significant difference in the prognosis of the studied patients with or without ITC (P= .22, .86 respectively).. The presence of ITC detected by immunohistochemistry in the regional lymph nodes did not affect the prognosis of American and Japanese patients with T2N0M0 gastric carcinoma who underwent gastrectomy with D2 lymph node dissection.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Biomarkers, Tumor; Cell Differentiation; Female; Follow-Up Studies; Gastrectomy; Humans; Immunoenzyme Techniques; Japan; Keratins; Lymph Node Excision; Lymph Nodes; Lymphatic Metastasis; Male; Middle Aged; Neoplasm Invasiveness; Neoplasm Recurrence, Local; Neoplasm Staging; Neoplastic Cells, Circulating; Prognosis; Risk Factors; Sentinel Lymph Node Biopsy; Stomach Neoplasms; Survival Rate; United States

The current FDA-approved standard of care for nonsmall cell lung cancer is Carboplastin/Taxol/Avastin based upon an impressive survival benefit; however, patients with squamous carcinoma (SQCC) cannot receive Avastin because of a 30% mortality rate due to fatal hemoptysis. In this study we evaluated the role of cytomorphology and immunohistochemistry in differentiating SQCC from adenocarcinoma (ADC) in lung FNA specimens. The case cohort included 53 FNA cases of nonsmall cell lung carcinoma with surgical pathology follow-up. All FNA specimens were reviewed independently by a panel of cytopathologists to differentiate between SQCC and ADC. The cell block material was available in 23 cases (11 ADC and 12 SQCC) to perform immunohistochemical stains for TTF-1, CK7, CK20, P63, and CK5/6. On surgical resection, 35/53 (66%) cases were diagnosed as ADC and 18/53 (34%) as SQCC. The number of cases classified correctly on the basis of cytomorphology was 66% for ADC and 53% for SQCC (combined accuracy 60%). By immunohistochemical staining, 14/23 (61%) cases expressed TTF-1. Nine cases were TTF-1 negative; eight of the TTF-1 negative cases (89%) were SQCC. Twenty-three cases expressed CK7 (87%); one ADC case (4%) showed focal CK20 positivity. Both P63 and CK5/6 expression was seen in 9/12 (75%) SQCC cases; none of the ADC cases showed this dual expression. Cytomorphology alone may not be able to stratify all cases of nonsmall cell lung carcinoma into ADC and SQCC in FNA specimens. The immune-panel of TTF-1, CK7, CK20, P63, and CK5/6 is useful in differentiating SQCC from ADC.

Topics: Adenocarcinoma; Aged; Aged, 80 and over; Biomarkers, Tumor; Biopsy, Fine-Needle; Carcinoma, Squamous Cell; Diagnosis, Differential; DNA-Binding Proteins; Female; Humans; Keratin-5; Keratin-6; Keratins; Lung Neoplasms; Male; Membrane Proteins; Middle Aged; Transcription Factors

To investigate the relationship between T lymphoma invasion and metastasis 1 (Tiam1) and epithelial-mesenchymal transition (EMT) in human colorectal carcinomas.. Tiam1, E-cadherin, CK, and vimentin expressions in normal colorectal epithelium, colorectal carcinomas (CRC) and CRC with lymphatic metastasis were determined by immunohistochemistry using a two-step method.. Tiam1 expression was significantly higher in CRC than in normal colorectal epithelium (P<0.01) in close correlation to the degree of tumor differentiation (P<0.05). Higher Tiam1 expression was detected in CRC with lymphatic metastasis than in primary CRC (P<0.05). The expressions of E-cadherin and CK in CRC tissues were significantly lowered in comparison with those in normal colorectal epithelium (P<0.01), showing a correlation to tumor differentiation (P<0.01) but not to lymphatic metastasis. Vimentin was significantly overexpressed in CRC (P<0.01) and correlated to tumor differentiation (P<0.01) but not to lymphatic metastasis. Tiam1 expression was inversely correlated to E-cadherin and CK, but positively to vimentin.. Tiam1 is related to the metastasis of colorectal carcinoma, and may induce EMT to promote CRC metastasis.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Cadherins; Cell Movement; Cell Transdifferentiation; Colorectal Neoplasms; Epithelial Cells; Female; Guanine Nucleotide Exchange Factors; Humans; Keratins; Male; Middle Aged; Neoplasm Invasiveness; Neoplasm Metastasis; T-Lymphoma Invasion and Metastasis-inducing Protein 1; Young Adult

The purpose of this report is to present the clinical and histological features of a basaloid squamous cell carcinoma (BSCC) occurring in the retromolar trigone of a 59-year-old man and to relate its immunohistochemical characteristics.. BSCC is an aggressive distinct variant of squamous cell carcinoma (SCC) requiring recognition as a separate entity from SCC due to its peculiar behavior.. A clinical examination revealed a 12x07x07 mm nodular mass with a rubbery consistency, defined borders, covered by reddish mucosa and an absence of bleeding upon palpation. Histologically, nests and cords of closely packed, moderately pleomorphic basaloid cells with nuclear palisading along the periphery of the neoplastic nests surrounded by a fibrous stroma were found.. Since this tumor can mimic other neoplasms such as adenoid cystic carcinoma, neuroendocrine carcinoma, and basal cell adenocarcinoma, histological features are essential to differentiate between them. Furthermore, immunohistochemical testing can provide valuable diagnostic information that can have a profound impact on treatment options and the prognosis.. BSCC needs to be differentiated from other neoplasms as early as possible because of its adverse prognosis. Clinicians are advised to conduct a mucosal evaluation during oral examinations and take a thorough medical history which could ultimately save the life of a patient.

Topics: Adenocarcinoma; Carcinoma, Adenoid Cystic; Carcinoma, Neuroendocrine; Carcinoma, Squamous Cell; Carcinoma, Transitional Cell; Cell Nucleus; Diagnosis, Differential; Follow-Up Studies; Humans; Immunohistochemistry; Keratins; Ki-67 Antigen; Laminin; Male; Middle Aged; Mitosis; Mouth Neoplasms; Necrosis; Tumor Suppressor Protein p53

Medullary carcinoma and serrated adenocarcinoma are two variants of colon cancer which are associated to particular pathways. Medullary carcinoma is invariably associated with MSI while serrated adenocarcinoma is characterized by excess of methylation. TNM classification and the tumoral grade are still the most important prognostic factors. Several parameters including morphological criteria, molecular features or immunohistochemical markers seem to be relevant but none of them are today used in clinical practice. A more accurate approach of the evaluation of these additional parameters should improve their prognosis values. double dagger.

Topics: Adenocarcinoma; Carcinoma, Medullary; Colorectal Neoplasms; DNA Mismatch Repair; Humans; Inflammation; Keratins; Neoplasm Invasiveness; Prognosis

Topics: Adenocarcinoma; Cell Line, Tumor; Cell Movement; Humans; Keratinocytes; Keratins

Topics: Adenocarcinoma; Aged; Biomarkers, Tumor; Breast Neoplasms; Carcinoma, Intraductal, Noninfiltrating; Carcinoma, Papillary; Cell Nucleus; Diagnosis, Differential; Female; Humans; Hyperplasia; Keratins; Membrane Proteins; Neoplasm Proteins; Neoplasms, Multiple Primary; Papilloma

The role of circulating tumor cells (CTCs) in blood of primary breast cancer patients is still under investigation. We evaluated the incidence of CTCs in blood, we evaluated the correlation between CTCs and disseminated tumor cells (DTCs) in the bone marrow (BM), and we characterized CTCs for the expression of HER2, the estrogen receptor (ER) and the progesterone receptor (PR).. Blood of 431 patients with primary breast cancer were analyzed for EpCAM, MUC1 and HER2 transcripts with the AdnaTest BreastCancer (AdnaGen AG, Germany). Expression of the ER and PR was assessed in an additional RT-PCR. BM aspirates from 414 patients were analyzed for DTCs by immunocytochemistry using the pan-cytokeratin antibody A45-B/B3.. DTCs were found in 107/414 patients (24%), CTCs were detected in 58/431 (13%) patients. DTCs were associated with PR status of the primary tumor (P = 0.04) and CTCs significantly correlated with nodal status (P = 0.04), ER (P = 0.05), and PR (P = 0.01). DTCs in the BM weakly correlated with CTCs (P = 0.05) in blood. Interestingly, the spread of CTCs was mostly found in triple-negative tumors (P = 0.01) and CTCs in general were mostly found to be triple-negative regardless of the ER, PR and HER2 status of the primary tumor.. (1) Due to the weak concordance between CTCs and DTCs the clinical relevance may be different. (2) The biology of the primary tumor seems to direct the spread of CTCs. (3) Since the expression profile between CTCs and the primary tumor differs, the consequence for the selection of adjuvant treatment has to be evaluated.

Topics: Adenocarcinoma; Antigens, Neoplasm; Biomarkers, Tumor; Bone Marrow; Bone Marrow Neoplasms; Breast Neoplasms; Cell Adhesion Molecules; Chemotherapy, Adjuvant; Epithelial Cell Adhesion Molecule; Estrogens; Female; Humans; Keratins; Mucin-1; Neoplasm Proteins; Neoplasm, Residual; Neoplasms, Hormone-Dependent; Neoplastic Cells, Circulating; Neoplastic Stem Cells; Progesterone; Receptor, ErbB-2; Receptors, Estrogen; Receptors, Progesterone; Reverse Transcriptase Polymerase Chain Reaction

Pancreatic stellate cells (PSCs) are key mediators of the desmoplastic reaction that characterizes pancreatic adenocarcinoma. We sought to isolate and characterize tumor-derived pancreatic stellate (TDPS) cells to further understand how these stromal cells influence pancreatic cancer behavior.. We established a stable line of non-immortalized PSCs from a patient with pancreatic adenocarcinoma using a modified prolonged outgrowth method. Cell staining for cytokeratin, vimentin, and alpha smooth muscle actin (alphaSMA) was performed. Total RNA was harvested from TDPS and panc-1 cells and gene expression determined by microarray analysis.. TDPS cells contain lipid droplets in the cytoplasm, and later stain positive for both vimentin and alphaSMA, indicative of activated myofibroblasts. Microarray analysis revealed a distinct gene expression profile compared with pancreatic cancer cells, including expression of proteases that facilitate cancer cell invasion and growth factors known to activate pancreatic cancer cells. Additionally, TDPS cells expressed many of the key components of the pancreatic tumor stroma, including collagen, fibronectin, and S100A4, confirming their importance in the tumor microenvironment.. Characterization of tumor-derived PSCs will facilitate further studies to determine how the tumor microenvironment promotes the aggressive behavior of pancreatic cancer.

Topics: Actins; Adenocarcinoma; Cell Communication; Cell Culture Techniques; Fibroblasts; Gene Expression Regulation, Neoplastic; Humans; Keratins; Oligonucleotide Array Sequence Analysis; Pancreatic Neoplasms; Phenotype; Stromal Cells; Tumor Cells, Cultured; Vimentin

Topics: Adenocarcinoma; Adult; Combined Modality Therapy; Diagnosis, Differential; Follow-Up Studies; Humans; Keratins; Lung Neoplasms; Male; Middle Aged; Neoplasm Recurrence, Local; Prostate-Specific Antigen; Prostatectomy; Prostatic Neoplasms; Sarcoma, Synovial; Vimentin

Co-expression of cytokeratin and vimentin has been traditionally associated with a few select tumors. However, this phenomenon is being recognized in a wider range of tumors. Twenty-one canine primary pulmonary epithelial neoplasms were evaluated for the co-expression of cytokeratin and vimentin. The histologic pattern and grade, and an immunohistochemical grade for cytokeratin and vimentin staining, were determined for each neoplasm. Adenocarcinomas predominated, and histologically, most tumors were grade II. All of the neoplasms stained positive for cytokeratin, while only 8 (38%) stained positive for both vimentin and cytokeratin. Papillary adenocarcinomas were consistently vimentin negative. The anaplastic histologic pattern had significantly more vimentin staining than the other histologic patterns. There was no significant difference in histologic grade or grading criteria between those tumors that stained with vimentin and those that did not. The present study established that cytokeratin and vimentin co-expression occurs in canine primary pulmonary epithelial tumors at a similar frequency to human pulmonary neoplasms. Further investigation will be needed to characterize the significance of this finding, particularly with respect to prognosis.

Topics: Adenocarcinoma; Animals; Dog Diseases; Dogs; Humans; Immunohistochemistry; Keratins; Lung Neoplasms; Necrosis; Vimentin

Endometrial stromal sarcomas can be confused with several neoplasms because of their inconsistent and widely varied morphologic appearance and frequent immunohistochemical expression of a variety of antigens including cytokeratin. The resulting diagnostic challenge becomes problematic particularly in the diagnosis of metastases resulting from such tumors. Because of the sometime epithelioid appearance of the tumor cells and their expression of cytokeratin, the metastases may be misdiagnosed as poorly differentiated carcinoma. We therefore studied the profile of cytokeratin proteins expression in 17 cases of endometrial stromal sarcomas using a panel of antibodies including cytokeratin cocktail antibody (AE1/AE 3), CK5/6, CK7, CK14, CK16, Cam5.2 (CK8), CK19, CK20, and 34Ebeta12 (CK1, 5, 10, and 14). Of the 17 cases, 8 (47%) stained positive with the cytokeratin cocktail antibody (AE1/AE 3). Of the 8 cases with cytokeratin expression, 5 (63%) stained positive with CK19, and 3 of them stained positive with Cam5.2. The 3 cases that stained positive with Cam5.2 also expressed CK19. Of the 5 cases with CK19, 1 was focally positive for CK5/6, CK7, and 34Ebeta12. None of the cases expressed CK14, CK16, or CK20. These results show that CK19 is most commonly expressed cytokeratin in endometrial stromal tumors. Hence, the inclusion of CK19 in the panel of immunostains may help resolve the diagnostic confusion created by keratin expression in endometrial stromal sarcoma and may also help in the correct diagnosis of endometrial stromal sarcoma at extrauterine sites.

Topics: Adenocarcinoma; Biomarkers, Tumor; Diagnosis, Differential; Endometrial Neoplasms; Female; Humans; Immunohistochemistry; Keratin-19; Keratins; Neoplasm Metastasis; Sarcoma, Endometrial Stromal; Tissue Array Analysis

Novel targeted treatment of non-small cell lung cancer (NSCLC) requires accurate classification of NSCLC as squamous cell carcinoma (SCC) and adenocarcinoma (AC). This study details the CK5/6 and TTF-1 immunoprofile of surgical resections of 45 NSCLCs (24 ACs and 21 SCCs) in tissue microarrays. All SCCs were CK5/6 positive, TTF-1 negative. 20 of 24 adenocarcinomas had the reverse pattern. In conclusion, all SCCs in this study were CK5/6 positive and TTF-1 negative, and therefore tumours that do not display this phenotype are unlikely to be SCCs. CK5/6 and TTF-1 is therefore a practical panel for the distinction between pulmonary SCC from AC in routine histopathology practice.

Topics: Adenocarcinoma; Biomarkers, Tumor; Carcinoma, Non-Small-Cell Lung; Carcinoma, Squamous Cell; DNA-Binding Proteins; Humans; Immunohistochemistry; Keratins; Lung Neoplasms; Tissue Array Analysis; Transcription Factors

Involvement of the urinary bladder by prostatic adenocarcinoma (PCA) occasionally occurs. In this study, we analyzed urine cytological findings in patients with secondary involvement of the urinary bladder by PCA with the help of the immunocytochemistry. The cases were divided into two groups: (1) prospective study group: three cases; and (2) retrospective study group: 12 cases which were retrieved from our cytopathological files. The urine cytology specimens (cytospins) from all cases were submitted for prostatic specific antigen (PSA) immunocytochemistry. Additional immunostaining for high-molecular-weight cytokeratin (HMWCK) was performed if PSA immunoreactivity was negative. All cytospin smears showed atypical cells characterized by large, round and uniform nuclei with prominent nucleoli and dense cytoplasm. They were present as single cells or in cell groups simulating urothelial carcinoma. The diagnosis of PCA was made if the atypical cells were either immunoreactive for PSA or nonreactive for HMWCK. The urothelial cells were PSA- and HMWCK+. The immunostaining supported the PCA diagnosis in all three cases from the prospective group and two cases in the retrospective group. The remaining 10 cases in the retrospective group were diagnosed as negative: 3, atypia: 5 urothelial carcinoma: 2. The positive diagnosis for PCA was based on the PSA immunoreactivity or nonreactivity to HMWCK and the cytological atypia. In conclusions, immunostaining for PSA and HMWCK performed on cytospins of urine specimens from patients with a prior history of high-grade and/or stage of PCA is helpful to make a positive diagnosis of secondary bladder involvement from PCA.

Topics: Adenocarcinoma; Aged; Aged, 80 and over; Biopsy, Needle; Humans; Immunohistochemistry; Keratins; Male; Prospective Studies; Prostate-Specific Antigen; Prostatic Neoplasms; Retrospective Studies; Urinary Bladder Neoplasms; Urine

A study is made of the clinical repercussions of occult metastases-micrometastases (MMs+)-or isolated tumour cells (ITCs+) in the lymph nodes of patients with stage IIA and IIB colon adenocarcinoma initially considered as corresponding to N0.. A retrospective study of 39 patients with stage IIA and IIB (T3-T4 N0 M0) colon adenocarcinoma, subjected to similar surgical and adjuvant chemotherapy treatment, with long and careful follow-up (minimum: 5 years, mean: 81.7 months) was performed on their previously resected lymph nodes, with the aid of new histological and immunohistochemical (cytokeratin) sections, in order to detect MMs or ITCs. Disease-free survival (DFS) and global survival (GS) in the two groups (patients with MMs+ or ITCs+ vs. patients without MMs or ITCs) were compared at 5 years based on the corresponding Kaplan-Meier survival curves, with the Breslow test.. A total of 382 lymph nodes from the 39 patients (mean: 9.8; standard deviation: 6.09) were revised. MMs+ were detected in 2 cases and ITCs+ in 2 more cases on the Cytokeratin study. GS of the whole series at 5 years was 89.74% (35 patients alive) with a DFS at 5 years of 79.49% (31 patients free of disease), but the 2 cases with MMs+ were dead at 5 years, with high statistical differences between both groups (MMs+/MMs-) (p<0.0001). When comparing the group of MMs+/ITCs+ patients and the group of MM-/ITCs- patients, the DFS and GS times at 5 years were higher in the MMs-/ITCs- group (p=0.0692 and p=0.006 respectively).. Although the incidence of MMs+ or ITCs+ in the examined lymph nodes was low, the presence of MMs is related to a dramatic reduction in GS and DFS at 5 years. We encourage a detailed histological study of lymph nodes resected in patients with deep penetrating colon tumours in order to assure a pN0 status.

Topics: Adenocarcinoma; Adenocarcinoma, Mucinous; Adult; Aged; Chemotherapy, Adjuvant; Colonic Neoplasms; Female; Follow-Up Studies; Humans; Immunoenzyme Techniques; Keratins; Lymph Nodes; Lymphatic Metastasis; Male; Middle Aged; Neoplasm Staging; Prognosis; Retrospective Studies; Survival Rate

Occasional nonspecific staining of prostate cancer cells with high molecular weight cytokeratin (HMWCK) can lead to false-negative diagnoses. We compared p63 and HMWCK immunostaining to check their specificity for basal cell identification. Out of 6887 prostate cancer cases sent in consultation to one of the authors over 1.5 years, we identified 22 (0.3%) cases with HMWCK labeling of cancer cells, including 20 needle biopsies and 2 transurethral resections of prostate (TURP). Cases were sent in consultation because of the confusing immunostaining pattern, where prostate cancer cells labeled with HMWCK at the outside institutions. In 6 cases, p63 immunostains were also received from the outside institution, whereas in the remaining 16 cases p63 immunohistochemistry was performed at our institution. In 14 cases, we used either an extra destained hematoxylin and eosin slide or a negative control slide for immunohistochemistry with antibodies to p63, and in the 2 remaining cases submitted unstained slides were used. The Gleason scores were 3+3=6 in 20 cases and 4+4=8 in 2 cases. The size of the tumor on needle biopsy ranged from 0.5 to 6.0 mm (mean 1 mm) and on the 2 TURP cases consisted of 44 and 68 cancer glands, respectively. The number of tumor cells positive for HMWCK in each of the needle biopsy cases ranged from 3 to 48 (mean 13 cells), whereas on the 2 TURP cases 26 and 10 cells were labeled with HMWCK. Corresponding stains for p63 on the same cases were negative in 18 cases. In 3 of 4 cases, p63 labeled 1, 1, and 2 tumor cells, respectively. The fourth case had 5 positive cells on p63 staining with 4 positive for HMWCK. To assess whether overstaining was a factor, we evaluated the intensity of HMWCK staining in the basal cells of the benign glands, which was moderate in 6 and strong in 16 cases. The cytoplasm of benign secretory cells showed focal weak (n=3), diffuse weak (n=1), and focal moderate (n=2) staining for HMWCK. HMWCK labeling of prostate cancer cells is uncommon and does not seem to be solely attributable to overstaining. p63 is a more specific marker for basal cells than HMWCK, with less labeling of tumor cells. Recognition of this phenomenon and performing stains for p63 when it occurs can help prevent underdiagnosing prostatic carcinoma.

Topics: Adenocarcinoma; Biomarkers, Tumor; False Positive Reactions; Humans; Immunohistochemistry; Keratins; Male; Membrane Proteins; Prostatic Neoplasms; Transurethral Resection of Prostate

High circulating serum vascular endothelial growth factor (VEGF) levels might reflect enhanced angiogenesis in patients suffering from non-small cell lung cancer (NSCLC). This study aimed at determining the prognostic significance of circulating VEGF as a prognostic factor in NSCLC.. Four hundred fifty-one histologically or cytologically proven and previously untreated NSCLC patients have been studied. Median follow-up was 13 years and 9 months. Eleven clinical and biologic variables were recorded. The levels of circulating VEGF were measured in the serum by quantitative immunoassay. Patients have had received conventional treatment (without anti-VEGF therapy) according to the international guidelines. All statistical tests were two-sided.. Receiver operating characteristic curves (area under the ROC curve: 0.66 +/- 0.05) showed that circulating VEGF serum level did not demonstrate a high sensitivity-specificity relationship, and therefore, demonstrated a low ability to differentiate NSCLC from benign lung diseases. A 600 pg/mL level of circulating VEGF serum was considered as threshold with 40.8% of NSCLC patients presenting with a high level. The circulating VEGF distribution differed significantly according to disease stage, nodal status, and performance status (PS), with the highest levels observed in metastatic stage, positive mediastinal nodal status, and poor PS. In univariate survival analysis, patients with a high pretreatment circulating VEGF serum level proved to have a shorter overall survival when compared with patients presenting with a circulating VEGF serum level /=2, nodal status N2-3, metastatic disease, neuron-specific enolase >12.5 ng/mL, CYFRA 21-1 >3.6 ng/mL.. The prognostic information given by a high circulating VEGF serum level is not an independent determinant of survival owing to a high relationship with main prognostic variables such as PS, stage of the disease, and nodal status. This finding does not preclude a putative prognostic impact of in situ detection of VEGF and VEGF receptors in tumor specimen.

Topics: Adenocarcinoma; Antigens, Neoplasm; Biomarkers, Tumor; Carcinoma, Large Cell; Carcinoma, Non-Small-Cell Lung; Carcinoma, Squamous Cell; Combined Modality Therapy; Female; Humans; Keratin-19; Keratins; Lung Neoplasms; Male; Middle Aged; Phosphopyruvate Hydratase; Prognosis; Prospective Studies; ROC Curve; Survival Rate; Vascular Endothelial Growth Factor A

Topics: Adenocarcinoma; Animals; Computational Biology; Esophageal Neoplasms; Genomics; Genotype; Humans; Keratins; Mutation, Missense; Neoplasm Transplantation; Phenotype; Vimentin

To evaluate the differences that exist between peripheral and mesenteric serum levels of carcinoembryonic antigen (CEA) and cytokeratins in patients with colorectal adenocarcinoma.. One hundred and thirty-eight patients with colorectal adenocarcinoma who underwent surgery at Hospital Sao Paulo (Discipline of Surgical Gastroenterology of UNIFESP-EPM) between December 1993 and March 2000 were retrospectively analyzed. Differences between CEA and cytokeratin (TPA-M) levels in peripheral blood (P) and in mesenteric blood (M) were studied. Associations were investigated between peripheral and mesenteric levels and the staging and histopathological variables (degree of cell differentiation, macroscopic appearance, tumor dimensions and presence of lymphatic and venous invasion).. Differences were observed in the numerical values of the marker levels: CEA (M) (39.10 mg/L +/- 121.19 mg/L) vs CEA (P) (38.5 mg/L +/- 122.55 mg/L), P < 0.05; TPA-M (M) (325.06 U/L +/- 527.29 U/L) vs TPA-M (P) (279.48 U/L +/- 455.81 U/L), P < 0.01. The mesenteric CEA levels were higher in more advanced tumors (P < 0.01), in vegetating lesions (34.44 mg/L +/- 93.07 mg/L) (P < 0.01) and with venous invasion (48.41 mg/L +/- 129.86 mg/L) (P < 0.05). Peripheral CEA was higher with more advanced staging (P < 0.01) and in lesions with venous invasion (53.23 mg/L +/- 158.57 mg/L) (P < 0.05). The patients demonstrated increased mesenteric and peripheral TPA-M levels with more advanced tumors (P < 0.01 and P < 0.01) and in non-ulcerated lesions [530.45 U/L +/- 997.46 U/L (P < 0.05) and 457.95 U/L +/- 811.36 U/L (P < 0.01)].. The mesenteric levels of the tumor markers CEA and cytokeratins were higher than the peripheral levels in these colorectal adenocarcinoma patients. Higher levels of these biologic tumor markers are associated with an advanced state of cancerous dissemination.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Arteries; Biomarkers, Tumor; Carcinoembryonic Antigen; Colorectal Neoplasms; Female; Humans; Keratins; Male; Mesenteric Arteries; Middle Aged; Neoplasm Staging; Retrospective Studies

To compare the immunoprofiles of intrahepatic cholangiocarcinoma and metastatic colorectal adenocarcinoma for mucin glycoproteins (including MUC1, MUC2, MUC5AC and MUC6) and cytokeratins (including CK7, CK19 and CK20), and to assess their diagnostic value.. One hundred cases of intrahepatic cholangiocarcinoma and 21 cases of metastatic colorectal adenocarcinoma were enrolled into the study. Immunohistochemical study for MUC1, MUC2, MUC5AC, MUC6, CK7, CK19 and CK20 was carried out in all cases by EnVision method.. In intrahepatic cholangiocarcinoma, the expression rates of MUC1, MUC2, MUC5AC and MUC6 were 61.0%, 2.0%, 22.0% and 8.0% respectively, as compared to 57.1%, 47.6%, 19.0% and 23.8% respectively in metastatic colorectal adenocarcinoma. On the other hand, the expression rates of CK7, CK19 and CK20 in intrahepatic cholangiocarcinoma were 73.0%, 53.0% and 15.0% respectively, in contrast to 14.3%, 90.5% and 85.7% respectively in metastatic colorectal adenocarcinoma. The difference in expressions of MUC2, MUC6, CK7 and CK20 carried statistical significance.. The immunoprofile for mucin glycoproteins and cytokeratins provides important clues in distinguishing between intrahepatic cholangiocarcinoma and metastatic colorectal adenocarcinoma to liver. The immunophenotype of MUC2-/MUC6-/CK7+/CK20- indicates the diagnosis of intrahepatic cholangiocarcinoma, while MUC2+/MUC6+/CK7-/CK20+ suggests the possibility of metastatic colorectal adenocarcinoma.

Topics: Adenocarcinoma; Aged; Bile Duct Neoplasms; Bile Ducts, Intrahepatic; Biomarkers, Tumor; Cholangiocarcinoma; Colorectal Neoplasms; Female; Glycoproteins; Humans; Keratins; Male; Middle Aged; Mucins; Neoplasm Staging

Currently it is necessary to define in almost each case whether a carcinoma is a small or non-small cell carcinoma, adenocarcinoma, pulmonary or metastatic in origin. Thyroid transcription factor-1 (TTF-1) was positive in more than 80% of primary pulmonary adenocarcinomas and in none from the sites other than the thyroid. Mucinous bronchioloalveolar carcinomas are usually negative. Immunocytochemistry with a panel of cytokeratins (CK) 7 and 20, along with TTF-1, is recommended for identification of the origin of adenocarcinoma in pulmonary cytology.. The aim of the study was to assess the value of TTF-1 reactivity in adenocarcinomas determined by immunocytochemistry in different pulmonary cytologic specimens.. Cytologic specimens of 83 patients with adenocarcinomas were analyzed. Immunocytochemistry was performed with a panel of antibodies: TTF-1, CK7, CK20 in all cases and CK5/6 if necessary. The study included 17 different bronchoscopic samples (aspirates, brushes, transbronchial FNA), 14 transthoracic FNA, 27 pleural effusions and 25 FNA of peripheral lymph nodes. TTF-1 was positive in 26/83 (31.3%) and negative in 47/83 (68.7%) samples. All TTF-1 positive adenocarcinomas were also CK7 positive, thus being conclusive of pulmonary origin. In TTF-1 negative group, pulmonary origin was proven in 10/57 (17.5%) adenocarcinomas, whereas 18/57 (31.6%) adenocarcinomas were metastatic; in 29/57 (50.9%) adenocarcinomas other diagnostic procedures failed to prove their origin. CK20 positivity with CK7 negativity was conclusive of metastatic gastrointestinal adenocarcinoma.. Numerous reports support TTF-1 expression in adenocarcinoma as being highly specific for pulmonary origin, if thyroid is excluded. We were able to identify 36/83 (43.4%) adenocarcinomas as pulmonary adenocarcinomas. Among them, only 31.3% were TTF-1 positive. In our study, about 60% of adenocarcinomas with uncertain origin were in the groups of pleural effusions and lymph nodes. In these groups, cytologic diagnosis of adenocarcinoma often provided evidence of the carcinoma expansion, aggressive behavior and poor differentiation, and served as a guideline for patient management. In the studies of mixed pulmonary adenocarcinomas, TTF-1 expression was lower in poorly differentiated segments as well as in the areas with bronchioloalveolar pattern. One explanation for the high percentage of TTF-1 negative adenocarcinomas in our material is morphological selection of adenocarcinomas of presumably non-pulmonary origin before immunocytochemistry.. TTF-1 in a panel with cytokeratins is specific for differentiation of the origin of adenocarcinomas. TTF-1 negative finding in adenocarcinomas does not exclude pulmonary origin, but only points to other diagnostic procedures for definitive diagnosis.

Topics: Adenocarcinoma; Humans; Immunohistochemistry; Keratins; Lung Neoplasms; Nuclear Proteins; Thyroid Nuclear Factor 1; Transcription Factors

During the normal turnover of prostate epithelium, stem cells in the basal cell layer produce an intermediate cell population that gives rise to fully differentiated secretory luminal cells. This process is extensively studied in relation to the development of prostate disease, in particular, to elucidate the origin and nature of prostate cancer. We previously showed that the mRNA of a poorly characterised intercellular adhesion molecule, cadherin-10, is strongly expressed in human prostate. Using anticadherin-10 antibodies, immunohistochemistry, and confocal microscopy, we have examined the pattern of cadherin-10 expression in relation to human prostate epithelial differentiation markers (E-cadherin, CD44, and cytokeratins (CK) 14, 18 and 19) in archival paraffin-embedded and fixed-frozen histopathological specimens in individual and serial sections. In non-neoplastic prostate, E-cadherin is expressed by all basal and luminal epithelial cells, while cadherin-10 is variably expressed in luminal cells where it is colocalised with E-cadherin at basolateral plasma membranes. Cadherin-10 is absent in CK14- and/or CD44-positive basal cells, but is expressed in CK18-positive luminal cells (differentiated secretory cells), a subset of CK19-positive intermediate/luminal cells, but not CK19-positive basal cells. Small foci of prostate cancer express E-cadherin, CK19 and CK18, but cadherin-10 expression is low or undetectable. These findings suggest that the expression of cadherin-10 is associated with the later stages of differentiation of luminal secretory cells, indicating a specific role in secretory cell terminal differentiation. While prostate cancer cells express secretory cell markers (eg, CK18, prostate-specific antigen) and the more generally expressed E-cadherin, their failure to express cadherin-10 further emphasises a role for this cadherin in normal prostate organisation and function.

Topics: Acid Phosphatase; Adenocarcinoma; Biomarkers; Cadherins; Cell Differentiation; Epithelial Cells; Humans; Hyaluronan Receptors; Immunoenzyme Techniques; Keratins; Male; Microscopy, Confocal; Prostate; Prostatic Hyperplasia; Prostatic Neoplasms; Protein Tyrosine Phosphatases

Prognostic implication of serum cytokeratin 19 fragments (CYFRA 21-1) was explored in 60 advanced NSCLC patients, whereas in 45 patients assessable for serological response a >or=35% CYFRA 21-1 decline after two chemotherapy cycles was strongly associated with non-progression (NP), defined as a sum of objective response (OR)+stable disease (P<0.0001) and survival (P=0.0002). Association of OR with survival was not significant. In multivariate survival analysis, >or=35% marker decline and radiological NP status were found as major determinants of prolonged survival with RR: 0.37 (P=0.01) and 0.63 (P=0.01), respectively. In advanced NSCLC patients, NP reflects therapeutic efficacy better than traditional OR. CYFRA 21-1 >or=35% decline seems to be a reliable surrogate marker of treatment efficacy in terms of survival.

Topics: Adenocarcinoma; Adult; Aged; Antigens, Neoplasm; Antineoplastic Combined Chemotherapy Protocols; Biomarkers, Tumor; Carcinoma, Large Cell; Carcinoma, Non-Small-Cell Lung; Carcinoma, Squamous Cell; Female; Humans; Keratin-19; Keratins; Lung Neoplasms; Male; Middle Aged; Neoplasm Staging; Prognosis; Prospective Studies; Survival Rate; Treatment Outcome

Recently, micrometastasis (MM) in the lymph node in gastric cancer has been detected by cytokeratin immunostaining. However, clinical significance of MM and its relationship with reduced expression of E-cadherin in primary lesion have not been well studied.. The 4,990 lymph nodes from 184 pT1~T3N0 patients from 1995 to 2000 at Korea University Hospital were immunostained with the anticytokeratin AE1/3 antibody for detection of micometastasis. The primary lesions were also immunostained for E-cadherin expression.. MM in the lymph node of gastric cancer was found in 131 (2.6%) of total dissected nodes, and 31 of 184 patients (16.8%) were shown to have MM. The MM was significantly correlated with the depth of invasion, tumor size, operation method, Lauren classification, lymphovascular invasion and loss of E-cadherin expression in primary tumor. On multivariate analysis, the independent risk factors for MM were the depth of invasion and loss of E-cadherin expression. The patients with MM had significantly lower 5-year overall and disease free survival rate than those without MM.. Lymph node MM in histologically node-negative gastric cancer was significantly correlated with poor 5-year survival rate. The determination of E-cadherin expression in primary gastric tumor may be useful in prediction of the MM.

Topics: Adenocarcinoma; Cadherins; Disease-Free Survival; Female; Follow-Up Studies; Gastrectomy; Humans; Keratins; Lymph Node Excision; Lymph Nodes; Lymphatic Metastasis; Male; Middle Aged; Neoplasm Invasiveness; Neoplasm Recurrence, Local; Neoplasm Staging; Stomach Neoplasms; Survival Rate

Topics: Adenocarcinoma; Antibodies, Monoclonal; Antineoplastic Agents, Hormonal; Biomarkers, Tumor; Combined Modality Therapy; DNA-Binding Proteins; Humans; Immunohistochemistry; Keratins; Male; Prostatic Neoplasms; Racemases and Epimerases; Reproducibility of Results; Trans-Activators; Transcription Factors; Tumor Suppressor Proteins

Topics: Adenocarcinoma; Biomarkers; CA-125 Antigen; Colon, Sigmoid; Colonic Diseases; Colonic Neoplasms; Colonoscopy; Diagnosis, Differential; Endometriosis; Female; Humans; Keratins; Middle Aged; Receptors, Estrogen; Tomography, X-Ray Computed

Recent advances in immunohistochemical techniques have made it possible to identify micrometastasis using antibodies to cytokeratins (CK). The aim of the study was to determine the prevalence and prognostic significance of immunohistochemically detected micrometastasis (IHM) in patients with localised colorectal cancer (CRC) (Dukes' A and B). A further aim was to study the prognostic role of histopathological factors such as vascular invasion.. The original histology of 168 consecutive patients with Dukes' A or B tumours who had undergone curative resection was reviewed. Immunohistochemical staining was performed using CK antibodies, AE1/AE3 and MNF116 on all (n=898) lymph nodes. Survival analysis was performed on 105 cases that had been followed up until death or for at least 5 years.. IHM were detected in 17.3% of lymph nodes analysed. Adverse outcome (death/local recurrence) was recorded in 8/49 (16%) patients with IHD-positive nodes and in 10/56 (18%) patients negative for IHM. IHM was not associated with adverse outcome on either univariate (p=0.540) or multivariate analyses (p=0.673). There was no correlation of IHM with age, gender, site, size and grade of tumour, depth of tumour invasion or perineural and vascular invasion. Vascular invasion was the only independent prognostic factor identified.. We have shown that isolated CK-positive epithelioid cells are commonly found in morphologically benign pericolic lymph nodes of patients with localised (Dukes' A or B) CRC. These cells may represent occult micrometastasis but are not clinically significant. Vascular invasion identifies patients with localised CRC likely to develop recurrences or die of disease.

Topics: Adenocarcinoma; Aged; Aged, 80 and over; Biomarkers, Tumor; Colorectal Neoplasms; Female; Humans; Keratins; Lymph Nodes; Lymphatic Metastasis; Male; Middle Aged; Neoplasm Invasiveness; Neoplasm Recurrence, Local; Neoplasm Staging; Prognosis; Survival Rate

The phospholipid fatty acid profiles of erythrocytes and platelets from fifty patients with advanced non-small cell lung cancer were investigated using gas chromatography/mass spectrometry, followed by "ROC" curves analysis to gain novel biomarker information. Sialic acid and cytokeratins were also examined. Potentially useful fatty acid markers: Erythrocytes: phosphatidylcholine, 18:2n6 and 20:4n6; phosphatidylethanolamine, 22:4n6 and 22:6n3 + 24:1n9. Platelets: phosphatidylcholine, 22.0; phosphatidylethanolamine, 22:5n3 + 24:0. At the cut-off value to obtain maximum accuracy, the best biomarkers were found in platelets: phosphatidylserine + phosphatidylinositol (PS + PI), 21:0; sphyngomyelin: 20:1n9 and 22:1n9. All these fatty acids showed similar/higher diagnostic yields than the commonly used markers sialic acid or cytokeratins.

Topics: Adenocarcinoma; Aged; Antigens, Neoplasm; Biomarkers, Tumor; Blood Platelets; Carcinoma, Non-Small-Cell Lung; Carcinoma, Squamous Cell; Erythrocytes; Fatty Acids; Female; Gas Chromatography-Mass Spectrometry; Humans; Keratin-19; Keratins; Lung Neoplasms; Male; Middle Aged; N-Acetylneuraminic Acid; Neoplasm Proteins; Peptides; Phospholipids; ROC Curve; Sensitivity and Specificity

Topics: Adenocarcinoma; Biomarkers, Tumor; Carcinoma, Squamous Cell; Diagnosis, Differential; Hamartoma; Humans; Inflammation; Keratins; Nasal Mucosa; Nasopharyngeal Neoplasms; Papilloma, Inverted; Paranasal Sinus Neoplasms; Polyps; Teratoma

Alpha-methylacyl-CoA racemase (AMACR) has recently been shown to be a highly sensitive marker for the diagnosis of prostate cancer. However, there is limited information concerning its utility as a marker for prostate carcinoma after hormonal therapy. Our current investigation was conducted to evaluate the expression of AMACR in patients with prostate carcinoma after hormonal therapy and assess its diagnostic utility in combination with p63 and high molecular weight cytokeratin (34betaE12) staining. Prostate tissues from 49 patients who had been treated with hormonal therapy were immunohistochemically analyzed for AMACR, 34betaE12, and p63 expression by a triple antibody cocktail stain. The staining intensities and the percentages of positively staining tumor cells were recorded. The correlations between AMACR expression and metastatic status, associated hormonal therapy regimens, and the extent of hormone therapy effect were analyzed. All malignant acini were completely negative for both basal cell markers (34betaE12 and p63). Tumor cells failed to demonstrate expression of AMACR in 14 (29%) of 49 cases. In the remaining 35 cases (71%), positive immunostaining for AMACR was noted, but with variable intensities and percentages of cells stained. Positive staining for AMACR in benign glands was not seen in any case. In all cases, basal cells were strongly stained by p63 in benign acini with a mean positive percentage of 96%. Similarly, basal cells in benign acini displayed moderate staining intensities for 34betaE12 in 3 (7%) of 41 cases and strong immunostaining for this marker in the remaining 38 cases (93%); the mean percentage of positive cells was 92%. alpha-methylacyl-CoA racemase expression may be substantially diminished or entirely lost in prostate carcinoma after hormonal therapy. This variation in AMACR expression does not correlate with the metastatic status, the modality of hormonal therapy, or the extent of therapy-related effect. It is important that pathologists be aware that some hormonally treated prostate carcinomas do not express AMACR, and that immunostaining in such cases must be interpreted with caution. A triple cocktail stain using AMACR, 34betaE12, and p63 can be helpful in evaluating prostate specimens for the presence of residual or recurrent carcinoma after hormonal therapy for cancer.

Topics: Adenocarcinoma; Aged; Aged, 80 and over; Antineoplastic Agents, Hormonal; DNA-Binding Proteins; Humans; Immunohistochemistry; Keratins; Male; Middle Aged; Neoplasm Recurrence, Local; Neoplasm, Residual; Prostatic Neoplasms; Racemases and Epimerases; Reproducibility of Results; Trans-Activators; Transcription Factors; Treatment Outcome; Tumor Suppressor Proteins

Tubulolobular carcinoma is a type of mammary carcinoma that displays an admixture of invasive tubules and lobular-like cells. Previous reports have shown it to share clinical similarities to lobular carcinoma, whereas more recent studies have shown it to be E-cadherin positive. The aim of the current study was to further explore the immunophenotype of tubulolobular carcinoma, and to document its natural behavior. Nineteen cases of tubulolobular carcinoma and 10 cases each of tubular and lobular carcinoma were retrieved for comparison analysis. Immunohistochemistry was performed with antibodies against estrogen receptor, progesterone receptor, HER2/neu, 34betaE12, E-cadherin, and the catenins. Twenty-five percent of patients with tubulolobular carcinoma presented with greater than stage I disease, compared to 0 and 60% of patients with tubular and lobular carcinoma, respectively. Two patients with tubulolobular carcinoma had tumor recurrence, one of whom also developed metastasis. The majority of all carcinomas were estrogen and progesterone receptor positive. E-cadherin displayed membranous staining in all tubular and tubulolobular carcinomas, and was negative in all lobular carcinomas. Half of each carcinoma subtype displayed granular cytoplasmic 34betaE12 immunoreactivity. alpha-Catenin exhibited partial or complete membranous staining in all tubulolobular and tubular carcinomas, and was negative in all lobular carcinomas. beta-Catenin displayed membranous staining in tubulolobular and tubular carcinomas, whereas all lobular carcinomas had coarse cytoplasmic immunoreactivity. p120 and gamma-catenin displayed membranous staining in 100% of tubulolobular and tubular carcinomas and cytoplasmic staining in 100% of lobular carcinomas. Tubulolobular carcinoma of the breast is thus a distinct type of mammary carcinoma that displays both tubular and lobular patterns histologically but displays the membranous E-cadherin/catenin complex characteristic of the ductal immunophenotype. Tubulolobular carcinoma appears to be more aggressive than tubular carcinoma, as 16% of patients had lymph node metastases, although all were alive at a mean follow-up of 40 months.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Breast Neoplasms; Cadherins; Carcinoma, Ductal, Breast; Carcinoma, Lobular; Catenins; Diagnosis, Differential; Female; Follow-Up Studies; Humans; Immunohistochemistry; Keratins; Lymph Nodes; Middle Aged; Neoplasm Invasiveness; Neoplasm Staging; Phenotype; Prognosis; Receptor, ErbB-2; Receptors, Estrogen; Receptors, Progesterone; Survival Analysis; Time Factors

Topics: Adenocarcinoma; Adult; Carcinoembryonic Antigen; Dermoid Cyst; Humans; Immunohistochemistry; Intestines; Keratins; Male; Mouth Floor; Mouth Neoplasms; Mucin-1

The pathogenesis of respiratory epithelial adenomatoid hamartoma (REAH) and inverted papilloma (IP) is poorly understood, especially compared with sinonasal adenocarcinoma (SNAC). One feature of malignant glandular lesions is loss of the basal/myoepithelial layer. The immunophenotype of the basal/myoepithelial layer has not been fully examined in benign glandular lesions of the sinonasal tract.. To examine benign and malignant glandular lesions in the sinonasal tract for the immunophenotype of basal/myoepithelial cells, proliferation index, and cytokeratin and intestinal differentiation profiles.. Sinonasal adenocarcinoma (intestinal-type adenocarcinoma [ITAC] and nonintestinal type adenocarcinoma [non-ITAC]), REAH, IP, and chronic sinusitis (CS) were stained for cytokeratin (CK) 7, CK20, 34betaE12, CDX-2, p63, Ki-67, smooth muscle actin (SMA), S100 protein, and calponin.. Basal/myoepithelial cells in CS and REAH were positive for p63 and 34betaE12 but negative for SMA, S100 protein, and calponin. Proliferative activity was localized to the compartment containing p63-positive cells. Inverted papilloma demonstrated broad areas staining for p63 and 34betaE12, with intermediate proliferative activity in these areas. Sinonasal adenocarcinoma had the highest Ki-67 labeling index, and p63-positive SNACs had higher proliferation indices than p63-negative SNACs. REAH, IP, CS, and most SNACs expressed CK7. Only SNAC expressed CK20. Sixty percent of morphologic ITACs expressed CDX-2.. Basal/myoepithelial cells in CS and REAH should be considered basal and not myoepithelial cells. In benign lesions, proliferative activity is limited to the compartments with p63 staining. In SNAC and IP, p63 expression correlates with proliferation index. REAH, IP, and CS share similar immunoprofiles (CK7+, CK20-, and CDX-2-), contrasting with SNAC (CK7+, CK20+/-, CDX-2-/+).

Topics: Actins; Adenocarcinoma; Biomarkers, Tumor; Calcium-Binding Proteins; Calponins; CDX2 Transcription Factor; Cell Proliferation; Chronic Disease; Diagnosis, Differential; Epithelial Cells; Female; Hamartoma; Homeodomain Proteins; Humans; Immunohistochemistry; Immunophenotyping; Keratins; Ki-67 Antigen; Male; Membrane Proteins; Microfilament Proteins; Middle Aged; Papilloma; Paranasal Sinus Neoplasms; S100 Proteins; Sinusitis; Trans-Activators

Mammary tumour samples (11 surgical and five post-mortem) from 16 adult European hedgehogs submitted between 1980 and 2004 were examined. Histologically, the tumours were classified as simple tubulo-papillary carcinomas with local invasive growth. In six cases, tumour cell emboli were present in blood vessels or lymphatic vessels, or both. However, metastasis to regional lymph nodes was found only in one hedgehog. Malignant neoplastic epithelial cells were immunolabelled by antibodies specific for various cytokeratins (CKs), including CK1-8, 10, 13-16, 19 and 20. CK expression did not differ from that in normal mammary gland tissue. CK20 was expressed in the mammary tissue of hedgehogs, in contrast to that of dogs and cats; CK7 immunolabelling, however, which commonly occurs in mammary epithelial cells, was negative. CK20 expression, together with the lack of CK7 as determined by a protein-specific antibody, represented an important difference from the CK profile shown by mammary epithelial cells of other mammalian species, including the dog and cat.

Topics: Adenocarcinoma; Animals; Carcinoma, Papillary; Female; Gene Expression Regulation, Neoplastic; Hedgehogs; Immunohistochemistry; Keratins; Male; Mammary Neoplasms, Animal

Topics: Adenocarcinoma; Aged; Carcinoma, Papillary; Carcinoma, Squamous Cell; Humans; Immunohistochemistry; Keratin-7; Keratins; Lung Neoplasms; Lymphatic Metastasis; Male; Mucin-1

There are cases of recurrence even after curative resection in early gastric cancer.. Seven hundred and sixty-five patients with early gastric cancer who underwent curative gastrectomy were analyzed to identify the prognostic factor. Micrometastases within lymph nodes were determined by immunohistochemistry using anti-cytokeratin antibody in node-negative early gastric cancer patients with recurrence.. The recurrence was observed in 17 patients. Hematogenous recurrence was observed most frequently (47.1%), followed by peritoneal recurrence (23.5%). Of 17 patients with recurrence, 6 (35.3%) patients died more than 5 years after operation. The prognosis was poorer when the patients were older, and the depth of invasion was greater, lymph node metastasis, lymphatic involvement, and vascular involvement were present, and lymph node dissection was limited. The independent prognostic factors were lymph node metastasis, lymph node dissection, and age by multivariate analysis using Cox proportional hazards. Micrometastases within lymph nodes were confirmed in 3 of 6 node-negative patients with recurrence.. When patients have lymph node metastases or are older, close and long-term follow-up and careful planning of postoperative adjuvant therapy might be necessary to avoid recurrence. The detection of micrometastases by anti-cytokeratin antibody might be useful for predicting the possibility of recurrence in early gastric cancer.

Topics: Adenocarcinoma; Age Factors; Aged; Aged, 80 and over; Female; Follow-Up Studies; Gastrectomy; Humans; Immunoenzyme Techniques; Keratins; Lymph Node Excision; Lymph Nodes; Lymphatic Metastasis; Male; Middle Aged; Neoplasm Invasiveness; Neoplasm Recurrence, Local; Neoplastic Cells, Circulating; Peritoneal Neoplasms; Prognosis; Proportional Hazards Models; Stomach Neoplasms

Overexpression of alpha-methylacyl coenzyme A racemase (AMACR) in combination with absence of basal cell markers [ie, p63 and high molecular weight cytokeratin (HMWCK)] is typical of classic acinar prostatic adenocarcinoma. We studied the expression and diagnostic utility of p63/HMWCK/AMACR immunohistochemical cocktail staining in ductal adenocarcinoma and cribriform Gleason pattern 4 acinar prostate cancer and compared it to noncribriform Gleason pattern 4 acinar prostate cancer. One to 4 representative formalin-fixed paraffin-embedded archival tissue blocks from 62 radical prostatectomy specimens harboring prostate cancer of ductal (n=51), cribriform Gleason pattern 4 acinar (n=27), and noncribriform Gleason pattern 4 acinar adenocarcinoma (n=48) were included in this study. Immunohistochemistry was performed using a triple stain of AMACR, p63, and HMWCK. Only staining that was moderate or strong was considered positive. The percentage of staining intensity and the presence of occasional basal cells positive with p63/HMWCK were recorded in each histologic type of prostatic adenocarcinoma. Seventy-seven percent of ductal prostatic adenocarcinoma, 67% of cribriform acinar prostatic carcinoma, and 81% of noncribriform acinar prostatic carcinoma showed positive staining for AMACR. There was no statistically significant difference between AMACR staining among the 3 histologic types, although there was a trend for noncribriform acinar prostatic carcinoma to have greater expression of AMACR than cribriform acinar prostatic carcinoma (P=0.07). Staining was often heterogeneous, varying in staining intensities within the same histologic type of carcinoma. Basal cells were detectable by p63 and HMWCK in a patchy fashion in 31.4% (16/51) of ductal and 29.6% (8/27) of cribriform acinar carcinomas compared with 2.1% (1/48) of noncribriform acinar carcinomas. In summary: (1) the majority of prostatic ductal and cribriform acinar carcinomas strongly expressed AMACR, however, subpopulations of these prostatic carcinoma were either completely negative or only weakly positive; (2) AMACR staining was often heterogeneous in intensity in the same histologic type of tumor, even within the same case; (3) patchy basal cell staining in noncribriform acinar prostatic carcinoma is rare. In contrast, remnants of basal cells identified by p63/HMWCK were seen in a patchy fashion in a significant minority of both ductal and cribriform acinar prostatic adenocarcinoma, which most likely

Topics: Adenocarcinoma; Antibodies; Biomarkers, Tumor; Humans; Immunohistochemistry; Keratins; Male; Membrane Proteins; Prostatic Neoplasms; Racemases and Epimerases

Although distinguishing metastatic colorectal adenocarcinoma from primary lung adenocarcinoma is often difficult, pre- or intra-operative identification is very important, as the resection areas for each diagnosis differ substantially. CDX2, a recently cloned homeobox gene, represents a highly specific and sensitive marker of colorectal adenocarcinoma. We evaluated CDX2 expression using pre- and intra-operative biopsy specimens. The study examined 50 consecutive colorectal adenocarcinoma metastases to the lung, including 20 biopsy specimens and 66 resected specimens, and 21 primary lung adenocarcinomas. All specimens were immunohistochemically stained for CDX2, cytokeratin (CK) 7, CK20 and thyroid transcription factor (TTF)-1, and scored in a semi-quantitative manner. Mean staining score in biopsy specimens was significantly higher for CDX2 than for CK20. Sensitivities for CDX2 and CK7-/20+ in biopsy specimens were 95.0 and 65.0%, respectively. If CDX2 immunostaining had not been performed, 8 biopsy specimens (40%), and 20 resected specimens (30.3%) might have been diagnosed as equivocal cases either as primary lung cancer or metastatic colorectal cancer, using other markers. These results suggest that positive CDX2 staining represents a highly sensitive and specific marker of metastatic colorectal carcinoma in both biopsy and resected specimens, and is superior to staining for the CK7-/20+ phenotype.

Topics: Adenocarcinoma; Biomarkers, Tumor; Biopsy; CDX2 Transcription Factor; Colorectal Neoplasms; Homeodomain Proteins; Humans; Immunoenzyme Techniques; Keratins; Lung Neoplasms; Male; Middle Aged; Phenotype; Preoperative Care; Sensitivity and Specificity

A reliable diagnosis of small cell lung cancers (SCLC) is of high clinical relevance. We investigated whether immunocytology substantially improves the diagnostic accuracy of conventional cytology in diagnosing SCLC.. 162 carcinomatous specimens clinically suspected to originate from pulmonary neoplasms were investigated by cytology and immunocytology. Immunocytology was performed on smears using HEA125 and pancytokeratin antibodies as epithelial markers and MOC-1 as SCLC probe.. As histologically clarified, 114 specimens corresponded to pulmonary neoplasms (SCLC = 51; non-small cell lung cancer: NSCLC = 59; mixed SCLC/NSCLC = 2; carcinoid = 2), 48 to nonpulmonary adenocarcinomas. By conventional cytology tumor cells were clearly detected in 93 (57.4%) and suspected in another 43 (26.5%) cases (83.9% overall sensitivity). Considering SCLC samples, tumor cells were diagnosed or suspected in 36 (70.5%), not identified in 10 (19.6%), and misdiagnosed as hematological malignancy in 5 cases. Only 2 specimens were accurately diagnosed as SCLC. Using the epithelial antibodies all samples were identified as carcinomatous. MOC-1 stained all but one SCLC, both SCLC/NSCLC, and both carcinoids. One SCLC brush smear was MOC-1 negative, containing only squamous epithelium. 3 pulmonary adenocarcinomas stained falsely positive, all nonpulmonary carcinomas MOC-1 negative.. Immunocytology substantially improves the diagnostic accuracy of cytology in diagnosing SCLC with a diagnostic sensitivity of 98% and specificity of 97%.

Topics: Adenocarcinoma; Antibodies, Monoclonal; Biomarkers, Tumor; Carcinoid Tumor; Carcinoma, Small Cell; Carcinoma, Squamous Cell; CD56 Antigen; Diagnosis, Differential; Humans; Immunoenzyme Techniques; Keratins; Lung; Lung Neoplasms; Predictive Value of Tests

The histogenesis and biological behaviour of peripheral intrahepatic cholangiocarcinoma (peripheral CC) remain unclarified. The aim of this study was to examine the growth pattern of peripheral CC (24 cases) in comparison with hepatocellular carcinoma (HCC, 27 cases) and metastatic colorectal adenocarcinoma (MCA, 24 cases).. Tumour/surrounding liver borders were classified as: (i) fibrous encapsulation, (ii) compressive growth, and (iii) infiltrating replacement. Nineteen of 24 peripheral CCs showed (iii), whereas 23 of 27 HCCs showed (i) and 17 of 24 MCAs showed (ii). In (iii), carcinoma cells infiltrated the surrounding liver without compression, and hepatic supporting vascular structures such as portal tracts were secondarily incorporated into the tumour. In (i) and (ii), the surrounding liver was compressed and no or few portal tracts were incorporated within the tumour. Fifteen of 24 peripheral CCs were composed of carcinoma cells resembling reactive bile ductules and these cells were positive for neural cell adhesion molecule (NCAM), a marker of proliferating bile ductules. The remaining nine peripheral CCs were composed of ordinary adenocarcinoma and negative for NCAM.. A subgroup of peripheral CCs with an infiltrating replacement growth pattern resembles reactive bile ductules and expresses NCAM. 'Bile ductular carcinoma' may be a better term for this subgroup.

Topics: Adenocarcinoma; Aged; Aged, 80 and over; Autopsy; Bile Duct Neoplasms; Bile Ducts; Bile Ducts, Intrahepatic; Carcinoma, Hepatocellular; CD56 Antigen; Cholangiocarcinoma; Colorectal Neoplasms; Female; Humans; Immunohistochemistry; Keratins; Liver; Liver Neoplasms; Male; Middle Aged; Neural Cell Adhesion Molecules; Organ Size; Vimentin

The 2004 WHO classification of lung tumours recognised basaloid carcinoma as a variant of squamous and large cell carcinoma. We report a unique case of primary pulmonary adenocarcinoma with a basaloid component. An 82-year-old man underwent pulmonary lobectomy for a 2.8 cm tumour. The patient is disease-free 13 months after diagnosis. Histologically, an invasive carcinoma having a glandular and a solid component was observed. The former was an adenocarcinoma with mucus containing spaces lined by columnar mucinous cells and basaloid cells. The solid component was an organoid proliferation of basaloid-type cells, as in cutaneous basal cell carcinoma. Basaloid cells, but not mucinous cells, were immunoreactive for high molecular weight cytokeratins (CK), CK 7 and, focally, for TTF-1. High Ki67 index, p53 and EGFR expression were also found. This tumour is unique in several respects: (1) The solid areas resemble a conventional basaloid carcinoma, except for the presence of small mucin-containing spaces. (2) The mucinous adenocarcinoma areas contain two layers of columnar and basaloid cells. (3) Both components are neoplastic based on cell morphology, invasive properties and phenotypic profile. These findings indicate that a basaloid variant of adenocarcinoma is also existing in the spectrum of basaloid carcinomas of the lung.

Topics: Adenocarcinoma; Aged, 80 and over; Carcinoma, Basal Cell; Humans; Keratins; Lung Neoplasms; Male; Mucins; Neoplasm Invasiveness; Phenotype; World Health Organization

Benign prostatic hyperplasia and prostatic adenocarcinoma exhibit prominent zonal predilections. Basal cells from the transitional zone and from the peripheral zone are postulated to have different underlying biological properties. We studied basal cells in both prostatic zones.. Tissue microarrays (TMA) were prepared from 65 whole-mounted prostatectomy specimens with prostatic adenocarcinoma. The transitional zone and peripheral zone were sampled from each prostate. TMA sections were stained with a basal cell cocktail (CK 34betaE12 + p63). The immunostaining pattern and the morphology of basal cells were recorded.. Triangular-shaped basal cells were highlighted by CK 34betaE12 cytoplasmic and p63 nuclear staining. These basal cells had their long axis oriented perpendicular to the basement membrane and their apex toward the lumen interdigited between secretory luminal cells. This morphology was seen in the majority of peripheral zone benign prostatic glands (92.0%) but only a minority of transitional zone benign prostatic glands (18.0%). Basal cells of the transitional zone showed weak or absent CK 34betaE12 staining in 65.9% of glands while maintaining p63. All glands with high-grade prostatic intraepithelial neoplasia (HGPIN) contained the triangular basal cells. In addition, basal cell clusters were identified in 8.7% of peripheral zone glands and 5.2% of HGPIN glands.. Our results indicate that the basal cell morphology and the basal cell immunophenotype have a zonal variation. The finding of a unique morphology of basal cells and the presence of basal cell clusters in the peripheral zone suggests that the peripheral zone might be the stem/progenitor cell-rich area in the human prostates.

Topics: Adenocarcinoma; Adult; Aged; Biomarkers, Tumor; Cell Nucleus; Humans; Image Processing, Computer-Assisted; Immunoenzyme Techniques; Keratins; Male; Membrane Proteins; Middle Aged; Neoplastic Stem Cells; Prostate; Prostatic Intraepithelial Neoplasia; Prostatic Neoplasms; Tissue Array Analysis

Despite significant advancement in breast cancer therapy, there is a great need for a better understanding of the mechanisms involved in breast carcinogenesis and progression, as well as of the role of epigenetic contributions from stromal cells in mammary tumorigenesis. In this study, we isolated and characterized murine mammary tumor-derived epithelial and myofibroblast cell lines, and investigated the in vitro and in vivo effect of cellular soluble factors produced by the epithelial cell line on tumor cells.. Morphology, immunophenotype, cytogenetics, invasiveness, and tumorigenicity of epithelial (LM-234ep) and myofibroblast (LM-234mf) cell lines isolated from two murine mammary adenocarcinomas with common ancestor were studied. The in vitro effects of LM-234ep conditioned medium on proliferation, cell cycle distribution, and expression of cell cycle proteins, were investigated in LM-234mf cells, mouse melanoma cells (B16-F10), and human cervical adenocarcinoma cells (HeLa). The in vivo anti-tumor activity of LM-234ep conditioned media was evaluated in subcutaneous tumors formed in nude mice by B16-F10 and HeLa cells.. LM-234ep cells were found to be cytokeratin positive and hipertriploid, whereas LM-234mf cells were alpha-smooth muscle actin positive and hypohexaploid. Chromosome aberrations were found in both cases. Only LM-234mf revealed to be invasive in vitro and to secrete active MMP-2, though neither of the cell types were able to produce progressing tumors. LM-234ep-derived factors were able to inhibit the in vitro growth of LM-234mf, B16-F10, and HeLa cells, inducing cell cycle arrest in G0/G1 phase. The administration of LM-234ep conditioned medium inhibited the growth of B16-F10 and HeLa tumors in nude mice.. Our data suggest the existence of epithelial cell variants with tumor suppressive properties within mammary tumors. To our knowledge, this is the first report showing antiproliferative and antineoplastic activities induced by tumor-derived epithelial cells.

Topics: Actins; Adenocarcinoma; Animals; Carcinogenicity Tests; Cell Line, Tumor; Cell Proliferation; Chromosome Aberrations; Culture Media, Conditioned; Epithelial Cells; Female; Gelatinases; Humans; Keratins; Mammary Neoplasms, Experimental; Melanoma; Mice; Mice, Inbred BALB C; Paracrine Communication; Uterine Cervical Neoplasms

Colorectal adenocarcinoma with rhabdoid phenotype is extremely rare, and only 1 case of adenocarcinoma showing rhabdoid dedifferentiation has been reported. The authors present another case of cecal adenocarcinoma with prominent rhabdoid feature in a 66-year-old man. The 13-cm sized tumor consisted mainly of rhabdoid cells and partly of adenocarcinoma, and transition from adenocarcinoma to rhabdoid areas was noted. Ultrastructural analysis revealed intracytoplasmic aggregates of intermediate filaments in the rhabdoid cells. Adenocarcinoma cells were diffusely immunoreactive to cytokeratin 7 and AE1/3, but occasionally positive for vimentin. The rhabdoid cells were negative for cytokeratin 7, weakly/focally immunoreactive to AE1/3, and diffusely positive for vimentin. These results suggested that the rhabdoid cells were dedifferentiated adenocarcinoma. Analysis of the rhabdoid cells with molecular techniques is also presented.

Topics: Adaptor Proteins, Signal Transducing; Adenocarcinoma; Aged; Biomarkers, Tumor; Cecal Neoplasms; Cell Nucleus; Fatal Outcome; Genes, ras; Humans; Immunohistochemistry; Intermediate Filaments; Keratins; Lymph Nodes; Male; Microscopy, Electron, Transmission; MutL Protein Homolog 1; Nuclear Proteins; Rhabdoid Tumor; Vimentin

The purpose of this study is to evaluate the value of cytokeratin (CK) MNF116 and vimentin in the differential diagnosis of malignant pleural effusions. There were evaluated smears from 30 patients with pleural effusions stained with May-Grünwald Giemsa and Papanicolaou techniques for the routine cytological diagnosis. Additional smears were immunostained with CK MNF116 and vimentin using LSAB2 technique. Two independent observers evaluated all smears. Smears were classified first by cytological examination in seven cases (23.33%) as benign, and in 23 cases (76.67%) as malignant pleural effusions. Mesothelial cells expressed CK MNF116 in 96.67% (29/30) of cases and vimentin in 33.33% (10/30) of cases. Malignant cells expressed CK MNF116 in 52.17% (12/23) of cases and vimentin in 30.43% (7/23) of cases. The pattern of immunostaining was diffuse cytoplasmic. In conclusion, CK MNF116 and vimentin may be used as a part of the panel of antibodies for differential diagnosis of malignant pleural effusions with primary unknown.

Topics: Adenocarcinoma; Antibodies; Carcinoma, Small Cell; Diagnosis, Differential; Eosine Yellowish-(YS); Female; Humans; Keratins; Lung Neoplasms; Lymphoma, Large B-Cell, Diffuse; Melanoma; Methylene Blue; Pleural Effusion, Malignant; Pleural Neoplasms; Vimentin

Topics: Adenocarcinoma; Biomarkers, Tumor; Humans; Immunohistochemistry; Keratins; Male; Prostatic Neoplasms

We report a unique case of adenoid cystic carcinoma (ACC) of the maxillary sinus, with gradual histologic transformation from lower-grade ACC (cribriform and tubular types) to high-grade adenocarcinoma (HGA) showing a sequential histologic spectrum via solid-type ACC. A 74-year-old man presented with swelling and mild pain of the right cheek. CT scan showed a mass measuring approximately 4 cm, with marked bone destruction in the right maxillary sinus. A surgically resected specimen revealed that the tumor was comprised of three different components: HGA and solid-type ACC in the central portion and lower-grade ACC in the periphery. The tumor was discriminated from a dedifferentiated carcinoma or hybrid tumor. Autopsy specimens also demonstrated both solid-type ACC and HGA components in the lung and spleen. Immunohistochemically, positive staining of p53 protein was detected on both solid-type ACC and HGA cells, but cyclin D1 and HER2/neu was only seen in HGA cells. Solid-type ACC cells were immunoreactive for CD117 (c-kit), but lower-grade ACC and HGA cells were negative. This case suggests that the overexpression of CD117, p53 protein, cyclin D1, and HER2/neu might be involved in the progression from lower-grade ACC to solid-type ACC and HGA.

Topics: Actins; Adenocarcinoma; Aged; Carcinoma; Carcinoma, Adenoid Cystic; Disease Progression; Fatal Outcome; Humans; Immunohistochemistry; Keratins; Liver Neoplasms; Lung Neoplasms; Male; Maxillary Sinus Neoplasms; Muscle, Smooth; S100 Proteins; Tumor Suppressor Protein p53

Metastasis from extracranial tumor into an intracranial primary tumor is an uncommon event. A predominant tendency of meningioma to be the host tumor for breast carcinoma has been found. In the current report, three cases of breast carcinoma metastatic to intracranial meningiomas are described. In our cases, metastasis in meningioma was the first clinical manifestation of the occult primitive breast carcinoma. We review widely the literature concerning such rare occurrences and discuss all the postulated pathogenetic mechanisms. There are few cases reported in the literature on resonance magnetic imaging of metastatic carcinoma in meningioma. Two of our patients have been studied by MRI, but we do not find predictive radiological finding of this particular association.

Topics: Adenocarcinoma; Adult; Aged; Breast Neoplasms; Female; Humans; Immunohistochemistry; Keratins; Magnetic Resonance Imaging; Male; Mammography; Meningeal Neoplasms; Meningioma; Middle Aged; Neoplasms, Multiple Primary; Receptors, Estrogen; Receptors, Progesterone; Vimentin

A total of 43 cases of postirradiation prostate cores were assessed in an attempt to determine if routine use of alpha-methylacyl-CoA racemase (AMACR) in conjunction with high-molecular weight cytokeratin (HMWCK) would increase the recognition of carcinoma in postirradiation prostate biopsies. We concluded that in most cases the addition of AMACR in conjunction with HMWCK does not increase the recognition of prostatic adenocarcinoma, however it is supportive in nature. In one case the use of AMACR highlighted the extent of the adenocarcinoma which otherwise would have been designated as atypical small acinar proliferation (ASAP). Further evaluation is required to assess the significance of a diagnosis of atypical small acinar proliferation in postirradiation prostate biopsies.

Topics: Adenocarcinoma; Biopsy; Diagnosis, Differential; Humans; Immunohistochemistry; Keratins; Male; Molecular Weight; Neoplasm Recurrence, Local; Prostate; Prostatic Neoplasms; Racemases and Epimerases; Reproducibility of Results; Sensitivity and Specificity

Cytokeratins are markers of epithelial cell differentiation useful in determining histogenesis for malignancies with an unknown primary. Application of this principle to a single malignancy may identify cancer subtypes with altered developmental programs. Herein, we investigate the relevance of two widely used cytokeratins (CKs), 7 and 20, to subtype pancreas cancer and identify associations with clinical features.. A tissue microarray was constructed using tumor specimens from 103 patients who underwent resection for pancreatic adenocarcinoma with curative intent. A subset of resection specimens was evaluated for pancreatic intraepithelial neoplasia (PanIN) lesions. Tissues were immunostained by using specific anticytokeratin 7 and 20 monoclonal antibodies.. CK 7 and 20 expression was present in 96% and 63% cases of pancreatic adenocarcinoma, respectively. Ubiquitous CK 7 expression precluded further analysis. Tumoral CK 20 expression was not associated with any histopathologic parameter but correlated with worse prognosis when considered as either a dichotomous (P=0.0098) or continuous (P=0.007) variable. In a multivariate model, tumoral CK 20 expression remained a significant independent prognosticator. CK 20 expression was absent in all PanIN lesions from eight resection specimens in which the tumor component was negative for CK 20. In contrast, presence of tumoral CK 20 was highly concordant with its expression in corresponding PanINs.. CK 20 expression defines a subtype of pancreas cancer with important biologic properties. When present, CK 20 expression is an early event in pancreatic carcinogenesis identifiable in precursor lesions. Further studies to identify the underlying genetic changes associated with this altered developmental pathway are warranted.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Cell Transformation, Neoplastic; Female; Gene Expression Profiling; Humans; Keratin-20; Keratin-7; Keratins; Male; Middle Aged; Oligonucleotide Array Sequence Analysis; Pancreatic Neoplasms; Prognosis; Retrospective Studies; Survival Analysis

In the past few years, tumour budding at the invasive margin has been reported as a new risk factor for lymph node metastasis in advanced colorectal cancers, but it is sometimes difficult to detect tumour budding in submucosal colorectal cancer by haematoxylin and eosin staining. We immunohistochemically examined tumour budding at the deepest invasive margin of 56 surgically resected submucosal colorectal carcinomas using anticytokeratin antibody CAM5.2, furthermore checked by AE1/AE3, and determined the relation between tumour budding and clinicopathological factors. Moreover, we used the monoclonal antibody D2-40 for immunohistochemistry to detect lymphatic involvement. Tumour budding was detected in 42 cases (75.0%), and the budding-positive group showed a significantly higher rate of lymph node metastasis (including isolated tumour cells) (16/42 vs 0/14; P=0.004) than the budding-negative group. The sensitivity and negative predictive value of tumour budding alone for lymph node metastasis were superior to those of lymphatic invasion alone. Furthermore, the specificity and positive predictive value of the combination of either lymphatic invasion or tumour budding were superior to those of lymphatic invasion alone. Tumour budding detected immunohistochemically by using CAM5.2 is a newly found risk factor for lymph node metastasis and may help to avoid oversurgery in the future.

Topics: Adenocarcinoma; Aged; Antibodies; Biomarkers; Colorectal Neoplasms; Female; Humans; Immunohistochemistry; Keratins; Lymphatic Metastasis; Male; Middle Aged; Predictive Value of Tests; Risk Factors; Sensitivity and Specificity

Topics: Adenocarcinoma; Aged; Carcinoma, Adenoid Cystic; Female; Humans; Immunohistochemistry; Keratins; Ki-67 Antigen; Mucin-1; Neoplasms, Multiple Primary; Salivary Gland Neoplasms

The recently identified claudins are dominant components of tight junctions, responsible for cell adhesion, polarity and paracellular permeability. Certain claudins have been shown to have relevance in tumor development, with some of them, especially claudin-4, even suggested as future therapeutic target. The aim of the present study was to analyze the expression of claudin-4 in the biliary tree, biliary tract cancers and hepatocellular carcinomas. A total of 107 cases were studied: 53 biliary tract cancers, 50 hepatocellular carcinomas, 10 normal liver and 10 normal extrahepatic biliary duct samples. Immunohistochemical analysis was performed on conventional specimens and on tissue microarrays as well. Claudin-4 was further investigated by Western blot analysis and real-time RT-PCR. Intense membranous immunolabeling was found for claudin-4 in all biliary tract cancers unrelated to the primary site of origin, namely intrahepatic, extrahepatic or gallbladder cancers. Normal biliary epithelium showed weak positivity for claudin-4. In contrast, normal hepatocytes and tumor cells of hepatocellular carcinomas did not express claudin-4. The results of Western immunoblot analysis and real-time RT-PCR were in correlation with the immunohistochemical findings. Cytokeratins, as CK7 (92%) and CK19 (83%) were mostly positive in biliary tract cancers, however, one-third of hepatocellular carcinomas also expressed CK7 (34%). HSA antibody (HepPar1) reacted with the majority of hepatocellular carcinomas (86%), while being positive in a low percentage of the biliary tract cancers (8%). In conclusion, this is the first report of a significantly increased claudin-4 expression in biliary tract cancers, which represents a novel feature of tumors of biliary tract origin. Claudin-4 expression seems to be a useful marker in differentiating biliary tract cancers from hepatocellular carcinomas and could well become a potential diagnostic tool.

Topics: Adenocarcinoma; Biliary Tract Neoplasms; Blotting, Western; Carcinoma, Hepatocellular; Claudin-4; Diagnosis, Differential; Gene Expression; Humans; Immunohistochemistry; Keratin-7; Keratins; Laminin; Liver; Liver Neoplasms; Membrane Proteins; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Tissue Array Analysis

It is important to discriminate between primary and secondary lung cancer. However, often, the discriminating diagnosis of primary lung acinar adenocarcinoma and lung metastasis of colorectal cancer based on morphological and pathological findings is difficult. The purpose of this study was to evaluate the clinical usefulness of immunohistochemistry of beta-catenin, cytokeratin (CK) 7, and CK20 for the discriminating diagnosis of lung cancer.. We performed immunohistochemistry of beta-catenin, CK7, and CK20 in 19 lung metastasis of colorectal cancer samples, 10 corresponding primary colorectal cancer samples and 11 primary lung acinar adenocarcinoma samples and compared the levels of accuracy of the discriminating diagnosis by using antibodies against these antigens.. Positive staining of beta-catenin was observed in all the lung metastasis of colorectal cancer samples as well as in the primary colorectal cancer samples but in none of the primary lung acinar adenocarcinoma samples. Positive staining of CK7 was observed in 90.9% of the primary lung acinar adenocarcinoma samples and in 5.3% of the lung metastasis of colorectal cancer samples, but in none of the primary colorectal cancer samples. Positive staining of CK20 was observed in all the primary colorectal cancer samples and in 84.2% of the lung metastasis of colorectal cancer samples, but in none of the primary lung acinar adenocarcinoma samples.. Combined immunohistochemistry of beta-catenin, CK7, and CK20 is useful for making a discriminating diagnosis between lung metastasis of colorectal cancer and primary lung acinar adenocarcinoma. This method will enable accurate diagnosis of a lung tumor and will be useful for selecting appropriate therapeutic strategies, including chemotherapeutic agents and operation methods.

Topics: Adenocarcinoma; beta Catenin; Biomarkers, Tumor; Colorectal Neoplasms; Diagnosis, Differential; Gene Expression Profiling; Humans; Immunohistochemistry; Keratin-20; Keratin-7; Keratins; Lung Neoplasms; Retrospective Studies; Sensitivity and Specificity

Distinction of intestinal-type sinonasal adenocarcinoma (ITAC) from adenocarcinoma of intestinal origin metastatic to the sinonasal cavity may be extremely difficult on histologic grounds alone. We studied the role of cytokeratin (CK) and mucin (MUC) expression in differentiating ITAC, metastatic adenocarcinoma of intestinal origin, and non-intestinal-type sinonasal adenocarcinoma (non-ITAC).. We stained specimens from 5 cases of ITAC and 4 cases of non-ITAC, along with 4 colonic and 3 duodenal adenocarcinoma controls, with CK7 and CK20, MUC2 and MUC5, neuron-specific enolase (NSE), chromogranin (CHR), and carcinoembryonic antigen (CEA) in order to examine the possible combinations of markers that best aid in the diagnosis of these lesions. We also performed a retrospective review of our clinical experience with these rare lesions.. CK7 staining was positive in all ITAC and non-ITAC cases, whereas all cases displaying gastrointestinal-type differentiation (ITAC and metastatic intestinal cases) stained positive for both CK20 and MUC2. Staining for MUC5, NSE, CHR, and CEA was variable.. Tumors with the CK7+, CK20+, MUC2+ immunophenotype are likely primary sinonasal lesions, whereas tumors with the CK7-, CK20+, MUC2+ profile warrant further clinical evaluation to exclude metastatic disease from the gastrointestinal tract. Complete surgical resection of ITAC remains the mainstay of therapy.

Topics: Adenocarcinoma; Adult; Aged; Biomarkers, Tumor; Colonic Neoplasms; Diagnosis, Differential; Duodenal Neoplasms; Female; Humans; Immunohistochemistry; Keratin-20; Keratin-7; Keratins; Male; Middle Aged; Mucin-2; Mucins; Paranasal Sinus Neoplasms; Retrospective Studies

Pancreatic endocrine tumours (PET) containing ductules are an uncommon histological variant. Considerable conjecture surrounds the origin and histogenesis of the ductules. Opinions range from the ductules being an inherent part of the tumour, to others who feel they are merely entrapped. A study of 21 cases of this variant was undertaken with particular attention paid to the distribution and morphology of the ductules, the presence of entrapped acinar tissue and the surrounding uninvolved pancreatic tissue.. Twenty-one cases were detailed occurring in either gender equally and with a wide age range (19-85 years). All cases, except one, were sporadic, the vast majority were located in the tail and were of small size (less than 2.0 cm). All cases were typified by stromal fibrosis, either diffuse (15) or in the form of septae (6). Embedded within the fibrous tissue were ductular structures, some of which were dilated and ectatic. The ductules were centrally located (5), at the periphery of the tumour (9) or diffusely scattered throughout the lesion (7). All cases showed ductulo-insular complexes. Insulin was demonstrated in 15 immunohistochemically.. It is likely that in some cases the ductules are entrapped as the tumour grows into surrounding normal pancreatic tissue and the ductular proliferation is a secondary phenomenon. In a proportion of cases, the ductules are likely to be a part of the tumour arising as part of focal chronic inflammation or as a result of the growth factor effects of insulin, in cases associated with insulin production. There is nothing to suggest that the ductules confer any special biological characteristics to the PET and are merely a histological nuance. However, some cases may have a dominant tubular component, which could present problems at frozen section where the association with fibrosis may invoke a mistaken diagnosis of pancreatic ductal adenocarcinoma or chronic pancreatitis.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Biomarkers; Carcinoma, Islet Cell; Carcinoma, Pancreatic Ductal; Diagnosis, Differential; Female; Fibrosis; Humans; Immunohistochemistry; Insulin; Islets of Langerhans; Keratins; Male; Middle Aged; Pancreatic Ducts; Pancreatic Neoplasms; Pancreatitis, Chronic

A 63-year-old man who had undergone resection of colon cancer 15 years previously was found to have a right hilar mass on chest X-ray, and an elevated serum carcinoembryonic antigen level. The hilar lymph nodes were resected with the right upper lobe, and the initial diagnosis was colon cancer metastasis to the right hilar lymph nodes. Although the resection was incomplete, and no additional treatment was given, the patient remained free of recurrence for 10 years. This prompted us to reconsider our diagnosis using immunohistochemistry. The resected lymph nodes were found to be positive for thyroid transcription factor 1 (TTF-1) and cytokeratin 7, and negative for surfactant apoprotein (SAP), cytokeratin 20, and napsin A. The neuroendocrine markers and thyroglobulin were also negative. These findings led us to diagnose T0N1 lung cancer. There are reports of patients with clinical T0N1,2 lung cancer having exceptionally good prognoses despite noncurative treatment; however, to our knowledge, this is the first case of a patient with T0N1 lung cancer diagnosed by immunohistochemistry, with a good prognosis despite incomplete resection. In this case, TTF-1 and cytokeratin staining was particularly helpful in the differential diagnosis.

Topics: Adenocarcinoma; Apoproteins; Aspartic Acid Endopeptidases; Colonic Neoplasms; Humans; Immunohistochemistry; Keratin-20; Keratin-7; Keratins; Lung Neoplasms; Lymph Nodes; Male; Middle Aged; Neoplasm Staging; Nuclear Proteins; Prognosis; Pulmonary Surfactant-Associated Proteins; Thyroid Nuclear Factor 1; Time Factors; Transcription Factors

We evaluated the sensitivity and specificity of 10 monoclonal and two polyclonal antibodies for distinguishing epithelioid mesothelioma from adenocarcinoma (AdCA) using immunohistochemistry (IHC). The antibodies were directed against the mesothelial-associated antigens mesothelin, calretinin, cytokeratin 5, thrombomodulin, Wilms' tumor-1 (WT-1) gene product and HBME-1, and the nonmesothelial antigens Lewis-Y blood group (antibody BG8), MOC-31, BerEp4, CD15, and carcinoembryonic antigen (CEA) family. The 133 tumors evaluated included 65 malignant epithelioid mesotheliomas, 22 lung AdCAs, 27 ovarian serous carcinomas, 24 breast carcinomas, and five gastric carcinomas. Diagnoses were based on clinical, histologic, ultrastructural, and/or IHC findings. Calretinin had the best sensitivity for mesothelioma (95%), followed by HBME-1 (84%), WT-1 (78%), cytokeratin 5 (76%), mesothelin (75%), and vimentin and thrombomodulin (68%). Thrombomodulin had the best specificity for mesothelioma (92%), followed by cytokeratin 5 (89%), calretinin (87%) vimentin (84%), and HBME-1 (45%). When ovarian carcinomas were excluded from the analysis, the specificity of mesothelin and WT-1 for the diagnosis of mesothelioma increased to 90 and 81%, respectively. The sensitivity of the nonmesothelial antigens for AdCA was organ dependent, with BG8 performing best in the breast cancer group (96%), and BerEp4, BG8, MOC-31 performing best in the lung cancer group (100%). The specificity of the nonmesothelial antigens for AdCA was 98% for BG8 and CEA, 97% for CD15, 95% for BerEp4, and 87% for MOC-31. A novel statistical analysis technique employing logic regression analysis identified a three-antibody immunohistochemical panel including calretinin, BG8, and MOC-31, which provided over 96% sensitivity and specificity for distinguishing epithelioid mesothelioma from AdCA.

Topics: Adenocarcinoma; Antibodies, Monoclonal; Antibody Specificity; Biomarkers, Tumor; Breast Neoplasms; Calbindin 2; Carcinoembryonic Antigen; Diagnosis, Differential; Female; GPI-Linked Proteins; Humans; Immunohistochemistry; Keratin-5; Keratins; Lung Neoplasms; Membrane Glycoproteins; Mesothelin; Mesothelioma; Multivariate Analysis; Ovarian Neoplasms; S100 Calcium Binding Protein G; Sensitivity and Specificity; Stomach Neoplasms; Thrombomodulin; WT1 Proteins

Thyroid transcription factor-1 (TTF-1), and cytokeratin 7 (CK7) and cytokeratin 20 (CK20) have recently been reported to be useful to distinguish between primary and metastatic lung adenocarcinoma. The aim of this study was to determine the usefulness of the staining patterns of pulmonary adenocarcinoma with antibodies to TTF-1, CK7, and CK20 in differentiating primary from metastatic pulmonary adenocarcinoma. Of the 66 lung adenocarcinoma specimens that were enrolled in our study, there were 40 primary lung adenocarcinomas, 12 metastatic adenocarcinomas from breast, 13 metastatic adenocarcinomas from colon, and 1 metastatic adenocarcinoma from stomach. The expression of TTF-1, CK7, and CK20 was assessed by immunohistochemistry. We found that 73% of primary lung adenocarcinomas expressed TTF-1, whereas all nonpulmonary adenocarcinomas lacked TTF-1 staining. CK7 expression was significantly more frequent in adenocarcinomas of pulmonary and breast origin than gastrointestinal (GI) origin (p < 0.001). In contrast, CK20 expression was significantly more prevalent in adenocarcinoma that originated in the GI tract than that of pulmonary or breast origin (p < 0.001). A combination of TTF-1+CK7+CK20- was highly significantly associated with primary adenocarcinoma of lung (vs GI tract, p < 0.001; vs breast, p < 0.001). A combination of TTF-1-CKCK20+ was highly significantly associated with adenocarcinoma of GI origin (vs lung, p < 0.001; vs breast, p < 0.001). Our study has confirmed that expression of CK7, CK20, and TTF-1 is a useful immunohistochemical marker for diagnosis of lung tumors and for differential diagnosis of primary pulmonary adenocarcinomas from extrapulmonary adenocarcinomas metastatic to the lung. Application of this panel of antibodies might be expected to increase the accuracy of diagnosis.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Biomarkers, Tumor; Female; Humans; Immunohistochemistry; Keratin-20; Keratin-7; Keratins; Lung Neoplasms; Male; Middle Aged; Nuclear Proteins; Thyroid Nuclear Factor 1; Transcription Factors

The aim of this study was to investigate the immunohistochemical expression of p16, p53, and p63 proteins according to some pathologic parameters related to colorectal adenomas and adenocarcinomas such as grade of dysplasia and histologic type.. Immunohistochemistry with the antibodies p16, p53, and p63 was performed in tubular, tubular-villous, and villous adenomas (n = 30) and in well, moderately, and poorly differentiated adenocarcinomas (n = 30). The p63-positive cases were submitted to double immunolabeling with the cytokeratin 5 (CK5).. The p16 and p53 labelings were observed in some adenomas and adenocarcinomas but without any association with p63 expression, histologic type, or grade of differentiation of the neoplasm. P63 expression was found mainly in the villous adenomas and in the poorly differentiated adenocarcinomas. The poorly differentiated adenocarcinomas also exhibited coexpression of CK5 and p63.. Despite both p16 and p53 having been detected in colorectal neoplasms, they were not related to the different histologic variables nor to the expression of p63. However, p63 expression was closely associated with villous adenomas and poorly differentiated adenocarcinomas. Thus, p63 may represent a marker of poor differentiation in colorectal neoplasms. The coexpression of p63 and CK5 observed in this study could be related to divergent differentiation during the development of colorectal cancer, although further studies are warranted to refine the understanding of this process.

Topics: Adenocarcinoma; Adenoma; Biomarkers, Tumor; Colorectal Neoplasms; DNA-Binding Proteins; Genes, p16; Genes, p53; Genes, Tumor Suppressor; Humans; Immunohistochemistry; Keratins; Phosphoproteins; Trans-Activators; Transcription Factors; Tumor Suppressor Proteins

Typically glands of prostatic adenocarcinoma have a single cell lining, although stratification can be seen in invasive carcinomas with a cribriform architecture, including ductal carcinoma. The presence and diagnostic significance of stratified cells within non-cribriform carcinomatous prostatic glands has not been well addressed. The histomorphological features and immunohistochemical profile of cases of non-cribriform prostatic adenocarcinoma with stratified malignant glandular epithelium were analyzed. These cases were identified from needle biopsy cases from the consultation files of one of the authors and from a review of 150 consecutive in-house needle biopsy cases of prostatic adenocarcinoma. Immunohistochemistry was performed utilizing antibodies reactive against high molecular weight cytokeratin (34betaE12), p63 and alpha-methylacyl-coenzyme-A racemase (AMACR). A total of 8 cases were identified, including 2 from the 150 consecutive in-house cases (1.3%). In 4 cases, the focus with glands having stratified epithelium was the sole carcinomatous component in the biopsy, while such a component represented 5-30% of the invasive carcinoma seen elsewhere in the remaining cases. The main attribute in all these foci was the presence of glandular profiles lined by several layers of epithelial cells with cytological and architectural features resembling flat or tufted high-grade prostatic intraepithelial neoplasia, but lacking basal cells as confirmed by negative 34betaE12 and/or p63 immunostains in all cases. The AMACR staining profile of the stratified foci was variable, with 4 foci showing positivity, and 3 foci being negative, including two cases that displayed AMACR positivity in adjacent non-stratified prostatic adenocarcinoma. Prostatic adenocarcinoma with stratified malignant glandular epithelium can be identified in prostate needle biopsy samples harboring non-cribriform prostatic adenocarcinoma and resembles glands with high-grade prostatic intraepithelial neoplasia. These 'PIN-like' carcinomas can present in pure form. Recognition of this pattern of prostatic adenocarcinoma is necessary to correctly diagnose such cases as invasive carcinoma.

Topics: Adenocarcinoma; Aged; Aged, 80 and over; Biopsy, Needle; Diagnosis, Differential; Epithelium; Humans; Immunohistochemistry; Keratins; Male; Membrane Proteins; Middle Aged; Neoplasm Invasiveness; Prostate-Specific Antigen; Prostatic Intraepithelial Neoplasia; Prostatic Neoplasms; Racemases and Epimerases; Retrospective Studies

Different histogenetic pathways have been suggested between ulcerative colitis (UC)-associated neoplasia and sporadic colorectal neoplasia. Little is known about the cytokeratin (CK) and mucin expression in UC-associated neoplasms. To clarify the characteristics of UC-associated colorectal carcinogenesis, we examined the immunohistochemical expression of CK7, CK20, MUC2, MUC5AC and MUC6 in 90 colorectal neoplasms, including 22 UC-associated adenocarcinomas (colitic cancer; CC), ten high-grade dysplasias (HGD) in UC, nine low-grade dysplasias (LGD) in UC, 24 sporadic tubular adenomas (TA) and 25 adenocarcinomas (AC). CK7 was positive in most of UC-associated neoplasms: 59% of CC cases, 80% of HGD and 89% of LGD, respectively, whereas, in non-UC associated neoplasia, 21% of TA and 12% of AC. The frequency of MUC6 expression in UC-associated neoplasia was 32% in CC, 30% in HGD and 44% in LGD, respectively, whereas, in non-UC associated neoplasia, 4.2% in TA and 0% in AC. MUC5AC expression in UC-associated neoplasia was detectable in 73% of CC, 90% of HGD and 89% of LGD, respectively; in non-UC associated neoplasia 67% in AC and 20% in TA. There were obvious differences in the expression of CK7 and MUC6 between UC-associated neoplasms and sporadic tumors. The incidence of MUC5AC expression in UC-associated neoplasms was also higher than sporadic tumors. These results suggest that gastric-type mucins play an important role in the initial step of CC-tumorigenesis, and CK7 and gastric-type mucins may be useful in the differential diagnosis between UC-associated neoplasms and sporadic ones.

Topics: Adenocarcinoma; Adenoma; Biomarkers, Tumor; Colitis, Ulcerative; Colorectal Neoplasms; Fluorescent Antibody Technique, Direct; Humans; Immunoenzyme Techniques; Keratin-20; Keratin-7; Keratins; Mucins; Precancerous Conditions

We report a rare case of unknown primary carcinoma. A 36-year-old man was admitted to the hospital because of a chest wall tumor. Serum carcinoembryonic antigen level was 160 ng/ml. The resected chest wall tumor was pathologically diagnosed as metastatic adenocarcinoma, showing positive immunoreactivity for cytokeratin 7 and negative immunoreactivity for cytokeratin 20, suggesting lung origin. Serum carcinoembryonic antigen level returned to normal limits. Twenty-one months later, a chest X-ray showed a nodular lesion in the left upper lobe and serum carcinoembryonic antigen level increased to 12.3 ng/ml. Left upper lobectomy was performed 23 months after chest wall resection. The resected tumor was pathologically diagnosed as primary lung adenocarcinoma, showing the same immunoreactivity as in the chest wall tumor. The combination of immunohistochemistry for cytokeratin 7 and 20 appeared to be a useful tool in determining the site of origin and helpful for premortem diagnosis of the origin of unknown primary carcinoma.

Topics: Adenocarcinoma; Adult; Humans; Immunohistochemistry; Keratin-20; Keratin-7; Keratins; Lung Neoplasms; Male; Neoplasms, Unknown Primary; Thoracic Neoplasms; Thoracic Wall

To reveal architectural structure and growth patterns of tubular carcinomas (TC) and tubulo-lobular carcinomas (TLC) of the breast.. We studied a series of 20 pure TC and 22 TLC, evaluating the architectural features of the two entities by bi-dimensional microscopy and by 3-D modelling. We traced the spatial organization of three TCs and three TLCs on serial sections using AE1/AE3 cytokeratin as a marker of the epithelial structures and reconstructed 3-D models of each histological type. The analysis of TC on serial cytokeratin-stained sections showed that the form of the 'tubules' was related to the plane of sectioning and that often they were tear-drop shaped, with a final tail of single cells connecting them together. 3-D models corresponded to a necklace appearance and the tubules of TC appeared as blebs bridging through solid cords to other blebs. In TLC the structure was similar, but the connecting single-cell files were usually longer. Both TC and TLC showed similar E-cadherin positivity and an indolent clinical behaviour.. TC and TLC share the same architectural and growth patterns and ultimately seem to represent variants of the same tumour type.

Topics: Adenocarcinoma; Breast Neoplasms; Carcinoma, Lobular; Female; Humans; Imaging, Three-Dimensional; Immunohistochemistry; Keratins; Microtomy; Models, Biological

In this study, we sought to validate the importance of p63, CK5/CK6, CK7, and surfactant-A (SP-A) to classify 42 non-small cell lung cancers in autopsy and surgical resection specimens and to study the usefulness of these markers in distinguishing between squamous cell carcinomas and adenocarcinomas because of their different implications regarding treatment and prognosis. All adenocarcinoma cases were negative for p63; 9 (56.2%) of 16 were CK5/CK6 positive, 16 (94.1%) of 17 were CK7 positive, and 4 (26.6%) of 15 were SP-A positive. In squamous cell carcinoma, 1 case was CK7 and SP-A positive and 14 (77.8%) of 18 were p63 positive. The latter appears to be useful in differentiating squamous cell carcinoma from adenocarcinoma of the lung in small biopsies without keratinization or glandular differentiation; thus, for advanced-stage cases, where there is no possibility of surgical resection and the treatment of choice is radiotherapy plus chemotherapy, we would be able to differentiate between the two histological types, establishing then a different therapy.

Topics: Adenocarcinoma; Biomarkers, Tumor; Carcinoma, Non-Small-Cell Lung; Carcinoma, Squamous Cell; Diagnosis, Differential; Humans; Immunoenzyme Techniques; Keratin-5; Keratin-6; Keratin-7; Keratins; Lung Neoplasms; Membrane Proteins; Pulmonary Surfactant-Associated Protein A

We here report a very rare case of female urethral adenocarcinoma. A 77-year-old woman presented with urinary retention. Cystoscopy showed a urethral tumor and the biopsy material showed adenocarcinoma. Macroscopically, the tumor measuring 3.0 x 3.0 x 2.4 cm was predominantly observed around the periurethral area on the proximal side. Histologically, patterns of columnar/mucinous adenocarcinoma, clear cell adenocarcinoma and papillary/micropapillary carcinoma were observed, but there was no evidence of a cribriform pattern. Immunohistochemically, neoplastic cells of at least one of three components were positive for CK7 and CK20 or CA125. We suggest that female urethral adenocarcinoma with a histologically and immunohistochemically heterogeneous phenotype may originate from cells within urethral or paraurethral tissue, such as urethritis glandularis or intestinal metaplastic epithelium and Mullerian tissue.

Topics: Adenocarcinoma; Aged; CA-125 Antigen; Female; Humans; Immunochemistry; Keratin-20; Keratin-7; Keratins; Phenotype; Urethral Neoplasms

In this study we evaluated pedunculated oncocytic carcinoma (OC) in the buccal mucosa via immunohistochemical and ultrastructural studies.. An 84-year-old man was referred to our clinic with a pedunculated mass about 4 cm in diameter in the right buccal mucosa. An incision biopsy revealed the diagnosis of oncocytic tumor, and enucleation was performed. The tumor was stained for immunohistochemical analysis using the ABC method and antibodies against cytokeratin (CK), epithelial membrane antigen (EMA), desmin, S-100 protein and muscle-specific actin, respectively. The tumor was stained with uranyl acetate and lead citrate for visualization by electron microscopy.. Histopathology results revealed that the tumor consisted of oncocytic cells, characterized by eosinophilic and granular cytoplasm, and atypical nuclei. These cells had infiltrated local blood vessels, salivary glands and muscles. Immunohistochemical staining indicated that these cells were positive for CK and EMA, and negative for desmin, muscle-specific actin and S-100 protein. Electron microscopy revealed numerous dilated cytoplasmic mitochondria, and the cell contours and nucleic shapes of tumor cells were often irregular.. Because the histopathologic features of OC are similar to those of benign oncocytoma, the diagnosis of OC must be confirmed by a combination of clinical and ultrastructural characteristics.

Topics: Adenocarcinoma; Aged, 80 and over; Cheek; Humans; Immunohistochemistry; Keratins; Male; Microscopy, Electron, Transmission; Mitochondria; Mouth Mucosa; Mouth Neoplasms; Mucin-1; Neoplasm Invasiveness

An optimal immunohistochemical panel to distinguish poorly differentiated prostate (PCa) from urothelial (UCa) carcinoma was selected from a panel consisting of prostate-specific antigen (PSA) and prostatic acid phosphatase (PAP), high-molecular-weight cytokeratin (HMWCK), clone 34betaE12, cytokeratin (CK) 7, CK20, p63, and alpha-methylacyl-coenzyme A racemase. The pilot group was composed of poorly differentiated UCa (n = 36) and PCa (n = 42). PSA and PAP stained 95% of PCa vs 0% and 11% of UCa cases, respectively. HMWCK and p63 stained 97% and 92% of UCa vs 2% and 0% of PCa cases respectively. CK7/CK20 coexpression was noted in 50% of UCa cases, whereas 86% of PCa cases were negative with both. A panel of PSA, HMWCK, and p63 was optimal for separating 95% PCa (PSA+/HMWCK and/or p63-) vs 97% UCa (PSA-/HMWCK and/or p63+). This panel was used on 26 diagnostically challenging cases and resolved 81% of cases as UCa vs PCa. The majority of PCa cases retain PSA. Negative PSA with positive HMWCK and/or p63 establishes a diagnosis of UCa.

Topics: Adenocarcinoma; Biomarkers, Tumor; Diagnosis, Differential; Humans; Immunohistochemistry; Keratins; Male; Membrane Proteins; Molecular Weight; Pilot Projects; Prostate-Specific Antigen; Prostatic Neoplasms; Urinary Bladder Neoplasms; Urothelium

Gastrointestinal adenocarcinoma arising in mature cystic teratomas of the ovary is extremely rare. We report a case of well-differentiated intestinal adenocarcinoma arising in a mature cystic teratoma of the ovary in a 77-year-old woman, presenting as acute abdomen with ovarian torsion. An immunohistochemical study revealed expression of CK20 and CK7, and the tumor was also positive for MUC2. The patient had no evidence of disease after 12 months of follow-up.

Topics: Adenocarcinoma; Aged; Biomarkers, Tumor; Cell Transformation, Neoplastic; Female; Humans; Intestinal Neoplasms; Keratin-20; Keratin-7; Keratins; Mucin-2; Mucins; Neoplasms, Multiple Primary; Ovarian Neoplasms; Teratoma; Tomography, X-Ray Computed; Treatment Outcome

To compare gene expression profiles of pancreatic adenocarcinoma tissue specimens, human pancreatic and colon adenocarcinoma and leukemia cell lines and normal pancreas samples in order to distinguish differentially expressed genes and to validate the differential expression of a subset of genes by quantitative real-time RT-PCR (RT-QPCR) in endoscopic ultrasound-guided fine needle aspiration (EUS-guided FNA) specimens.. Commercially dedicated cancer cDNA macroarrays (Atlas Human Cancer 1.2) containing 1176 genes were used. Different statistical approaches (hierarchical clustering, principal component analysis (PCA) and SAM) were used to analyze the expression data. RT-QPCR and immunohistochemical studies were used for validation of results.. RT-QPCR validated the increased expression of LCN2 (lipocalin 2) and for the first time PLAT (tissue-type plasminogen activator or tPA) in malignant pancreas as compared with normal pancreas. Immunohistochemical analysis confirmed the increased expression of LCN2 protein localized in epithelial cells of ducts invaded by carcinoma. The analysis of PLAT and LCN2 transcripts in 12 samples obtained through EUS-guided FNA from patients with pancreatic adenocarcinoma showed significantly increased expression levels in comparison with those found in normal tissues, indicating that a sufficient amount of high quality RNA can be obtained with this technique.. Expression profiling is a useful method to identify biomarkers and potential target genes. Molecular analysis of EUS-guided FNA samples in pancreatic cancer appears as a valuable strategy for the diagnosis of pancreatic adenocarcinomas.

Topics: Acute-Phase Proteins; Adenocarcinoma; Biomarkers, Tumor; Biopsy, Fine-Needle; Cell Line, Tumor; Colonic Neoplasms; Endosonography; Gene Expression Profiling; Gene Expression Regulation, Neoplastic; Genes, Neoplasm; Humans; Keratin-7; Keratins; Leukemia; Lipocalin-2; Lipocalins; Pancreatic Neoplasms; Prognosis; Proto-Oncogene Proteins; Reproducibility of Results; Reverse Transcriptase Polymerase Chain Reaction; Tissue Plasminogen Activator

Prostate basal cell lesions can have architectural and cytologic atypia that mimic prostate adenocarcinoma. Immunohistochemical stains for basal cell markers are most helpful in the differential diagnosis. All of the published studies show basal cell lesions are positive for basal cell keratins, whereas adenocarcinoma is negative for both. We reported two cases of prostate basal cell lesions with negative basal cell keratin expression by immunohistochemistry.. We reported the histologic and immunohistochemical profiles of two cases of basal cell lesions of the prostate.. Histologically, both cases were highly suspicious for prostate adenocarcinoma with infiltrative growth pattern and significant nuclear atypia. The atypical glands in both cases were negative for basal cell keratins. However, both lesions were positive for another basal cell marker, p63, confirming that they were basal cells in origin, rather than prostate adenocarcinoma.. Prostate basal cell lesions can occasionally be negative for basal cell keratins by immunohistochemistry and therefore may be misdiagnosed as prostate adenocarcinoma. We recommend using both p63 and basal cell keratins simultaneously in the workup of atypical prostate lesions to avoid such a misdiagnosis.

Topics: Adenocarcinoma; Aged, 80 and over; Biomarkers, Tumor; Cell Nucleus; Diagnosis, Differential; Humans; Immunohistochemistry; Keratins; Male; Membrane Proteins; Middle Aged; Prostate; Prostatic Hyperplasia; Prostatic Neoplasms

To evaluate the efficacy of postoperative serial assay of carcinoembryonic antigen (CEA) and cytokeratins for the detection of recurrent disease in patients with colorectal adenocarcinoma after radical surgery.. Between 1993 and 2000, 120 patients with colorectal adenocarcinoma underwent radical surgery in the Department of Surgical Gastroenterology, Federal University of Sao Paulo-Escola Paulista de Medicina, Sao Paulo, Brazil. Periodic postoperative evaluation was performed by assaying markers in peripheral serum, colonoscopy and imaging examination. Presence of CEA was detected using the Delfia method with 5 microg/L threshold, and cytokeratins using the LIA-mat TPA-M Prolifigen method with 72 U/L threshold.. In the first postoperative year, patients without recurrent disease had normal levels of CEA (1.5 +/- 0.9 microg/L) and monoclonal tissue polypeptide antigen-M (TPA-M, 64.4 +/- 47.8 U/L), while patients with recurrences had high levels of CEA (6.9 +/- 9.8 microg/L, P < 0.01) and TPA-M (192.2 +/- 328.8 U/L, P < 0.05). During the second postoperative year, patients without tumor recurrence had normal levels of CEA (2.0 +/- 1.8 microg/L) and TPA-M (50.8 +/- 38.4 U/L), while patients with recurrence had high levels of CEA (66.3 +/- 130.8 microg/L, P < 0.01) and TPA-M (442.7 +/- 652.8 U/L, P < 0.05). The mean follow-up time was 22.3 mo. There was recurrence in 23 cases. Five reoperations were performed without achieving radical excision. Rises in tumor marker levels preceded identification of recurrences: CEA in seven (30%) and TPA-M in eleven individuals (48%).. Intensive follow-up by serial assay of CEA and cytokeratins allows early detection of colorectal neoplasm recurrence.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Biomarkers, Tumor; Carcinoembryonic Antigen; Colorectal Neoplasms; Female; Follow-Up Studies; Humans; Keratins; Male; Middle Aged; Neoplasm Recurrence, Local; Predictive Value of Tests

Rectal tissue is often seen in needle biopsies of the prostate gland. On rare occasion distorted rectal glands can mimic prostatic adenocarcinoma, an issue not previously addressed in the peer-reviewed literature. We evaluated 16 prostate needle biopsies received in consultation where the submitting pathologist questioned whether a focus of rectal tissue was prostate cancer. In addition to the distorted architecture, features mimicking prostate cancer included: (1) blue-tinged intraluminal mucinous secretions in 10 cases (63%), (2) prominent nucleoli in 6 cases (37%), (3) mitotic activity in 6 cases (37%), (4) extracellular mucin in 5 cases (31%), and (5) adenomatous changes of the rectal tissue in 1 case (6%). Immunohistochemical results further mimicked prostate cancer with negative stains for the basal cell markers high-molecular weight cytokeratin (n=6) and p63 (n=4), and positive stains for racemase in 4 of 5 biopsies. Diagnostic clues to recognizing that these foci were distorted rectal fragments were the presence of (1) lamina propria in 12 cases (75%), (2) rectal tissue located on a detached fragment of tissue in 10 biopsies (63%), (3) associated inflammation in 10 cases (63%), (4) goblet cells in 7 cases (44%), and (5) muscularis propria in 6 cases (37%). In 2 cases, there was negative staining for prostate specific antigen (PSA) and in 1 case negative staining for cytokeratin 7 and positivity for cytokeratin 20. Rectal glands are associated with many of the classical features of prostate cancer, and immunohistochemistry may be misleading. Recognition of these features mimicking prostate cancer and awareness of other findings that are diagnostic of rectal tissue on biopsy can prevent a misdiagnosis of atypical prostate glands or prostate cancer.

Topics: Adenocarcinoma; Biomarkers, Tumor; Biopsy, Needle; Diagnosis, Differential; Diagnostic Errors; Humans; Intestinal Mucosa; Keratins; Male; Mucins; Prostate-Specific Antigen; Prostatic Neoplasms; Racemases and Epimerases; Rectum

Macropathologic types of gallbladder cancer are mostly polyp type, intumescent type, and cauliflower form lump. Its histological types include well or poorly differentiated adenocarcinoma, mucinous adenocarcinoma, and undifferentiated cancer. This research was to explore the clinicopathologic features of gallbladder adenocarcinoma with marked stromal fibrosis.. Pathology of 19 cases of gallbladder adenocarcinoma with marked stromal fibrosis was observed using a light microscopy and SP immunohistochemistry. Clinicopathologic features of 19 patients were analyzed.. Most of the patients had long-term history of cholecystitis gallbladder calculus. B ultrasound showed that the gallbladder wall was irregularly thickened or presented nodosity. Observed with naked eyes, gallbladder adenocarcinoma with marked stromal fibrosis did not form cancer nodule and extrude into the gallbladder lumen, the gallbladder wall showed regional thickening, a few cases showed diffuse irregular thickening. Observed under a light microscope, the adenocarcinoma cells were mostly arranged as single layers, seldom arranged as multiple layers, and formed adenoid structures with different sizes, various shapes, and irregular arrangement; the nuclei were heterogenic with haryomitosis presented in a few cases; inflammatory cells were infiltrated in hyperplastic fibrous connective tissue of some cases. According to immune phenotyping, CK (AE1/AE3), CK (AE1), CK7 (OV-TL12/30), CK8 (C51), CK18 (Dc-10), CK19 (RCK108), and EMA (Mc-5) showed strong expression, CEA (COL-1), CK20 (Ks20. 4), and MUC-5AC (CLH2) showed moderate expression, and MUC-2 (B306. 1) showed weak expression; CK17 (E3) showed focal expression.. The clinical manifestation, macropathologic type, histological characteristics of gallbladder adenocarcinoma with stromal fibrosis are different from other types of adenocarcinoma. Its genesis may be related to chronic cholecystitis: long-term inflammation causes regional hyperplasia and heterogeneity of the gland body, lead to focal or regional thickening of the gallbladder wall, and result in gallbladder adenocarcinoma with stromal fibrosis finally.

Topics: Adenocarcinoma; Adult; Aged; Cholecystectomy; Diagnosis, Differential; Female; Fibrosis; Follow-Up Studies; Gallbladder; Gallbladder Neoplasms; Humans; Immunohistochemistry; Immunophenotyping; Keratins; Male; Middle Aged

The diagnosis of invasive adenocarcinoma of the prostate is often difficult in needle prostatic cores, where, additionally, the assessment of the presence of basal cells has demonstrated to be of paramount importance. Currently, the immunohistochemical expression of 34betaE12 antigen and p63 protein are the most utilized markers. In our study, we analyzed comparatively the expression of 34betaE12, p63, bcl-2 and alpha-methylacyl-CoA racemase in order to evaluate the usefulness of bcl-2 as a new marker of the basal cells in prostatic pathology.. This study comprises radical prostatectomy specimens from 48 patients which were studied in order to determine the lack of staining of basal cells in invasive tumor areas together with the expression of racemase. Likewise, the presence of basal cells in areas of atrophy, hyperplasia, adenosis, and high-grade prostatic intraepithelial neoplasia (PIN) was also examined. Within the areas of adenosis and PIN a discontinuous pattern of basal cell expression was found in some cases. In 2 out of 48 cases (4,2%) of invasive carcinoma a weak bcl-2 expression without a basal cell distribution was found. Moreover, the expression of bcl-2 in the stromal lymphocytes appeared to be essential as an internal positive control of the technique.. In addition to classical markers, we demonstrated the diagnostic value of bcl-2 as a new basal cell marker.

Topics: Adenocarcinoma; Biomarkers, Tumor; Epithelial Cells; Humans; Keratins; Lymphocytes; Male; Membrane Proteins; Neoplasm Proteins; Prostatectomy; Prostatic Neoplasms; Proto-Oncogene Proteins c-bcl-2; Racemases and Epimerases; Stromal Cells

Mucosal ablation and endoscopic mucosal resection have been proposed as alternatives to surgical resection as therapy for intramucosal adenocarcinoma (IMC) of the esophagus. Acceptance of these alternative therapies requires an understanding of the clinical biology of IMC and the results of surgical resection modified for treatment of early disease.. Retrospective review of 78 patients (65 men, 13 women; median age 66 years) with IMC who were treated with progressively less-extensive surgical resections (ie, en bloc, transhiatal, and vagal-sparing esophagectomy) from 1987 to 2005.. The tumor was located in a visible segment of Barrett's esophagus in 65 (83%) and in cardia intestinal metaplasia in 13 (17%). A visible lesion was present in 53 (68%) and in all but 4 the lesion was cancer. In those patients with visible Barrett's, the tumor was within 3 cm of the gastroesophageal junction in 66% and within 1 cm in 37%. Esophagectomy was en bloc in 23, transhiatal in 31, vagal-sparing in 20, and transthoracic in 4. Operative mortality was 2.6%. Vagal-sparing esophagectomy had less morbidity, a shorter hospital stay, and no mortality. Of the patients who had en bloc resection, a median of 41 nodes were removed. One patient had one lymph node metastasis on hematoxylin and eosin staining and two others, normal on hematoxylin and eosin staining, had micrometastases on immunohistochemistry. Actuarial survival at 5 years was 88% and was similar for all types of resections. Two patients died from systemic metastases and seven from noncancer causes.. IMC occurred in cardia intestinal metaplasia and in Barrett's esophagus. Two-thirds of patients with IMC had a visible lesion. Most tumors occurred near the gastroesophageal junction. Node metastases were uncommon, questioning the need for lymphadenectomy. A vagal-sparing technique had less morbidity than other forms of resection and no mortality. Survival after all types of resection was similar. Outcomes of endoscopic techniques should be compared with this benchmark.

Topics: Adenocarcinoma; Aged; Biomarkers, Tumor; Biopsy; Esophageal Neoplasms; Esophagectomy; Esophagoscopy; Female; Follow-Up Studies; Humans; Immunohistochemistry; Intestinal Mucosa; Keratins; Male; Middle Aged; Retrospective Studies; Treatment Outcome

Sentinel lymph node (SLN) mapping has become a cornerstone of oncologic surgery because it is a proven method for identifying nodal disease in melanoma and breast cancer. In addition, it can ameliorate the surgical morbidity secondary to lymphadenectomy. However, experience with SLN mapping for carcinoma of the colon and other visceral malignancies is limited. This study represents an update to our initial pilot experience with SLN mapping for carcinoma of the colon. Consenting patients over the age of 18 diagnosed with adenocarcinoma of the colon were included in this study. At the time of operation, 1 to 2 mL of isosulfan blue was injected with a 25-gauge needle into the subserosa at 4 sites around the edge of the palpable tumor. The SLN was identified visually and excised followed by a standard lymphadenectomy and surgical resection. SLNs were evaluated by standard hematoxylin and eosin (H&E) evaluation as well as immunohistochemical (IHC) techniques for carcinoembryonic antigen and cytokeratin if the H&E was negative. Sixty-nine patients underwent SLN mapping. A SLN was identified in 93 per cent (64 of 69) of patients. Nodal metastases were identified in 38 per cent (26 of 69) of patients overall. In 5 patients, the only positive node identified was the SLN, 2 of which were positive by IHC criteria alone. Therefore, 3 per cent (2 of 69) of patients were upstaged by SLN mapping. This technique was 100 per cent specific while being 46 per cent sensitive. Fourteen patients had false-negative SLNs. Metastasis to regional lymph nodes remains the key prognostic factor for colon cancer. SLN mapping is feasible for colon cancer and can identify a subset of patients who could benefit from adjuvant chemotherapy. Although SLN mapping did not alter the surgical management of colon cancer, it does make possible a more focused and cost-effective pathologic evaluation of nodal disease. We do not suggest routine utilization of SLN mapping for colon cancer, but we believe that the data supports proceeding with a national trial.

Topics: Adenocarcinoma; Aged; Body Mass Index; Carcinoembryonic Antigen; Colectomy; Colonic Neoplasms; Coloring Agents; False Negative Reactions; Feasibility Studies; Female; Fluorescent Dyes; Humans; Keratins; Lymph Node Excision; Lymphatic Metastasis; Male; Neoplasm Staging; Pilot Projects; Rosaniline Dyes; Sensitivity and Specificity; Sentinel Lymph Node Biopsy

Coordinate expression profiles for cytokeratins 7 and 20 (CK7 and CK20) are useful for distinguishing certain types of adenocarcinomas but use for distinction of primary and secondary mucinous tumors in the ovary is limited due to the existence of a number of tumor types exhibiting overlapping CK7/CK20 immunoprofiles; the use of staining distribution patterns in the distinction of tumors with shared profiles has not been evaluated in detail. We report analysis of both coordinate expression profiles and staining distribution in 179 rigorously classified mucinous tumors in the ovary, including 53 primary tumors [35 atypical proliferative (borderline) mucinous tumors of gastrointestinal type and 18 invasive mucinous carcinomas] and 126 secondary tumors [28 colorectal adenocarcinomas, 54 appendiceal tumors (23 adenocarcinomas, 31 low-grade adenomatous mucinous tumors associated with pseudomyxoma peritonei), 14 pancreatic adenocarcinomas, 8 endocervical adenocarcinomas, 5 gastric adenocarcinomas, 4 gallbladder/biliary tract adenocarcinomas, and 13 adenocarcinomas of unknown primary sites). A CK7+/CK20+ immunoprofile was the most common profile in primary ovarian tumors (74%), upper gastrointestinal tract tumors (78%), and endocervical tumors (88%) but was occasionally observed in lower intestinal tract tumors (colorectal: 11%; appendiceal: 13% of low-grade tumors, 35% of carcinomas). A CK7-/CK20+ immunoprofile was the most common profile in lower intestinal tract tumors (79%) and was uncommon in upper gastrointestinal tract tumors (9%), rarely seen in primary ovarian tumors (4%), and not seen in endocervical tumors. A CK7+/CK20- profile was observed in some primary ovarian (23%), upper gastrointestinal tract (13%), and endocervical tumors (13%) but not in lower intestinal tract tumors. For CK7+ tumors, staining distribution was very frequently diffuse (>50% of tumors cells positive) in primary ovarian, upper gastrointestinal tract, and endocervical tumors, whereas staining distribution was often focal (<50% of tumors cells positive) when present in colorectal and appendiceal carcinomas but not in low-grade appendiceal tumors. For CK20+ tumors, staining distribution was variable but often focal in primary ovarian tumors and nonlower intestinal tract tumors, whereas the pattern was almost always diffuse in lower intestinal tract tumors. Immunohistochemical staining distribution can supplement CK7/CK20 coordinate expression profiles to distinguish subsets of prim

Topics: Adenocarcinoma; Adenocarcinoma, Mucinous; Coloring Agents; Female; Gastrointestinal Neoplasms; Humans; Immunohistochemistry; Keratin-20; Keratin-7; Keratins; Ovarian Neoplasms; Pseudomyxoma Peritonei; Uterine Cervical Neoplasms

Approximately 30% of patients with lymph node (LN)-negative colorectal carcinoma (CRC) die of tumor recurrence, which can be related to the presence of tumor cells in LNs not detected by conventional histopathologic analysis. However, the prognostic significance of occult cancer cells still remains uncertain. We evaluated the incidence and the prognostic significance of occult cancer cells in LNs from 395 consecutive patients with curatively resected stage IIA CRC using immunohistochemistry for cytokeratin 20. Immunostained tumor cells were categorized as micrometastases (MCMs) or isolated tumor cells (ITCs) according to the American Joint Committee on Cancer criteria. The detection rates were compared with the clinicopathologic characteristics of the patients and with cancer-specific survival. The median follow-up time was 128 months. Micrometastases were detected in 39 patients (9.9%), whereas ITCs were found in 112 (28.4%), for an overall frequency of 38.2%. None of the clinicopathologic parameters examined was correlated with the presence of occult cancer cells. Patients with ITCs and those with negative LNs showed a similar survival rate (77.7% and 78.3%, respectively), whereas patients with MCMs had a lower survival rate (64.1%). At the univariate analysis, MCMs, tumor growth pattern, extent of tumor spread, and Crohn's-like lymphoid reaction influenced the survival rate significantly. Nevertheless, at the multivariate analysis, only the pattern of tumor growth and the extent of tumor spread were independent prognostic factors. The detection of immunostained tumor cells in the LNs of patients with stage IIA CRC occurs relatively frequently but has no significant effect on prognosis.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Biomarkers, Tumor; Colorectal Neoplasms; Female; Fluorescent Antibody Technique, Direct; Humans; Immunoenzyme Techniques; Incidence; Keratin-20; Keratins; Lymph Nodes; Lymphatic Metastasis; Male; Middle Aged; Neoplasm Staging; Prognosis; Survival Rate

Topics: Adenocarcinoma; Biomarkers, Tumor; Biopsy; Carcinoma, Signet Ring Cell; Diagnosis, Differential; Diagnostic Errors; Endometrial Neoplasms; Endometrium; Female; Humans; Keratins

Survival results of stage II colorectal cancer patients have led to major efforts to identify the subset of patients at risk for disease relapse and adjuvant therapies benefit. Immunohistochemistry is being explored to detect undetectable microscopic lymph node micrometastases.. A retrospective analysis of a 105 consecutive stage II colorectal cancer patients was performed. Two four-micres sections were obtained from each lymph node. These slides were stained with AE1-AE3 monoclonal antibodies against cytoskeleton using DAKO EnVision visualization system. Micrometastases were identified either as isolated cells or as well-defined glandular cell clusters with cytoplasm but not the nucleus stained with cytoskeleton antibodies.. 665 lymph nodes isolated from 105 patients were analyzed. Lymph nodes micrometastases were assessed in 26 out of the 105 patients. 42 (6.3%) out of 665 lymph nodes were infiltrated. Most of these metastases consisted of isolated cell cluster localized in marginal and interfollicular sinus of lymph nodes. The relapse rate was 23.1% among the patients with immunohistochemical detected lymph node micrometastes and 20.3% for the patients without lymph node involvement. This result lacked statistical significance (p = 0.759).. AE1/AE3 lymph node immunohistochemical staining in stage II colorectal cancer is an interesting biological phenomenon but it fails to identify patients at higher risk of relapse who deserve a more aggressive adjuvant attitude.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Colorectal Neoplasms; Female; Humans; Immunohistochemistry; Keratins; Lymph Nodes; Lymphatic Metastasis; Male; Middle Aged; Neoplasm Staging; Prognosis; Retrospective Studies; Survival Analysis

This study was designed to examine whether disseminated tumor cells in peripheral blood of locally advanced rectal cancer patients undergoing preoperative chemoradiation have the potential to serve as a marker for therapy response. Studies suggest that patients with advanced rectal cancer who respond to preoperative chemoradiation most likely benefit from this treatment.. From advanced rectal cancer patients undergoing preoperative chemoradiation, peripheral blood was obtained at defined times: before, during, and after chemoradiation and during surgery. Patients were divided into histopathologic responders (ypT0-T2) and nonresponders (ypT3-T4). Cytokeratin 20 and carcinoembryonic antigen reverse transcriptase-polymerase chain reaction were performed to detect disseminated tumor cells. A blood sample was deemed positive for disseminated tumor cells if both carcinoembryonic antigen and cytokeratin 20 were detected.. The overall population (n = 26) showed a positivity rate of 32 percent for disseminated tumor cells before initiation of chemoradiation. Of the responders (n = 8), 63 percent were positive for disseminated tumor cells before chemoradiation, whereas only 18 percent of nonresponders (n = 18) were positive (P = 0.026). From initiation of chemoradiation to the end of surgery, a significant decrease was seen in tumor cell positivity in the blood of responders (P = 0.042). Moreover, the responders represented a trend toward a decrease in tumor cell positivity during chemoradiation (P = 0.079). In contrast, there were no noticeable alterations within the treatment course in nonresponders.. This prospective proof of principle study demonstrates that locally advanced rectal cancer with preoperative chemoradiation shows different biologic behavior in terms of tumor cell dissemination in peripheral blood when therapy responders compared with nonresponders.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Antineoplastic Agents; Biomarkers, Tumor; Carcinoembryonic Antigen; Combined Modality Therapy; Feasibility Studies; Female; Humans; Keratins; Male; Middle Aged; Preoperative Care; Prospective Studies; Radiotherapy; Rectal Neoplasms; Reverse Transcriptase Polymerase Chain Reaction

To further develop the hen as a model of ovarian adenocarcinoma, we have studied normal and neoplastic ovaries as well as cultured cells from the ovarian surface epithelium (OSE). We characterized the OSE layer of the hen for specific histologic markers and evaluated these markers on tumor tissue. We also isolated and characterized the epithelial cells that are the likely source of the ovarian tumors of the hen. The surface epithelium of normal ovaries demonstrated positive staining for cytokeratin, proliferating cell nuclear antigen (PCNA), progesterone receptor (PR), and negative staining for vimentin. Ovarian tumors demonstrated positive cytokeratin, PCNA, PR, and weak vimentin staining in the gland-like areas. Epithelial cell cultures were obtained by an explant method utilizing small and large yellow follicles. These cells were positive for cytokeratin and negative for vimentin on Days 1 and 3. By Day 10, cytokeratin protein expression was less for some cells, and vimentin expression was weakly present in some cells. Expression of PCNA was observed at Days 1 and 3, but was rarely seen in cells cultured for 10 days. Expression of PR was observed on Day 10 after 24-hr estrogen treatment. Epithelial cells grew slowly in culture, and were susceptible to trypsin or other dissociation treatments.

Topics: Adenocarcinoma; Animals; Biomarkers; Chickens; Disease Models, Animal; Epithelial Cells; Female; Keratins; Ovarian Neoplasms; Ovary; Proliferating Cell Nuclear Antigen; Receptors, Progesterone; Reference Values; Vimentin

Rhabdoid tumor is a distinct entity reported in renal and extrarenal sites. Malignant tumors of various types may have rhabdoid phenotype. There are eight case reports of carcinomas of thyroid with rhabdoid phenotype. All of these cases, except two, have been reported in middle-aged women (42-72 yr) and have had an aggressive clinical course with death occurring within few months to 4 yr after diagnosis. We report a case of poorly differentiated carcinoma of the thyroid with rhabdoid phenotype in a 22-yr-old male. The rhabdoid cells were immunopositive for thyroid transcription factor-1, vimentin, epithelial membrane antigen, and focally for cytokeratin. Synaptophysin, chromogranin, thyroglobulin, carcinoembryonic antigen, smooth muscle actin, myogenin, and desmin were all negative. To the best of our knowledge this is the ninth case report of carcinoma of the thyroid with rhabdoid phenotype. This case, unlike the previous reported cases, has certain unusual features including presentation in a young male, the absence of either follicular/papillary differentiation, and immunohistochemical profile of the rhabdoid cells.

Topics: Adenocarcinoma; Adult; Biomarkers, Tumor; Fatal Outcome; Humans; Keratins; Male; Mucin-1; Nuclear Proteins; Rhabdoid Tumor; Thyroid Neoplasms; Thyroid Nuclear Factor 1; Transcription Factors; Vimentin

Six cases of an unusual variant of primary pulmonary adenocarcinoma resembling colorectal and sinonasal adenocarcinoma are presented. Pulmonary intestinal-type adenocarcinoma occurs in elderly Caucasians and is associated with a histology characteristic of colorectal/enteric adenocarcinoma: a garland-like architecture with a 'gland in gland' periphery, central 'dirty' necrosis, and elongated stratified columnar cells, lacking significant goblet or signet ring differentiation. While a resemblance to intestinal adenocarcinoma by light microscopy is present, immunohistochemical studies comparing these carcinomas with metastatic colorectal adenocarcinoma clearly show a respiratory phenotype with the neoplastic cells expressing thyroid transcription factor-1 and cytokeratin 7 to the exclusion of cytokeratin 20, and failing to express CDX-2. Stains for a variety of epithelial mucins (MUC1, MUC2, MUC5AC) also support this observation. The differential diagnosis with other pulmonary adenocarcinomas, especially those with mucinous differentiation, is discussed.

Topics: Adenocarcinoma; Aged; Aged, 80 and over; CDX2 Transcription Factor; Cell Differentiation; Colonic Neoplasms; Female; Homeodomain Proteins; Humans; Immunohistochemistry; Intermediate Filament Proteins; Keratin-20; Keratin-7; Keratins; Lung Neoplasms; Male; Middle Aged; Mucin 5AC; Mucin-1; Mucin-2; Mucins; Nuclear Proteins; Thyroid Nuclear Factor 1; Trans-Activators; Transcription Factors

Staging of gastric carcinoma depends on exact lymph node status. However, very small lymph nodes can easily be missed during routine examination as they are obscured by the surrounding adipose tissue. The purpose of the present study was to verify the usefulness of a lymph node revealing solution (LNRS) in gastric cancer and compare its accuracy concerning the detection of lymph node metastases to immunostaining with cytokeratin antibodies. A total of 11 consecutive patients underwent standardized D2 gastrectomy for primary gastric adenocarcinoma. Non-fixed, the entire surgical specimen was searched for lymph nodes by palpation and visualization. The remaining tissue was immersed for 24 h in LNRS. The lymph nodes stood out as white chalky nodules on the background of yellow fat. All identified lymph nodes were resected and analyzed histologically. In 5 patients with pN0 status, immunostaining of the lymph nodes was performed using cytokeratin-specific antibodies. The conventional preparation of lymph nodes from the unfixed tissue yielded a total of 452 lymph nodes (mean 41.1 lymph nodes/patient; range, 26 to 56), and 201 of them had a pN0 status. After fixation using LNRS, 138 additional nodes could be detected (mean 12.5 lymph nodes/patient; range, 3 to 21), and 70 of them with a pN0 status. The detection rate of extremely small lymph nodes (<3 mm) increased by 27% compared to the conventional preparation technique (p=0.0017). After application of the LNRS lymph node analysis, it was not necessary to change the UICC node (N) stage in any cases. Additionally, we performed immunostaining in 5 specimens with pN0 status. In one patient, 10 micrometastases/disseminated tumour cells were detected. Thus, after immunohistochemical re-evaluation, one patient had to be upstaged pN(i+). By performing standardized LAD systematically and detailed lymph node preparation by the pathologist, a routine application of the LNRS method in gastric carcinoma is not recommended. Immunohistochemical techniques aid in identifying micrometastatic disease in lymph nodes missed in routine H&E staining in order to define the pN(i) status according to the TNM classification.

Topics: Acetic Acid; Adenocarcinoma; Ethanol; Ether; Formaldehyde; Humans; Immunohistochemistry; Keratins; Lymphatic Metastasis; Neoplasm Staging; Reproducibility of Results; Stomach Neoplasms

To evaluate the serum levels of cytokeratins and carcinoembryonic antigen (CEA) in diagnosis, staging and prognosis of patients with colorectal adenocarcinoma.. The sample consisted of 169 patients. One hundred blood donors formed the control group. Radical surgery was performed on 120 patients, with an average follow-up duration of 22.3 mo. Relapses occurred in 23 individuals after an average of 18.09 mo. CEA was assayed via the Delfia method with a limit of 5 ng/mL. Cytokeratins were assayed via the LIA-mat TPA-M Prolifigen method with a limit of 72 U/L.. In the diagnosis of patients with colorectal adenocarcinoma, CEA showed a sensitivity of 56%, a specificity of 95%, a positive predictive value of 94%, a negative predictive value of 50% and an accuracy of 76.8%. TPA-M had a sensitivity of 70%, a specificity of 96%, a positive predictive value of 97%, a negative predictive value of 66% and an accuracy of 93.6%. The elevation of one of the markers was shown to have a sensitivity of 76.9%, a specificity of 91%, a positive predictive value of 93.5%, a negative predictive value of 70% and an accuracy of 83.6%. There was no variation in the levels of the markers according to the degree of cell differentiation while there was an elevation in their concentrations in accordance with the increase in neoplastic dissemination. There was a statistically significant difference between the patients with stage IV lesions and those with stages I, II and III tumors. With regard to CEA, the average level was 14.2 ng/mL in patients with stage I lesions, 8.5 ng/mL in patients with stage II lesions, 8.0 ng/mL in patients with stage III lesions and 87.7 ng/mL in patients with stage IV lesions. In relation to TPA-M, the levels were 153.1 U/L in patients with stage I tumors, 106.5 U/L in patients with stage II tumors, 136.3 U/L in patients with stage III tumors and 464.3 U/L in patients with stage IV tumors. There was a statistical difference in patients with a high CEA level in relation to a shorter survival (P<0.05). However, there was no correlation between patients with high TPA-M levels and prognostic indices of patients undergoing radical surgery.. Cytokeratins demonstrate a greater sensitivity than CEA in the diagnosis of colorectal adenocarcinoma. There is an increase in the sensitivity of the markers with tumor dissemination. Cytokeratins cannot identify the worse prognosis in patients undergoing radical surgery. Cytokeratins constitute an advance in the direction of a perfect tumor marker in the treatment of patients with colorectal cancer.

Topics: Adenocarcinoma; Adolescent; Adult; Biomarkers, Tumor; Carcinoembryonic Antigen; Colorectal Neoplasms; Female; Follow-Up Studies; Humans; Keratins; Male; Middle Aged; Neoplasm Staging; Prognosis; Survival Rate

We present 51 cases of primary small cell carcinoma of the bladder in a clinicopathological study with emphasis on features that aid in the initial recognition and diagnosis of small cell carcinoma of the bladder.. The patients were 40 men and 11 women between the ages of 39 and 87 years (mean age 67 years). Clinical data were available in 41 cases. The most common symptomatology was haematuria in 63% of the patients while dysuria was present in 12%. Thirty-eight patients were caucasians; seven patients were Hispanics; two patients were Asian; one patient was African-American; in the three additional patients no racial information was obtained. Biopsy material was obtained in all of the patients. Cystectomy was performed in 20 patients. At diagnosis, clinical stage was as follows: stage I in two (5%), stage II in 18 (44%), stage III in 10 (24%), and stage IV in 11 (27%). Histologically, urothelial carcinoma was present in 70% of the cases, adenocarcinoma in 8%, and squamous cell carcinoma in 10% of the cases. Small cell carcinoma was the only histology present in only 12% of the cases studied. Immunohistochemical studies using chromogranin, synaptophysin and chromogranin were positive in 30-70% of the cases.. The present study highlights the unusual phenomenon of pure small cell carcinoma of the bladder and its association with other non-small cell carcinomas in that anatomical location. In addition, the study highlights the different modalities employed to treat patients in whom there is a component of small cell carcinoma of the bladder.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Biomarkers; Carcinoma, Small Cell; Carcinoma, Squamous Cell; Chromogranins; Disease-Free Survival; Female; Follow-Up Studies; Humans; Immunohistochemistry; Keratins; Male; Middle Aged; Neoplasm Staging; Synaptophysin; Urinary Bladder Neoplasms

To investigate the incidence of direct hematogenous spread of cancer cells in patients with early-stage breast cancer by studying the presence of occult tumor cytokeratin-19 (CK-19) mRNA(+) cells in the peripheral blood in relation to the status of sentinel (SLNs) and (ALNs) axillary lymph nodes.. SLNs and ALNs from 111 patients with operable stage I-II breast adenocarcinoma were evaluated for the presence of tumor cells by hematoxylin-eosin (H&E) staining and, if negative, by immunohistochemistry (IHC) using an anti-CK-19 antibody. Peripheral blood was also analyzed for the presence of CK-19 mRNA(+) cells by nested RT-PCR, before the initiation of adjuvant treatment and in CK-19 mRNA(+) patients following the completion of adjuvant chemotherapy and hormonal treatment.. After both H&E staining and IHC analysis, 29 (26%) patients were ALN negative (N0). In 78 (70%) patients H&E staining and in four (3.6%) IHC analysis revealed tumors cells, and these patients were considered as ALN positive (N+). Peripheral blood CK-19 mRNA(+) cells were detected in nine (31%) out of 29 N0 and in 31 (38%) out of 82 N + patients (P=0.5) before any adjuvant treatment. Adjuvant chemotherapy and hormone treatment resulted in the disappearance of the CK-19 mRNA(+) cells in all N0 patients and in 15 out of 31 N + patients. After a median follow-up of 40 months, all the N0 CK-19 mRNA(+) patients were relapse-free whereas four (13%) N + CK-19 mRNA(+) patients had relapsed.. Direct hematogenous dissemination of occult tumor cells may occur in a substantial proportion of patients with early-stage breast cancer. The prognostic implication of the detection of these cells requires long follow-up periods and further studies.

Topics: Adenocarcinoma; Adult; Aged; Antibodies; Axilla; Biomarkers, Tumor; Breast Neoplasms; Chemotherapy, Adjuvant; Female; Humans; Immunohistochemistry; Keratins; Lymphatic Metastasis; Middle Aged; Neoplasm Staging; Neoplastic Cells, Circulating; Prognosis; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Sentinel Lymph Node Biopsy

Adenomatoid tumors are relatively uncommon benign neoplasms of mesothelial origin, usually occurring in the male and female genital tracts. Rare extragenital adenomatoid tumors have been identified in the adrenal glands, heart, mesentery, pleura, and lymph nodes. In the adrenal gland, adenomatoid tumors may pose a diagnostic challenge. The differential diagnosis includes adrenocortical carcinoma and metastatic carcinoma, especially signet ring cell carcinoma. Because of its glandular pattern, an adenomatoid tumor may be confused with an adenocarcinoma. We present 3 cases of adrenal adenomatoid tumors, including one with a concurrent large hemorrhagic vascular adrenal cyst. The adenomatoid tumors were unilateral, appeared solid and white, and varied from 1.7 to 4.2 cm in diameter. They occurred in 3 male patients aged 33, 33, and 46 years. One patient presented with abdominal pain due to the presence of a concurrent large adrenal cyst. The tumor was an incidental radiological finding in another case and was discovered during the course of a workup for hypertension in the third case. The light microscopic appearances were consistent with those of typical adenomatoid tumors. Immunohistochemical stains for calretinin and cytokeratin 5/6 were positive, confirming the tumors' mesothelial origin. Ultrastructural studies performed in 2 cases revealed microvilli and desmosomes. Follow-up showed no evidence of recurrence or metastasis. In our experience, the key to the diagnosis of this rare benign tumor is to consider adenomatoid tumor in the differential diagnosis of any glandular tumor occurring in the adrenal gland.

Topics: Adenocarcinoma; Adenoma; Adrenal Gland Neoplasms; Adult; Biomarkers, Tumor; Calbindin 2; Carcinoma, Signet Ring Cell; Cysts; Diagnosis, Differential; Humans; Immunohistochemistry; Keratins; Male; Middle Aged; S100 Calcium Binding Protein G; Treatment Outcome

Epithelioid angiosarcoma of the bone is a rare tumor and is a diagnostic challenge. Here we present an autopsy case of a 62-year-old man with multifocal osteolytic lesions in the extremities and the pelvis. The initial diagnosis of a tibial biopsy was poorly differentiated adenocarcinoma. On the occasion of autopsy, a fungating thrombotic nodule was found at the anterior wall of the right atrium, and small hemorrhagic infarcts with tumor thrombi were found in the lung. Histologically, the above lesions were identical to the former tibial biopsy and they showed large eosinophilic epithelioid cells with irregular ovoid nuclei and prominent eosinophilic nucleoli. Rare intracytoplasmic lumina were identified. Immunohistochemically, the tumor cells were positive for cytokeratins (CAM5.2 and AE1/AE3), CD31, factor VIII-related antigen, and vimentin. This case showed angiotropic spread of the tumor only to the right atrium and the lung, with no solid mass in other organs. Multicentric epithelioid angiosarcoma of the bone is a pitfall in pathological diagnoses, especially if a strong radiological impression of metastatic carcinoma is provided. Therefore, pathologists should be aware of this rare variant.

Topics: Adenocarcinoma; Biomarkers, Tumor; Biopsy; Bone Neoplasms; Diagnosis, Differential; Epithelioid Cells; Fatal Outcome; Hemangiosarcoma; Humans; Immunohistochemistry; Keratins; Male; Middle Aged; Neoplasm Invasiveness; Neoplasms, Multiple Primary; Platelet Endothelial Cell Adhesion Molecule-1; Tibia; Vimentin; von Willebrand Factor

This study was designed to evaluate molecular markers for the detection of micrometastasis in esophageal adenocarcinoma, define algorithms to distinguish positive from benign lymph nodes and to validate these findings in an independent tissue set and in patients with p(N0) esophageal adenocarcinoma.. Potential markers were identified through literature and database searches. All markers were analyzed by quantitative reverse transcription (QRT)-PCR on a limited set of primary tumors and benign lymph nodes. Selected markers were further evaluated on a larger tissue set and classification algorithms were generated for individual markers and combinations. Algorithms were statistically validated internally as well as externally on an independent set of lymph nodes. Selected markers were then used to identify occult disease in lymph nodes from 34 patients with p(N0) esophageal adenocarcinoma.. Thirty-nine markers were evaluated, six underwent further analysis and five were analyzed in the external validation study. Two markers provided perfect classification in both the screening and validation sets, although parametric bootstrap analysis estimated 2% to 3% optimism in the observed classification accuracy. Several marker combinations also gave perfect classification in the observed data sets, and estimates of optimism were lower, implying more robust classification than with individual markers alone. Five of thirty-four patients with esophageal adenocarcinoma had positive nodes by multimarker QRT-PCR analysis and disease-free survival was significantly worse in these patients (P = 0.0023).. We have identified novel QRT-PCR markers for the detection of occult lymph node disease in patients with esophageal adenocarcinoma. The objective nature of QRT-PCR results, and the ability to detect occult metastases, make this an attractive alternative to routine pathology.

Topics: Adenocarcinoma; Antigens, Neoplasm; Biomarkers, Tumor; Carcinoembryonic Antigen; Cell Adhesion Molecules; Epithelial Cell Adhesion Molecule; Esophageal Neoplasms; Humans; Immunohistochemistry; Intermediate Filament Proteins; Keratin-20; Keratin-7; Keratins; Lymph Nodes; Lymphatic Metastasis; Microfilament Proteins; Neoplasm Staging; Predictive Value of Tests; Reverse Transcriptase Polymerase Chain Reaction; RNA, Neoplasm; Survival Analysis

Paraffin-embedded sections of various adenocarcinomas (13 colonic, 11 mucinous ovarian, 5 serous ovarian, 8 pancreatic, 6 ampullary, 12 gastric, 5 esophageal, 10 endometrial, 29 breast, and 55 lung) and 29 additional lung carcinomas (nonadenocarcinomas) were immunostained with antibodies to CDX2 protein, cytokeratin 7 (CK7), and cytokeratin 20 (CK20). The 84 lung carcinomas were also stained with antibody to thyroid transcription factor-1 (TTF-1). All colorectal and most ovarian mucinous carcinomas were strongly and diffusely immunoreactive for CDX2. Esophageal, gastric, and ampullary adenocarcinomas showed variable immunoreactivity for CDX2. All breast, nonmucinous ovarian, and most endometrial and pancreatic adenocarcinomas showed no immunoreactivity for CDX2. CK7 and CK20 expression was similar to previous reports. Ten of 84 primary lung carcinomas (12%) were immunoreactive for CDX2 expression. Of these, 5 (4 adenocarcinomas and 1 large cell carcinoma) were reactive for TTF-1. Gene expression profiling data--available for 32 of these 84 tumors--showed CDX2 gene expression in 7 of 8 (88%) CDX2 immunoreactive tumors whereas only 1 of 24 (4%) tumors negative for CDX2 immunoreactivity showed CDX2 gene expression. The authors conclude that CDX2 is a relatively specific marker for tumors with intestinal differentiation, with the caveat that its expression can be seen in primary large cell and adenocarcinomas of the lung and mucinous carcinomas of the ovary.

Topics: Adenocarcinoma; Biomarkers, Tumor; CDX2 Transcription Factor; Gastrointestinal Neoplasms; Homeodomain Proteins; Humans; Immunohistochemistry; Intermediate Filament Proteins; Keratin-20; Keratin-7; Keratins; Lung Neoplasms

Pancreatobiliary and ampulla of Vater adenocarcinomas frequently metastasize to regional lymph nodes, liver, or lung and are difficult to diagnose because they lack specific immunohistochemical markers. We studied the expression of cytokeratin 7 (CK7), cytokeratin 17 (CK17), cytokeratin 20 (CK20), CDX2, mucin 1 (MUC1), mucin 2 (MUC2), and mucin 5AC (MUC5AC) in 46 cases of pancreatic ductal carcinoma, 18 ampulla of Vater adenocarcinomas, and 24 intrahepatic cholangiocarcinomas. The expression of MUC1 and CK17 was restricted to pancreatic ductal carcinoma (41 of 46, 89%; 38 of 46, 83%, respectively), the ampullary carcinoma of pancreatobiliary origin (6 of 6, 100%; 5 of 6, 83%, respectively), and intrahepatic cholangiocarcinoma (20 of 24, 83%; 17 of 24, 71%, respectively). More than 50% of cases of pancreatobiliary adenocarcinomas showed diffuse cytoplasmic CK17 positivity. In contrast, less than 5% cases (8 of 184) of extra-pancreatobiliary nonmucinous adenocarcinomas expressed CK17, and only 3 of them showed diffuse CK17 positivity. The expression of MUC2 and CDX2 was restricted to the intestinal, mucinous, and signet-ring cell-type adenocarcinomas of duodenal papillary origin (9 of 11, 82%; 11 of 11, 100%, respectively). MUC2 was rarely expressed in pancreatic ductal carcinoma (1 of 46, 2%) and was negative in the ampullary carcinoma of pancreatobiliary origin and in intrahepatic cholangiocarcinoma. A heterogeneous CDX2 staining pattern was seen in 1 of 6 cases of the ampullary carcinoma of pancreatobiliary origin (17%), 5 of 24 intrahepatic cholangiocarcinomas (21%), and 10 of 46 (22%) pancreatic ductal carcinomas. In contrast, all 11 cases of the intestinal, mucinous, and signet-ring cell-type adenocarcinomas of duodenal papillary origin showed homogeneous CDX2 nuclear positivity. We concluded that CK17 is a useful marker in separating pancreatobiliary adenocarcinomas from extra-pancreatobiliary nonmucinous adenocarcinomas, including adenocarcinomas from the colon, breast, gynecologic organs, stomach, lung, prostate, thyroid, kidney, and adrenal gland, and malignant mesothelioma. MUC1+/CK17+ can be used as positive markers for pancreatic ductal carcinomas, the ampullary carcinoma of pancreatobiliary origin, and cholangiocarcinomas with positive predictive values of 76%, 83%, and 58%, respectively. MUC2+/CDX2+ can be used as positive markers for the intestinal-type adenocarcinoma of duodenal papillary origin with a positive predictive value of 82%.

Topics: Adenocarcinoma; Ampulla of Vater; Bile Ducts, Intrahepatic; Biomarkers, Tumor; Carcinoma, Pancreatic Ductal; CDX2 Transcription Factor; Cholangiocarcinoma; Common Bile Duct Neoplasms; Female; Homeodomain Proteins; Humans; Immunohistochemistry; Keratins; Male; Mucins; Neoplasm Proteins; Pancreatic Neoplasms

In human breast cancer, overexpression of the protooncogene MET is strongly associated with poor prognosis and high risk of metastasis. It stands out as a reliable prognostic indicator of survival and defines a set of tumors exclusive of those that express HER2 or hormone receptors. Studies have shown that overexpression of mutant forms of MET cause cancer in mice. However, MET mutations have not been found in human breast cancer, and the consequences of overexpression of normal MET are unknown. To investigate the role of MET and other putative oncogenes in breast cancer, we developed an experimental system that involves retroviral delivery of genes into primary mammary epithelial cells, followed by transplantation of the transduced cells into mammary fat pads. Using this approach, we found that overexpression of wild-type MET leads to the development of nonprogressive neoplasms. The lesions progressed to mammary adenocarcinoma when a second protooncogene, MYC, was overexpressed, indicating that MET and MYC cooperate in mammary tumorigenesis. Both the nonprogressive neoplasms and adenocarcinomas display characteristics consistent with transformation and expansion of mammary progenitor cells. The approach described here should provide a useful model with which to efficiently test effects of various genes on tumor development in the breast.

Topics: Adenocarcinoma; Animals; Cells, Cultured; Epithelial Cells; Female; Gene Expression; Genes, myc; Genetic Vectors; Humans; Keratins; Mammary Glands, Animal; Mammary Neoplasms, Experimental; Mice; Mice, Transgenic; Mutation; Proto-Oncogene Proteins c-met; Proto-Oncogenes; Retroviridae; Stem Cells; Transduction, Genetic

The ability to use archival tissue to test externally valid hypotheses of carcinogenesis is dependent on the availability of population-based samples of cancer tissue. Tissue microarrays (TMAs) provide an efficient format for developing population-based samples of tissue. A TMA was constructed consisting of archival tissue from patients diagnosed with invasive colorectal cancer in the state of Hawaii in 1995. The population representativeness of the TMA was evaluated by comparing patient and clinical characteristics of TMA cases to that of all cases of colorectal carcinoma diagnosed statewide in 1995. Cytokeratin 20 (CK20) and cytokeratin 7 (CK7) immunohistochemistry was used to validate the utility of the TMA, and the expression of these proteins was correlated with patient and tumor characteristics. The TMA comprised tissue specimens from 286 patients representing 47% of all invasive cases diagnosed statewide in 1995. TMA cases were comparable to all invasive colorectal cases statewide with respect to age, sex, race/ethnicity, anatomic site, and survival. There were some differences between TMA cases and all cases with respect to tumor stage, histological classification, and treatment. There were significant differences in the relative expression of CK20 and CK7 proteins between malignant and normal tissues and by tumor stage. Advanced cancers were more likely to have CK20+/cytokeratin 7+ (CK7+) profiles than early-stage cancers, which were predominantly CK20+/cytokeratin 7- (CK7-). CK7+ expression was not correlated with anatomic location of carcinomas. This well-characterized TMA offers a powerful tool for testing hypotheses regarding colorectal carcinogenesis, including the identification of potential markers of neoplastic development and progression.

Topics: Adenocarcinoma; Aged; Aged, 80 and over; Colorectal Neoplasms; Female; Humans; Immunohistochemistry; Intermediate Filament Proteins; Keratin-20; Keratin-7; Keratins; Male; Middle Aged; Mortality; Neoplasm Invasiveness; Neoplasm Staging; Protein Array Analysis; Survival Rate

Lymph node infarction is a spontaneous coagulative necrosis of the affected lymph node and is frequently associated with concurrent and subsequent malignant lymphoma. However, this phenomenon appears to be rarely associated with metastatic carcinomas. Here, we report on the histopathologic and immunohistologic findings of three cases showing lymph node infarction in the regional lymph node associated with metastatic colorectal adenocarcinoma. Histologically, coagulative necrosis of metastatic carcinoma was surrounded by a thick rim of granuloma consisting of histiocytes with or without epithelioid features, foamy cells, and a small number of lymphocytes. The immunohistochemical study of the coagulative necrosis demonstrated that cytokeratins (AEI/AE3 and CAM5.2) and carcinoembryonic antigen (CEA) were well preserved in all three cases. However, compared with viable tumor tissues, only a few tumor cells were positive for epithelial membrane antigen. Using formalin-fixed and paraffin-embedded tissues, immunostaining for cytokeratins and CEA of the lymph node containing necrotic carcinoma may provide clinically valuable information.

Topics: Adenocarcinoma; Adult; Aged; Biomarkers, Tumor; Carcinoembryonic Antigen; Colorectal Neoplasms; Female; Humans; Immunohistochemistry; Infarction; Keratins; Lymph Nodes; Lymphatic Diseases; Lymphatic Metastasis; Middle Aged; Necrosis

A case of primary hepatic carcinoma is reported, which occurred in a 24-year-old woman with a 10-year history of oral contraceptive use, and demonstrated unique morphologic and immunohistochemical features. The tumor was located in the left hepatic lobe, measured 14 cm at its widest, and showed histologic heterogeneity. The neoplastic cells were mostly arranged in trabecular and pseudoglandular growth patterns simulating hepatocellular carcinoma; however, in focal areas, small cystic, organoid and tubular patterns predominated. Immunohistochemical stains showed a phenotype consistent with biliary differentiation (positive staining for cytokeratin 7, cytokeratin 19, carcinoembryonic antigen and CA 19-9 antigen). The tumor cells were negative for markers that would be suggestive of hepatocytic or neuroendocrine differentiation. Interestingly, they were positive for inhibin, a protein that is known to be expressed in sex cord-stromal tumors of the ovary, trophoblastic neoplasms and adrenal cortical tumors, but not in hepatic tumors. However, no definite evidence of gonadal stromal, trophoblastic, or adrenocortical differentiation was identified on extensive immunohistochemical work-up. In conclusion, this unique case may represent a rare variant of cholangiocarcinoma expressing inhibin.

Topics: Abdominal Pain; Adenocarcinoma; Adult; CA-19-9 Antigen; Carcinoembryonic Antigen; Contraceptives, Oral, Combined; Female; Humans; Immunohistochemistry; Inhibins; Keratin-7; Keratins; Liver Neoplasms; Magnetic Resonance Imaging; Nausea; Tomography, X-Ray Computed; Vomiting

We report a 73-year-old male patient with leptomeningeal metastasis from urinary bladder adenocarcinoma. He was presented with prominent hyperactive delirium during the course of the disease. Meningeal carcinomatosis was detected 5 days before his death, but the primary site of the malignant tumor could not be determined. Necropsy revealed leptomeningeal infiltration of many adenocarcinoma cells that covered the cerebrum. The leptomeninges of the right middle frontal gyrus, superior temporal gyrus, precentral gyrus and inferior parietal lobe were most severely affected by tumor cell infiltration. Cerebral edema was found to extensively cover the basal part of the temporal lobe. In the cerebrum, tumor cells were clustered in the perivascular spaces and had invaded localized areas of the frontal lobe. Vascular cell adhesion molecule (VCAM)-1 expression was detected in the small vessels of the cerebral upper cortical layers and of temporal subcortical u-fibers. Numerous astrocytes positive for cytokeratin AE1/AE3 were found in the frontal and temporal lobes. Meningeal carcinomatosis from urinary bladder adenocarcinoma is extremely rare and up-regulation of the adhesion molecules in the meningeal adenocarcinoma was confirmed.

Topics: Adenocarcinoma; Aged; Astrocytes; Fatal Outcome; Humans; Immunohistochemistry; Keratins; Magnetic Resonance Imaging; Male; Meningeal Neoplasms; Urinary Bladder Neoplasms; Vascular Cell Adhesion Molecule-1

An adenocarcinoma in the seminal vesicles of a 15-month-old male Wistar rat from a 30-month inhalation study is described. The rat was killed because of cachexia, apathy and a large palpable mass in the abdominal cavity. Macroscopic examination of the abdominal cavity revealed a 3.8 cm x 3.2 cm yellow-grey to pink mass, firm to soft in consistency. The cut section revealed cystic spaces. Histologically, the mass consisted of epithelial cells arranged in glandular and solid patterns with abundant amounts of connective tissue. Epithelial tumour cells were round-to-cylindrical with round-to-oval basophilic nuclei and one or two prominent nucleoli and a distinct eosinophilic cytoplasm. The glandular structure contained clusters of macrophages in their lumen with eosinophilic cytoplasm and indented nuclei. Extensive necrosis and reactive inflammation were present. The histological features of the small nodules in the pancreas and on the surface of the liver, rectum and urinary bladder resembled those of the primary tumour in the seminal vesicles. Based on these criteria, the neoplasm (mass) was diagnosed as an adenocarcinoma of the seminal vesicles. The immunohistological examination confirmed the diagnosis, i.e. immunostaining was positive for cytokeratins (4, 7, 14, 15, 18, and 19), vimentin, PCNA, and ED(1).

Topics: Adenocarcinoma; Animals; Fatal Outcome; Genital Neoplasms, Male; Immunohistochemistry; Keratins; Male; Rats; Rats, Wistar; Rodent Diseases; Seminal Vesicles

Squamous metaplasia of endometrium is mostly manifested by morules or nodules of benign nonkeratinizing squamous cells intimately mixed with benign or malignant endometrial glands. It has been described with low-grade adenocarcinoma of the endometrium, as well as with various benign conditions, including hyperplasia, chronic endometritis, and endometrial polyps. However, extensive plaquelike, keratinizing squamous change is distinctly uncommon. To our knowledge, we describe the first case of extensive benign squamous keratinization with underlying endometrial adenocarcinoma.

Topics: Adenocarcinoma; Aged; Endometrial Neoplasms; Female; Gynecologic Surgical Procedures; Humans; Ichthyosis; Keratins; Uterus

CDX2 is a transcription factor expressed by intestinal epithelium. It is considered as a sensitive marker for a colorectal or-less frequently-gastric origin of adenocarcinomas. The pattern of coordinated expression of cytokeratin (CK) 7 and CK20 is also useful for the diagnosis of the origin of metastatic adenocarcinomas. Expression of CDX2, CK7 and CK20 was investigated in 14 cases of sinonasal intestinal-type adenocarcinoma (SIA), a particular tumor with an enteric-cell-type appearance. Formalin-fixed, paraffin embedded tissue sections were immunostained with monoclonal antibodies using the biotin-labeled streptavidin technique. All of the cases expressed CDX2, being stained 50 to 100% of the tumor cells (mean: 87.2%). CK7 positivity was detected in 8 cases (57.1%), with the staining of 10 to 100% of cells (mean: 65.6%), and CK20 was found in all the tumors (10 to 100% of cells; mean: 78.8%). The histologic resemblance between SIA and colorectal adenocarcinoma is reinforced by the expression of CDX2 and CK20, which are virtually constant in both neoplasms. CDX2 seems to be a marker for cellular phenotype better than an indicator of the origin of adenocarcinomas. CK7 is expressed in SIA less frequently than in colonic adenocarcinoma, but with a rate similar to the subset of rectal tumors, making the differential diagnosis between the two neoplasms difficult.

Topics: Adenocarcinoma; Aged; Aged, 80 and over; CDX2 Transcription Factor; Homeodomain Proteins; Humans; Immunohistochemistry; Intermediate Filament Proteins; Intestinal Neoplasms; Keratin-20; Keratin-7; Keratins; Middle Aged

To characterize the cellular component in pleomorphic adenoma (PA) that undergoes malignant transformation in carcinoma ex pleomorphic adenoma (CXPA).. A panel of antibodies against cytoskeletal proteins was applied in 16 cases of CXPA: intracapsular carcinoma (five cases), minimally invasive (four cases) and frankly invasive (seven cases). The CXPAs were classified into two main groups according to their predominant cellular component as detected by the panel of antibodies: (i) carcinomas with only epithelial differentiation (75% of the cases), and (ii) carcinomas with a myoepithelial component (25%). CXPA with only epithelial differentiation showed two types of malignant areas in the part of the tumour that was confined by the PA capsule: (i) intraductal carcinoma areas characterized by ductal structures containing both benign myoepithelial cells positive for alpha-smooth muscle actin (alpha-SMA), vimentin and cytokeratin (CK)14 and proliferating atypical luminal cells reactive for CK7, CK8 and CK19, and (ii) carcinoma areas composed only of epithelial cells reactive for CK7, CK8 and CK19. In the latter, the cells presented morphological and immunohistochemical characteristics similar to those found in areas of invasive carcinoma outside the PA capsule. CXPAs with a myoepithelial component were composed mainly or exclusively of cells that expressed vimentin and alpha-SMA. In this group, ductal structures reminiscent of PA filled by malignant cells were not identified.. Most CXPAs consist only of epithelial cells that have an immunoprofile comparable to ductal luminal cells of PA. These malignant luminal cells arise in the duct-like structures as intraductal carcinoma and probably only at this early stage of development should the lesion be considered as a non-invasive carcinoma.

Topics: Actins; Adenocarcinoma; Adenoma, Pleomorphic; Adolescent; Adult; Aged; Aged, 80 and over; Biomarkers, Tumor; Disease Progression; Female; Humans; Immunohistochemistry; Keratin-14; Keratin-7; Keratins; Male; Middle Aged; Muscle, Smooth; Vimentin

Identification of early invasion in vulvar intraepithelial neoplasia 3 (VIN 3) and cervical intraepithelial neoplasia 3 (CIN 3) may be difficult with the use of routine hematoxylin-eosin staining. Presence of obscuring inflammation and tangential tissue sectioning are the most common diagnostic pitfalls.. To examine the utility of double immunostaining for cytokeratin-collagen IV or cytokeratin-laminin in the detection of early invasion in VIN 3 and CIN 3.. The study group consisted of 10 cases of "VIN 3, suspicious for invasion" and 10 cases of "CIN 3, suspicious for invasion." The negative control group consisted of VIN 3 (n = 15) and CIN 3 (n = 10). The positive control group consisted of cases of invasive vulvar carcinoma (n = 11) and invasive cervical carcinoma (n = 25). All cases were double immunostained for cytokeratin and collagen IV and, in a separate reaction, for cytokeratin and laminin. The continuity of the basement membrane and the presence of stromal invasion were assessed in the stained sections.. The staining for collagen IV and laminin yielded identical results. A well-defined, continuous basement membrane was visualized in all cases of VIN 3 and CIN 3. A discontinuous or absent basement membrane was observed around the malignant cells on the invasive tumor front in all cases of vulvar and cervical carcinoma. In 2 of 10 cases of VIN 3, suspicious for invasion and in 4 of 10 cases of CIN 3, suspicious for invasion definitive foci of microinvasion were identified with the use of double immunostaining. A well-defined, continuous basement membrane was present in the remaining cases "suspicious for invasion.". Double immunostaining for cytokeratin- collagen IV or cytokeratin-laminin is useful for evaluation of early invasion in equivocal cases of VIN 3 and CIN 3.

Topics: Adenocarcinoma; Basement Membrane; Biomarkers, Tumor; Collagen Type IV; Female; Humans; Keratins; Laminin; Neoplasm Invasiveness; Retrospective Studies; Uterine Cervical Dysplasia; Uterine Cervical Neoplasms; Vulvar Neoplasms

To study diagnostic significance of blood serum cancer antigens levels in patients who subsequently develop pulmonary cancer (PC) and gastrointestinal cancer (GIC).. ELISA was used to study expression of tumor antigens (CEA, NSE, CA19-9, CA242, AFP) in the blood serum of 27 PC and 31 GIC patients; 22 patients with lymphatic tumors and 32 patients with pulmonary and gastrointestinal inflammation served control. After removal of the tumor the same antigens including cytokeratines (CK) and differentiated leukocytic markers were studied immunocytochemically in the tumor cells with relevant monoclonal antibodies.. Sera of patients with verified afterwards cancer contained elevated concentrations of the antigens: NSE and CEA in PC, CA19-9, CA242 in GIC. The expression of these antigens including CK was found also in tumor cells of these patients. Atypical cells of lymphatic tumors had hemopoietic markers in the absence of CK. In inflammation and in lymphatic tumors, tumor antigens levels remained normal.. The test for tumor antigens levels in the serum may be used for early (preoperative) diagnosis of cancer, especially in tumors with difficult access or if they are asymptomatic.

Topics: Adenocarcinoma; Adult; Aged; Antibodies, Monoclonal; Antigens, Neoplasm; Early Diagnosis; Enzyme-Linked Immunosorbent Assay; Female; Gastrointestinal Neoplasms; Humans; Immunohistochemistry; Keratins; Lung Neoplasms; Male; Middle Aged

This study was designed to consider the cytomorphological spectrum, differential diagnosis, and the role of ancillary studies in small-cell tumors of the liver. Three independent pathologists reviewed cytological slides from 91 cases of small-cell tumors of the liver. The results were compared with the findings of three recently published studies (Cytopathology 11 (2000) 262-267; Diagn Cytopathol 19 (1998) 29-32; and Acta Cytol 40 (1996) 937-947). The role of immunohistochemistry in reaching timely and specific diagnoses was also examined. The diagnostic categories included 44 cases of metastatic small-cell undifferentiated carcinoma, 15 cases of metastatic neuroendocrine carcinoma, 10 cases of metastatic adenocarcinoma, 7 cases of malignant lymphoma, 4 cases of hepatocellular carcinoma with small-cell features, 2 cases of cholangiocarcinoma, 1 case of poorly differentiated carcinoma, and 8 cases of rare tumors including granulosa cell tumor (2 cases), sarcoma (4 cases), malignant melanoma with small-cell features (1 case), and meningioma with small-cell features (1 case). Metastatic granulosa cell-tumor, metastatic melanoma, and metastatic meningioma should be included in the differential diagnoses of small-cell malignancies found in the liver.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Biopsy, Fine-Needle; Carcinoma, Hepatocellular; Carcinoma, Neuroendocrine; Carcinoma, Small Cell; Cholangiocarcinoma; Diagnosis, Differential; Female; Humans; Immunohistochemistry; Keratins; Liver; Liver Neoplasms; Lymphoma; Male; Middle Aged; Mucin-1; Review Literature as Topic; S100 Proteins; Vimentin

It is sometimes difficult to distinguish between cardia cancer and oesophageal cancer.. To evaluate whether cytokeratin (CK) expression of the tumour can be of value in differentiating between the two tumour types.. Consecutive patients with a malignant tumour in the oesophagus or stomach were recruited. Biopsy specimens were taken for routine haematoxylin and eosin staining. One tissue block with representative tissue was selected for immunohistochemical staining (CK7 and CK20).. Endoscopically located adenocarcinoma of the oesophagus was present in 84 patients (64 men, 20 women; mean age, 68 years; range, 44-91). Cancer located primarily in the gastric cardia was present in 63 patients (42 men, 21 women; mean age, 68 years; range, 42-88). The histological diagnosis was metastasis from a primary tumour outside the oesophagus or stomach in 19 patients. The patients were divided into three groups for the immunohistochemical analysis. Patients in group A had definite oesophageal cancer, group B patients had a definite carcinoma located in the gastric cardia, and group C patients had an obstructing tumour distal in the oesophagus at the level of the diaphragm, which could not be passed with the endoscope. Paraffin wax embedded material was available from 122 patients for immunostaining and CK analysis. There was no significant difference in expression or distribution of CK7 or CK20 in the three groups of patients.. CK phenotyping cannot distinguish between cancer arising from a Barrett's oesophagus and carcinoma originating in the gastric cardia.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Barrett Esophagus; Biomarkers, Tumor; Carcinoma, Squamous Cell; Cardia; Diagnosis, Differential; Esophageal Neoplasms; Female; Humans; Keratins; Male; Middle Aged; Neoplasm Proteins; Precancerous Conditions; Stomach Neoplasms

To evaluate five serum tumor markers used alone or in combination for the diagnosis of lung cancer.. The level of five serum tumor markers: NSE, pro-GRP, CYFRA21-1, p53 antibody and CEA was detected by ELISA in 50 healthy adults, 170 lung cancer patients and 60 patients with respiratory infection.. The level of the five serum tumor markers in lung cancer patients was significantly higher than that of healthy adults and patients with respiratory infection (P < 0.01). The level of NSE and pro-GRP in patients with small-cell lung cancer was significantly higher than those of the other subtypes of lung cancer (P < 0.01); The level of CYFRA21-1 in patients with squamous-cell carcinoma was significantly higher than that of other subtypes (P < 0.01). The specificity of p53 antibody was 100% in diagnosing lung cancer and the sensitivity of NSE, pro-GRP was much higher for small-cell lung cancer than for other subtypes (P < 0.01); The same was observed in CYFRA21-1 for the diagnosis of squamous-cell carcinoma (P < 0.01). The sensitivity of the tumor markers in diagnosing lung cancer was significantly enhanced if used in combination (P < 0.01).. These five tumor markers are valuable auxiliary parameters in diagnosing lung cancer. The combination of NSE and pro-GRP is more appropriate than other combinations in diagnosing small-cell lung cancer; the combination of CYFRA21-1, CEA and p53 antibody is the most valuable combination for diagnosing non-small-cell lung cancer. p53 antibody has the highest specificity for diagnosing lung cancer; CYFRA21-1 is the most valuable parameter for diagnosing squamous carcinoma.

Topics: Adenocarcinoma; Antibodies, Neoplasm; Antigens, Neoplasm; Biomarkers, Tumor; Carcinoembryonic Antigen; Carcinoma, Squamous Cell; Female; Gastrin-Releasing Peptide; Humans; Keratin-19; Keratins; Lung Neoplasms; Male; Middle Aged; Phosphopyruvate Hydratase; Tumor Suppressor Protein p53

Topics: Adenocarcinoma; Aged; Aged, 80 and over; Carcinoma, Endometrioid; Female; Humans; Immunohistochemistry; Keratin-7; Keratins; Lung Neoplasms; Male; Middle Aged; Nuclear Proteins; Thyroid Nuclear Factor 1; Transcription Factors

To evaluate the clinical and prognostic significance of the tumor markers cytokeratin 19 fragment, carcinoembryonic antigen and neuron-specific enolase in lung cancer patients.. Serum levels of cytokeratin 19 fragment, carcinoembryonic antigen and neuron-specific enolase were measured using electrochemical luminescence immunoassay in 46 lung cancer patients. Serum levels of cytokeratin 19 fragment, carcinoembryonic antigen, and neuron-specific enolase higher than 3.6 ng/ml, 5.0 ng/ml and 13.0 ng/ml, respectively, were considered as elevated.. Cytokeratin 19 fragment, carcinoembryonic antigen, and neuron-specific enolase were elevated in 19.6%, 43.5%, and 63% of patients, respectively. Elevated levels of neuron-specific enolase were detected more frequently in smokers than in ex-smokers (p=0.003). Likewise preoperative levels of carcinoembryonic antigen (p=0.023) and neuron-specific enolase (p=0.007) were statistically higher in smokers than in ex-smokers. A significant correlation was detected between the level of cytokeratin 19 fragments and smoking cumulative exposure (r=0.542, p=0.037). The number of patients with elevated levels of cytokeratin 19 fragment and neuron-specific enolase was higher in more advanced disease than in early lung cancer (p=0.036 and p=0.036, respectively). Preoperative levels of cytokeratin 19 fragment (p=0.017 and p=0.016, respectively) and neuron-specific enolase (p=0.03 and p=0.006, respectively) were significantly associated with more advanced disease and tumor size, as well as tumor histology in non-small cell lung cancer (p=0.03 and p=0.016, respectively). Preoperative levels of cytokeratin 19 fragments were higher in squamous cell carcinoma than in adenocarcinoma (p=0.026). Elevated preoperative serum levels of cytokeratin 19 fragment predict a poor prognosis for lung cancer patients (p=0.007).. Alteration of serum tumor markers cytokeratin 19 fragment, carcinoembryonic antigen and neuron-specific enolase is associated with particular tumor histology, smoking habit, more advanced disease and poor prognosis.

Topics: Adenocarcinoma; Adult; Aged; Carcinoembryonic Antigen; Carcinoma, Non-Small-Cell Lung; Carcinoma, Squamous Cell; Female; Humans; Keratins; Lung; Lung Neoplasms; Male; Middle Aged; Neoplasm Staging; Phosphopyruvate Hydratase; Prognosis; Smoking

The entity of serrated adenoma of the colorectum was first proposed in 1990, and it was characterized as epithelial neoplasia combining the architectural features of a hyperplastic polyp with the cytological features of an adenoma. Over the past few years, various clinicopathological studies on serrated adenoma have been reported, but its histogenesis remains unclear. Recently the existence of a "serrated neoplasia pathway" leading to malignancy, which is different from the so-called adenoma-carcinoma sequence, has been discussed. Yao et al. reported that hyperplastic polyps and serrated adenomas share a common cell lineage with gastric differentiation. To clarify the existence of the serrated neoplasia pathway, we performed immunohistochemical staining of cytokeratin 7 (CK7) and cytokeratin 20 (CK20), which are commonly used to determine the primary site of a metastatic lesion, and we examined the pattern of CK7/CK20 expression in various colorectal lesions including 44 serrated adenomas, 25 hyperplastic polyps, 20 traditional adenomas, and 48 carcinomas. An obvious difference existed in the pattern of CK7/CK20 expression between the serrated lesions (hyperplastic polyps and serrated adenomas) and others. The majority of serrated adenomas and hyperplastic polyps presented a CK7+/CK20+ pattern, whereas most conventional adenomas and adenocarcinomas expressed CK7-/CK20+. Adenocarcinoma developing in serrated adenoma also presented a CK7+/CK20+ pattern. There are several reports that CK7 is a possible marker of transient dedifferentiation in the gastric carcinogenesis process. Taken together with the present results, a distinct pathway of colorectal carcinogenesis must exist, which is different from the adenoma-carcinoma sequence. CK7 is a possible marker for the serrated neoplasia pathway of colorectal carcinogenesis.

Topics: Adenocarcinoma; Adenoma; Adult; Aged; Aged, 80 and over; Biomarkers, Tumor; Cell Transformation, Neoplastic; Colonic Polyps; Colorectal Neoplasms; Female; Gene Expression Profiling; Humans; Immunohistochemistry; Intermediate Filament Proteins; Keratin-20; Keratin-7; Keratins; Male; Middle Aged

CYFRA21 - 1, a fragment of cytokeratin19, has been widely assessed as a serum marker of squamous malignancies. Previous studies using CYFRA21 - 1 and SCC-Antigen have shown mixed results but have indicated a better predictive prognostic value for SCC-Ag as compared to CYFRA21-1. The aim of our prospective, observational, pilot study was to evaluate the role of CYFRA21-1 and SCC-Ag in primary cervical carcinoma. Pre-operative serum CYFRA21-1 and SCC-Ag were measured (n = 14) in women with cervical carcinoma and correlated with staging, clinico-pathological parameters and prognostic data. Logistic regression analysis with CYFRA 21 - 1 test status (positive or negative) as a dependent variable showed that nodal metastases (p = 0.001) and lymphovascular space invasion (LVSI) (p = 0.005) were significant predictors, whereas stage and SCC-Ag levels were not significant. There was also no statistically significant correlation between SCC-Ag and CYFRA21-1 levels. If larger studies confirm these preliminary results, the option of laparoscopic surgical staging in patients with raised CYFRA21-1 levels could be considered.

Topics: Adenocarcinoma; Adult; Aged; Antigens, Neoplasm; Biomarkers, Tumor; Carcinoma, Adenosquamous; Carcinoma, Squamous Cell; Female; Humans; Keratin-19; Keratins; Lymphatic Metastasis; Middle Aged; Pilot Projects; Predictive Value of Tests; Prognosis; Prospective Studies; Serpins; Uterine Cervical Neoplasms

Hepatectomy and pancreatectomy are often associated with significant intraoperative blood loss leading to postoperative anemia, which has been demonstrated to lead to increased perioperative morbidity, a prolonged hospital stay, and decreased overall survival. Cancer has remained an absolute contraindication to autotransfusion because of the unproven concern about reinfusion of malignant cells. Thus, the aim of this study was to test for the presence of malignant cells in autotransfused filtered blood in patients undergoing major pancreatic and liver resection.. A prospective study of 20 consecutive patients evaluated the presence of malignant cells from autotransfusion filtered blood after resection by flow cytometric and immunohistochemical methods.. Ten patients underwent major hepatectomy for metastatic colorectal cancer, with a median blood loss of 500 mL (range, 200-700 mL). Three patients received a total of six units of packed red blood cells. Ten patients underwent pancreaticoduodenectomy for adenocarcinoma with a median blood loss of 400 mL (range, 200-1300 mL). Five patients received a total of nine units of packed red blood cells. Flow cytometry did not demonstrate the presence of any cytokeratin-positive carcinoma cells in filtered blood.. Intraoperative autotransfusion for major hepatectomy in metastatic colorectal cancer and pancreatectomy for adenocarcinoma is safe and should begin to be evaluated in a phase II study for efficacy.

Topics: Adenocarcinoma; Blood Loss, Surgical; Blood Transfusion, Autologous; Colorectal Neoplasms; Contraindications; Female; Flow Cytometry; Hemofiltration; Hepatectomy; Humans; Immunohistochemistry; Intraoperative Period; Keratins; Liver Neoplasms; Pancreatectomy; Pancreatic Neoplasms; Pancreaticoduodenectomy; Prospective Studies

A 6-year-old, spayed, female, domestic shorthair cat was presented for decreased activity. A nodular lesion was found in the skin extending into the subcutaneous tissue of the right abdominal flank. On lateral and ventrodorsal radiographs of the thorax, an opacity involving the entire right caudal lung lobe and pleural effusion were noted. Cytologic evaluation of cells in the thoracic fluid and in the mass revealed a population of atypical epipthelial cells with marked anisocytosis and high N:C ratios, organized in acinar-like clusters. Multinucleated cells and several mitotic figures were found. The cytologic interpretation was carcinoma. Because of the progressive severity of clinical signs, the cat was euthanized. Histologic evaluation of tissues obtained at necropsy indicated a bronchogenic adenocarcinoma in the lung, with metastasis to the skin of the right flank, but no involvement of the digits. Based on immunohistochemical stains, the neoplastic cells strongly co-expressed cytokeratin and vimentin, and were negative for S-100 and actin-specific antigen. Bronchogenic adenocarcinoma is an uncommon neoplasm in cats, and the digits are the most common sites of metastasis. This case was unusual in that the skin of the abdominal wall was the primary site of metastasis, with no involvement of the digits.

Topics: Adenocarcinoma; Animals; Carcinoma, Bronchogenic; Cat Diseases; Cats; Female; Immunohistochemistry; Keratins; Pleural Effusion, Malignant; Skin Neoplasms; Vimentin

Reported herein is a case of hepatocellular carcinoma (HCC) with unusual peritoneal dissemination masquerading as peritoneal mesothelioma. A 61-year-old man was clinically found to have multiple tumors in his abdominal cavity; peritonitis carcinomatosa was suspected. An autopsy revealed numerous tumors of various sizes in the abdominal serosa, omentum, and diaphragm. No signs of tumor, fibrosis, or cirrhosis were found in the liver, except for a small nodule in the hepatic triangular ligament. Histologically, the tumor cells proliferated in thick trabeculae or in sheets and formed a few canaliculi and tubules with homogenously brown contents in their lumina, which stained positively with Hall stain. Immunohistochemically, these tumors were positive for hepatocyte, alpha-fetoprotein (AFP) and low-molecular-weight cytokeratin; were focally positive for pan-cytokeratin and epithelial membrane antigen (EMA); and were negative for high-molecular-weight cytokeratin, vimentin, and calretinin. Carcinoembryonic antigen (CEA) produced a bile canalicular immunohistochemical staining pattern. Thus, the tumor was diagnosed as an HCC (Edmondson II type) of the triangular ligament with massive peritoneal dissemination. The origin of this tumor and its differential diagnosis (malignant mesothelioma, hepatoid adenocarcinoma, and hepatoid yolk sac tumor) are discussed.

Topics: Adenocarcinoma; alpha-Fetoproteins; Calbindin 2; Carcinoembryonic Antigen; Carcinoma, Hepatocellular; Diagnosis, Differential; Humans; Immunohistochemistry; Keratins; Liver Neoplasms; Male; Mesothelioma; Middle Aged; Mucin-1; Peritoneal Neoplasms; S100 Calcium Binding Protein G; Vimentin

Distinguishing between primary adenocarcinomas and secondary colonic adenocarcinomas of the urinary bladder is often difficult because they appear morphologically similar but invariably require different treatment strategies. The aim of the study was to define the utility of a limited immunohistochemical panel consisting of CDX-2, cytokeratins 7 (CK7) and 20 (CK20), and carcinoembryonic antigen (CEA) in differentiating primary from secondary bladder adenocarcinomas. Formalin-fixed, paraffin-embedded tissues from 8 primary bladder adenocarcinomas and 23 colorectal adenocarcinomas involving the bladder were included in the study. Statistical analysis was performed using the Fisher exact test. The majority (87.5%) of primary bladder adenocarcinomas were CDX-2 negative, and only one case of primary bladder adenocarcinoma was positive, while CDX-2 was strongly expressed in the nucleus of all cases of secondary (colonic) bladder tumor (P < 0.0005). Five cases (62.5%) of primary bladder adenocarcinoma and one case (4.3%) of secondary bladder tumor showed positive staining for CK7 (P = 0.002), whereas CK20 showed positive staining in five cases (62.5%) of primary bladder adenocarcinoma and in all the secondary bladder tumors (P = 0.012). All 23 secondary bladder tumors and 7 primary bladder adenocarcinomas (87.5%) expressed CEA (P = 0.25). These data demonstrate that a restricted immunohistochemical panel consisting of CDX-2, CK7, CK20, and CEA may be of use in differentiating primary bladder adenocarcinoma from secondary adenocarcinoma of colorectal origin.

Topics: Adenocarcinoma; Aged; Biomarkers, Tumor; Carcinoembryonic Antigen; CDX2 Transcription Factor; Colorectal Neoplasms; Diagnosis, Differential; Female; Homeodomain Proteins; Humans; Immunohistochemistry; Intermediate Filament Proteins; Keratin-20; Keratin-7; Keratins; Male; Trans-Activators; Urinary Bladder Neoplasms

Topics: Adenocarcinoma; Aged; alpha-Fetoproteins; Carcinoembryonic Antigen; Carcinoma, Hepatocellular; Cholecystectomy; Endosonography; Female; Gallbladder Neoplasms; Humans; Immunohistochemistry; Keratins; Liver; Lymph Node Excision; Neprilysin; Treatment Outcome

We discuss here five cases of epithelioid sarcoma (ES) with final diagnosis established after reexamination of initial findings. Problems with differential diagnosis of these neoplasms arise since their microscopic picture may simulate several other pathological conditions such as non-neoplastic granulomatous reactions, squamous cell carcinomas and adenocarcinomas, melanomas and soft tissue sarcomas with epithelioid component. Final ES diagnosis requires presence of cytokeratin, EMA and vimentin in neoplastic cells, as confirmed by immunohistochemical reactions. Differential diagnosis is also helped by concurrent cytology assessment that allows recognizing more easily such characteristic features as presence of plasmacytoid or spindle-shaped cells.

Topics: Adenocarcinoma; Adult; Aged; Antigens, CD34; Carcinoma, Squamous Cell; Diagnosis, Differential; Female; Granuloma; Humans; Immunohistochemistry; Keratins; Male; Melanoma; Middle Aged; Mucin-1; S100 Proteins; Sarcoma; Soft Tissue Neoplasms; Vimentin

Our understanding of cancer has largely come from the analysis of aberrations within the tumor cell population. Yet it is increasingly clear that the tumor microenvironment can significantly influence tumorigenesis. For example, the mesenchyme can support the growth of tumorigenic epithelium. However, whether fibroblasts are subject to genetic/epigenetic changes as a result of selective pressures conferred by oncogenic stress in the epithelium has not been experimentally assessed. Recent analyses of some human carcinomas have shown tumor-suppressor gene mutations within the stroma, suggesting that the interplay among multiple cell types can select for aberrations nonautonomously during tumor progression. We demonstrate that this indeed occurs in a mouse model of prostate cancer where epithelial cell cycle disruption via cell-specific inhibition of pRb function induces a paracrine p53 response that suppresses fibroblast proliferation in associated stroma. This interaction imposes strong selective pressure yielding a highly proliferative mesenchyme that has undergone p53 loss.

Topics: Actins; Adenocarcinoma; Animals; Antigens, Polyomavirus Transforming; Cell Proliferation; Connective Tissue; Disease Models, Animal; Epithelial Cells; Fibroblasts; Gene Deletion; Genotype; Keratin-8; Keratins; Loss of Heterozygosity; Male; Mice; Mice, Knockout; Mice, Transgenic; Models, Biological; Mutation; Paracrine Communication; Prostate; Prostatic Neoplasms; Retinoblastoma Protein; S100 Calcium-Binding Protein A4; S100 Proteins; Stromal Cells; Tumor Suppressor Protein p53

Aim of the work is to estimate the role of the metastases molecular signs (MMS) in paraaortal lymphatic nodes, revealed using combined molecular-biological method with application of K-RAS markers and cytokeratine 20 (CK20) for the survival prognostication in the pancreatic head cancer patients after performing pancreatoduodenal resection. Actuarial index of general survival of the patients with MMS in paraaortal lymphatic nodes was trustworthy lower than in patients without such a signs. The two-year survival index in patients without MMS was 60%, the survival mediana--32 mo. Any of the patients with MMS did not survive two years, the survival mediana was 13 mo.

Topics: Adenocarcinoma; Biomarkers, Tumor; Disease-Free Survival; Genes, ras; Humans; Keratin-20; Keratins; Lymphatic Metastasis; Mutation; Pancreatic Neoplasms; Pancreaticoduodenectomy; Polymorphism, Restriction Fragment Length; Reverse Transcriptase Polymerase Chain Reaction

Topics: Adenocarcinoma; Amputation, Surgical; Anal Canal; Anus Neoplasms; Carcinoma, Squamous Cell; Colostomy; Combined Modality Therapy; Female; Humans; Keratin-20; Keratin-7; Keratins; Middle Aged; Neoplasms, Second Primary

The absence of basal cell layer of prostatic acini containing high-molecular cytokeratin, which is immunohistochemically detected by monoclonal antibody 34betaE12, is an essential diagnostic characteristic of prostatic cancer. The absence of immunohistochemical reaction in 3 or more pseudoglandular structures of prostatic tissue indicates malignant process. The percentage of immunohistochemically completely negative glandular structures was determined by semiquantitative measurement in tissue specimens obtained by TRUS biopsy of the prostate, and it was correlated with serum PSA concentration and Gleason score. The increase of percentage of glandular prostatic formations completely negative to high-molecular cytokeratin detected by 34betaE12 led to simultaneous rise of mean value of Gleason prostatic cancer score (p < 0.001) as well as the average serum PSA concentration in subjects (p < 0.05).

Topics: Adenocarcinoma; Biopsy, Needle; Humans; Immunohistochemistry; Keratins; Male; Molecular Weight; Prostate; Prostate-Specific Antigen; Prostatic Neoplasms

To investigate the monoclonal antibody M30 for the assessment of apoptosis in colorectal tissues. Although Terminal deoxyribonucleotidyl transferase mediated nick end labelling (TUNEL) and in-situ end labelling (ISEL) are the methods most often used to demonstrate and quantify apoptosis in histological tissue sections, the interpretation and specificity of these techniques have been controversial. Immunohistochemistry using the monoclonal antibody M30 that recognizes caspase-cleaved cytokeratin 18 is considered to be a promising alternative but has yet to be validated against a generally accepted standard.. Paraffin sections of normal colonic mucosa (n = 30), normal mucosa obtained from resection margins from carcinomas (n = 30), colorectal adenomas (n = 84) and carcinomas (n = 40) were studied. Apoptosis of epithelial cells was assessed by M30 immunoreactivity and morphological criteria and expressed as a proportion of the total number of cells counted (apoptotic index). Mean apoptotic indices using M30 were 0.18 +/- 0.04% in normal mucosa, 0.42 +/- 0.04% in adenomas and 1.97 +/- 0.24% in carcinomas. Using morphological criteria, these indices were 0.23 +/- 0.03%, 0.62 +/- 0.06% and 1.78 +/- 0.19%, respectively. Apoptotic counts were higher in normal mucosa obtained from resection margins than in genuinely normal mucosa using the M30 antibody. Apoptotic indices obtained by M30 immunoreactivity and morphological criteria were positively correlated (r = 0.71, P < 0.01).. Assessment of apoptotic cells by M30 immunoreactivity correlates well with morphological criteria. Apoptotic indices increase in the course of the adenoma-carcinoma sequence. Apoptosis in normal mucosa obtained from resection margins differs from genuinely normal mucosa necessitating caution when interpreting studies of apoptosis in normal colonic mucosa. Our findings support the use of the M30 method in the study of apoptosis in colorectal tissues.

Topics: Adenocarcinoma; Adenoma; Adult; Aged; Aged, 80 and over; Antibodies, Monoclonal; Apoptosis; Cell Count; Colon; Colorectal Neoplasms; Female; Humans; Immunoenzyme Techniques; In Situ Nick-End Labeling; Intestinal Mucosa; Keratins; Male; Middle Aged

To report three cases of primary carcinoma of the neck arising in multilocular thymic cysts (MTC).. The patients were three men aged 47, 50 and 52 years who presented with a painless neck mass of several weeks' duration. The patients had no history of previous surgical procedures or of malignancy elsewhere. The tumours in all three patients were located on the right lateral side of the neck; all patients underwent complete surgical resection of the mass. Grossly, the tumours were cystic and measured between 20 and 30 mm in greatest diameter. Histologically, the tumours showed cyst walls lined by squamous epithelium. The cyst walls contained prominent germinal centres with lymphoid hyperplasia, cholesterol cleft granulomas, and scattered keratinized structures reminiscent of Hassall's corpuscles. In addition, a neoplastic cellular proliferation composed of round to oval cells arranged in sheets and originating from the lining of the cystic structures was present. The neoplastic cells showed moderate amounts of eosinophilic cytoplasm, round nuclei, and, in some areas, prominent nucleoli. Mitotic figures were easily found, and cellular pleomorphism was present in several areas. In two cases the tumours showed features of basaloid carcinoma of the thymus, while in one case the pattern was that of squamous cell carcinoma. Immunohistochemical studies for keratin showed a strong positive reaction in the tumour cells, while leucocyte common antigen strongly stained the lymphoid background. Follow-up information obtained in two patients showed them to be alive 6 months after initial diagnosis. One patient was lost to follow-up.. The cases described here represent an unusual variant of carcinoma arising in multilocular thymic cyst in the neck region.

Topics: Adenocarcinoma; Biomarkers, Tumor; Disease-Free Survival; Head and Neck Neoplasms; Humans; Immunohistochemistry; Keratins; Male; Mediastinal Cyst; Middle Aged

The human metastasis-associated protein 1 (MTA1) is a constituent of the nucleosome-remodelling and -deacetylation complex. Its expression has been correlated with the invasion and metastasis of epithelial neoplasms. To address the functional consequences of MTA1 expression in pancreatic carcinoma cells, we have established PANC-1 pancreatic carcinoma cells that stably express MTA1 as an enhanced green fluorescent fusion protein (EGFP-MTA1). Here, we demonstrate that heterologous expression of EGFP-MTA1 markedly enhanced the cellular motility and the invasive penetration of epithelial barriers by the cells. Expression of EGFP-MTA1 had no effect on substrate-independent growth, but reduced substrate-dependent cell proliferation. In addition, the organisation of the cytokeratin filament system and the localisation of the actin cytoskeleton-associated protein IQGAP1 were distinctly altered in EGFP-MTA1-expressing cells. These results indicate that enhanced expression of MTA1 promotes the acquisition of an invasive, metastatic phenotype, and thus enhances the malignancy of pancreatic adenocarcinoma cells by modulation of the cytoskeleton.

Topics: Adenocarcinoma; Cell Division; Cell Movement; Cytoskeleton; Gene Expression Regulation, Neoplastic; Histone Deacetylases; Humans; Keratins; Neoplasm Invasiveness; Neoplasm Metastasis; Pancreatic Neoplasms; Phenotype; Repressor Proteins; Trans-Activators; Tumor Cells, Cultured

Atypical glands on prostate needle biopsy with a negative 34betaE12 (cytokeratin 903; CK903) immunostain, indicating a lack of a basal cell layer, are typically diagnostic of prostate cancer. However, in certain cases a negative 34betaE12 immunostain in a small focus of atypical glands is still not convincing enough to make the diagnosis of cancer. This study is the first report to evaluate the incidence of prostate cancer on follow-up biopsy in individuals with this diagnosis. A total of 543 men who had prostate core biopsy specimens diagnosed as a small focus of atypical-appearing glands with a negative 34betaE12 immunostain between January 1, 1997 and December 31, 2000 were selected for study. Some 61% of these 543 individuals (n = 332) had undergone at least one follow-up biopsy procedure. Of these, 43% of repeat biopsy cases (n = 142) were diagnostic of prostate cancer. A total of 46 individuals had at least 2 follow-up biopsy procedures, with 48% of these (n = 22) being diagnosed as cancer. The Gleason grades of the detected carcinomas were broken down as follows: Gleason grade 3 + 2 = 5, 6%; grade 3 + 3 = 6, 86%; grade 3 + 4 = 7, 1%; grade 4 + 3 = 7, 4%; and grade 4 + 4 = 8, 3%. The median amount of time to the first follow-up biopsy was 79 days, with 52% of follow-up biopsies performed within 90 days. A negative 34betaE12 immunohistochemical stain in a small focus of atypical glands is not associated with an increased prediction of prostate cancer on follow-up biopsy (43%), compared with previously published data for "small focus of atypical glands" alone (approximately 45%). Because 48% of men with an initial negative biopsy and multiple follow-up biopsy procedures were found to have cancer, more than one repeat biopsy session or more extensive sampling on the first repeat biopsy procedure may be necessary to maximize the identification of cancer. This finding is similar to that found in men with atypical diagnoses in general, without a negative 34betaE12 immunohistochemical stain. Only half of all individuals with a diagnosis of 34betaE12-negative focus of atypical glands underwent repeat biopsy within 3 months. Urologists need to be educated as to the significance of an atypical diagnosis and the need for repeat biopsy. In a small focus of atypical glands on prostate biopsy, negative staining for 34betaE12 should not necessarily lead to a definitive malignant diagnosis in all cases, because almost half of these biopsies on follow-up sampling ar

Topics: Adenocarcinoma; Biomarkers, Tumor; Biopsy, Needle; Exocrine Glands; Follow-Up Studies; Humans; Keratins; Male; Prostate; Prostate-Specific Antigen; Prostatic Intraepithelial Neoplasia; Prostatic Neoplasms

From 1.5% to 9.0% of prostatic needle biopsy specimens disclose atypical small acinar proliferations (ASAPs) suggestive of malignancy, carrying an approximate 45% predictive value for cancer. We applied keratin 34 beta E12 and P504S monoclonal immunostains to 93 cases that were judged as ASAP after H&E staining alone. Forty-one ASAP foci survived recutting for both immunostains. Three urologic pathologists independently assigned post-keratin 34 beta E12 diagnoses of cancer, ASAP, high-grade prostatic intraepithelial neoplasia, or benign and then reviewed P504S slides and assigned final diagnoses. Eight foci (20%) were resolved unanimously after keratin 34 beta E12 staining; 18 (44%) were resolved by 1 or 2 evaluators and 29 (71%) by at least 1. According to whether post-keratin 34 beta E12 ASAP designation was given by 3, 2, or 1 evaluator(s), P504S immunostaining unanimously resolved an additional 5 (12%), 10 (24%), or 23 (56%) of 41 ASAP foci and cumulatively, 31 foci (76%). Among 35 men (excluding 6 with cancer in other cores of the original biopsy), these immunostains could have permitted cancer diagnosis in 11 (31%), without repeated biopsy. Thus, the consensus diagnosis rate improved from poor to good after supplementing 34 beta E12 immunostaining with P504S.

Topics: Adenocarcinoma; Antibodies, Monoclonal; Biomarkers, Tumor; Biopsy, Needle; Humans; Immunoenzyme Techniques; Keratins; Male; Prostate; Prostatic Neoplasms; Racemases and Epimerases; Reproducibility of Results

Topics: Adenocarcinoma; Aged; Antibodies, Monoclonal; Biomarkers, Tumor; Carcinoma, Transitional Cell; Diagnosis, Differential; Humans; Keratins; Male; Neoplasm Recurrence, Local; Prostatic Neoplasms; Urinary Bladder Neoplasms

On the basis of the heterogeneity of cytokeratins 7 and 20 expression in malignant epithelial tumors, the cytokeratin 7/20 immunophenotype has served as a useful diagnostic tool for discrimination of primary and/or metastatic carcinomas of unknown origin. However, the expression pattern of these cytokeratins in malignant salivary gland tumors has not been thoroughly studied. Our study material was composed of 84 malignant tumors of primary major or minor salivary gland origin. Nine histologic types of carcinoma were represented, including mucoepidermoid (26 cases), adenoid cystic (25), polymorphous low grade (11), salivary duct (8), acinic cell (4), ex mixed tumor (3), not otherwise specified (3), clear cell (2), and basal cell (2). In all, 13 cases of primary skin or mucosal squamous cell carcinoma with secondary salivary gland involvement were also examined. Immunoreactivity for cytokeratin 7 was evident in all malignant salivary gland tumors; the staining pattern was diffuse and strong in 62 cases, and focal and strong in 22 cases. In contrast, 78 cases were negative for cytokeratin 20, whereas only six cases (two mucoepidermoid, one adenoid cystic, and three salivary duct) displayed focal weak positivity. Overall, 92.9% of malignant salivary gland tumors were characterized by a cytokeratin 7 positive/20 negative immunoprofile, the remaining 7.1% of cases being positive for both cytokeratins. The latter phenotype was more common in salivary duct carcinomas (P< or =0.05). On the other hand, most squamous cell carcinomas (69%) were negative for both cytokeratins, while the remaining cases (31%) were negative for cytokeratin 20 and focally weakly positive for cytokeratin 7. We suggest that assessment of cytokeratin 7/20 immunoprofile may facilitate the differential diagnosis of (a) primary malignant salivary gland tumors from metastatic tumors, (b) metastatic salivary gland tumors, (c) primary salivary gland tumors, especially mucoepidermoid carcinomas, from squamous cell carcinomas, and (d) salivary duct carcinomas from other malignant salivary gland tumors.

Topics: Adenocarcinoma; Adolescent; Adult; Aged; Aged, 80 and over; Biomarkers, Tumor; Child; Child, Preschool; Female; Humans; Immunoenzyme Techniques; Intermediate Filament Proteins; Keratin-20; Keratin-7; Keratins; Male; Middle Aged; Salivary Gland Neoplasms

We investigated 27 pleomorphic carcinomas of the lung for exon 1 K-ras gene mutations using polymerase chain reaction-single-strand conformation polymophism analysis and direct sequencing. All pleomorphic carcinomas were biphasic, that is, composed of an adeno-, squamous- or large-cell-carcinomatous component associated with a spindle- and/or giant-cell component. Of 27 cases, six (22%) showed K-ras codon 12 mutations, which is a figure higher than that previously reported on in pure sarcoma-like pleomorphic carcinomas. Five tumors displayed the same mutation in both the epithelial and the sarcomatoid components, whereas in one tumor the mutation was restricted to the epithelial component. All mutations occurred in smokers, and were transversions, including GGT (glycine) to TGT (cysteine) change in two cases, to GCT (alanine) in two and to GTT (valine) in two. No significant relationships were found between the occurrence and type of mutations and patients' survival or any other clinicopathological variable, suggesting that K-ras mutations are early events in the development of these tumors. Our results indicate that most, though not all, biphasic pleomorphic carcinomas of the lung are monoclonal in origin, and that cigarette smoking may have a causative role in the development of K-ras alterations in these tumors, as all mutations are transversions.

Topics: Adenocarcinoma; Adult; Aged; Carcinoma, Large Cell; Carcinoma, Non-Small-Cell Lung; Carcinoma, Squamous Cell; Clone Cells; DNA Mutational Analysis; DNA, Neoplasm; Female; Genes, ras; Humans; Immunohistochemistry; Keratins; Lung Neoplasms; Male; Middle Aged; Mutation; Mutation, Missense; Polymerase Chain Reaction; Polymorphism, Single-Stranded Conformational; Smoking; Survival Analysis; Vimentin

Primary villoglandular adenocarcinomas of the vulva are rare, and only seven cases have been described to date. Hypotheses about the origin of this neoplasm remain highly speculative. We report the case of a 58-year-old woman who developed this very uncommon malignant tumor. Immunohistochemical studies of the tumor revealed positive staining for cytokeratins 7 and 20 and a negative staining for estrogen and progesterone receptors. Special stains showed the presence of intracellular mucin. No other primary lesion was found on clinical evaluation and extensive investigation. The patient was first treated by radical hemivulvectomy, followed by ipsilateral inguinal lymph node dissection and laparoscopic right salpingo-oophorectomy for an incidental finding of an ovarian cyst. The patient remained free of disease 16 months after the initial surgery.

Topics: Adenocarcinoma; Biomarkers, Tumor; Cloaca; Disease-Free Survival; Female; Humans; Intermediate Filament Proteins; Keratin-20; Keratin-7; Keratins; Middle Aged; Mucins; Vulvar Neoplasms

A case history is presented of a 53-year-old woman with an incidental finding of a breast lump, identified after having had chemotherapy for lung metastases from a rectal carcinoma. Clinical examination, ultrasound, mammography, fine needle aspiration and core biopsies could not prove definitively whether the breast lump represented a metastasis from colorectal carcinoma. Following local excision, the final diagnosis of metastatic colorectal carcinoma to the breast was based on the absence of any site of origin within the breast (i.e. no surrounding DCIS) and on the expression of cytokeratin CK7 and CK20 on immunohistochemistry. Postoperative chemotherapy was initiated. Four months later, although without local recurrence in the breast, the patient developed cutaneous metastatic deposits and active treatment was stopped. A review of other cases of breast metastases from extramammary sources is presented. Possible mechanisms for this rare and unusual phenomenon are discussed.

Topics: Adenocarcinoma; Biomarkers; Breast Neoplasms; Colorectal Neoplasms; Female; Humans; Immunohistochemistry; Intermediate Filament Proteins; Keratin-20; Keratin-7; Keratins; Lung Neoplasms; Middle Aged; Skin Neoplasms

We studied the staining patterns of bronchioloalveolar carcinoma (BAC) with antibodies to cytokeratin (CK) 7, CK20, and thyroid transcription factor-1 (TTF-1) to determine the diagnostic usefulness of this panel in differentiating BAC from metastatic adenocarcinoma in material obtained by fine-needle aspiration biopsy (FNAB) of the lung. We identified 16 cases of BAC. Of these, 6 were mucinous, 4 were nonmucinous, and 6 were mixed with focal mucinous differentiation. Immunohistochemical analysis with antibodies to CK7, CK20, and TTF-1 was performed on cell-block sections. Of the 6 mucinous BACs, 4 (67%) were CK7+, CK20+, and TTF-1-. All 4 nonmucinous BACs were CK7+ and CK20-, and 2 (50%) were TTF-1+. All 6 mixed BACs were diffusely positive for CK7 and focally positive for CK20; 5 (83%) were TTF-1+. Nonmucinous BACs display CK7, CK20, and TTF-1 immunoreactivity similar to conventional pulmonary adenocarcinoma. Mucinous and mixed BACs have an immunohistochemical phenotype that is different from that of conventional pulmonary adenocarcinoma. Knowledge of these staining patterns is crucial for distinguishing mucinous and mixed BACs from metastatic adenocarcinoma involving the lungs.

Topics: Adenocarcinoma; Adenocarcinoma, Bronchiolo-Alveolar; Aged; Aged, 80 and over; Biomarkers, Tumor; Biopsy, Fine-Needle; Diagnosis, Differential; Female; Humans; Immunohistochemistry; Intermediate Filament Proteins; Keratin-20; Keratin-7; Keratins; Lung Neoplasms; Male; Middle Aged; Nuclear Proteins; Thyroid Nuclear Factor 1; Transcription Factors

We present a case of adenocarcinoma developing at the vesicocutaneous edge of a vesicostomy, 40 years after it was created, in a patient who underwent cadaveric kidney transplant. Although transitional and squamous cell carcinoma of a vesicostomy have been reported, to our knowledge, the presence of adenocarcinoma at the vesicostomy edge has not been reported previously.

Topics: Abnormalities, Multiple; Adenocarcinoma; Adult; Biomarkers, Tumor; Cell Transformation, Neoplastic; Cystostomy; Dermatologic Surgical Procedures; Female; Humans; Immunosuppression Therapy; Intermediate Filament Proteins; Keratin-20; Keratin-7; Keratins; Kidney Failure, Chronic; Kidney Transplantation; Neoplasm Proteins; Postoperative Complications; Surgical Stomas; Time Factors; Urinary Bladder Neoplasms; Urinary Bladder, Neurogenic; Urogenital Abnormalities; Urothelium

Topics: Adenocarcinoma; Biomarkers, Tumor; Cytoplasmic Granules; Humans; Keratins; Male; Middle Aged; Neoplasm Proteins; Parotid Neoplasms

Immunohistochemistry plays an important role in tracing the primary site in metastatic tumors of unknown origin. Therefore, determining the cytokeratin (CK) 20/CK7 pattern of metastases is one of the most helpful procedures as the CK20+/CK7- pattern is typical of colorectal adenocarcinomas. Expression of CDX2 protein is a new, highly specific and sensitive marker of the intestinal origin of adenocarcinomas. In the present study we compared the sensitivity and specificity of CDX2 expression and the CK20+/CK7- phenotype in predicting the colorectal origin of liver metastases.. The study was carried out on a consecutive series of 125 core-needle biopsies of metastatic adenocarcinomas of the liver. Most of the patients were followed up to death, and primary tumor localization could be established in 102 cases by a combination of clinical, radiological, histological and, in some cases, autopsy data. All the needle biopsies were immunohistochemically stained for CK7, CK20 and CDX2. CDX2 expression (at 10% and 50% cut-off levels) and the CK20/CK7 pattern of the metastases were correlated to the primary site established.. The CK20+/CK7- pattern showed a specificity of 98.7% in predicting colorectal primary localization, which was superior to that of CDX2 expression at both cut-off levels (90% and 95.3% respectively). The sensitivity of CDX2 expression in these circumstances was 84% at the 10% cut-off, somewhat higher than that of the CK20+/CK7- phenotype (79.5%), but lower at the 50% cut-off level (72.7%).. The CK20+/CK7- immunophenotype is more specific in predicting the colorectal origin of liver metastasis than CDX2 expression.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Antibodies; CDX2 Transcription Factor; Colorectal Neoplasms; Female; Homeodomain Proteins; Humans; Immunohistochemistry; Immunophenotyping; Intermediate Filament Proteins; Keratin-20; Keratin-7; Keratins; Liver Neoplasms; Male; Middle Aged; Neoplasm Metastasis; Phenotype; Sensitivity and Specificity; Trans-Activators

To study the diagnosis and differential diagnosis of renal epithelial neoplasms.. Ninety-one cases of renal epithelial neoplasms with detailed pathologic records were enrolled. In addition to microscopic examination, Mowy's colloidal iron staining and immunohistochemical studies (CD10, vimentin and CK7) were also performed.. Among the 91 cases, there were 78 (86%) clear cell renal carcinoma cases, 8 (9%) papillary renal carcinoma cases, 4 (4%) chromophobe renal carcinoma cases and 1 (1%) renal oncocytoma case. Sixty-three of the 78 clear cell renal carcinoma cases were positive for CD10 and 69 were positive for vimentin (81% and 88% respectively), with prominent cell membrane staining. The majority (74/78) of clear cell renal carcinoma were negative for CK7. All 17 clear cell renal carcinoma cases showed negative or focal coarse droplet-like staining pattern for Mowy's colloidal iron stain. All 4 chromophobe renal cell carcinoma cases showed prominent cell membrane staining for CK7 and blue reticular staining pattern for Mowy's colloidal iron stain. All of which were negative for CD10 and vimentin. The case of renal oncocytoma failed to react with antibodies to CD10, vimentin and CK7, or Mowy's colloidal iron stain.. CD10, vimentin, CK7 and Mowy's colloidal iron stains have proved to be useful in differential diagnosis of common renal tumors which may not be easily distinguished on the basis of histologic examination alone.

Topics: Adenocarcinoma; Adenocarcinoma, Clear Cell; Carcinoma, Papillary; Colloids; Diagnosis, Differential; Humans; Immunohistochemistry; Iron; Keratin-7; Keratins; Kidney Neoplasms; Neprilysin; Staining and Labeling; Vimentin

Only very limited data are available on the presence of circulating tumor cells during cytotoxic chemotherapy for hormone-refractory prostate cancer. We analyzed 241 blood samples from 32 patients with hormone-refractory PCa under a chemotherapy schedule. The etoposide, estramustine phosphate and paclitaxel scheme as well as the mitoxantrone and prednisone schedule were used to treat patients with advanced prostate cancer. The pre-therapy serum PSA values were in the range from 1.4 ng/ml to 2,870.9 ng/ml (median 74.5 ng/ml). We isolated the CD45-negative cell population by immunomagnetic depletion from 16 ml of peripheral blood samples. These cells were stained for pan-cytokeratin and evaluated. Patients were observed for an average of 67 weeks (range 16-120). In 77 (32%) samples originating from 27 (84%) patients, tumor cells were detected at least once. Twenty of these patients had shown an initial response to therapy as indicated by a >/=50% decrease of the pre-therapy PSA value. Of these, 14 patients experienced a biochemical and/or a clinical progression. For 13 (93%) of them, circulating tumor cells were detectable during the time of PSA response, i.e. during the PSA decline and before a biochemical or clinical progression. However, we could not correlate the amount of circulating tumor cells with the observed PSA levels. This study demonstrates that circulating tumor cells are detectable during chemotherapy for hormone-refractory prostate cancer regardless of the degree of PSA response.

Topics: Adenocarcinoma; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Estramustine; Humans; Immunomagnetic Separation; Keratins; Leukocyte Common Antigens; Male; Middle Aged; Mitoxantrone; Neoplasms, Hormone-Dependent; Neoplastic Cells, Circulating; Paclitaxel; Prednisone; Prostate-Specific Antigen; Prostatic Neoplasms; Tumor Cells, Cultured

Telomerase is a ribonucleoprotein complex mainly composed of a reverse transcriptase catalytic subunit (telomerase reverse transcriptase gene, hTERT) that copies a template region of its RNA subunit to the end of the telomere. For detecting telomerase activity in a tissue specimen the TRAP assay is a relatively sensitive and specific method, but it can be used only on fresh tissue extracts and offers no information at the single cell level. Immunohistochemistry (IHC) allows to detect hTERT protein expression at an individual cell level in human tissues. We have tested commercially available anti-hTERT antibodies in formalin-fixed and paraffin-embedded human tissues by IHC. Only one monoclonal antibody (NCL-hTERT; Novacastra) was sufficiently specific and this was applied to human tissues in which telomerase activity had been shown by TRAP assay and hTERT mRNA expression by RT-PCR. hTERT protein localized diffusely in the nucleoplasm and more intensely in the nucleoli of cancer cells and proliferating normal cells. Mitotic cells showed diffuse staining of the entire cell. Granular cytoplasmic staining was occasionally found in some tumor cells. In telomerase-positive tumors not all the tumor cells showed hTERT immunoreactivity. A significantly heterogeneous hTERT protein expression was observed in human tumor tissues. The hTERT immunostaining in fixed tissues was concordant with telomerase activity and hTERT mRNA expression in corresponding non-fixed samples. Quantitative RT-PCR of microdissected sections showed that hTERT mRNA expression was higher in cells with nuclear expression than in those with cytoplasmic expression. Double staining with the M30 antibody showed that a subpopulation of hTERT-negative cells is apoptotic. We conclude that: (1) hTERT protein can be detected by IHC in fixed human tissues, but the choice of the antibody, tissue processing, and reaction conditions are critical, (2) hTERT protein localizes in the nucleoplasm, more strongly in the nucleolus, and occasionally in the cytoplasm, (3) telomerase-positive tumors show significant heterogeneity of hTERT protein expression, and (4) a subpopulation of hTERT protein negative tumor cells is identified as apoptotic cells.

Topics: Adenocarcinoma; Antibodies, Monoclonal; Apoptosis; Breast Neoplasms; Cell Nucleolus; Cell Nucleus; Colonic Neoplasms; Cytoplasm; DNA-Binding Proteins; Female; Gene Expression; Humans; Immunohistochemistry; Keratins; Lung Neoplasms; Lymphocytes; Male; Neoplasms; Reverse Transcriptase Polymerase Chain Reaction; RNA, Neoplasm; Sarcoma; Spermatogonia; Telomerase; Urinary Bladder Neoplasms

Topics: Adenocarcinoma; Adult; Carcinoembryonic Antigen; Cysts; Female; Humans; Immunohistochemistry; Keratin-7; Keratins; Laparoscopy; Retroperitoneal Neoplasms

Intrabiliary growth of liver metastases from colorectal cancer has rarely been studied. A surgically resected case of a metastatic liver tumor with prominent intrabiliary growth derived from rectal cancer is reported. The patient was a 62-year-old man who had received a low anterior resection for rectal cancer in March 2000. He was re-admitted due to obstructive jaundice in January 2003, and was diagnosed with hepatic malignancy in segment II of the liver with an intrabiliary tumor extending from the intrahepatic bile duct of segment II to the common hepatic duct. He underwent a left hepatectomy, a partial resection of segment VI, and an extrahepatic bile duct resection with reconstruction of the biliary tract. In the resected specimen, there were whitish tumors of 3 cm and 1.5 cm in diameter in segments II and VI, respectively, and an intrabiliary tumor originating from the main tumor in segment II extended to the common hepatic duct. Both the liver tumors and the intrabiliary tumor consisted of a well- to moderately differentiated adenocarcinoma, which showed the same histological features as the rectal cancer. The immunohistochemical findings strongly supported that these tumors, including the intrabiliary growth, were liver metastasis from the rectal cancer. The intrabiliary invasion and growth of metastatic liver tumors has generally been overlooked, notwithstanding their frequently observed biological behavior. The present case is informative, and further investigation into this type of metastatic liver tumor may be warranted.

Topics: Adenocarcinoma; Bile Ducts, Intrahepatic; Biomarkers, Tumor; Chemotherapy, Adjuvant; Cholangiography; Cholestasis, Intrahepatic; Hepatectomy; Humans; Immunohistochemistry; Keratins; Liver Neoplasms; Male; Middle Aged; Neoplasm Invasiveness; Rectal Neoplasms; Tomography, X-Ray Computed

Because the histopathological features of some primary adenocarcinomas of the sinonasal tract may show considerable overlap, we assessed the diagnostic value of a panel of immunohistochemical markers in the distinction between these malignancies. Paraffin-embedded tumour tissue sections from a series of 39 primary adenocarcinomas of the sinonasal tract, including 25 cases of intestinal-type adenocarcinoma (ITAC), 10 cases of salivary gland-type carcinoma and 4 cases of tubulopapillary low-grade adenocarcinoma were immunostained for CDX-2, cytokeratin 7 and cytokeratin 20. Diffuse nuclear staining for CDX-2 was identified in 80% of ITACs, while all non-ITACs were negative. Staining for cytokeratin 20 was positive in 84% of ITACs, including all cases negative for CDX-2, but negative in all other adenocarcinomas. Cytokeratin 7 was consistently positive in 88% of ITACs and in 100% of non-ITACs. Normal sinonasal epithelia expressed cytokeratin 7, but not CDX-2 and cytokeratin 20. Staining for CDX-2 and cytokeratin 20 has potential use in separating ITACs from other primary malignant glandular neoplasms of the nasal cavities and paranasal sinuses.

Topics: Adenocarcinoma; Biomarkers, Tumor; CDX2 Transcription Factor; Cell Count; Diagnosis, Differential; Homeodomain Proteins; Humans; Immunoenzyme Techniques; Intermediate Filament Proteins; Keratin-20; Keratin-7; Keratins; Paranasal Sinus Neoplasms; Trans-Activators

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Carcinoma, Transitional Cell; Diagnosis, Differential; Female; Humans; Immunohistochemistry; Intermediate Filament Proteins; Keratin-20; Keratin-7; Keratins; Male; Middle Aged; Prostatic Neoplasms; Receptors, Androgen; Urinary Bladder Neoplasms

Topics: Adenocarcinoma; Biomarkers, Tumor; Brain; Brain Neoplasms; Cerebrospinal Fluid; Diagnosis, Differential; Facial Nerve; Humans; Keratin-7; Keratins; Lateral Ventricles; Lung; Lung Neoplasms; Male; Meningeal Neoplasms; Middle Aged; Miller Fisher Syndrome; Oculomotor Nerve

To assess cytokeratin (CK) and thyroid transcription factor (TTF)-1 expression in primary epithelial lung tumours by comparison with non-pulmonary carcinomas and to correlate it with their histological type and grade.. Immunohistochemistry using antibodies against CKs 5/6, 7, 19, 20 and TTF-1 was applied to 165 primary and 37 secondary epithelial lung tumours. CK5/6 is a sensitive and specific marker of lung squamous carcinomas being positive in 100% of cases. CK7 is a common marker of primary lung adenocarcinomas (100% of cases) but with a lower specificity since it is also observed in other primary lung carcinomas (70% of large-cell neuroendocrine carcinomas, 40% of large-cell carcinomas, 23% of squamous carcinomas) but also in 27% of non-pulmonary adenocarcinomas. Addition of an anti-CK20 may be useful to prove or disprove the pulmonary origin of an adenocarcinoma when there is a history of colon cancer. CK19 is ubiquitous but a predominant or exclusive 'dot-like' pattern is very suggestive of high-grade neuroendocrine carcinoma. TTF-1 is a very sensitive and specific marker to document the pulmonary origin of an adenocarcinoma if a thyroid origin is excluded. Its expression in neuroendocrine lung tumours depends on the tumour grade.. Immunohistochemical expression of CKs and TTF-1 may be correlated with histological type and grade of lung primary epithelial tumours and may allow them to be distinguished from non-pulmonary carcinomas.

Topics: Adenocarcinoma; Aged; Biomarkers, Tumor; Carcinoma, Squamous Cell; Female; Humans; Immunoenzyme Techniques; Keratins; Lung Neoplasms; Male; Middle Aged; Nuclear Proteins; Thyroid Nuclear Factor 1; Transcription Factors

To investigate the expression of CEA mRNA and CK(19) mRNA in peripheral blood cells of patients with lung cancer and evaluate its clinical significance.. Peripheral blood nucleated cells of 50 patients with lung cancer were studied by RT-PCR to detect the expression of CEA mRNA and CK(19) mRNA.. The combined positive rate of CEA mRNA and CK(19) mRNA in patients with lung cancer (82.0%) was significantly higher than that in patients with benign lung diseases (28.0%) and healthy volunteers (8.1%) (P < 0.001). The expression rate had no relation to the clinical staging or histological type. Compared with single detection, combined detection increased the detection rate but did not decrease the specificity.. Combined detection of CEA mRNA and CK(19) mRNA expression in peripheral blood nucleated cells increase the sensitivity of detecting hematogenous dissemination of cancer cells. Long-term survival analysis and more specimens would be helpful for evaluating its clinical significance.

Topics: Adenocarcinoma; Adult; Aged; Carcinoembryonic Antigen; Carcinoma, Small Cell; Carcinoma, Squamous Cell; Female; Humans; Keratins; Lung Neoplasms; Male; Middle Aged; Neoplasm Staging; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger

To evaluate the clinicopathological profile of 14 cases of nasal and paranasal sinusal adenocarcinoma, and to assess the usefulness of immunohistochemistry in the differential diagnosis of primary and metastatic intestinal-type adenocarcinoma.. Fourteen cases of nasal and paranasal adenocarcinoma, treated at IPOFG, Lisbon, between 1976 and 2002, were studied. Clinical records were reviewed and expression of cytokeratin (CK)7 and CK20 and of neuroendocrine markers was evaluated. The male : female ratio was 3 : 1, and the mean age of the patients was 65.3 years. Ten cases occurred in the paranasal sinuses. There was a history of professional exposure to dust in three patients. Twelve cases were high-grade intestinal type adenocarcinomas (ITAC) and two were low-grade. CK7 was present in 2/9 ITAC cases and CK20 in 8/9 ITAC and in cases of mixed and mucinous histology. All high-grade cases showed neuroendocrine differentiation. Seven of the 12 patients with high-grade adenocarcinoma died of the disease, with a mean follow-up of 47.4 months.. Nasal and paranasal adenocarcinoma mostly occurs in men in the 7th decade. ITAC is the most frequent histological type. The pattern of CK7/CK20 was not useful in the distinction between primary and metastatic intestinal adenocarcinoma. However, in the former, neuroendocrine differentiation proved to be a valuable tool in that distinction.

Topics: Adenocarcinoma; Aged; Aged, 80 and over; Chromogranin A; Chromogranins; Female; Follow-Up Studies; Humans; Immunohistochemistry; Intermediate Filament Proteins; Keratin-20; Keratin-7; Keratin-8; Keratins; Male; Middle Aged; Nose Neoplasms; Paranasal Sinus Neoplasms; Synaptophysin

Intestinal-type sinonasal adenocarcinoma (ITAC) is an uncommon neoplasm, which resembles adenocarcinoma of the gastrointestinal tract. ITAC occurs sporadically or in association with occupational exposure to hardwood dust and other agents.. To investigate the phenotype and possible pathogenetic mechanisms of primary sinonasal and nasopharyngeal adenocarcinomas by staining for cytokeratin 7 (CK7), CK20, CDX-2, and villin.. Twelve sporadic sinonasal and nasopharyngeal adenocarcinomas were stained with monoclonal antibodies to CK7, CK20, CDX-2, and villin. The ITACs were classified as papillary, colonic, solid, mixed, or mucinous types.. The diagnosis of ITAC was confirmed in 10 cases: five were colonic type and five were papillary. One was a sinonasal papillary low grade adenocarcinoma, and one a papillary nasopharyngeal adenocarcinoma, and these tumours were CK7 positive, but CK20, CDX-2, and villin negative. All ITACs were positive for CK20, CDX-2, and villin, and six were CK7 positive. One ITAC had a focus of intestinal metaplasia away from the invasive carcinoma.. Sinonasal ITACs have a distinctive phenotype, with all cases expressing CK20, CDX-2, and villin. Most ITACs also express CK7, although a proportion of tumours are CK7 negative. ITAC seems to be preceded by intestinal metaplasia of the respiratory mucosa, which is accompanied by a switch to an intestinal phenotype. Although ITACs are morphologically similar, differences in cytokeratin expression patterns suggest two distinct types. The expression pattern of CK7, CK20, CDX-2, and villin positive may be useful in separating these tumours from other non-ITAC adenocarcinomas of the sinonasal tract and nasopharynx.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Biomarkers, Tumor; Carrier Proteins; CDX2 Transcription Factor; Female; Homeodomain Proteins; Humans; Immunohistochemistry; Industry; Intermediate Filament Proteins; Intestinal Mucosa; Intestinal Neoplasms; Keratin-20; Keratin-7; Keratins; Male; Metaplasia; Microfilament Proteins; Middle Aged; Nose Neoplasms; Occupational Diseases; Paranasal Sinus Neoplasms; Trans-Activators; Wood

We studied the diagnostic value of Cdx2 to distinguish mucinous bronchioloalveolar carcinoma from mucinous colorectal adenocarcinoma metastatic to the lung. We retrieved 92 via the hospital computer system, including 30 mucinous bronchioloalveolar carcinomas, 32 nonmucinous bronchioloalveolar carcinomas, and 30 mucinous colorectal adenocarcinomas metastatic to the lung. All cases were confirmed by clinical history and surgical resection with occasional immunohistochemical studies. Cases were stained with antibodies against Cdx2, thyroid transcription factor-1 (TTF-1), cytokeratin (CK) 7, and CK20. Bronchioloalveolar carcinoma, mucinous type, showed positive staining for Cdx2, TTF-1, CK7, and CK20 in 0 (0%), 5 (17%), 30 (100%), and 18 (60%) of 30 cases, respectively; nonmucinous tumors were positive in 0 (0%), 30 (94%), 32 (100%), and 0 (0%) of 32 cases, respectively. For colorectal adenocarcinoma, the positive staining for Cdx-2, TTF-1, CK7, and CK20 was 29 (97%), 0 (0%), 7 (23%), and 29 (97%) of 30 cases, respectively. Our results demonstrated Cdx2 as a sensitive and specific marker for differentiating metastatic colorectal adenocarcinoma from mucinous bronchioloalveolar adenocarcinoma.

Topics: Adenocarcinoma; Adenocarcinoma, Bronchiolo-Alveolar; Avian Proteins; Biomarkers, Tumor; Colorectal Neoplasms; Diagnosis, Differential; Homeodomain Proteins; Humans; Immunohistochemistry; Intermediate Filament Proteins; Keratin-20; Keratin-7; Keratins; Lung Neoplasms; Nuclear Proteins; Thyroid Nuclear Factor 1; Transcription Factors

Twenty-four cases of primary nonampullary small intestinal adenocarcinoma were immunohistochemically examined for the expression of cytokeratin (CK) 7 and CK20 and compared with 23 colorectal adenocarcinomas secondarily involving the small intestine by direct extension or metastasis. While normal small intestinal mucosa was diffusely positive for CK20 and completely negative for CK7 expression, all small intestinal adenocarcinomas (24 of 24) showed a variable degree of CK7 expression. Specifically, the CK7 staining pattern was diffuse in 13 cases (54%) and focal in the remaining cases. Sixteen small intestinal adenocarcinomas (67%) coexpressed CK7 and CK20, and 8 (33%) completely lost CK20 immunoreactivity when compared with adjacent non-neoplastic small intestinal mucosa. In the latter cases, the loss of CK20 immunoreactivity with a reciprocal emergence of CK7 expression was evident. This was in contrast to secondary colorectal adenocarcinomas where 22 cases (96%) expressed CK20, among which only 1 case showed focal CK7 expression. The remaining 1 case was negative for both CK7 and CK20. Interestingly, adenomatous epithelium associated with small intestinal adenocarcinomas identified in 18 cases also exhibited CK7 positivity with a sharp transition from CK7-negative normal-appearing epithelium. Taken together, these observations delineate an alteration of CK7 and CK20 expression profile that occurs early in small intestinal tumorigenesis. This unique pattern may be of diagnostic value in distinguishing primary small intestinal adenocarcinoma from secondary colorectal adenocarcinoma.

Topics: Adenocarcinoma; Adult; Aged; Colorectal Neoplasms; Female; Humans; Immunohistochemistry; Infant, Newborn; Intermediate Filament Proteins; Intestinal Neoplasms; Intestine, Small; Keratin-20; Keratin-7; Keratins; Male; Middle Aged; Retrospective Studies

Recently, the authors identified molecular signatures and pathways associated with nonsmall cell lung carcinoma histology and lung development. They hypothesized that genetic classifiers of histology would provide insight into lung tumorigenesis and would be associated with clinical outcome when evaluated in a broader set of specimens.. Associations between patient survival and immunostaining for 11 representative histologic classifiers (epidermal growth factor receptor [EGFR], CDK4, syndecan-1, singed-like, TTF-1, keratin 5, HDAC2, docking protein 1, integrin alpha3, P63, and cyclin D1) were examined using a tissue microarray constructed from nonsmall cell lung carcinoma specimens.. Sixty-three tumors were examined, including 43 adenocarcinomas, 11 large cell carcinomas, and 9 squamous cell carcinomas. Sixty-three percent of tumors were clinical Stage I lesions, and 37% were Stage II-III lesions. In a multivariate analysis that controlled for age, gender, and race, syndecan-1 expression was found to be associated with a significant reduction in the risk of death (hazard ratio, 0.31 [95% confidence interval, 0.18-0.87]; P < 0.05). Multivariate analysis also indicated that EGFR expression was associated with a significant reduced risk of death.. The authors demonstrated that expression of either of the nonsmall cell lung carcinoma subtype classifiers syndecan-1 and EGFR was associated with a 30% reduction in the risk of death, with this reduction being independent of histology and other confounders. The results of the current study suggest that loss of expression of these histologic classifiers is associated with biologic aggressiveness in lung tumors and with poor outcome for patients with such tumors. If their significance can be validated prospectively, these biomarkers may be used to guide therapeutic planning for patients with nonsmall cell lung carcinoma.

Topics: Adenocarcinoma; Aged; Carcinoma, Large Cell; Carcinoma, Non-Small-Cell Lung; Carcinoma, Squamous Cell; Cyclin D1; Cyclin-Dependent Kinase 4; Cyclin-Dependent Kinases; ErbB Receptors; Female; Histone Deacetylase 2; Histone Deacetylases; Humans; Immunohistochemistry; Integrin alpha Chains; Keratin-5; Keratins; Lung Neoplasms; Male; Membrane Glycoproteins; Membrane Proteins; Multivariate Analysis; Nuclear Proteins; Proteoglycans; Proto-Oncogene Proteins; Repressor Proteins; Syndecan-1; Syndecans; Thyroid Nuclear Factor 1; Transcription Factors

Primary squamous cell carcinoma (SCC) of the breast is an extremely rare entity and it has a low incidence in comparison with all other mammary cancers.. We describe a case of SCC of the breast in a 55 year old woman who presented with a painless mass located in the external quadrant of the left breast. The neoformation, once removed, was tamponate formalin fixed and routinely processed for inclusion in paraffin. Sections were stained with haematoxilin-eosin and immunohistochemical and electron microscopy investigations were performed.. Histologically, the neoplasia was characterized by cystic cavities covered by nests and sheaths of poorly differentiated squamous cells with keratinized areas. Mitotic activity was high, as well as cellular proliferative index, evaluated by Mib-1 (ki 67) antibody. At immunohistochemistry, the tumor cells were diffusely positive for high molecular weight cytokeratins and c-erbB-2, negative for vimentin, estrogen and progesterone. CD68 and LCA were positive only in the inflammatory cells. Electron microscopy confirmed the epithelial nature of the neoplastic cells. A diagnosis of SCC of the breast was made, and a radical mastectomy was performed.. We make a brief review of the literature and discuss the main histologic criteria for the differential diagnosis with adenocarcinoma of the breast with squamous metaplasia.

Topics: Adenocarcinoma; Biomarkers, Tumor; Breast Neoplasms; Carcinoma, Squamous Cell; Cell Differentiation; Diagnosis, Differential; Female; Humans; Keratins; Mastectomy, Radical; Microscopy, Electron; Middle Aged; Neoplasm Proteins; Receptor, ErbB-2

Lung cancer and pancreatic cancer are the most lethal tobacco-associated malignancies. To elucidate possible clinical interrelationships, the authors reviewed the clinicopathologic characteristics of patients treated for both pulmonary and pancreatic neoplasms.. Patients presenting with a potentially resectable pancreatic mass and a diagnosis of metachronous malignant neoplasm of the lung were studied by retrospective chart audit and review of histopathologic material.. Seven patients were identified over 6 years, representing five different clinical entities: metachronous presence of lung cancer and pancreatic cancer (n = 3), lung cancer metastatic to the pancreas (n = 1), lung cancer with a benign pancreatic neoplasm (n = 1), periampullary cancer metastatic to the lung (n = 1), and malignant melanoma metastatic to both lung and pancreas (n = 1). A tobacco history was present in all patients but one. Primary treatment modality was complete resection of isolated sites whenever feasible (lung resection, n = 6; pancreatic resection, n = 5). In four cases, a differential diagnosis of adenocarcinomas of both lung and pancreas was obtained after cytokeratin (CK) 7 and CK 20 immunohistochemistry. All patients with evidence of nodal or visceral metastasis from either primary site (n = 4) died within 5 to 9 months after the last operation. Three of four patients who had undergone resection of both pulmonary and pancreatic tumors were alive between 17 and 67 months after the last operation. All three survivors had presented with early disease stages and/or a protracted course (diagnostic interval, 16-66 months).. Our experience with neoplastic conditions that can involve lungs and pancreas metachronously may be useful to the clinician who is confronted with a similar situation. If therapeutic decision-making depends on differential diagnostic analysis, examination of CK 20 expression appears to be helpful. Although biologically favorable circumstances are rarely present, long-term survival seems possible after complete operative treatment in selected patients with early-stage disease.

Topics: Adenocarcinoma; Aged; Aged, 80 and over; Female; Humans; Keratin-7; Keratins; Lung Neoplasms; Male; Middle Aged; Pancreatic Neoplasms; Postoperative Period; Retrospective Studies; Smoking

The number or ratio of lymph node metastases detected by hematoxylin & eosin (H&E) staining is the most important predictor of survival in esophageal cancer. The survival effect of lymph node metastases detected on immunohistochemistry (IHC) is controversial. My colleagues and I hypothesized that the extent of nodal disease determined by both H&E and IHC examination would more accurately predict survival than either technique alone.. The study population consisted of 37 patients who underwent en bloc esophagectomy as primary therapy for esophageal adenocarcinoma 5 or more years ago. All had mediastinal and upper abdominal lymphadenectomy. No patient received neoadjuvant or adjuvant therapy. Tissue blocks were sectioned for H&E staining to confirm the initial histology, and a second slide was stained with monoclonal antibodies AE1 and CAM 5.2, which are directed at a number of cytokeratin antigens. The slides were reviewed by an investigator blinded to clinical outcome. The effect of IHC staining on prognosis was assessed by comparing 5-year survival based on H&E and IHC findings.. A total of 1,970 nodes were examined in the 37 patients. Routine H&E staining detected metastases in 29 patients (78%); the remaining 8 with N0 disease all survived at least 5 years after operation (median not reached). In the 29 patients with N1 disease, survival was 41% at 5 years. In 20 of the 29 N1 patients, metastases were detected by H&E in less than 10% of the nodes removed; 55% of the patients survived 5 years, and 39% survived 8 years. Nine of the 29 patients had metastases detected in more than 10% of the nodes removed, and all died at a median of 17 months. IHC staining was performed on the nodes from the 8 N0 patients and the 20 patients with less than 10% nodal involvement (a total of 28 patients). Additional nodal metastases, not identified on H&E examination, were found in 51 nodes from 17 patients (60.7%). Of the 8 patients who were node negative on H&E examination, 3 had metastases detected by IHC, and all survived 5 years or more free of disease. Of the 20 patients with less than 10% nodal metastases on H&E, 14 (70%) had additional metastases detected by IHC (median, 2 nodes per patient). When combined with the results of H&E staining, the node ratio remained less than 10% in 13 patients and exceeded 10% in 7. Survival in patients whose ratio remained less than 10% was significantly better than in those whose ratio exceeded 10% (actual 5-year survival, 77% vs 14%; chi2 = 4.662; p = 0.03).. IHC staining techniques can identify nodal metastases missed by routine H&E examination in a large number of patients. The combination of H&E and IHC examination is useful in patients with less than 10% nodal involvement by H&E examination in that IHC detection of micrometastases allows classification into low-risk (> 75% survival) and high-risk (< 15% survival) groups. IHC-detected micrometastases are not of prognostic importance in N0 patients or those with greater than 10% nodal metastases on H&E.

Topics: Adenocarcinoma; Aged; Antibodies, Monoclonal; Chi-Square Distribution; Coloring Agents; Eosine Yellowish-(YS); Esophageal Neoplasms; Esophagectomy; Female; Follow-Up Studies; Hematoxylin; Humans; Immunoenzyme Techniques; Keratins; Life Tables; Lymph Node Excision; Lymphatic Metastasis; Male; Middle Aged; Neoplasm Invasiveness; Neoplasm Proteins; Prognosis; Single-Blind Method; Staining and Labeling; Survival Analysis

To assess the utility of P504S immunohistochemistry in the diagnosis and differential diagnosis of prostatic adenocarcinoma.. Light microscopy and immunohistochemistry examinations (EnVision staining) were performed in 117 cases of prostatic adenocarcinoma, PIN, AAH, ASAP, BPH and normal prostatic tissue to correlate the morphology and protein expression of P504S, 34betaE12, and P63.. Seventy-one of the 78 (91%) cases of prostatic adenocarcinoma stained positive for P504S, with strong cytoplasmic granular staining in most cases, and a weak or intense granular staining along the circumferential luminal and apical cell border membrane in a few cases. Negative P504S immunostaining was observed in 7 of 78 (9%) cases of prostatic adenocarcinoma, all of which were clear cell type prostatic adenocarcinoma. Cases of PIN (9 cases), AAH (6 cases) and ASAP (2 cases) showed various expression levels of P504S. Sixty-five of 68 (96%) cases of normal prostates and BPH were negative for P504S and basal cell hyperplasia cases were also negative.. P504S is a useful marker for microscopic diagnosis of prostatic adenocarcinoma, and immunohistochemistry study using a combination of P504S and 34betaE12/p63 may be of greater benefit in aiding the differential diagnoses.

Topics: Adenocarcinoma; Diagnosis, Differential; DNA-Binding Proteins; Genes, Tumor Suppressor; Humans; Immunohistochemistry; Keratins; Male; Phosphoproteins; Precancerous Conditions; Prostate; Prostatic Hyperplasia; Prostatic Intraepithelial Neoplasia; Prostatic Neoplasms; Racemases and Epimerases; Trans-Activators; Transcription Factors; Tumor Suppressor Proteins

Ampullary carcinomas (AC) account for 33% of all surgically operable pancreatoduodenal tumors. The 5-year relative survival rate is 50% and tumoral stage is the main prognostic factor. However, among the three AC histological subtypes (intestinal, pancreatobiliary and mixed), a favorable prognostic has been reported for the intestinal subtype.. The aims of this study were to determine the prognostic impact of AC histologic subtype and of cytokeratins (CK) 7 and 20 immunostaining profile in these tumors.. Clinical data of 54 AC were obtained retrospectively. Macroscopic and histologic documents were reviewed and immunostainings for CK7 and CK20 were performed.. The classification of tumors, according to histological subtype, was: intestinal 26%, pancreatobiliary 65% and mixed 9%. No correlation was found between histological subtype and tumor stage. The 5-year survival rate varied from 100% for intestinal subtype to 35% for pancreatobiliary subtype. A strong correlation (p < 0.0001) was found between histological subtype and CK7/CK20 immunostaining profile. The 5-year survival rate varied from 100% for CK7-/CK20 + AC to 40% for CK7 + /CK20- AC.. In our study, the intestinal histological subtype had a favorable prognostic value. CK7/CK20 immunostaining profile was helpful for the identification of histological subtype and appears to provide additional prognostic information.

Topics: Adenocarcinoma; Ampulla of Vater; Biomarkers; Common Bile Duct Neoplasms; Female; Humans; Immunohistochemistry; Intermediate Filament Proteins; Keratin-20; Keratin-7; Keratins; Male; Middle Aged; Retrospective Studies

To determine whether a micropapillary component is a prognostic predictor, with particular reference to nodal micrometastasis, in patients with stage I lung adenocarcinomas.. Thirty-five cases with stage I lung adenocarcinomas, obtained from lobectomies or pneumonectomies, and 434 dissected hilar and mediastinal lymph nodes, were retrospectively reviewed. A micropapillary component and nodal micrometastasis were found in 16 (45.7%) and 14 (40%) of the 35 cases, respectively, with nodal micrometastasis in 24 (5.5%) of the 434 lymph nodes, in an immunohistochemical study using an anti-cytokeratin antibody. Ten (62.5%) of the 16 cases with a micropapillary component, and four (21.1%) of the remaining 19 cases, showed nodal micrometastases (P = 0.014). Kaplan-Meier survival curves demonstrated that there was no significant difference between the cases with and without a micropapillary component (P = 0.28). However, the 5 years' survival of the cases with and without nodal micrometastases were 71.4% and 35.7%, respectively (P = 0.03).. A micropapillary component may be a manifestation of aggressive behaviour, as shown by frequent micrometastasis, for stage I lung adenocarcinomas.

Topics: Adenocarcinoma; Adult; Aged; Carcinoma, Papillary; Female; Humans; Immunohistochemistry; Keratins; Lung Neoplasms; Lymph Nodes; Lymphatic Metastasis; Male; Middle Aged; Neoplasm Staging; Retrospective Studies; Survival Analysis

We selected a 4-stain immunopanel including thyroid transcription factor (7ITF)-], cytokeratin (CK)7, 34betaE12, and CD56/neural cell adhesion molecule(NCAM) to subclassify a series of 45 pulmonary large cell carcinomas (LCCs) on bronchial biopsy. All cases consisted of a large tumor cell proliferation with abundant cytoplasm, vesicular nuclei, and prominent nucleoli. Immunohistochemically, 27 tumors (60%)were subclassified as adenocarcinoma (7TF-1 +/CK7+,24; CK7+ only, 3), 10 (22%) as squamous cell carcinoma (34betaE12+ only), and 4 (9%) as LCC with neuroendocrine differentiation (CD56+, variably stained with TTF-I and CK7, 34betaE12-). In 4 cases, the tumors coexpressed CK7 and 34betaE12 (3 cases) or were completely unstained (I case). Surgically resected tumors matched exactly with the corresponding original biopsy specimens in 21 of 23 cases; consistent CD56 expression was a reliable marker in confirming a diagnosis of large cell neuroendocrine carcinoma even on biopsy. Our results suggest that the proposed 4-stainset of commercially available markers might help subclassify LCC even in small biopsy material, validating expression-profiling studies aimed at lung cancer classification and permitting more consistent patient enrollment for trials with targeted treatments.

Topics: Adenocarcinoma; Aged; Aged, 80 and over; Biomarkers, Tumor; Carcinoma, Large Cell; Carcinoma, Squamous Cell; CD56 Antigen; Diagnosis, Differential; Female; Humans; Immunohistochemistry; Keratin-7; Keratins; Lung Neoplasms; Male; Middle Aged; Neuroendocrine Tumors; Nuclear Proteins; Thyroid Nuclear Factor 1; Transcription Factors

The differentiation of primary cutaneous adnexal neoplasms (CANs) from dermal-based metastatic lesions can be difficult. Cytokeratin 5/6 (CK 5/6) has a relatively limited expression profile, being relatively specific for mesothelium and other "pavement" type epithelium such as squamous epithelium. To date, the degree and distribution of CK 5/6 expression in cutaneous neoplasms has not been extensively studied. We speculate that since most of CANs arise from similar epithelium, they should express CK 5/6 and, therefore, CK 5/6 could potentially be helpful in distinguishing these lesions from most of metastatic neoplasms, which usually do not express this marker. Formalin-fixed, paraffin-embedded tissue sections from 228 previously classified CANs and 27 metastatic adenocarcinomas (17 breast, 4 colon, 2 prostate, 2 ovary, 1 lung, and 1 esophagus) were immunostained with anti-CK 5/6. Anti-CK 5/6 labeled 2 of 2 proliferating trichilemmal tumors, 6 of 6 poromas, 4 of 5 hydrocystomas, 10 of 10 cylindromas, 10 of 10 eccrine acrospiromas, 8 of 10 pilomatricoma, 10 of 10 nevus sebaceus, 9 of 9 desmoplastic trichoepitheliomas, 7 of 7 nevus sebaceus with basal cell carcinomas, 10 of 10 pilar cysts, 14 of 14 trichilemmomas, 10 of 10 syringomas, 6 of 7 chondroid syringomas, 10 of 10 hidradenoma papilliferum, 9 of 9 sebaceus adenomas, 3 of 3 microcystic adnexal carcinomas, 10 of 10 eccrine spiradenomas, 4 of 4 syringocystadenoma papilliferum, 3 of 5 ocular sebaceous carcinomas, 28 of 28 basal cell carcinomas, 16 of 16 trichoepitheliomas, and 33 of 33 trichoepitheliomas with basal cell features. By contrast, 9 of 27 metastatic adenocarcinomas stained positively, although only two of these stained strongly. Cumulatively, CK 5/6 was expressed by most (97%) of CANs, while only 33% of metastatic adenocarcinomas showed positive expression. The sensitivity of this marker in the malignant lesions (other than basal cell carcinoma) is 78%, while the specificity is 67%. If all lesions are considered, the sensitivity increases to 97%. Therefore, CK 5/6 may prove to be a useful adjunct marker in distinguishing CANs from metastatic lesions.

Topics: Adenocarcinoma; Biomarkers, Tumor; Diagnosis, Differential; Female; Humans; Immunohistochemistry; Keratins; Male; Neoplasms, Adnexal and Skin Appendage; Sensitivity and Specificity; Skin Neoplasms

Prostatic adenocarcinoma is the most common malignancy among men in the western world but the diagnostic and prognostic criteria for it are still not clearly defined. Additional means for its diagnosis and prognosis are clearly needed. Previously it has been shown that cystatin A is expressed in the basal cells of normal prostate and the expression disappears in prostatic carcinoma.. We have now studied the expression of both cystatins A and B in benign prostatic hyperplasias (BPH), prostatic intraepithelial neoplasias (PIN) and carcinomas of the prostatic epithelium and compared it with the expression of high molecular weight (HMW) cytokeratin as well as the proliferation markers cyclin A and Ki-67. The expression of the proteins was immunohistochemically assessed using 33 total prostatectomy specimens.. Cystatin A was expressed in the basal cells in all cases of BPH, low-grade PIN, and high-grade PIN whereas carcinomas showed no staining of cystatin A. The 34 beta E12 cytokeratin expression was similar to basal cystatin A staining and was not seen in carcinoma foci. Cystatin B showed both nuclear and cytoplasmic expression in the columnar epithelial cells. The decrease in median cytoplasmic staining of cystatin B in carcinomas compared to other lesions was significant, but there was a significant increase in expression with dedifferentiation of carcinoma. Also cyclin A and Ki-67 staining were significantly different in non-carcinomatous foci compared to carcinoma foci and had a remarkably similar negative correlations with basal cystatin A and 34 beta E12 staining.. The results show that cystatin expression can be used as an aid in the diagnosis of prostatic adenocarcinoma and especially cystatin A in the distinction between high grade PIN and grade I carcinoma.

Topics: Adenocarcinoma; Aged; Biomarkers, Tumor; Cell Division; Cyclin B; Cystatin B; Cystatins; Humans; Keratins; Ki-67 Antigen; Male; Middle Aged; Molecular Weight; Neoplasm Recurrence, Local; Predictive Value of Tests; Prognosis; Prostatic Hyperplasia; Prostatic Neoplasms

The differential expression of cytokeratin (CK) 7 and 20 by carcinomas may help in determining the primary site of a metastatic tumour. The aim of this study was to extend the published data on CK7 and CK20 expression in epithelial neoplasms of the gastrointestinal tract by considering the degree of differentiation and including some unusual neoplasms.. Cases referred to the Armed Forces Institute of Pathology were studied prospectively for immunohistochemical expression of CK7 and CK20. Lesions from 105 patients were analysed. Adenocarcinomas of the upper gastrointestinal tract were positive for both CK7 and CK20 in 78% of cases; only poorly differentiated lesions were CK7-. Well-differentiated and moderately differentiated adenocarcinomas of the large intestine, including appendix, were CK7-/CK20+ in the great majority of cases, as were goblet cell carcinoids, but half of the poorly differentiated adenocarcinomas exhibited aberrant expression, as did most of the mixed goblet cell carcinoid/adenocarcinomas. All five high-grade neuroendocrine carcinomas were negative for both CK7 and CK20.. Not only the site but also the grade and histological type of a gastrointestinal carcinoma should be considered when assessing cytokeratin phenotype.

Topics: Adenocarcinoma; Carcinoid Tumor; Gastrointestinal Neoplasms; Humans; Immunoenzyme Techniques; Intermediate Filament Proteins; Keratin-20; Keratin-7; Keratins; Neoplasms, Multiple Primary; Prospective Studies

There is no well-established positive immunomarker for urothelial carcinoma. We evaluated the diagnostic utility of high molecular weight cytokeratin (HMWCK) antibody clone 34betaE12 in differentiating high-grade invasive urothelial carcinoma from prostate cancer.. Formalin-fixed paraffin-embedded sections from 28 cases of high-grade invasive urothelial carcinoma (20 not otherwise specified (UC-NOS), eight with glandular differentiation) and 20 cases of poorly differentiated prostate carcinoma were immunostained with a monoclonal antibody to carcinoembryonic antigen (CEA), clone 85A12 and with HMWCK antibody clone 34betaE12 after microwave pretreatment or protease 24 predigestion. All cases of UC-NOS expressed HMWCK on 34betaE12 immunostaining after microwaving or enzyme predigestion. Immunoreactivity was intense and diffuse in all the cases after microwave pretreatment, whilst with enzyme predigestion immunoreactivity was sometimes patchy with <50% tumour cells positive in 20% of cases. In comparison with 34betaE12, 85A12 was insensitive with 15% of UC-NOS cases totally CEA-negative and <50% tumour cell immunoreactivity in 60% of cases. Rare positive cells were present in two (10%) cases of prostate cancer with monoclonal anti-CEA and 34betaE12 on microwaved sections, but all the cases were HMWCK-negative using 34betaE12 on sections pretreated by enzyme digestion.. HMWCK antibody clone 34betaE12, particularly when used with microwave heat retrieval, is a very sensitive positive marker for high-grade invasive urothelial carcinoma.

Topics: Adenocarcinoma; Antibodies, Monoclonal; Biomarkers, Tumor; Carcinoembryonic Antigen; Carcinoma, Transitional Cell; Diagnosis, Differential; Humans; Immunohistochemistry; Keratins; Male; Prostatic Neoplasms; Urinary Bladder Neoplasms

We examined histologically the bile duct lesions from 53 patients with end-stage primary sclerosing cholangitis (PSC) and compared them with similar lesions found in 25 surgically excised carcinomas of the extrahepatic bile ducts not associated with PSC. Of the 53 cases of PSC, 50 bile ducts were obtained at liver transplantation, two common bile ducts were segmentally resected for almost complete obstruction, and the entire extrahepatic biliary tract of another case was obtained at autopsy. Twenty bile ducts from patients who died without evidence of biliary tract disease served as controls. A modest increase in the number of intramural glands (mild hyperplasia) was noted in 13 cases (24.5%) of PSC. A marked increase in the number of intramural glands (florid hyperplasia) was found in 14 cases (26.4%) of PSC. In one case of florid hyperplasia, there was perineural and intraneural invasion of benign hyperplastic glands, which still maintained their lobular pattern. All cases of florid hyperplasia of intramural glands were accompanied by extensive fibrosis and marked nerve proliferation. Three of 24 (12.5%) invasive adenocarcinomas of the extrahepatic bile ducts showed mild hyperplasia of intramural glands without excessive nerve proliferation. Four invasive adenocarcinomas and one in situ carcinoma of the extrahepatic bile ducts showed florid hyperplasia of intramural glands (16%). The hyperplastic intramural glands were p53 negative and had low proliferative activity as measured by the low MIB-1 labeling index. In contrast, both in situ and invasive carcinoma expressed p53 protein and had a high MIB-1 labeling index. Focal high-grade dysplasia was found in one case of PSC (1.8%) and a small invasive adenocarcinoma in another (1.8%). Hyperplasia of intramural glands of the extrahepatic bile ducts is a reactive process that lacks specificity and is part of the morphologic spectrum of end-stage PSC. The incidence of dysplasia in PSC is low. Small invasive adenocarcinomas may be incidentally found in end-stage PSC, and detecting their presence before liver transplantation may be impossible.

Topics: Adenocarcinoma; Adult; Aged; Bile Duct Neoplasms; Carcinoma in Situ; Cholangitis, Sclerosing; Female; Humans; Immunohistochemistry; Keratin-7; Keratins; Male; Middle Aged; Neoplasm Invasiveness; Neoplasm Staging

Topics: Adenocarcinoma; Bile Duct Neoplasms; Bile Ducts, Intrahepatic; Biomarkers, Tumor; Biopsy, Needle; Carcinoma, Hepatocellular; Cholangiocarcinoma; Diagnosis, Differential; Humans; Immunohistochemistry; Keratins; Male; Middle Aged; Sarcoma; Vimentin

The aims of this study were to determine the rate of lymph node micrometastases and to evaluate their prognostic value in lateral lymph nodes in lower rectal cancer at or below the peritoneal reflection.. A retrospective analysis was made of 892 lymph nodes from 66 consecutive patients who had undergone radical resection with lateral lymph node dissection. These lymph nodes were examined immunohistochemically with an antibody against cytokeratins 7 and 8, CAM5.2.. Routine hematoxylin-eosin staining revealed 9 patients with positive lateral lymph nodes that were stained consistently with CAM5.2. Among 57 patients in whom lateral lymph node metastases were not detected by hematoxylin-eosin staining, cytokeratin staining was positive in 19 nodes (2.7 percent) from 11 patients (19.3 percent). These 11 patients with micrometastases in lateral nodes showed a significantly high recurrence rate (P = 0.048) and worse overall survival (P = 0.01) than the 46 patients without lateral node metastases. The recurrence rate and overall survival of patients with micrometastases did not differ significantly from those of patients with positive lateral nodes with hematoxylin-eosin staining. Local recurrence developed in 6 of 66 patients, but neither the presence nor the absence of micrometastases in lateral nodes influenced the local recurrence rate.. The presence of nodal micrometastases leads to a poor prognosis. The survival of patients with micrometastases was not different from that of patients with overt metastases. Therefore, patients with cytokeratin-positive cells in lateral lymph nodes should be regarded as having overt metastases.

Topics: Abdominal Cavity; Adenocarcinoma; Adult; Aged; Aged, 80 and over; Biomarkers; Colectomy; Female; Humans; Immunohistochemistry; Keratin-7; Keratins; Lymph Node Excision; Lymph Nodes; Lymphatic Metastasis; Male; Middle Aged; Neoplasm Metastasis; Neoplasm Recurrence, Local; Prognosis; Rectal Neoplasms; Retrospective Studies; Survival Analysis

Adenocarcinomas of the uterine cervix show a wide range of morphological features, and can be confused with endometrial adenocarcinoma in biopsy or curetting specimens. The objective of this study was to use tissue microarray technology to evaluate the immunoprofile of a large set of uterine adenocarcinomas with an extended panel of antibodies, comparing the profile of primary cervical and endometrial adenocarcinomas. A tissue microarray was constructed using paraffin-embedded, formalin-fixed tissues from 141 hysterectomy specimens. Duplicate 0.6-mm cores were obtained from 57 cervical adenocarcinomas (16 in situ and 41 invasive) and 84 endometrial adenocarcinomas. Tissue array sections were immunostained with 21 commercially available antibodies [B72.3, CD 99, carcinoembryonic antigen (CEA), c-kit, pancytokeratin, CK 5/6, CK 7, CK8/18, CK19, CK 20, CK 22, EMA, estrogen receptor (ER), KP-1, melan-A, p53, PLAP, S-100, synaptophysin, TTF-1, and vimentin] utilizing the avidin-biotin (ABC) technique. Hierarchical clustering analysis of the tumors was done based on the immunostaining results. Only ER ( P<0.001), CEA ( P=0.04), vimentin ( P<0.001), and CK 8/18 ( P=0.002) showed a significantly different frequency of positivity in endometrial relative to cervical adenocarcinomas. ER, vimentin, and CK 8/18 were more likely to be expressed in endometrial adenocarcinomas, while cervical adenocarcinomas more frequently expressed CEA. We were able to identify immunoprofiles that were highly specific for endocervical adenocarcinoma (ER(-), vimentin(-), CK 8/18(-), CEA(+)) or endometrial adenocarcinoma (ER(+), vimentin(+), CK 8/18(+), CEA(-)), but most tumors showed an intermediate, non-specific immunophenotype. Hierarchical clustering analysis was useful in the interpretation of these intermediate immunophenotypes. Papillary serous adenocarcinoma of the endometrium was less likely to express vimentin ( P=0.002) than endometrioid carcinoma of the endometrium.

Topics: Adenocarcinoma; Carcinoembryonic Antigen; Diagnosis, Differential; Endometrial Neoplasms; Female; Humans; Immunohistochemistry; Immunophenotyping; Keratins; Receptors, Estrogen; Uterine Cervical Neoplasms; Vimentin

It has been reported previously in cases of adenosquamous carcinoma of the lung in Okinawa, a subtropical island 2000 km south of mainland Japan, that the squamous cell carcinoma components were positive for human papillomavirus (HPV) by non-isotopic in situ hybridisation (NISH). The adenocarcinoma cells adjacent to the squamous cell carcinoma components were enlarged and also positive for HPV. This is thought to indicate that after adenocarcinoma cells are infected with HPV, they undergo morphological changes, and that "squamous metaplasia" follows. In this present study, the effects of HPV transfection into adenocarcinoma cells were examined. The relation between the region expressing the HPV gene and squamous metaplasia was also studied.. Plasmid pBR322 containing HPV type 16 (HPV-16) was transfected into cultured colonic adenocarcinoma (DLD-1) and lung adenocarcinoma (PC-14) cells using the calcium phosphate method. Neomycin was used as a selection marker. The presence of HPV E1, E2, E4, E5, E6, E7, L1, and L2 mRNAs and also transglutaminase 1, involucrin, cyclin dependent kinases (CDKs), cyclins, caspases, apoptosis inducing factor, DNase gamma, Fas, and Fas ligand mRNAs in HPV transfected cells was investigated by means of reverse transcription polymerase chain reaction (RT-PCR). The G0-G1 cell population was analysed by flow cytometry. Morphological examination under light and electron microscopes was also carried out.. The virus transfected cells showed squamous metaplasia when they were injected into severe combined immunodeficient mice, expressing the high molecular weight keratin (Moll's number 1 keratin) and involucrin molecules immunohistochemically, and involucrin and transglutaminase I mRNAs by RT-PCR. The squamous metaplasia was most conspicuous in the HPV transfected DLD-1 cell when compared with HPV transfected PC-14 cells. Squamous metaplasia was most clearly demonstrated in one HPV transfected DLD-1 cell clone, which expressed not only E2 but also E6-E7 fusion gene mRNA. Viral L1 mRNA expression was absent in HPV transfected cell clones, and was not related to squamous metaplasia. The growth rate of HPV transfected cells was reduced. Transfection of the virus into the cultured adenocarcinoma cells increased the G0-G1 cell population greatly, as assessed by flow cytometer analysis. Furthermore, in the virus transfected cells, apoptosis was also observed by means of the terminal deoxynucleotidyl transferase mediated dUTP biotin nick end labelling method.. HPV transfection into adenocarcinoma cells induced clear squamous metaplasia. One of the HPV transfected cell clones that expressed E2 and E6-E7 fusion gene mRNA showed the squamous metaplasia particularly clearly, and apoptosis was also demonstrated.

Topics: Adenocarcinoma; Animals; Apoptosis; Blotting, Western; Carcinoma, Squamous Cell; Cell Cycle; Cell Differentiation; DNA, Viral; Humans; Keratins; Lung Neoplasms; Metaplasia; Mice; Mice, SCID; Neoplasm Proteins; Neoplasm Transplantation; Papillomaviridae; Protein Precursors; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; RNA, Viral; Transfection; Tumor Cells, Cultured

Animal models that closely mimic clinical disease can be exploited to hasten the pace of translational research. To this end, we have defined windows of opportunity in the transgenic adenocarcinoma of the mouse prostate (TRAMP) model of prostate cancer as a paradigm for designing pre-clinical trials.. The incidence of cancer, metastasis, and distribution of pathology were examined as a function of time in TRAMP mice. The expression of various markers of differentiation were characterized.. The TRAMP model develops progressive, multifocal, and heterogeneous disease. Each lobe of the prostate progressed at a different rate. Cytokeratin 8, E-cadherin, and androgen receptor (AR) were expressed during cancer progression but levels were reduced or absent in late stage disease. A distinct epithelial to neuroendocrine (ENT) shift was observed to be a stochastic event related to prostate cancer progression in TRAMP.. This study will serve as the basis for the rational design of pre-clinical studies with genetically engineered mouse models.

Topics: Adenocarcinoma; Animals; Cadherins; Cell Differentiation; Disease Models, Animal; Disease Progression; Drug Screening Assays, Antitumor; Female; Humans; Immunohistochemistry; Keratins; Male; Mice; Mice, Inbred C57BL; Mice, Transgenic; Prostatic Neoplasms; Receptors, Androgen

A frequent genetic alteration found in premalignant stages of pancreatic adenocarcinoma is K-ras oncogene point mutation. The mechanistic basis for the inability of K-ras mutation to transform pancreatic ductal cells is unclear, although cooperating events with p16 inactivation, p53 mutation, and SMAD 4 mutation are recognized to be necessary. We have generated a novel mouse model in which the cytokeratin 19 promoter, specifically active in pancreatic ductal cells but not other cell types of the pancreas, is fused to mutant K-ras. This is of direct relevance to human pancreatic cancer because premalignant lesions are found specifically in ductal cells. There is dramatic periductal lymphocytic infiltration in the pancreata of transgenic mice, predominantly CD4+ T lymphocytes, which may act as an adaptive immune response to activated ras-mediated signaling. In addition, gene array analysis reveals an induction of N-cadherin in transgenic mice pancreatic ductal cells, the significance of which relates to promotion of cell adhesion and deterrence of cell migration. Apart from these important biological considerations, there is parallel activity of the cytokeratin 19 promoter in the stem cell region of the gastric epithelium, namely in mucous neck cells. Activated K-ras in this context causes mucous neck cell hyperplasia, a precursor to gastric adenocarcinoma. There is concomitant parietal cell decrease, which is a key step toward gastric adenocarcinoma. Taken together, we have defined how mutant K-ras signaling modulates important molecular events in the initiating events of pancreatic and gastric carcinogenesis.

Topics: Adenocarcinoma; Animals; Carcinoma, Pancreatic Ductal; Cell Transformation, Neoplastic; Gastric Mucosa; Genes, ras; Humans; Hyperplasia; Keratins; Lymphocytes, Tumor-Infiltrating; Mice; Mice, Transgenic; Mutation; Pancreatic Neoplasms; Precancerous Conditions; Promoter Regions, Genetic; Stomach Neoplasms; Transfection; Tumor Cells, Cultured

The intraoperative diagnosis of lymph node micrometastasis (LNM) may help guide the area of appropriate lymph node dissection. This study aimed to evaluate the rapid immunohistochemical detection of LNMs using frozen sections during operation for gastro-oesophageal cancer.. Rapid immunostaining with anticytokeratin (AE1/AE3) antibody was compared with conventional immunostaining. A total of 210 lymph nodes obtained from 47 patients with oesophageal squamous cell carcinoma and from 32 with gastric adenocarcinoma were examined during operation. Lymph nodes were frozen, sectioned, and examined by histological and immunohistochemical methods.. It took 30 min to complete the rapid immunostaining procedure; the expression of cytokeratin by rapid immunostaining was similar to that by conventional immunostaining. The incidence of lymph node metastasis detected by histological and immunohistochemical examination was 17 and 23 per cent respectively. LNM was solely detected in 12 lymph nodes by immunostaining: three micrometastases and nine with tumour cell microinvolvement.. : Intraoperative rapid immunostaining is a simple and useful technique for detecting LNMs. Further study should investigate the role of rapid immunostaining during cancer surgery to select appropriate areas for lymphadenectomy.

Topics: Adenocarcinoma; Adolescent; Adult; Aged; Aged, 80 and over; Carcinoma, Squamous Cell; Esophageal Neoplasms; Female; Humans; Immunohistochemistry; Intraoperative Care; Keratins; Lymph Node Excision; Lymphatic Metastasis; Male; Middle Aged; Neoplasm Staging; Stomach Neoplasms

Our objective was to test the prognostic importance of both the pretreatment level and change in serum CYFRA 21-1 after one cycle of chemotherapy in patients with advanced non-small cell lung cancer (NSCLC) and to compare these two CYFRA variables to routine clinical stage and response as measured by imaging.. Our patients consisted of 58 with advanced NSCLC who were treated with chemotherapy. Fourteen were stage IIIa, 8 stage IIIb, and 36 stage IV, and none had received previous treatment. The choice of chemotherapy was left to the discretion of the treating physicians. We collected two serum samples, one before the first cycle of chemotherapy and the second before the second cycle, and analyzed these for serum CYFRA 21-1 using an electrochemiluminescence immunoassay and the ElecSys 2010 system (Roche Diagnostics Corp., Indianapolis, IN). We expressed changes in CYFRA in terms of the natural ratio logarithm of post-treatment to pretreatment CYFRA, and we used the Cox proportional hazards model to analyze survival time.. Patients experienced an average drop of 27% in serum CYFRA after the first cycle of chemotherapy. Furthermore, the Cox model demonstrated that both the initial natural logarithm of serum CYFRA and presence of >27% drop in CYFRA were significantly related to subsequent survival (model P < 0.0006), but neither clinical stage nor clinical response related to survival (P > 0.1).. In advanced stage NSCLC, the initial level of serum CYFRA appears to provide more prognostic information than clinical stage. Furthermore, a drop of >27% in CYFRA after one cycle of therapy adds prognostic information, so that this threshold appears to be an early measure of response to chemotherapy.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Antigens, Neoplasm; Antineoplastic Combined Chemotherapy Protocols; Biomarkers, Tumor; Carcinoma, Non-Small-Cell Lung; Carcinoma, Squamous Cell; Female; Humans; Keratin-19; Keratins; Lung Neoplasms; Male; Middle Aged; Neoplasm Staging; Pilot Projects; Prognosis; Sensitivity and Specificity; Survival Rate

To determine the most optimal treatment of cancer patients, it is fundamental to classify human carcinomas according to their primary anatomical site of origin. As for some patients, it is difficult to identify cancers occurring at obscure location and overlapping adjacent sites. The aim of this study is to partition the primary site of 486 patients in cancers of the digestive system by the expression pattern of the mucins and cytokeratins typifying each site. The expressions of MUC1, MUC2, MUC5AC, MUC6, CK7, CK8, CK13, CK14, CK18, CK19 and CK20 were evaluated immunohistochemically in 426 adenocarcinomas and 60 hepatocellular carcinomas using the tissue-array method. The finding of MUC series showed their characteristics in case of MUC2 in the appendix cancer and MUC1 and 5AC in pancreas cancer. As for CKs 7, 13, and 19, and 20 had a feature in cancers of common bile duct, liver, and appendix, respectively. We classified cancers in 11 sites by characteristic expression of antibodies. The sensitivity, specificity, positive predictive value, and diagnostic efficacy of significant antibodies were calculated with deducing the dichotomous tree made by SPSS 10.0. Six of 11 antibodies, CK 7, CK13, CK19, CK20, MUC1, and MUC5AC distinguished 6 groups from 11 sites. We also executed the clustering of cancers to investigate total relationship among cancers. They fell into three categories, which corresponded to embryologic origin. Unlike other sites, the small intestine and colorectum cancers expressed significantly different patterns to their sublocations. Mucins and CKs showed expression patterns to classify the primary sites of digestive cancers and may be helpful in predicting the primary sites of digestive cancers.

Topics: Adenocarcinoma; Biomarkers, Tumor; Cluster Analysis; Decision Trees; Digestive System Neoplasms; Humans; Immunoenzyme Techniques; Keratins; Mucins; Protein Array Analysis; Tissue Embedding

M cells are found in intestinal follicle associated epithelium. Studies into the physiological and pathological roles of human M cells have been hampered by the lack of well-substantiated, specific markers for these cells. A critical literature review suggests the following molecules may potentially serve as such markers: CK7, FcaR (CD89), S100, CD1a, CD21, CD23, sialyl Lewis A, and cathepsin E. Normal ileum, appendix and colorectum were studied using paraffin-embedded, formalin-fixed tissue and immunohistochemistry for these 8 markers. Cathepsin E immunohistochemistry was also performed on cases of colorectal adenocarcinoma, colorectal adenoma, colorectal hyperplastic/metaplastic polyp, lymphocytic colitis, collagenous colitis, pseudomembranous colitis and active ulcerative colitis. Of the 8 markers tested, only cathepsin E appeared to be specific to follicle associated epithelium (expressed by cells with and without M cell morphology) and follicular crypt epithelium; this specificity was limited to the colorectum. Focal epithelial expression of cathepsin E was seen in adenocarcinoma, adenoma, hyperplastic/metaplastic polyp, ulcerative colitis and pseudomembranous colitis. In conclusion, cathepsin E is a specific marker of normal colorectal follicle associated epithelium and follicular crypt epithelium though is not specific to M cells within these compartments. None of the other 7 markers studied is exclusively expressed by human M cells.

Topics: Adenocarcinoma; Adenoma; Biomarkers; CA-19-9 Antigen; Cathepsin E; Colitis; Colorectal Neoplasms; Epithelial Cells; Humans; Immunoenzyme Techniques; Intestinal Mucosa; Keratin-7; Keratins; Lower Gastrointestinal Tract; Peyer's Patches

There is increasing evidence that neuropeptides, including bombesin, may influence growth, angiogenesis, invasiveness, and metastasis in prostate cancer. One of the molecules tightly involved in the regulation of neuropeptide activity is the integral membrane glycoprotein CD10, or neutral endopeptidase 24.11. The pattern of CD10 expression in hyperplastic and neoplastic conditions of the prostate gland has not been previously described. Immunohistochemical staining for CD10 and high-molecular-weight cytokeratin was performed on 92 cases of paraffin-embedded tissue from needle-core biopsy specimens and prostatectomy specimens. Normal and hyperplastic acini showed strong and distinct membrane (apical and intercellular) and cytoplasmic CD10 expression in basal and secretory cells. In contrast, no intercellular membrane or cytoplasmic staining of secretory cells was seen in any cases of adenocarcinoma with Gleason patterns 2 or 3. A subset of high-Gleason grade adenocarcinoma (patterns 4 and 5) displayed CD10 expression in the secretory cells; those cases shared a distinct morphological pattern. Prostatic intraepithelial neoplasia (PIN) showed consistent absence of intercellular membrane and cytoplasmic CD10 expression in the secretory cells, with preserved expression in basal cells. Interestingly, the basal cells in basal cell hyperplasia lacked CD10 expression, and no expression was noted in the secretory cells in all cases examined. Atrophic acini and those associated with acute and chronic inflammation retained CD10 expression. In conclusion, a consistent differential pattern of CD10 expression was seen in basal cell hyperplasia, PIN, and adenocarcinoma, suggesting a role for CD10 in the pathobiology of the prostate gland.

Topics: Adenocarcinoma; Humans; Keratins; Male; Neprilysin; Prostate; Prostatic Hyperplasia; Prostatic Intraepithelial Neoplasia; Prostatic Neoplasms; Seminal Vesicles

Basal cell proliferation is a common finding in a benign hyperplastic prostate gland. Occasionally, basal cell hyperplasia is so florid that it can be mistaken for prostatic adenocarcinoma. We characterized histological, ultrastructural, and immunohistochemical features of florid basal cell hyperplasia from transurethral resections (n = 11) and prostatectomy specimens (n = 4). Fifteen cases of prostatic adenocarcinoma were used as comparison. Intraluminal calcification was present in 40% of florid basal cell hyperplasia cases (6 of 15) and a unique finding of intracytoplasmic hyaline globules was detected in 53.3% of florid basal cell hyperplasia cases (8 of 15). Ultrastructural analysis revealed luminal calcification and intracytoplasmic electron-dense globules in foci of basal cell hyperplasia. Crystalloids, a frequent finding in low-grade prostate cancer, were absent in all 15 cases of florid basal cell hyperplasia. By immunohistochemistry, the basal cell-specific 34betaE12 and p63 as well as glutathione-s-transferase pi were positive in all basal cell hyperplasia cases but negative in all prostatic adenocarcinomas. These distinguishing features of florid basal cell hyperplasia are helpful in differential diagnosis from prostatic adenocarcinoma. Cytokeratins 8 and 18 were both positive in basal cells, benign secretory cells, and carcinoma cells, failing to be of discrimatory value. Immunostaining for alpha-methylacyl-coenzyme racemase, a new prostate cancer marker, was negative in hyperplastic basal cells but detected a distinct minor benign cell population in basal cell hyperplasia of possible neuroendocrine origin.

Topics: Adenocarcinoma; Biomarkers, Tumor; Diagnosis, Differential; Humans; Immunohistochemistry; Keratins; Male; Microscopy, Electron; Prostatic Hyperplasia; Prostatic Neoplasms; Racemases and Epimerases

Damaged mucosal sites seem to be vulnerable to tumor cell implantation. We describe a case of exfoliated tumor cells from a sigmoid colon cancer seeding a long-standing anal fistula. The implications of this finding are reviewed.

Topics: Adenocarcinoma; Aged; Chronic Disease; Humans; Immunohistochemistry; Intermediate Filament Proteins; Keratin-20; Keratin-7; Keratins; Male; Neoplasm Seeding; Sigmoid Neoplasms

Although tumors consisting of a combination of transitional cell carcinoma (TCC) and adenocarcinoma have been described in the endometrium, they have not been documented in the uterine cervix to our knowledge. Three such cervical cases are reported in this article. Three patients, whose ages ranged from 40 to 61 years, presented with vaginal bleeding and malignant cells on routine Papanicolaou smears. The initial diagnoses based on a biopsy specimen were poorly differentiated squamous cell carcinoma in two patients and adenocarcinoma with a solid component in the third patient. All patients underwent radical hysterectomy. The hysterectomy specimens each contained a polypoid endocervical mass with minimal invasion of the cervical stroma. On microscopic examination, each tumor consisted of a component of papillary TCC admixed with an adenocarcinoma of endometrioid type. Both carcinomatous components were immunoreactive for cytokeratin (CK) 7 but not CK20. The three patients were alive and disease-free from 10 months to 4 years postoperatively. Recognition of this unusual variant of cervical carcinoma is important to delineate its clinical and pathologic features and establish prognostic differences, if any, from other histologic subtypes of cervical carcinoma. Papillary TCC mixed with adenocarcinoma broadens the morphologic spectrum of transitional cell neoplasms of the uterine cervix.

Topics: Adenocarcinoma; Adult; Carcinoma, Transitional Cell; Female; Humans; Hysterectomy; Immunohistochemistry; Intermediate Filament Proteins; Keratin-20; Keratin-7; Keratins; Middle Aged; Neoplasms, Multiple Primary; Papanicolaou Test; Uterine Cervical Neoplasms; Uterine Hemorrhage; Vaginal Smears

Uterine tumors resembling ovarian sex-cord tumors (UTROSCTs) are unusual neoplasms with histologic features that resemble those within ovarian Sertoli and granulosa cell tumors. We report the case of a 24-year-old woman with a UTROSCT presenting as a cervical mass, which on initial evaluation was thought to represent cervical adenocarcinoma. The patient's cervical biopsy specimen contained epithelioid cells arranged in tubules and anastomosing cords, without significant cellular atypia or mitotic activity. Because this morphology elicited a broad differential diagnosis, immunohistochemical studies were performed. The tumor was found to be diffusely positive for cytokeratin cocktail, calretinin, and desmin, focally positive for CK7 and SMA, and negative for EMA, CEA, inhibin, CD10, CK20, chromogranin, and synaptophysin. Ultrastructural examination revealed occasional gland-like lumens with cells joined by desmosomes and a continuous basal lamina. UTROSCTs have features that may cause them to be confused with more common tumors, especially in limited biopsy samples, and should be included in the differential diagnosis when a gland-forming neoplasm with an unusual appearance is identified in a cervical or endometrial biopsy specimen.

Topics: Actins; Adenocarcinoma; Adult; Biopsy; Calbindin 2; Cell Nucleus; Cytoplasm; Desmin; Diagnosis, Differential; Female; Humans; Hysterectomy; Immunohistochemistry; Keratin-7; Keratins; Microscopy, Electron; Muscle, Smooth; Ovarian Neoplasms; S100 Calcium Binding Protein G; Sex Cord-Gonadal Stromal Tumors; Uterine Cervical Neoplasms; Uterine Neoplasms

Intestinal metaplasia is a histologic hallmark of Barrett's esophagus and chronic gastritis. Intestinal metaplasia may progress to dysplasia or carcinomas without proper treatment. Most cases of intestinal metaplasia are easily recognized on hematoxylin and eosin-stained sections. However, some cases of intestinal metaplasia may be hard to recognize if they lack the characteristic mucin-producing cells and Paneth cells, or if they are small in size. Recently, keratin 7, keratin 20, and MUC2 expression patterns were reported to be useful in confirming the diagnosis of intestinal metaplasia. We studied hepatocyte (Hep) antigen (a hepatocellular antigen mainly expressing in normal and neoplastic hepatic tissues) in 33 cases of Barrett's esophagus (9 cases associated with esophageal adenocarcinoma) and 13 cases of chronic gastritis associated with intestinal metaplasia and gastric adenocarcinoma. Hep monoclonal antibody recognizes intestinal metaplasia in all cases. We also compared expression of Hep with that of keratin 7, keratin 20, and MUC2 in intestinal metaplasia. The specificity and sensitivity of Hep for intestinal metaplasia were higher than that of keratin 7 and keratin 20, or MUC2. We conclude that Hep may be used as a single diagnostic marker for intestinal metaplasia.

Topics: Adenocarcinoma; Antibodies, Monoclonal; Barrett Esophagus; Biomarkers, Tumor; Chronic Disease; Esophageal Neoplasms; Gastritis; Hepatocytes; Humans; Immunohistochemistry; Intermediate Filament Proteins; Keratin-20; Keratin-7; Keratins; Metaplasia; Mucin-2; Mucins; Precancerous Conditions; Sensitivity and Specificity; Stomach Diseases

Lung adenocarcinoma presenting as malignant pleural effusion (MPE) is common in Taiwan. Microscopically, the involved pleurae are infiltrated by numerous tumor foci, which suggests that the cancer cells are highly invasive. Overexpression of HER-2/neu has been related to proliferation, antiapoptosis, and the high invasiveness of various cancer cells. We therefore were interested in studying the role of HER-2/neu in MPE-associated adenocarcinoma cell lung cancer (ADCLC).. The expression of HER-2/neu in pleural effusion was measured by ELISA. The HER-2/neu protein expression on tumor cells was evaluated by immunohistochemical (IHC) staining, and gene amplification was assayed by fluorescence in situ hybridization.. The mean value of HER-2/neu in pleural effusions of patients with ADCLC and other nonmalignant lung diseases was 9.9 and 2.7 ng/ml, respectively. The difference is statistically significant (P < 0.001). Compared with cytokeratin 19 fragment CYFRA 21-1, the performance of HER-2/neu as a tumor marker in pleural effusion diagnosis was better. Overexpression of HER-2/neu in tumor tissues was found in 70% (23 of 32) of patients with MPE-associated ADCLC, 30% (13 of 43) with stage I/II non-small cell lung cancer (NSCLC), and 44% (14 of 32) with stage III NSCLC. The incidence of HER-2/neu overexpression in tumor tissues of patients with MPE-associated ADCLC was significantly higher than that of patients with stage I-III NSCLC without MPE. HER-2/neu gene amplification was uncommon (1.9%). The correlation between the IHC H-score in tumor samples and the pleural effusion level of HER-2/neu was significant (P < 0.01). A higher incidence of HER-2/neu expression beyond the cutoff point (5.5 ng/ml) in pleural effusions was also found in patients whose IHC H-scores were >50.. These findings indicate that HER-2/neu is important in the pathogenesis of MPE-associated ADCLC and is a potential tumor marker for a diagnosis of pleural effusion.

Topics: Adenocarcinoma; Antigens, Neoplasm; Apoptosis; Biomarkers, Tumor; Cell Division; Cell Line, Tumor; Dose-Response Relationship, Drug; Enzyme-Linked Immunosorbent Assay; Humans; Immunohistochemistry; In Situ Hybridization, Fluorescence; Keratin-19; Keratins; Lung Neoplasms; Neoplasm Metastasis; Pleural Effusion; Receptor, ErbB-2

Intermediate filament expression in the canine prostate, unlike that in human prostate, is represented in the literature by only a few reports. In this study, the expression of cytokeratin (CK) and vimentin was examined in three normal canine prostates and 11 canine prostatic carcinomas. Monoclonal antibodies directed against vimentin, CK AE1/AE3, CK 18-8 (for luminal epithelial cells), CK 5, CK clone 8.12 and CK 14 (for basal cells) were employed. As in man, normal canine prostatic luminal cells were positive for CK 8-18. Basal cells were positive for CK 5 and CK clone 8.12 but, in contrast to findings in man, were negative for CK 14. Luminal cells were vimentin-negative, whereas in man they have been reported as vimentin-positive. The majority of carcinomas showed an undifferentiated histological pattern and all were positive for CK AE1/AE3 and for vimentin. Ten tumours were positive for CK 8-12, but six of them showed many cells co-expressing CK 14. Moreover, in two of these six cases a large number of neoplastic cells also reacted with CK clone 8.12 antibody, and in one of them co-expression of CK 5 was detectable. This co-expression, of luminal and basal cytokeratins, suggests a possible origin of the tumours from prostatic epithelial stem cells. Vimentin expression is an inconstant finding in human prostatic carcinomas; its almost uniform occurrence in canine carcinomas suggests a lesser degree of differentiation than in the human neoplasm.

Topics: Adenocarcinoma; Animals; Biomarkers, Tumor; Dogs; Immunoenzyme Techniques; Keratins; Male; Prostate; Prostatic Neoplasms

Adenocarcinomas of the distal oesophagus and especially the oesophago-gastric junction have shown an increasing incidence during the last decade. Definition of subgroups according to different sites of development, histogenesis or aetiology may prove to be valuable for clinical diagnosis and treatment. Previous studies have shown differences in cytokeratin patterns between Barrett's metaplasia of the oesophagus and intestinal metaplasia in the stomach. The aim of our study was to investigate whether the expression of certain cytokeratins (CK7, CK20) and mucins (MUC1, MUC2, MUC5AC) exhibit clear-cut patterns, thus allowing a subclassification of adenocarcinomas of the oesophago-gastric junction. The possibility of a relationship between antigen expression and the presence or absence of Barrett's metaplastic epithelium was also studied.. CK7, CK20, MUC1, MUC2 and MUC5AC were visualized in six adenocarcinomas of the distal oesophagus, 29 adenocarcinomas of the oesophago-gastric junction and eight adenocarcinomas of the proximal stomach. CK7, CK20 and MUC1 were strongly expressed in the great majority of all neoplasms under study, whereas MUC2 and MUC5AC were absent or only faintly detectable. CK20 exhibited a significantly stronger expression in poorly differentiated tumours (G3) and MUC1 immunoreactivity correlated with tubular and papillary versus signet-ring cell histopathology. Other statistically significant correlations between antigens and histopathological features (pTNM stage, grading, histopathological subtype, presence/absence of Barrett's epithelium) were not observed.. According to our results, most adenocarcinomas of the oesophago-gastric junction show a CK7+, CK20+, MUC1+ phenotype irrespective of the presence or absence of Barrett's epithelium. The immunohistochemical data suggest a similar histogenesis of these tumours.

Topics: Adenocarcinoma; Barrett Esophagus; Biomarkers, Tumor; Cardia; Esophageal Neoplasms; Esophagogastric Junction; Humans; Immunohistochemistry; Keratins; Metaplasia; Mucins; Neoplasm Staging; Stomach Neoplasms

Expression of the alpha-methylacyl-CoA racemase (AMACR) gene has recently been demonstrated by several groups to be markedly elevated in prostate cancer cells with little expression in benign prostate tissue and has been suggested as a molecular marker of prostate cancer on needle biopsy. There is scant data, however, as to the sensitivity and specificity of AMACR in the diagnosis of small foci of cancer on needle biopsy. A total of 209 needle biopsies of the prostate with small foci (<5% of a core) of prostatic adenocarcinoma were identified. A total of 175 cases were received in consultation by one of the authors (140 from a single institution and 35 from different outside institutions) and 34 cases were from our hospital file. Immunohistochemistry for high molecular weight cytokeratin and p63 was performed in all cases to confirm the diagnosis of cancer. Only AMACR staining that was significantly stronger than that of background benign glands was considered positive; 88% of all cases of prostate cancer were positive for AMACR. The sensitivity varied among the different groups: 100% for the in house cases, 87.1% for the cases from a single institution, and 80% for cases from different outside institutions. The mean percentage of stained glands in positive cases was 95.9%, with 150 (71.8%) cases showing 100% of the glands positive and 25 (12.0%) cases showing no staining. Because negative staining for basal cell markers, especially in a small focus of atypical glands, is not necessarily diagnostic of prostate cancer, positive staining for AMACR can increase the level of confidence in establishing a definitive malignant diagnosis. However, the sensitivity of AMACR staining may vary in specimens from different pathology laboratories, possibly related to differences in fixation and processing. It is important to optimize the staining technique for each laboratory and recognize that some small cancers on needle biopsy may be AMACR negative.

Topics: Adenocarcinoma; Biomarkers, Tumor; Biopsy, Needle; DNA-Binding Proteins; Genes, Tumor Suppressor; Humans; Immunohistochemistry; Keratins; Male; Membrane Proteins; Phosphoproteins; Prostatic Neoplasms; Racemases and Epimerases; Sensitivity and Specificity; Trans-Activators; Transcription Factors; Tumor Suppressor Proteins

It was recently shown that neuropilin-1 (NRP-1), which was described originally as a receptor for the semaphorins/collapsins (ligands involved in neuronal guidance), is a coreceptor for vascular endothelial growth factor (VEGF) and increases the affinity of specific isoforms of VEGF to its receptor, VEGF-R2.. The authors investigated the expression and regulation of NRP-1 in human pancreatic adenocarcinoma specimens and cell lines.. Immunohistochemical analysis revealed that NRP-1 was expressed in 12 of 12 human pancreatic adenocarcinoma specimens but was absent in nonmalignant pancreatic tissue. Northern blot analysis revealed NRP-1 mRNA expression in 8 of 11 human pancreatic adenocarcinoma cell lines. NRP-1 mRNA expression was increased by epidermal growth factor (EGF) but not by tumor necrosis factor alpha in several of the human pancreatic adenocarcinoma cell lines studied. Treating human Panc-48 adenocarcinoma cells with EGF activated Akt and Erk but not P-38. Blockade of the phosphatidylinositol-3 kinase (PI-3K)/Akt, mitogen-activated protein kinase (MAPK)/Erk, or P-38 pathways abrogated EGF-induced NRP-1 expression. Finally, EGF receptor blockade in vivo led to a decrease in NRP-1 expression in an orthotopic model of human pancreatic carcinoma.. NRP-1 is expressed in most human pancreatic adenocarcinomas and cell lines but not in nonmalignant pancreatic tissue. EGF regulates NRP-1 expression through the PI-3K/Akt and MAPK/Erk signaling pathways, and blockade of the EGF receptor is associated with decreased expression of NRP-1 in vivo. NRP-1 may act as a coreceptor for VEGF in pancreatic carcinoma, as it does in other tumor systems, thereby enhancing angiogenesis and the effect of VEGF on the growth of pancreatic adenocarcinoma.

Topics: Adenocarcinoma; Blotting, Northern; Dose-Response Relationship, Drug; Epidermal Growth Factor; Humans; Immunohistochemistry; Keratins; Mitogen-Activated Protein Kinases; Neuropilin-1; Pancreas; Pancreatic Neoplasms; Phosphatidylinositol 3-Kinases; Receptors, Vascular Endothelial Growth Factor; RNA, Messenger; Signal Transduction; Tumor Cells, Cultured; Tumor Necrosis Factor-alpha

The sentinel node (SN) is the first lymph node in the lymphatic basin to be affected by metastasis from the primary tumour and is used to predict the status of the remaining nodes in the basin. We succeeded in detecting SNs of clinically early gastric cancers by intraoperative injection of a blue dye around the tumour. In the study presented here, multiple-marker reverse transcription-polymerase chain reaction (RT-PCR) was used to detect micrometastases in SNs and results were compared with those obtained with conventional histology. Expressions of cytokeratin-18 (CK-18), carcinoembryonic antigen (CEA), human telomerase reverse transcriptase (hTRT) and MUC-1 in SNs were determined by RT-PCR and Southern blot assay. Of the 213 SNs obtained from 35 cases of gastric cancer, eight nodes (3.8%) from five patients contained metastases that could be identified by conventional histology. However, CK-18 mRNA was expressed in 15 (7.0%), CEA in 12 (5.6%), hTRT in 10 (4.7%), and MUC-1 in 12 (5.6%) nodes, with at least one mRNA marker expressed in 25 nodes (11.7%) obtained from six patients. In the five patients with nodal metastases identified by conventional histology, two had metastases in both SNs and non-SNs. And, in the 30 patients without nodal metastases identified by conventional histology, one patient with micrometastases in the SNs identified by RT - PCR and Southern blot assay also had metastases in non-SNs as identified by serial sectioning and immunostaining of CK-18. All additional metastases were detected in non-SNs located in the same lymphatic basin as the previously detected SNs. This suggests that lymph node dissection of early-stage gastric cancer in the lymphatic basin may be mandatory even for patients without histologically detectable metastases in SNs.

Topics: Adenocarcinoma; Adenocarcinoma, Papillary; Blotting, Southern; Carcinoembryonic Antigen; Carcinoma, Signet Ring Cell; Case-Control Studies; DNA Primers; DNA-Binding Proteins; Gastrectomy; Humans; Keratins; Lymph Node Excision; Lymphatic Metastasis; Mucin-1; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; RNA, Neoplasm; Sensitivity and Specificity; Sentinel Lymph Node Biopsy; Stomach Neoplasms; Telomerase

To evaluate the utility of thyroid transcription factor-1 (TTF-1), surfactant protein-B, (SP-B) cytokeratin 7 (CK7) and CK20 immunostaining in the discrimination between primary adenocarcinomas and metastatic adenocarcinomas.. Formalin fixed, paraffin embedded tissue blocks from 42 primary lung adenocarcinomas and 30 metastatic carcinomas resected during operation were immunostained with monoclonal antibodies to TTF-1, SP-B, CK7, and CK20.. Positive immunostaining with TTF-1 and SP-B was noted in 74% and 52% of primary lung tumor, respectively. The positive immunostaining and specificity of such a combination for discriminating between primary and metastatic adenocarcinoma were 79% and 94%, respectively. All primary lung adenocarcinomas were CK7 positive, 24 (57%) were CK7 positive/CK20 negative and 18 were CK7 positive/CK20 positive in immunophenotype. Colon and breast were the most common sites of metastasis. All metastatic colorectal adenocarcinomas were CK20 positive, 11 (92%) were CK7 negative/CK20 positive and 1 was CK7 positive/CK20 positive in immunophenotype. The results of cytokeratin immunostaining in the metastatic breast tubular carcinomas were similar to those in the primary lung adenocarcinomas: 4 were CK7 positive/CK20 negative and 4 were CK7 positive/CK20 positive. CK7 positive, and TTF-1 or SP-B positive immunophenotype was seen in 33 (79%) primary lung tumors. A combination of CK7 negative, CK20 positive, and TTF-1 and SP-B negative was highly significantly associated with metastatic colorectal carcinomas compared with either primary lung adenocarcinomas or metastatic breast carcinomas (both P < 0.001). A combination of CK7 positive, CK20 negative, and TTF-1 and SP-B negative was highly significantly associated with metastatic breast carcinomas compared with either primary lung adenocarcinomas or metastatic colorectal carcinomas (both P < 0.001).. Use of a panel of antibodies including TTF-1, SP-B, CK7 and CK20 is helpful in discriminating between primary and metastatic adenocarcinomas of the lung and suggesting the primary sites of some metastatic adenocarcinomas.

Topics: Adenocarcinoma; Diagnosis, Differential; Humans; Immunohistochemistry; Intermediate Filament Proteins; Keratin-20; Keratin-7; Keratins; Lung Neoplasms; Nuclear Proteins; Pulmonary Surfactant-Associated Protein B; Thyroid Nuclear Factor 1; Transcription Factors

Expression of Fas ligand (FasL/CD95L) may help to maintain colon cancers in a state of immune privilege by inducing apoptosis of antitumor immune effector cells. Colon tumor-derived cell lines appear to be relatively insensitive to apoptosis mediated by their own or exogenous FasL in vitro, despite expression of cell surface Fas. In our present study, we sought to investigate if FasL upregulated in human colon cancers leads to any increase in apoptosis of the tumor cells in vivo. FasL and Fas receptor (APO-1/CD95) expression by tumor cells were detected immunohistochemically. Apoptotic tumor cell death was detected by immunohistochemistry for caspase-cleaved cytokeratin-18. FasL expression did not correlate with the extent of apoptosis of tumor cells. There was no significant local difference in the frequency of apoptosis of tumor cells between tumor nests that expressed FasL (mean = 2.4%) relative to those that did not (mean = 2.6%) (p = 0.625, n = 10; Wilcoxon signed rank). FasL expressed by the tumor cells appeared to be functional, since FasL expression in tumor nests correlated with diminished infiltration of tumor-infiltrating lymphocytes (TILs). TILs were detected using immunohistochemistry for CD45. Expression of FasL by tumor nests was associated with a mean 4-fold fewer TILs relative to FasL-negative nests (range 2.4-33-fold, n = 10, p < 0.003). Together, our results indicate that colon tumors are insensitive to FasL-mediated apoptosis in vivo.

Topics: Adenocarcinoma; Apoptosis; Colonic Neoplasms; Fas Ligand Protein; fas Receptor; Female; Humans; Immunoenzyme Techniques; In Situ Nick-End Labeling; Keratins; Leukocyte Common Antigens; Ligands; Lymphocyte Depletion; Lymphocytes, Tumor-Infiltrating; Male; Membrane Glycoproteins; Up-Regulation

We evaluated the sensitivity and specificity of cytokeratin (CK) 5/6 for distinguishing foci of atrophy from prostatic adenocarcinoma with and without previous hormonal adjuvant therapy and observed the intensity and pattern of staining in mimickers of prostatic adenocarcinoma (basal cell hyperplasia, atypical adenomatous hyperplasia, and tangentially cut high-grade prostatic intraepithelial neoplasia [PIN]). We reviewed 146 acinar proliferations in 81 specimens (radical prostatectomy, previously untreated, 41; radical prostatectomy, following androgen-deprivation therapy, 11; transurethral resection, previously untreated, 29). All benign acinar proliferations stained positively for CK5/6, with immunoreactivity restricted to basal cells. Untreated and androgen-deprived prostatic adenocarcinomas were invariably negative. The pattern of staining was continuous in 79% of the atrophy cases (15/19), and all foci stained with CK5/6. Characteristic double-layer staining in basal cell hyperplasia was observed in 93% of cases (13/14), and foci of high-grade PIN had a characteristic "checkerboard" staining with areas of discontinuity. Foci of atypical adenomatous hyperplasia showed continuous staining, including cauterized acini in 53% of cases (8/15), with a fragmented basal cell layer pattern in 47% of cases (7/15). CK5/6 staining of the basal cells in foci of atrophy is sensitive and specific for excluding prostatic adenocarcinoma with and without androgen-deprivation effect.

Topics: Adenocarcinoma; Androgen Antagonists; Atrophy; Diagnosis, Differential; Humans; Keratins; Male; Prostate; Prostatic Hyperplasia; Prostatic Intraepithelial Neoplasia; Prostatic Neoplasms

The current authors previously identified circulating cells expressing carcinoembryonic antigen (CEA) messenger ribonucleic acid (mRNA) in 80% of lung cancer patients bearing distant metastases. The current study prospectively validated the data on a novel cohort and extended the study to other mRNAs expressed by neoplastic cells. CEA, cytokeratin 19 and 20, aldolase A and epithelial glycoprotein 2 (EPG2) mRNA was analysed by reverse transcriptase-polymerase chain reaction in circulating cells from 19 healthy controls, and in biopsies and blood at diagnosis from 32 lung cancer patients monitored for 24 months. Aldolase A and cytokeratin 19 mRNA occurred in circulating cells of all controls; cytokeratin 20 was not expressed by any lung cancer biopsy. EPG2 mRNA occurred in all biopsies but not in the patients' circulating cells. CEA mRNA occurred in 29/32 (90.6%) biopsies and in 17/32 mRNA samples from circulating cells from lung cancer patients. Of these positive patients 12/17 developed metastases within 9 months of mRNA analysis. Three positive patients died, one was lost to follow-up, and one did not develop metastases within 24 months. Of the negative patients 12/15 did not develop metastases during the 24-month follow-up; one patient was lost to follow-up, one did not express CEA, and another developed metastases. Unlike in other neoplasias, cytokeratin 19 and 20, aldolase A and epithelial glycoprotein 2 messenger ribonucleic acid are not useful for the detection of circulating cancer cells in lung cancer. Carcinoembryonic antigen messenger ribonucleic acid analysis in circulating cells helps to identify lung cancer patients at a greater risk of metastases.

Topics: Adenocarcinoma; Antigens, Neoplasm; Biomarkers, Tumor; Carcinoembryonic Antigen; Carcinoma, Squamous Cell; Case-Control Studies; Cell Adhesion Molecules; Epithelial Cell Adhesion Molecule; Female; Fructose-Bisphosphate Aldolase; Humans; Intermediate Filament Proteins; Keratin-20; Keratins; Lung Neoplasms; Male; Middle Aged; Neoplasm Metastasis; Neoplasm Staging; Prospective Studies; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger

Immunohistochemistry is an important tool when dealing with salivary gland neoplasms. Canalicular adenoma and polymorphous low-grade adenocarcinoma may share some histologic characteristics that can cause difficulties in their separation. In the present study, cases of polymorphous low-grade adenocarcinoma and canalicular adenoma were submitted to a panel of antibodies to evaluate the differences in their immunoprofiles. The results obtained showed that, while vimentin is only expressed by polymorphous low-grade adenocarcinoma, CK7 and CK8 are present in both neoplasms. Therefore, vimentin is the best marker to differentiate between these tumors.

Topics: Adenocarcinoma; Adenoma; Biomarkers, Tumor; Humans; Immunohistochemistry; Keratin-7; Keratins; Salivary Gland Neoplasms; Salivary Glands, Minor; Vimentin

Making a preoperative pathologic diagnosis in patients with small lung nodules remains challenging. We have developed a new, noninvasive bronchoscopic microsampling probe to examine biochemical substances in epithelial lining fluid. We used this probe to measure tumor markers in fluid from tissues surrounding lung nodules less than 30 mm in diameter to test its adjunctive diagnostic utility in lung cancer.. In 12 patients, epithelial lining fluid was collected in triplicate or duplicate from tissue within 2 cm of small peripheral lung nodules and from the contralateral lung. The diagnosis of adenocarcinoma was surgically confirmed in all patients. Fifteen patients without lung cancer served as controls. Concentrations of carcinoembryonic antigen, cytokeratin fragment 19, and sialyl SSEA-1 were measured in the fluid.. Carcinoembryonic antigen and cytokeratin fragment 19 concentrations were significantly higher in fluid near the nodules (median, 8.7 and 87.2 ng/mg, respectively) than on the contralateral sides (median, 1.5 and 3.7 ng/mg, respectively) or in fluid collected from the controls (median, 2.0 and 2.8 ng/mg, respectively).. Measurements of carcinoembryonic antigen and cytokeratin fragment 19 collected by our microsampling probe may be a useful diagnostic adjunct in patients with small peripheral lung nodules.

Topics: Adenocarcinoma; Aged; Aged, 80 and over; Biomarkers, Tumor; Biopsy, Needle; Bronchoscopes; Bronchoscopy; Carcinoembryonic Antigen; Case-Control Studies; Equipment Design; Female; Humans; Immunohistochemistry; Keratins; Lewis X Antigen; Lung Neoplasms; Male; Middle Aged; Neoplasm Staging; Prognosis; Prospective Studies; Sensitivity and Specificity; Treatment Outcome

Cdx-2 is expressed in normal colonic epithelia and in most colorectal adenocarcinomas. No data exist on Cdx-2 expression in primary cervical adenocarcinoma with colonic differentiation.. To ascertain the utility of Cdx-2 and a limited immunohistochemical panel in differentiating between primary cervical adenocarcinoma with intestinal differentiation and secondary (colonic) cervical adenocarcinoma, which call for different surgical and chemotherapeutic treatment protocols.. We examined cervical tract adenocarcinomas in women with previously negative medical histories for neoplastic disease and in women with colonic carcinoma. An immunohistochemical panel consisting of cytokeratin 7, cytokeratin 20, carcinoembryonic antigen, and a new marker, Cdx-2, was evaluated in all cases. The clinical data, the morphologic features, and the immunohistochemical staining patterns were compared.. Of the tumors diagnosed as metastatic intestinal adenocarcinoma of the cervix, based on clinical data and hematoxylin-eosin-stained sections, all were Cdx-2 positive, whereas Cdx-2 was not expressed in any of our cases of primary cervical adenocarcinoma with colonic differentiation. Carcinoembryonic antigen was expressed both in primary cervical tumor and in secondary (intestinal) cervical adenocarcinoma. Cytokeratin 20 was not expressed in our cases of cervical adenocarcinoma, and it was not expressed in 7.15% of cervical metastases from intestinal carcinoma. Immunostaining with cytokeratin 7 was positive in cervical adenocarcinoma, but was negative in secondary (intestinal) cervical adenocarcinoma.. Our immunohistochemical analysis shows that Cdx-2 has good specificity and would be a good marker to use in a limited panel of immunohistochemical markers, such as cytokeratin 7, cytokeratin 20, and carcinoembryonic antigen, to distinguish primary cervical adenocarcinoma from intestinal metastases to the cervix.

Topics: Adenocarcinoma; Carcinoembryonic Antigen; Carcinoma; CDX2 Transcription Factor; Cell Differentiation; Colon; Colonic Neoplasms; Diagnosis, Differential; Female; Homeodomain Proteins; Humans; Immunohistochemistry; Intermediate Filament Proteins; Keratin-20; Keratin-7; Keratins; Trans-Activators; Uterine Cervical Neoplasms

The current study examined cytokeratin (CK)7 and 20 as well as MUC1-6 immunoprofiles in oesophageal, gastric and gastro-oesophageal junction (GOJ) adenocarcinomas. The aim was to compare expression patterns in these locations as aids to accurate classification of these morphologically similar carcinomas which all may involve the GOJ.. Tissue microarrays were constructed using tissue from 14 oesophageal, 78 gastric and 39 GOJ adenocarcinomas. Sections were immunostained with CK7, CK20, MUC1, MUC2, MUC5AC and MUC6. The results of this study showed no differences in CK7 and CK20 expression patterns in the three locations. MUC2 expression was higher proximally (43% of oesophageal, 28% of GOJ and 17% of gastric carcinomas) and MUC6 expression was higher distally (7% of oesophageal, 28% of GOJ and 15% of gastric carcinomas). MUC1 expression was associated with higher pTNM-stage.. CK 7/20 profiles have no role in distinguishing tumours of the three locations. Mucin expression patterns differed in oesophageal and gastric adenocarcinomas, although not sufficiently to classify individual cases. GOJ adenocarcinomas showed a mucin expression pattern that was partly 'gastric', and partly 'oesophageal'. MUC1 expression was associated with a higher pTNM stage.

Topics: Adenocarcinoma; Aged; Biomarkers, Tumor; Esophageal Neoplasms; Female; Humans; Immunohistochemistry; Intermediate Filament Proteins; Keratin-20; Keratin-7; Keratins; Male; Middle Aged; Mucins; Neoplasm Staging; Stomach Neoplasms

Adenocarcinomas of nonsalivary origin represent approximately 10% to 20% of all sinonasal malignancies and are characterized by varying histopathologic features and uncertain histogenesis. To better understand the histogenesis and phenotypic heterogeneity of these tumors, we performed immunohistochemical analyses for cytokeratin (CK) 7 and CK20 on 12 primary sinonasal adenocarcinomas (SNACs) representing the histopathologic spectrum of these tumors, adjacent normal mucosa, and 2 metastatic adenocarcinomas from colonic primaries. The demographic and clinicopathologic characteristics of our cohort were similar to those in previously published series. Our results indicate that histologically normal respiratory-type epithelium and submucosal seromucous glands show restricted reactivity to CK7. Epithelial metaplasia of surface epithelium associated with enteric SNACs was accompanied by a conversion from CK7 positivity to CK20 positivity. All primary enteric-type carcinomas and the 2 colonic metastases were reactive to CK20, but all nonenteric-type tumors were negative for CK20 (P=0.003) and positive for CK7. In some of the enteric types, coexpression of CK7 and CK20 was noted. We conclude that (1) nonenteric-type (seromucinous) adenocarcinoma may originate directly from surface respiratory-type epithelium or from seromucous glands, (2) metaplastic transformation of surface respiratory to enteric-type epithelium precedes the development of enteric adenocarcinoma, and (3) coordinate analyses of CK7 and CK20 reactivity may aid the differential diagnosis of adenocarcinoma in the sinonasal tract.

Topics: Adenocarcinoma; Aged; Aged, 80 and over; Biomarkers, Tumor; Cell Transformation, Neoplastic; Colonic Neoplasms; Diagnosis, Differential; Humans; Immunohistochemistry; Intermediate Filament Proteins; Keratin-20; Keratin-7; Keratins; Male; Middle Aged; Nose Neoplasms; Paranasal Sinus Diseases; Phenotype; Respiratory Mucosa

Colonic mucosa typically expresses cytokeratin (CK) 20 but not CK7. This CK20+/CK7- profile has been used to distinguish colonic adenocarcinoma from others arising in the lung, breast, or genitourinary tract. CK7 expression in colorectal adenocarcinoma has been reported to be rare, and when present, a metastatic origin needs to be excluded. However, we have observed a higher frequency of CK7 positivity in rectal adenocarcinomas. Paraffin sections of 42 rectal tumors (7 adenomas and 35 adenocarcinomas), 11 colonic adenocarcinomas proximal to the rectum, and 18 nonneoplastic rectoanal mucosa were randomly selected and immunostained for CK7 and CK20 with a standard avidin-biotin complex method. Immunoreactivity was recorded semiquantitatively. Cytoplasmic CK7 immunoreactivity was noted in 29 of 42 (69%) rectal glandular neoplasms (3 of 7 adenomas [43%] and 26 of 35 adenocarcinomas [74%]) and 9 of 18 (50%) nonneoplastic anorectal mucosal samples. In contrast, only 3 of the 11 (27%) colonic adenocarcinomas proximal to rectum were CK7 positive. Because of the relatively higher frequency of CK7 expression in rectal epithelial neoplasms, when CK7 is applied to distinguish primary colorectal versus metastatic origin, its reactivity should be interpreted with caution and should not be used as the sole evidence for excluding a rectal primary, particularly in tumors involving the rectal or pelvic region.

Topics: Adenocarcinoma; Antigens, Neoplasm; Colonic Neoplasms; Diagnosis, Differential; Humans; Immunohistochemistry; Intermediate Filament Proteins; Keratin-20; Keratin-7; Keratins; Neoplasm Metastasis; Rectal Neoplasms; Sensitivity and Specificity

Although cytokeratin (CK) phenotyping of metastatic tumors is now routine in many laboratories, the clinical relevance of the procedure has seldom been addressed. We carried out a prospective clinical study of 134 consecutive cases of metastatic adenocarcinoma of the liver diagnosed by needle biopsies stained routinely for CK20 and CK7. The most probable localization of the primary tumor, deduced from this staining pattern, was stated in the original pathology report. The present study compared this assignment with the information available at the time of interpretation of the liver biopsy, to the results of the subsequent clinical investigation, and to the officially reported cause of death as outcome. As expected, the primary tumors were localized in the colon or in the rectum in 85% (34/40) of the CK20+/CK7- metastases. The definite diagnosis remained metastatic colorectal carcinoma in 83% (15/18) of the cases with diagnosed colorectal cancer before the liver biopsy. In the cases without a known primary tumor when the liver biopsy was interpreted, primary colorectal localization was accurately predicted in 86% (19/22) of the patients. Compared to the outcome, 77% (36/47) of the CK20+/CK7+ metastases had the expected pancreaticobiliary primary localization in 83% (30/36) without any primary tumor being known at the time of interpretation of the liver biopsy. In contrast, the majority of CK20- metastatic carcinomas had an unexpected primary localization, 50% (16/32) in the CK20-/CK7+ and 60% (9/15) in the CK20-/CK7- subgroup. In addition, the origin of the liver metastasis remained unknown in 37% (12/32) of CK20-/CK7+ cases. Thus, the CK20+/CK7- phenotype indicates a colorectal origin of the liver metastasis with considerable accuracy and independently of the available clinical information. The same is true for CK20+/CK7+ metastases, which indicate primary tumor localization in the pancreas or in the biliary tree. The results in the CK20- subgroups of the liver metastases are disappointing and cannot substantially help the clinical investigation.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Biliary Tract Neoplasms; Biomarkers; Biopsy, Needle; Colorectal Neoplasms; Female; Humans; Immunohistochemistry; Intermediate Filament Proteins; Keratin-20; Keratin-7; Keratins; Liver; Liver Neoplasms; Male; Middle Aged; Neoplasms, Unknown Primary; Pancreatic Neoplasms; Phenotype; Retrospective Studies

Micrometastases consisting of one to a few cells in lymph nodes resected during gastrectomy are difficult to identify using conventional hematoxylin and eosin (H&E) stains. It has been shown that immunostaining for cytokeratins is effective in detecting lymph node micrometastasis in a variety of human tumors, but only a few previous reports demonstrated its use in the treatment of patients with early and advanced gastric carcinoma, and those reports had conflicting results.. In this study, 3625 regional lymph nodes that were dissected in gastrectomy specimens from 153 patients with early-stage gastric carcinoma (46 patients) and advanced gastric carcinoma (107 patients) were immunostained with the anticytokeratin cocktail AE1/3 for micrometastasis (median, 23 lymph nodes; range, 8-66 lymph nodes). Micrometastasis (MM) was defined as a single tumor cell or clusters of tumor cells that were missed on conventional examination with H&E stains but were detected by immunostaining with broad-spectrum anticytokeratin antibodies.. Lymph node metastasis (LNM) was detected in 609 lymph nodes (17%) by H&E staining. MM was identified in another 191 of the remaining lymph nodes (6.3%) from 75 patients. Twenty-eight of those patients were up-staged. There was a significant correlation between MM and depth of tumor invasion (P < 0.01). Patients with MM had a decreased 5-year survival rate (49%) compared with patients without MM (76%) for both early and advanced gastric carcinoma. The effect of MM on survival was most pronounced for patients in the Stage I and LNM negative group.. Immunohistochemical examination using broad-spectrum anticytokeratin antibodies increased the detection rate of LNM and had a significant impact on staging and survival in patients with gastric carcinoma.

Topics: Adenocarcinoma; Follow-Up Studies; Humans; Immunoenzyme Techniques; Intestinal Neoplasms; Keratins; Lymph Nodes; Lymphatic Metastasis; Neoplasm Staging; Prognosis; Stomach Neoplasms; Survival Rate

Keratin 903 (also known as anti-cytokeratin antibody 34betaE12) is widely used to differentiate benign glands from malignant glands in prostate needle biopsies. However, it is subject to considerable staining heterogeneity. We sought to evaluate the use of cytokeratin 5/6 (CK5/6) as an effective alternative to K903 in the evaluation of prostate needle biopsies in clinical practice.. Thirty Hollandes-fixed prostate needle biopsies were randomly selected over a period of 2 months from the surgical specimens accessioned over that period of time. Twelve cases had diagnosed prostatic adenocarcinoma (Gleason scores 3 + 3, 3 + 4 and 4 + 4) and the remaining cases (n = 18) were negative for carcinoma. Four sequential sections were stained with H&E (x2), K903, and CK5/6. Care was taken to preserve tissue so that matching glands were evaluated on all four sections. All cases were run routinely over a period of 3 weeks on a daily basis with matching positive controls. All slides were evaluated in a blinded fashion independently by two pathologists using a semiquantitative analysis of staining: <25%, 25-50%, 50-75%, >75% and >95% of benign glands (verified on H&E). Cases that showed no staining were repeated to ensure no false negatives. Both observers agreed with respect to percentage of staining in 96% of the cases. Twenty-nine of 30 cases (97%) showed staining in >95% of benign glands with CK5/6. In contrast, K903 staining was seen in <50% of benign glands in five of 30 (17%), 50-75% in nine of 30 (30%), and >75% in 10 of 30 (33%), with only two cases (7%) showing >95% staining for K903. In four cases (13%) the K903 failed to stain any tissue even after repeat staining. K903 was conspicuously negative in atrophic glands in three of 30 cases (10%). Neither K903 nor CK5/6 stained malignant glands. Using a cut-off of >75% staining in benign glands the sensitivity of CK5/6 and K903 was 97% and 40%, respectively.. CK5/6 has superior sensitivity and reliability compared with that of K903 when evaluating routine prostate needle biopsies, including improved staining of atrophic prostatic glands. While K903 is traditionally used to differentiate benign glands from malignant glands, these results support the use of CK5/6 as an effective and reliable substitute for K903 in routine clinical practice.

Topics: Adenocarcinoma; Antibodies, Monoclonal; Biomarkers, Tumor; Biopsy, Needle; Diagnosis, Differential; Humans; Immunoenzyme Techniques; Keratins; Male; Prostate; Prostatic Neoplasms; Reproducibility of Results

Basaloid squamous carcinoma (BSC) is an aggressive variant of squamous cell carcinoma (SCC) with a predilection for the upper aerodigestive tract. In the English literature, approximately 40 cases of BSC have been described in the oral cavity. BSC has frequently been confused with adenoid cystic carcinoma (ACC), basal cell adenocarcinoma, and undifferentiated SCC. The purpose of the investigation was to examine the histological features and immunohistochemical expression of differentiation-related substances, including cytokeratin (CK) subtypes, vimentin, S-100, chromogranin, laminin, and type IV collagen, for the characterization of biological features of these tumours. We studied three cases of BSC of the oral cavity, three cases of ACC, and one case of basal cell adenocarcinoma. Well-differentiated and undifferentiated SCCs were also studied for comparison. The BSCs showed many histopathologic similarities to cases previously reported. Among the CK subtypes analyzed, CK14 was the only subtype expressed by all basaloid cells of BSC. Potentially useful for the differential diagnosis was the finding of CKs 7 and 19 expression in the basaloid cells of ACC, and CKs 7 and 8 in basal cell adenocarcinoma. In BSCs, laminin and type IV collagen were found in the microcystic spaces between basaloid cells, but neither ACCs nor basal cell adenocarcinoma showed this feature. These data suggest that immunohistochemical findings are helpful in distinguishing BSC of the oral cavity from other histopathologically similar tumours.

Topics: Adenocarcinoma; Carcinoma, Adenoid Cystic; Carcinoma, Squamous Cell; Carcinoma, Transitional Cell; Diagnosis, Differential; Humans; Immunohistochemistry; Keratins; Mouth Neoplasms

The aim of this study was to determine the immunoprofile of salivary duct carcinoma and to differentiate intraductal growth from invasive growth.. We applied a panel of antibodies (cytokeratins 7, 8, 13, 14, 19, vimentin and alpha-smooth muscle actin) in five cases of salivary duct carcinoma. This panel is currently used for identification of different components of salivary gland tumours in our laboratory. All tumour cells were positive for cytokeratins 7 and 8. Few neoplastic structures expressed cytokeratin 14 in cells surrounding tumour islands.. The finding of cytokeratin 14 was important to confirm the in-situ intraductal growth, which probably characterizes this low-grade neoplasm.

Topics: Adenocarcinoma; Aged; Biomarkers, Tumor; Female; Humans; Immunohistochemistry; Keratins; Male; Middle Aged; Parotid Neoplasms

Rare reports describe high molecular weight cytokeratin (clone 34betaE12) antibody cross-reactivity in scattered prostate carcinoma (PCa) cells, yet most often not in a true basal cell distribution. There are no data specifically describing 34betaE12 reactivity in basal cells in PCa. From August 10, 1995 to May 1, 2000, a total of 3198 consult prostate needle biopsies with PCa and a 34betaE12 immunoperoxidase stain were reviewed at our institution. Thirty-six cases (1.1%), which on hematoxylin and eosin stain were unequivocal cancer, had at least focal 34betaE12 positivity in a basal cell distribution. Twenty-five had original diagnostic slides for review. All cancers were Gleason score 6. The mean number of cancer glands per case was 36.9 (10-108) with an average of 39% of glands (1-100%) showing 34betaE12 reactivity. Twenty-one cases had patchy staining in a basal cell distribution with one other case showing continuous staining. An additional case showed mainly tumor cell reactivity with rare basal cell staining. The final two cases showed a zonal staining pattern with small glands toward one side of the lesion showing basal cells [one with high grade prostatic intraepithelial neoplasia (HGPIN); one without HGPIN]. HGPIN was present in 16 of 25 (64%) cases adjacent to PCa. The mean number of HGPIN glands was 1.36 (1-6). In cases with HGPIN the mean ratio of cancer to HGPIN glands was 6.8 (0.5-13.0). In 12 cases in which the lesion was still present on deeper sectioning, we were able to confirm in nine cases the presence of basal cells using antibodies to p63, another marker for prostatic basal cells. Four of the 25 men underwent radical prostatectomy; all showed Gleason score 6 PCa. Three radical prostatectomies demonstrated 34betaE12 reactivity: two with patchy staining in a basal cell distribution and one with mainly tumor cell staining. Adjacent HGPIN was present in all three radical prostatectomy specimens. Rare lesions with the appearance of PCa show 34betaE12 staining in a basal cell distribution either from retention of basal cells by early invasive cancer or from HGPIN outpouching. The lack of adjacent HGPIN in some cases and the large ratio of small atypical glands to HGPIN glands argue against HGPIN outpouching as the sole explanation. In cases with adjacent HGPIN a comparison of the proximity and number of the small, atypical, infiltrative appearing glands to HGPIN is helpful. The diagnosis of PCa in the face of positive 34betaE12 basal cell

Topics: Adenocarcinoma; Biomarkers, Tumor; Biopsy, Needle; Fluorescent Antibody Technique, Indirect; Humans; Immunoenzyme Techniques; Keratins; Male; Molecular Weight; Prostatic Intraepithelial Neoplasia; Prostatic Neoplasms; Staining and Labeling

The basal cell-specific cytokeratin antibody (34betaE12) is widely used to aid in the diagnosis of cancer in challenging prostate needle biopsies (NBX) and transurethral resections of the prostate (TURP). Because prostate carcinoma (PCa) lacks basal cells, the absence of basal cell as determined by 34betaE12 can aid in the confirmation of a histologically suspicious lesion. However, false-negative staining occurs because of patchy cytoplasmic staining, making a definitive diagnosis difficult. A recently identified basal cell marker p63, a p53 homologue, stains basal cell nuclei but not secretory cells. The aim of this study is to determine if the p63 antibody offers any clinically useful advantage over 34betaE12 in the diagnosis of challenging atypical prostate lesions. Ninety-four cases, comprised of 25 consecutive prostate NBX and 2 TURP with an atypical suspicious focus, 55 NBX cases of histologically unequivocal PCa and 12 TURP specimen removed for benign prostate hyperplasia, were stained with the monoclonal antibodies 34betaE12 and 4A4 anti-p63. Basal cell staining intensity, percentage basal cell-positive glands in benign, malignant, and atypical foci, and number of benign glands not staining were evaluated for 34betaE12 and p63 stains. A total of 67 prostate NBX cases, including one TURP, were diagnosed with PCa, 1 atypical small acinar proliferation, 10 benign, and 4 cases excluded because of lost tissue on step sections. None of the 67 PCa NBX cases demonstrated 34betaE12 or p63 immunoreactivity (100% specific). Whereas 57 of 108 (53%) prostate NBX cores from 78 cases demonstrated a similar percentage of basal cell staining for both antibodies, 45 of 108 (41%) NBX cores demonstrated a higher percentage of p63 basal cell staining in benign glands. Only 6 of 108 NBX (6%) cores had a higher percentage of basal cell staining with 34betaE12 (Wilcoxon signed rank test, p <0.0001). Lack of basal cell staining in more than two benign glands occurred in 25 of 108 (23%) and 10 of 108 (9%) prostate NBX cores stained with 34betaE12 and p63, respectively. In the vast majority of atypical cases, both 34betaE12 and p63 staining differences were not clinically significant, except in 2 of 27 (7%) cases p63 offered diagnostic utility beyond the 34betaE12 immunostain. p63 in these cases demonstrated discontinuous but strong staining in atypical glands and adjacent benign glands, whereas 34betaE12 failed to stain optimally in this critical area. For 12 TURP cases t

Topics: Adenocarcinoma; Biomarkers, Tumor; Biopsy, Needle; DNA-Binding Proteins; Fluorescent Antibody Technique, Indirect; Genes, Tumor Suppressor; Humans; Immunoenzyme Techniques; Keratins; Male; Membrane Proteins; Molecular Weight; Phosphoproteins; Prostate; Prostatic Neoplasms; Reproducibility of Results; Staining and Labeling; Trans-Activators; Transcription Factors; Transurethral Resection of Prostate; Tumor Suppressor Proteins

Establishing a definitive diagnosis of malignancy in prostate needle biopsies with very small foci of adenocarcinoma is a major diagnostic challenge for surgical pathologists. A positive diagnostic marker specific for prostatic adenocarcinoma may enhance our ability to detect limited prostate cancer and reduce errors in diagnosis. P504S, also known as alpha-methylacyl-CoA racemase, recently identified by cDNA subtraction and microarray technology, might serve as such a specific marker because it has been demonstrated to be highly expressed in prostatic adenocarcinoma, but not in benign prostatic glands. However, whether small foci of carcinoma can be reliably detected by this marker is a crucial question for its clinical application. The aim of this study was to assess the utility of P504S immunohistochemistry in detecting small amounts of prostate cancer in prostate needle biopsies. A total of 142 prostate needle biopsies, including 73 cases with a small focus of prostatic adenocarcinoma (

Topics: Adenocarcinoma; Biomarkers, Tumor; Biopsy, Needle; Humans; Immunoenzyme Techniques; Keratins; Male; Molecular Weight; Prostatic Neoplasms; Racemases and Epimerases; Sensitivity and Specificity

Adenocarcinomas of the esophagogastric junction form a heterogeneous group of tumors. We aimed to evaluate the value of the expression pattern of cytokeratins 7, 19, and 20 for their diagnosis and classification. A total of 85 cases of adenocarcinoma of the distal esophagus and 67 cases of adenocarcinoma of the proximal stomach, defined on strict topographical criteria, were investigated. About 90% of the adenocarcinomas of distal esophagus were positive for cytokeratins 7 and 19, in contrast to <45% of the adenocarcinomas of proximal stomach (p <0.01); 17.6% of the adenocarcinomas of the distal esophagus and 55.2% of the adenocarcinomas of the proximal stomach expressed cytokeratin 20 (p <0.01); and 74.1% of the adenocarcinomas of the distal esophagus and 23.8% of the adenocarcinomas of the proximal stomach had a CK7+/CK20- immunophenotype (p <0.01). In intestinal-type tumors a CK7+/CK20- immunophenotype had a sensitivity of 76.5%, a specificity of 84.5%, and a predictive positive value of 87.3% for the diagnosis of adenocarcinoma of the distal esophagus. Cytokeratin patterns are different in adenocarcinomas of the distal esophagus and in adenocarcinomas of the proximal stomach. A CK7+/CK20- pattern is highly suggestive of an esophageal origin and may be helpful for the correct classification of esophagogastric adenocarcinomas.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Barrett Esophagus; Biomarkers, Tumor; Esophageal Neoplasms; Esophagogastric Junction; Female; Humans; Keratins; Male; Middle Aged; Neoplasm Proteins; Predictive Value of Tests; Sensitivity and Specificity; Stomach Neoplasms

Prostatic adenocarcinoma and urothelial carcinoma (transitional cell carcinoma) may coexist in the prostate. However, a carcinoma with mixed features has not been recognized. Four cases, three surgical pathology cases and one autopsy case of prostatic adenocarcinoma with urothelial carcinoma features, were retrospectively found in a urological pathology teaching file maintained from 1984 to 1993. Subsequently, 181 consecutive cases of radical prostatectomy from 1994 to 1999 were reviewed, and two prostatic adenocarcinoma areas with features of urothelial carcinoma were identified. Areas with urothelial carcinoma features were identified in the intraductal component of the carcinoma in five cases and in the invasive component in three cases. The intraductal carcinoma with urothelial carcinoma areas usually merged with regions of prostatic adenocarcinoma with a papillary or cribriform pattern. All prostatic adenocarcinomas having areas with urothelial carcinoma features were of high stage, and five of six cases had ductal features. The urothelial carcinoma component displayed a positive reactivity for thrombomodulin and negative or weaker reactivity for PAP and PSA than the prostatic adenocarcinoma component in the same tumor. Excluding the case noted at autopsy, all patients died of the disease within 3 years. Urothelial carcinoma features were usually associated with ductal carcinoma of high stage. Areas of prostatic adenocarcinoma with urothelial carcinoma features should be considered histopathologically as areas of mixed carcinoma of the prostate. Prostatic adenocarcinoma with areas of urothelial carcinoma features may pose a difficult differential diagnosis problem with urothelial carcinoma, especially with small biopsies with focal weak immunoreactivity for PAP, PSA, and thrombomodulin.

Topics: Acid Phosphatase; Adenocarcinoma; Aged; Aged, 80 and over; Biomarkers, Tumor; Carcinoembryonic Antigen; Carcinoma, Transitional Cell; Humans; Immunohistochemistry; Intermediate Filament Proteins; Keratin-20; Keratin-7; Keratins; Male; Middle Aged; Prostate-Specific Antigen; Prostatic Neoplasms; Protein Tyrosine Phosphatases; Thrombomodulin

Inconsistent conclusions have been drawn about the clinical significance of micrometastases in lymph nodes (LNs) of node-negative colorectal cancer (CRC) patients. We performed a comparative study of detection of micrometastases using immunohistochemistry (IHC) by anti-cytokeratin antibody and carcinoembryonic antigen (CEA)-specific reverse-transcriptase polymerase chain reaction (RT-PCR) in the same patients, in an attempt to move closer to their clinical application.. Sixty-four CRC patients, with RNA of good quality available from paraffin-embedded LN specimens, were selected from 84 stage II patients who underwent curative surgery between 1988 and 1996. We investigated associations between the presence of micrometastases by each method and prognosis.. Micrometastases were detected in 19 (29.6%) of 64 patients by RT-PCR and in 35 (54.7%) of 64 patients by IHC. By RT-PCR analysis, patients exhibiting a positive band for CEA mRNA had a significantly worse prognosis than those who were RT-PCR-negative, with respect to both disease-free and overall survival (P =.027 and.015, respectively). By IHC analysis, the presence of micrometastasis did not predict patient outcome in terms of either disease-free or overall survival. Infiltrating pattern of tumor growth characteristic was significantly associated with shorter disease-free survival among various clinical or pathologic factors. By multivariate Cox regression analysis, micrometastasis detected by RT-PCR and the Crohn's-like lymphoid reaction were both independent prognostic factors.. Micrometastases detected by RT-PCR, but not IHC, may be of clinical value in identifying patients who may be at high risk for recurrence of CRC and who are therefore likely to benefit from systemic adjuvant therapy.

Topics: Adenocarcinoma; Aged; Carcinoembryonic Antigen; Colorectal Neoplasms; Female; Humans; Immunohistochemistry; Keratins; Lymphatic Metastasis; Male; Middle Aged; Neoplasm Staging; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Survival Analysis

Mucinous bronchioloalveolar carcinomas (BACs) can closely mimic metastatic adenocarcinoma to the lung both clinically and morphologically. Several studies have demonstrated that the differential expression of cytokeratin 7 (CK7) and cytokeratin 20 (CK20) is a valuable diagnostic tool in differentiating primary pulmonary adenocarcinomas (PPAs) (usually CK7 positive/CK20 negative) from metastatic colonic adenocarcinoma (usually CK7 negative/CK20 positive). The present study is designed to correlate the histologic subtypes of PPA with expression of 7 and 20. A total of 113 cases of bonafide PPA were selected and classified according to the 1999 World Health Organization criteria as adenocarcinoma, NOS (n = 80), nonmucinous BAC (n = 14), and mucinous BAC (n = 19). Representive sections of all the tumors were immunohistochemically analyzed for CK7 and CK20 expression. To evaluate the diagnostic utility of CK7 and CK20 expression, 6 cases of colonic adenocarcinoma metastatic to the lung were tested with the same antibodies and compared with mucinous BAC. Results were expressed in a semiquantitative fashion based on the percentage of positive tumor cells: <10%, focal; 10% to 25%, 1+; 26% to 75%, 2+; > or =76%, 3+. All 113 PPAs exhibited strong, diffuse CK7 expression. With respect to CK20 expression, 17 of the 19 cases (89.4%) of mucinous BAC showed moderate to strong expression of this protein, whereas only 10 cases of conventional adenocarcinomas and 4 cases of nonmucinous BAC exhibited expression. All 6 examples of metastatic colonic adenocarcinomas were negative for CK7 and strongly positive for CK20. In summary, mucinous BAC is distinct from other PPAs by virtue of its CK20 expression. Although the CK7/CK20 immunoprofile is a valuable diagnostic marker for differentiating primary lung adenocarcinoma from metastatic colonic adenocarcinoma, caution should be exercised when dealing with mucinous BAC.

Topics: Adenocarcinoma; Adenocarcinoma, Bronchiolo-Alveolar; Adenocarcinoma, Mucinous; Biomarkers, Tumor; Colonic Neoplasms; Diagnosis, Differential; Humans; Immunoenzyme Techniques; Intermediate Filament Proteins; Keratin-20; Keratin-7; Keratins; Lung Neoplasms; Retrospective Studies

To document the incidence of metastatic disease in complete axillary lymph node dissections (CALND) of patients with invasive carcinoma after a sentinel lymph node (SLN) biopsy, positive only by immunohistochemical staining for cytokeratin (CK-IHC).. Sections of all SLNs, negative by routine histology, were immunostained and examined for cytokeratin positive cells. Sections of lymph nodes from CALND specimens were interpreted using routine hematoxylin and eosin (H&E) staining.. A total of 409 patients (29.6%) had metastatic disease in at least one sentinel lymph node on H&E examination. Of 971 H&E negative patients, 78 (8.0%) were positive only by CK-IHC. Sixty-two of the CK-IHC positive only patients underwent CALND. Nine of these 62 patients (14.5%) had metastases identified in the CALND specimen.. Because 14.5% of patients with invasive breast cancer and SLNs positive only by CK-IHC were found to have H&E positive lymph nodes on CALND, we conclude first, that CK-IHC should be used to evaluate SLNs, and second, that CALND should be considered when SLNs are positive by CK-IHC only. This approach will result in an absolute reduction of the false negative rate (absolute false negative rate reduced by 2.6% in our series).

Topics: Adenocarcinoma; Axilla; Breast Neoplasms; False Negative Reactions; Female; Humans; Immunohistochemistry; Keratins; Lymph Node Excision; Lymphatic Metastasis; Neoplasm Staging; Predictive Value of Tests; Prognosis; Retrospective Studies; Sentinel Lymph Node Biopsy

Bone marrow is a prognostically relevant indicator organ for micrometastasis. In the present study, real time quantitative reverse transcriptase polymerase chain reaction (RT-PCR) was used to detect disseminated gastric cancer cells in bone marrow. We compared CEA, CK18 and CK20 expression using four gastric cancer cell lines and three normal tissue cell lines in order to select the most appropriate marker for detection of disseminated gastric cancer cell in bone marrow. CK20 proved to be the most promising marker since the expression level of normal cell lines was extremely low and about 50--100-fold differences were found between gastric carcinoma cell lines and normal tissue cell lines. We also screened bone-marrow RNA of 47 patients with gastric cancers, using this system. Among the three markers we tested, with only about CK20 could we find that 27 of 47 patients were positive. Though long-term clinical follow up studies are needed to evaluate the clinical significance of this method, real time quantitative RT-PCR is sensitive and quantitative for detection of micrometastasis in bone marrow.

Topics: Adenocarcinoma; Biomarkers, Tumor; Bone Marrow Neoplasms; DNA Primers; Female; Humans; Intermediate Filament Proteins; Keratin-20; Keratins; Male; Middle Aged; Reverse Transcriptase Polymerase Chain Reaction; RNA, Neoplasm; Stomach Neoplasms

Multidirectional differentiation in colorectal carcinomas is a rare phenomenon. Four cases are reported herein, and their clinical and pathologic characteristics are discussed. Two men and 2 women between the ages of 56 and 76 years who presented with abdominal symptoms are included in this report. Two tumors were located in the right colon, one in the splenic flexure, and one in the descending colon. Distant metastases were evident at presentation in 3 of 4 cases. Histologically, two tumors exhibited neuroendocrine and glandular differentiation; the third tumor was an adenocarcinoma with a sarcomatous component and the fourth tumor showed 3 lines of differentiation (glandular, squamous, and sarcomatoid). In all tumors evaluated, areas of adenocarcinomas were positive for low-molecular weight cytokeratin (CAM 5.2) and mucicarmine, but negative for high-molecular weight cytokeratin (AE3). The squamous cell component was AE3 positive and CAM 5.2 negative. The neuroendocrine component was highlighted by neuroendocrine markers and the sarcomatoid component revealed smooth muscle differentiation. All tumors (except one mucinous tumor) were negative for cytokeratin-20 staining. One patient was on supportive care for terminal metastatic carcinoma, and 2 patients were being treated with adjuvant chemotherapy at the time of this report. Colon carcinoma with multidirectional differentiation is a rare event and may originate from stem cells within the gastrointestinal mucosa, and/or represent the convergence of multiple tumors arising at the same site. This type of tumor should be considered in the differential diagnosis of a bowel biopsy with multiple histopathologic variants.

Topics: Adenocarcinoma; Aged; Carcinoma, Squamous Cell; Carmine; Cell Transformation, Neoplastic; Colorectal Neoplasms; Coloring Agents; Female; Humans; Immunohistochemistry; Keratins; Male; Middle Aged; Neoplasm Metastasis

The expressions of cytokeratin (CK) 7 and 20 have been studied in various primary and metastatic carcinomas, and their determination may help distinguish the site of origin of metastatic carcinomas. However, little is known about the factors that determine variations in their expression patterns in primary gastric and colorectal carcinomas. We investigated the expressions of CK7 and CK20 in 289 cases of gastric carcinoma and 225 cases of colorectal carcinoma using a tissue microarray. To evaluate CK7 and CK20 expression patterns of ovarian metastases from gastric or colorectal carcinomas, 54 cases of metastatic carcinomas to the ovary were examined. It was found that 71% (207 of 289) of the gastric carcinomas stained positively for CK7, whereas only 9% (21 of 225) of the colorectal carcinomas proved to be CK7 positive, and that 41% (117 of 289) of the gastric carcinomas and 73% (165 of 225) of the colorectal carcinomas were CK20 positive. The proportion of CK7+/CK20- was highest in the gastric carcinomas at 46% (132 of 289), and was independent of the histologic classification of Lauren (46% of the intestinal type, 45% of the diffuse type). The CK7 and CK20 expression patterns were different in colorectal carcinomas according to histologic grade and location of the tumor. CK7-/CK20+ had the greatest proportion (68%) in colorectal carcinomas, and this was dependent on the tumor's histologic grade (75% of low-grade versus 52% of high-grade) and location (46% of right-sided versus 76% of left-sided). Moreover, 42% (18 of 43) of gastric carcinomas metastatic to the ovary were CK7+/CK20-, whereas 19% (8 of 43) were CK7-/CK20+. All colorectal cancers metastatic to the ovary were CK7-/CK20+, except 1 case that was CK7-/CK20-. In conclusion, the CK7 and CK20 expression patterns in primary gastric carcinomas vary considerably, and those in colorectal carcinomas are associated with histologic grade and tumor location. The CK7-/CK20+ expression pattern is specific for metastatic colorectal carcinomas to the ovary, but has low predictability for colorectal origin in metastatic ovarian carcinoma.

Topics: Adenocarcinoma; Colorectal Neoplasms; Diagnosis, Differential; Female; Humans; Immunohistochemistry; Intermediate Filament Proteins; Keratin-20; Keratin-7; Keratins; Ovarian Neoplasms; Stomach Neoplasms; Tissue Embedding

Cure for ductal adenocarcinoma of the pancreas is restricted to resectable tumors, but survival after surgery is still poor. Despite apparently curative resection, these cancers rapidly recur. Thus, the present pathologic examination should be enriched by sensitive methods to detect minimal residual disease. In a prospective setting we studied the frequency of minimal residual disease after curative resection by routine histopathology, immunohistology, and polymerase chain reaction (PCR) for mutated K-ras. Furthermore, the prognostic implication of detecting of MRD was determined. Prospectively, tumor tissue and corresponding paraaortic lymph nodes were obtained from 78 patients, who underwent surgery for pancreatic head tumors between 1999 and 2001. Sixty-nine of 78 cases were diagnosed for ductal adenocarcinoma (study group), whereas nine cases were diagnosed for benign pancreatic tumors (control group). Paraaortic lymph nodes were examined in step sections by routine histopathology (hematoxylin and eosin) and immunohistology using a pan-cytokeratin antibody. DNA of the primary tumor and corresponding paraaortic lymph nodes were analyzed by PCR-based assays with respect to mutated K-ras in codon 12. The recurrence-free survival and overall survival were correlated with the results of the latter methods. In 3 of 69 patients tumor cells were detected in paraaortic lymph nodes by routine histopathology and in 5 of 69 patients by immunohistology. K-ras mutations were detected in 42 of 69 ductal adenocarcinomas (61%), whereas 12 (17%) were positive in paraaortic lymph nodes. All of the latter patients had recurrence after surgery and a significant poorer survival than those without mutated K-ras. Furthermore, paraaortic lymph nodes diagnosed for K-ras mutation were independent prognostic markers in multivariate analysis. In the control group K-ras mutations were detected in one adenoma of Vater's papilla but not in paraaortic lymph nodes. Tumor cell DNA can be detected more sensitively by the described PCR method than with hematoxylin and eosin or immunohistologic staining, leading to a higher sensitivity for detection of micrometastases. The described PCR method clearly determines subgroups of patients after curative resection with early recurrence and poor survival and could therefore enrich the pathologic examination.

Topics: Adenocarcinoma; Aged; Aorta; Chronic Disease; Cystadenoma; Diagnostic Tests, Routine; DNA, Neoplasm; Female; Genes, ras; Humans; Immunohistochemistry; Keratins; Lymphatic Metastasis; Male; Middle Aged; Multivariate Analysis; Mutation; Neoplasm Staging; Pancreatic Neoplasms; Pancreaticoduodenectomy; Pancreatitis; Polymerase Chain Reaction; Polymorphism, Restriction Fragment Length; Predictive Value of Tests; Prognosis; Sequence Analysis, DNA; Survival Analysis

We report a case of early adenocarcinoma arising in foci of intestinal metaplasia (IM) at a normal-appearing gastroesophageal junction (GEJ). The tumor infiltrated the submucosa without nodal involvement (T1N0). Non-neoplastic mucosa adjacent to neoplasia had foci of incomplete IM with a band-like CK20 positivity of the surface epithelium and a diffuse CK7 staining of both superficial and deep glands. There were histological features of reflux esophagitis as well as chronic non-atrophic, Helicobacter pylori-related pangastritis, without IM, at the extensively assessed gastric mucosa. In this case, the CK7/20 pattern of IM adjacent to neoplasia, the demonstration of reflux esophagitis, and the absence of IM in the stomach favor the theory that the pathogenesis of IM and associated adenocarcinoma of the GEJ is related to gastroesophageal reflux rather than H. pylori infection.

Topics: Adenocarcinoma; Aged; Cardia; Chronic Disease; Esophagogastric Junction; Gastrectomy; Gastric Mucosa; Gastritis; Humans; Immunohistochemistry; Keratins; Male; Metaplasia; Stomach Neoplasms

Twenty-three patients with primary small cell carcinoma of the uterine cervix are presented. Their ages ranged between 23 and 63 years (average, 43 years). Blood spotting or vaginal bleeding was the most common clinical presentation. Histologically, the tumors were densely cellular and showed trabecular nesting or a sheet-like pattern. The neoplastic cells had scant cytoplasm, round nuclei, absence of nucleoli, and finely dispersed chromatin. Nuclear molding, single cell necrosis, and high mitotic activity were found in all tumors. There was a minor component of large cell neuroendocrine carcinoma in three cases, while foci of adenocarcinoma were identified in two cases. Immunohistochemical studies were performed in all 23 tumors which showed immunoreactivity for cytokeratin. Ten small cell carcinomas were immunoreactive for chromogranin, 13 for synaptophysin, and 10 expressed p53 protein. Treatment modalities included hysterectomy alone or combined with chemotherapy and/or radiation therapy. A few patients received chemotherapy and/or radiation alone. Follow-up information was obtained in 22 cases; 15 patients died of tumor between 6 and 43 months, while seven patients have remained alive 12 to 273 months. One patient was lost to follow-up. Small cell carcinoma of the cervix is a highly aggressive neoplasm. However, early diagnosis and combined therapeutic modalities may lead to longer survival in some patients. Although the use of immunohistochemistry may be helpful in the diagnosis, small cell carcinoma still remains a morphologic diagnosis.

Topics: Adenocarcinoma; Adult; Biomarkers; Carcinoma, Small Cell; Chromogranins; Female; Follow-Up Studies; Humans; Immunohistochemistry; Keratins; Middle Aged; Synaptophysin; Treatment Outcome; Tumor Suppressor Protein p53; Uterine Cervical Neoplasms

Diagnostically reliable identification of prostatic basal cells has depended on staining for high molecular weight cytokeratin. The diagnosis of malignancy is often based on the absence of basal cells. False-negative staining is occasionally observed. Thus, a second method of identifying basal cells might prove useful. Selective expression of p63, a homologue of p53, has been demonstrated in prostatic basal cells. We investigated the diagnostic utility of p63 staining in 70 consecutive specimens for which the differential diagnosis included prostatic adenocarcinoma: 68 needle biopsies and 2 transurethral resection blocks. High molecular weight cytokeratin staining was the gold standard when material was available. A total of 61 specimens were diagnosed as carcinoma, 4 as atrophy, 2 as high-grade prostatic intraepithelial neoplasia, 2 as unclassified collections of benign glands, and 1 as carcinoma versus high-grade prostatic intraepithelial neoplasia. Sections mounted on charged slides were used for p63 staining for 14 specimens. Sections previously hematoxylin and eosin stained on uncharged slides were used for 56 specimens. In every case in which there was successful p63 staining (55 specimens), basal cells in benign lesions were properly marked and other cell types were not stained. Uninformative staining in the remaining 15 specimens was due to failure of tissue adherence in 14 specimens in which sections were on uncharged slides and, in 1 specimen, to poor positive internal control staining of benign glands. Thus, p63 staining was informative in 55 of 56 specimens (98%) for which there was material for examination. No case with satisfactory p63 and high molecular weight staining showed disagreement between the two stains. An additional group of 21 transurethral resection specimens was stained (p63 and high molecular weight cytokeratin). There was less false-negative staining for p63 compared with the case of high molecular weight cytokeratin. No false-positive staining was seen. We conclude that p63 staining is at least as sensitive and specific for the identification of basal cells in diagnostic prostate specimens as is high molecular weight cytokeratin staining.

Topics: Adenocarcinoma; Atrophy; Biomarkers; Diagnosis, Differential; DNA-Binding Proteins; Genes, Tumor Suppressor; Humans; Immunohistochemistry; Keratins; Male; Membrane Proteins; Phosphoproteins; Prostate; Prostatic Neoplasms; Sensitivity and Specificity; Trans-Activators; Transcription Factors; Tumor Suppressor Proteins

The purpose of this study was to evaluate the markers' clinical usefulness for early prediction of recurrence, by serial and simultaneous measurements of serum cytokeratin fragment 19 (CYFRA 21-1), before and after surgery on patients with non-small cell lung cancers (NSCLC). The 48 patients enrolled in this study had adenocarcinoma of the lung (adenoCa) (including 24 patients with recurrence and 24 patients without recurrence 1 year after surgery) and 48 patients with squamous cell carcinoma of the lung (SCC) (including 24 cases with recurrence and 24 without recurrence 1 year after surgery). Serial serum levels of CYFRA 21-1 were measured before the operation and 1 week, 1 month, 3 months, 6 months, 9 months, and 12 months after surgery for the early detection of recurrence. The results revealed that (1) the mean serum values of CYFRA 21-1 were significantly higher beginning at 1 month after surgery in the 24 patients with recurrent adenoCa compared with the 24 patients without recurrent adenoCa, (2) mean serum values of CYFRA 21-1 were significantly higher beginning at 1 month after surgery in 24 patients with recurrent SCC when compared with 24 patients without recurrent SCC, and (3) mean serum values of CYFRA 21-1 were significantly higher beginning at 1 month after operation in the total 48 patients with recurrent NSCLC when compared with 48 patients without recurrent NSCLC. We conclude that CYFRA 21-1 is not a good marker for early prediction of NSCLC recurrence including adenoCa and SCC after surgery.

Topics: Adenocarcinoma; Adult; Aged; Antigens, Neoplasm; Biomarkers, Tumor; Carcinoma, Squamous Cell; Female; Humans; Keratin-19; Keratins; Lung Neoplasms; Male; Middle Aged; Neoplasm Recurrence, Local; Predictive Value of Tests; Retrospective Studies

Distinguishing hepatocellular carcinoma (HCC) from cholangiocarcinoma (CC) and metastatic adenocarcinoma (MA) involving the liver can be problematic, often requiring the use of immunohistochemistry to facilitate diagnosis. Hep Par 1, a monoclonal antibody with expression confined primarily to benign and malignant hepatocytes, has recently become commercially available. We evaluated Hep Par 1 along with other immunohistochemical markers used to differentiate HCC, CC, and MA, including AE1/AE3, CAM 5.2, B72.3, monoclonal carcinoembryonic antigen (mCEA), polyclonal CEA (pCEA), alpha-fetoprotein (AFP), factor XIIIa, inhibin, CD10, villin, MOC-31, cytokeratin (CK) 7, CK 19, and CK 20, to determine the markers most useful in differentiating these entities. Forty-two cases of HCC, 9 cases of CC, and 56 cases of MA (24 colon, 15 pancreas, 8 ovary, 5 breast, and 4 stomach) were studied. Hep Par 1 was sensitive and specific for HCC, with 38 of 42 (90%) cases staining positively, whereas reactivity was observed in only 8 of 56 (14%) MAs and 0 of 9 CCs. Though limited somewhat by poor sensitivity, a bile canalicular pattern of staining with pCEA, CD10, and villin was specific for HCC and was not observed in the other tumors. Lack of mCEA and MOC-31 immunoreactivity was also characteristic of HCCs. CK 19 positivity favored CC over HCC, but was not useful in differentiating CC from MA. Expression of AFP, although observed in only about one third of the cases, favored HCC over CC and MA. CK 7 and CK 20 were also useful in this differential diagnosis, particularly when dealing with MA of colonic origin. AE1/AE3, CAM 5.2, B72.3, inhibin, and factor XIIIa were noncontributory in differentiating these entities.

Topics: Adenocarcinoma; alpha-Fetoproteins; Antibodies, Monoclonal; Biomarkers, Tumor; Carcinoembryonic Antigen; Carcinoma, Hepatocellular; Carrier Proteins; Cholangiocarcinoma; Diagnosis, Differential; Humans; Immunohistochemistry; Keratins; Liver Neoplasms; Microfilament Proteins; Neprilysin; Sensitivity and Specificity

In gynecologic oncology valid prognostic factors are necessary to define biologically similar subgroups for analysis of therapeutic efficacy. This study is the first published prospective study concerning prognostic significance of DNA ploidy and S-phase fraction in cervical and endometrial cancer following enrichment of tumor cells by cytokeratin labelling. Epithelial cells were labeled by FITC-conjugated cytokeratin antibody (CK 5, 6, 8, and CK 17) prior to flow cytometric cell cycle analysis in 91 specimens of cervical cancer and 73 samples of endometrial cancer. In cervical cancer neither DNA-ploidy nor S-phase fraction were relevant prognostic parameters. But CV of the G(0)G(1)-peak showed prognostic relevance in cervical cancer cells, even in multivariate analysis. This interesting observation, however, seems to have no therapeutic consequence due to the small discrimination capacity of CV. In endometrial carcinoma, gross DNA-aneuploidy (DNA-index > 1.3) and a high percentage of proliferating cells (>75th percentile) were univariate and multivariate highly significant prognostic factors for recurrence-free survival. Especially DNA-aneuploidy (DI>1.3) is one of the most important independent molecular biological prognostic factors. While diagnostic curettage we could identify risk patients even preoperatively by determination of the prognostic factors like histologic tumor type, grading, cervical involvement and DNA-ploidy. Thereby these patients could be treated primarily in an oncologic center. In conclusion, our investigations showed that the determination of DNA-ploidy should be done in endometrial carcinoma. In cervical cancer no clinical significance for determination of DNA-parameters was found.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Carcinoma, Mucoepidermoid; Carcinoma, Squamous Cell; DNA, Neoplasm; Endometrial Neoplasms; Evaluation Studies as Topic; Female; Flow Cytometry; G1 Phase; G2 Phase; Humans; Keratins; Middle Aged; Mitosis; Multivariate Analysis; Neoplasm Recurrence, Local; Ploidies; Predictive Value of Tests; Prognosis; Resting Phase, Cell Cycle; S Phase; Survival Analysis; Uterine Cervical Neoplasms

A correct histologic differential diagnosis between salivary acinic cell carcinoma (ACC) and adenocarcinoma not otherwise specified (AC-NOS) is highly relevant because of the strikingly different biologic behavior and related therapeutical strategies. The distinction between both tumor types can be difficult because of an enormous variation in histologic appearance, with either type showing partially overlapping morphologic features. Owing to a lack of approved markers, the expression of PAS-staining, alpha-Amylase, alpha-1 Anti-trypsin, cytokeratin (CK)-subtypes 7/18 and Ki-67 was evaluated in 16 cases of ACC and 16 cases of AC-NOS. CK 7 is identified as the most reliable marker with strong positivity in AC-NOS, and complete or preponderant negativity in ACC. The characteristic membranous staining pattern of CK 18 in ACC, in contrast to a diffuse cytoplasmic pattern in AC-NOS, proved to be an additional valuable criterion. PAS and alpha-Amylase are only of little value when ACC is diagnosed, as many cases are only faintly positive or completely negative. The proliferation index (Ki-67) proved to be significantly higher in AC-NOS; however, the diagnostic usefulness is limited by a relevant overlap. In conclusion, we recommend CK 7 and 18 as the most valuable markers in cases with difficult differential diagnosis between ACC and AC-NOS.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Antibodies, Monoclonal; Biomarkers, Tumor; Carcinoma, Acinar Cell; Diagnosis, Differential; Female; Humans; Immunohistochemistry; Keratin-7; Keratins; Male; Middle Aged; Salivary Gland Neoplasms

We report a case of acinic cell adenocarcinoma of the parotid in a 18-year-old young man. Clinical examination showed a firm mobile mass of the gland. Light microscopy revealed the tumor composed of two distinct cell populations: a main one with large, polyhedrical or round cells with eosinophilic cytoplasm and a smaller proportion of granular cytoplasm clear cells. These tumor cells were periodic acid Schiff reaction (PAS) and mucicarmine staining negative. Immunohistochemically tumor main cells exhibited diffuse positive reactivity for cytokeratin and focal for S-100 protein. Both reactions were negative in smaller cell population. Was formulated a diagnosis of "non-specific glandular cell-type of acinic cell adenocarcinoma.

Topics: Adenocarcinoma; Adolescent; Humans; Keratins; Male; Parotid Gland; Parotid Neoplasms; S100 Proteins

The histological distinction between a primary endometrial and a primary endocervical adenocarcinoma is often difficult, especially in small biopsy specimens. A preoperative distinction is important because primary surgical management differs between the two tumors. Cases of primary endometrioid endometrial (n=30) and primary endocervical (n=26) adenocarcinoma of endocervical type were stained immunohistochemically with the monoclonal antibodies against carcinoembryonic antigen (CEA), vimentin, estrogen receptor (ER), and 34 beta E12. In all cases the origin of the adenocarcinoma was confirmed by examination of the definitive pathology specimen. There was diffuse positive nuclear staining for ER in 28 of 30 (93%) endometrial adenocarcinomas. ER was negative in 16 of 26 endocervical adenocarcinomas, and there was focal weak nuclear staining in the other cases. Vimentin was positive in 29 of 30 (97%) endometrial adenocarcinomas but in only 2 of 26 (8%) endocervical adenocarcinomas. CEA was positive in 25 of 26 (96%) endocervical adenocarcinomas, mostly with diffuse membranous and cytoplasmic staining. Positivity with CEA was present in 21 of 30 (70%) endometrial adenocarcinomas but was largely confined to squamoid areas with only 12 tumors exhibiting focal membranous staining of the glandular component. 34 beta E12 was diffusely positive in all except one cervical adenocarcinoma. In endometrial carcinomas, positivity was strongest in squamoid areas but there was positive staining, either focally or diffusely, of the glandular component in 27 cases. In summary, primary endometrioid endometrial adenocarcinomas are characterized by diffuse, strong, positive staining for vimentin and ER and negative or very focal, positive staining of the glandular component for CEA. In contrast, primary endocervical adenocarcinomas are characterized by CEA positivity, which is usually but not always diffuse, negativity for vimentin, and negativity or focal weak positivity for ER. 34 beta E12 is of no value in the distinction between endometrial and endocervical adenocarcinomas. A panel of immunohistochemical stains, comprising CEA, vimentin, and ER, generally allows confident preoperative distinction between a primary endometrial and endocervical adenocarcinoma.

Topics: Adenocarcinoma; Antibodies, Monoclonal; Biomarkers, Tumor; Carcinoembryonic Antigen; Endometrial Neoplasms; Female; Humans; Immunohistochemistry; Keratins; Receptors, Estrogen; Uterine Cervical Neoplasms; Vimentin

We investigated the possibility of distinguishing between primary endometrial and endocervical adenocarcinomas by using a panel of immunohistochemical stains, which included vimentin (VIM), carcinoembryonic antigen (CEA), epithelial membrane antigen (EMA), and cytokeratins 7 and 20 (CK7 and CK20). Twenty-nine endocervical adenocarcinomas (CCAs) and 30 endometrial adenocarcinomas (EMCAs) including cases with overlapping histologic features (CCAs with endometrioid differentiation [15/29] and EMCAs with mucinous differentiation [16/30]) were evaluated. Most EMCAs (29/30, 97%) were VIM positive, whereas only 2/29 (7%) CCAs were VIM positive. The great majority of EMCAs (28/30) and all 29 CCAs were CK7 positive, whereas all 30 EMCAs and 27/29 CCAs were negative for CK20. CEA positivity was more common in CCAs (18/29, 62%) than in EMCAs (8/30, 27%). EMA positivity was present in all 30 EMCAs and in 26 of 29 (90%) CCAs. We conclude that VIM and CEA are useful immunohistochemical markers in distinguishing EMCAs and CCAs, but CK7, CK20, and EMA are not useful in this distinction.

Topics: Adenocarcinoma; Antibodies, Monoclonal; Biomarkers, Tumor; Carcinoembryonic Antigen; Diagnosis, Differential; Endometrial Neoplasms; Female; Humans; Immunohistochemistry; Intermediate Filament Proteins; Keratin-20; Keratin-7; Keratins; Mucin-1; Uterine Cervical Neoplasms; Vimentin

Cytokeratin 5/6 (CK 5/6) immunoreactivity has been observed in the vast majority of cases of malignant mesothelioma but only rarely in pulmonary adenocarcinomas. Thus, CK 5/6 has been used to distinguish malignant mesothelioma from pulmonary adenocarcinoma. However, the utility of CK 5/6 in distinguishing pleural malignant mesothelioma from pleural metastases from nonpulmonary adenocarcinoma, as well as peritoneal malignant mesothelioma from peritoneal metastatic adenocarcinoma, has not yet been adequately addressed because the tissue expression of CK 5/6 in nonpulmonary neoplasms has not been well defined. We have studied the CK 5/6 expression in 509 cases of various epithelial tumors by immunohistochemistry. We found that the vast majority of cases of squamous cell carcinoma, basal cell carcinoma, thymoma, salivary gland tumor, and biphasic malignant mesothelioma were positive for CK 5/6. In addition, CK 5/6 immunoreactivity was detected in 15 of 24 cases (62%) of transitional cell carcinoma, in 5 of 10 cases (50%) of endometrial adenocarcinoma, in about one third of cases of pancreatic adenocarcinoma (38%) and breast adenocarcinoma (31%), and in one quarter of cases of ovarian adenocarcinomas (25%). Our study confirms the diagnostic utility of CK 5/6 immunohistochemistry in distinguishing biphasic mesothelioma from pulmonary adenocarcinoma but raises caution about its use for the differential diagnosis of pleural or peritoneal malignant mesothelioma versus pleural or peritoneal metastatic nonpulmonary adenocarcinoma, because many types of nonpulmonary adenocarcinomas may be positive for CK 5/6.

Topics: Adenocarcinoma; Biomarkers, Tumor; Carcinoma, Squamous Cell; Diagnosis, Differential; Female; Humans; Immunoenzyme Techniques; Keratin-14; Keratin-5; Keratin-7; Keratins; Male; Mesothelioma; Neoplasms

The presence of disseminated tumor cells in bone marrow is considered to be a premetastatic state, which is called micrometastasis. To evaluate the relationship between micrometastasis and cellular adhesion molecules in the primary lesion, E-cadherin and beta-catenin were immunohistochemically investigated. Methods. Fifty-eight patients with non-small cell lung cancer who underwent a complete resection were entered into this study. Tumor cells in bone marrow aspirates were detected by immunohistochemistry using cytokeratin (CK) 18. Immunohistochemical studies of E-cadherin and beta-catenin were performed in the corresponding primary tumor.. CK-positive cells were detected in the bone marrow aspirates from 27 of 58 patients. A reduced expression of the E-cadherin and beta-catenin was found in 16 (27.6%) and in 22 (37.9%) of 58 patients, respectively. In 26 cases with a reduced expression of E-cadherin and/or beta-catenin, 16 cases had CK-positive cells, whereas 11 of 32 cases with normal expression of both factors had CK-positive cells (P=.0392). The patients with micrometastasis demonstrated an earlier recurrence (P =.0642) and a significantly poorer survival (P =.0437) than those without such cells.. Micrometastasis in the bone marrow might be a significant predictor of poor prognosis, and a reduced expression of E-cadherin and beta-catenin are important determinants for the metastatic capability of individual cancer cells.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; beta Catenin; Bone Marrow Neoplasms; Cadherins; Carcinoma, Squamous Cell; Cytoskeletal Proteins; Disease-Free Survival; Female; Humans; Immunohistochemistry; Keratins; Lung Neoplasms; Male; Middle Aged; Predictive Value of Tests; Prognosis; Risk Factors; Survival Rate; Trans-Activators

Cadmium is a ubiquitous environmental human carcinogen. Epidemiological and animal studies have suggested its carcinogenic potential on the prostate. In the present study, non-tumorigenic human prostate epithelial cells (pRNS-1-1) immortalized by simian papovavirus (SV40) were transformed after repeated exposures to cadmium. Such transformants showed morphological alterations, anchorage-independent growth in soft agar, and formed tumors when transplanted into SCID mice. The tumors were characterized histologically as poorly-differentiated adenocarcinomas, expressing prostate-specific antigen (PSA), androgen receptor (AR), prostate stem cell antigen (PSCA), NKX3.1 and cytokeratin 8 (CK8). These findings provide evidence of malignant transformation of human prostate epithelial cells exposed to this environmentally important chemical.

Topics: Adenocarcinoma; Animals; Cadmium; Cell Transformation, Neoplastic; Epithelial Cells; Humans; Karyotyping; Keratins; Male; Mice; Mice, SCID; Prostate-Specific Antigen; Prostatic Neoplasms; Receptors, Androgen; Reverse Transcriptase Polymerase Chain Reaction; Simian virus 40; Time Factors; Tumor Cells, Cultured

The role of tumor markers in the diagnosis and prognosis of lung cancer is under investigation.. The aim of this study was to investigate the diagnostic and prognostic significance of pre-therapeutic levels of various serum tumor markers, CYFRA 21-1, neuron-specific enolase (NSE), tissue polypeptide antigen (TPA), carcinoembryonic antigen (CEA), CA 125 and squamous cell carcinoma antigen (SCCAg), in patients with lung cancer.. We studied 102 consecutive patients (mean age 65.2 +/- 11 years) with newly diagnosed lung cancer (96 males, 94%, with a mean age of 66.3 +/-10.5 years). All patients had a 5-year follow-up. Measurements of the serum tumor markers were performed on initial diagnosis.. Eighty-four patients (82%) had non-small-cell lung cancer (NSCLC) and 18 (18%) small-cell lung cancer (SCLC). From the 84 patients with NSCLC, 34 patients (33%) had squamous-cell lung cancer, 23 (22%) adenocarcinoma and 23 (22%) large-cell carcinomas. The overall median survival was 8.5 months. All SCLC patients had extensive disease with a median survival of 10.1 months and NSCLC patients of 8.4 months. Significant differences in the mean values of NSE and CYFRA 21-1 were observed between SCLC and NSCLC. In NSCLC, CYFRA 21-1, TPA, CA 125 and SCCAg serum levels were related to the stage of the disease at diagnosis, and CYFRA 21-1, NSE, TPA and CA-125 were related to a poor outcome. None of the above tumor markers was related to survival in the SCLC group.. CYFRA 21-1 and NSE may help to differentiate cell types in lung cancer patients. Also, CYFRA 21-1 with TPA and CA 125 may provide useful information regarding the staging of the disease at diagnosis and the prognosis of patients with NSCLC.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Analysis of Variance; Antigens, Neoplasm; Biomarkers, Tumor; CA-125 Antigen; Carcinoembryonic Antigen; Carcinoma, Large Cell; Carcinoma, Non-Small-Cell Lung; Carcinoma, Squamous Cell; Female; Humans; Keratin-19; Keratins; Lung Neoplasms; Male; Middle Aged; Phosphopyruvate Hydratase; Probability; Prognosis; Prospective Studies; Regression Analysis; Sensitivity and Specificity; Survival Analysis

Micropapillary carcinoma or a micropapillary carcinoma component has been reported in the ovary, breast, and urinary bladder and is generally thought to have prognostic significance. However, little has been written on micropapillary differentiation in lung carcinoma. We studied 35 cases of primary lung adenocarcinoma with a micropapillary component seen at the M.D. Anderson Cancer Center. The micropapillary component in these tumors ranged from focal to prominent and was seen at both primary and metastatic sites. This component was not associated with any particular histologic subtype of lung adenocarcinoma. Of the 15 cases with available material, 14 (93%) stained positive for cytokeratin 7, whereas only two of the 15 cases (13%) stained positive for cytokeratin 20. Thyroid transcription factor-1 immunostaining of tumor nuclei was seen in 12 of the 15 cases (80%). Immunostaining was seen in areas both with and without micropapillary differentiation. Thirty-three of 35 patients (94%) developed metastases, which occurred most commonly in the lymph nodes (n = 26), and also in the lung (n = 17), brain (n = 9 cases), bone (n = 9 cases), and other sites. Most metastases had a prominent micropapillary component, irrespective of the extent of the micropapillary carcinoma component in the primary lung tumor. Adequate clinical follow-up information was available for 29 patients. The mean follow-up was 25 months. At their last follow-up, 16 of 29 patients (55%) were still alive with disease, 5 (17%) were dead of disease, and 8 (28%) were alive with no evidence of disease. We believe that a micropapillary component occurring in lung adenocarcinoma should be reported, as this component may be more likely to metastasize. The presence of this component should alert the clinician to search more carefully for metastases and have a closer follow-up on these patients. It is also important to recognize this component in evaluating a metastasis from an unknown primary site, as it should alert the pathologist to a possible primary in the lung in addition to breast, urinary bladder, and ovary.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Bone and Bones; Carcinoma, Papillary; Female; Follow-Up Studies; Humans; Immunohistochemistry; Keratins; Lung Neoplasms; Lymph Nodes; Male; Middle Aged; Neoplasm Metastasis; Nuclear Proteins; Prognosis; Thyroid Nuclear Factor 1; Transcription Factors

This study provides detailed staining results for 225 prostate adenocarcinomas, including 150 Gleason score 8, 9, and 10 adenocarcinomas with cytokeratins (CKs) 7, 20, 5/6, and 17, prostate-specific antigen (PSA), prostatic acid phosphatase (PAP), carcinoembryonic antigen (CEA), WT1, thyroid transcription factor-1 (TTF-1), and villin. CK7 was reactive in 112 adenocarcinomas (49.8%). The percentage of CK7-reactive adenocarcinomas and the percentage of CK7-stained cells increased in higher Gleason score adenocarcinomas; most reactive neoplasms had CK7 staining of fewer than 25% of cells. CK20 had similar results. The percentage of PSA- and PAP-reactive adenocarcinomas and the percentage of stained cells in reactive neoplasms decreased in higher Gleason score adenocarcinomas. CK5/6 and CK17, WT1, CA-125, TTF-1, and villin were nonreactive. The prostate can be the primary site of metastatic adenocarcinoma that is nonreactive for PAP and PSA and has CK7 or CK20 reactivity in fewer than 50% of the cells. The likelihood that a metastatic adenocarcinoma is from the prostate is low if reactivity with any of the cytokeratin antibodies, CEA, TTF-1, CA-125, WT1, or villin is extensive.

Topics: Acid Phosphatase; Adenocarcinoma; CA-125 Antigen; Carcinoembryonic Antigen; Carrier Proteins; Humans; Immunophenotyping; Intermediate Filament Proteins; Keratin-20; Keratin-7; Keratins; Male; Microfilament Proteins; Nuclear Proteins; Prostate-Specific Antigen; Prostatic Neoplasms; Thyroid Nuclear Factor 1; Transcription Factors; WT1 Proteins

The purpose of this study was to evaluate the biological mechanisms of docetaxel (TXT) on salivary gland carcinoma.. The effects of TXT on a spontaneous murine salivary carcinoma were determined. Proliferation, cell cycle regulation, connexin43 expression, gap-junctional intercellular communication, apoptosis, and Fas receptor (FasR) expression were measured.. We characterized a spontaneous mouse salivary gland carcinoma (SGC1). SGC1 is a poorly differentiated carcinoma that originated from the parotid gland of a BALB/c mouse. SGC1 cells were cultured and found to be immortal past 30 passages. Initially, cells formed tumor nodules in severe combined immunodeficient (SCID) mice. Afterward, SGC1 cells that were subcultured from SCID tumors readily formed colonies in soft agar and were highly tumorigenic in SCID mice and immune-competent BALB/c hosts. Dose response for TXT with respect to growth suppression, G(2)-M cell cycle arrest, and apoptosis was found. Induction of apoptosis by TXT coincided with an increase in cell surface FasR expression. Up-regulation of FasR with lower doses of TXT rendered cells susceptible to FasR agonist antibody-mediated apoptosis. In the absence of TXT, anti-FasR antibodies were completely without effect, suggesting that TXT is critical for priming apoptosis mediated through the Fas pathway. In addition, gap-junctional intercellular communication was augmented by TXT in SGC1 cells concomitant with increased connexin43 expression and membrane localization.. We have identified several novel targets of TXT that contribute to its antitumor activity in poorly differentiated salivary gland carcinoma. These results suggest that TXT may be appropriate for additional in vivo studies and clinical trials in patients with salivary cancers.

Topics: Adenocarcinoma; Animals; Antineoplastic Agents, Phytogenic; Apoptosis; Blotting, Western; Cell Communication; Cell Cycle; Cell Division; Connexin 43; Docetaxel; fas Receptor; Female; Flow Cytometry; Fluorescent Antibody Technique; Gap Junctions; Immunoenzyme Techniques; Keratins; Mice; Mice, Inbred BALB C; Mice, SCID; Paclitaxel; Precipitin Tests; Proliferating Cell Nuclear Antigen; S100 Proteins; Salivary Gland Neoplasms; Taxoids; Tumor Cells, Cultured

The intermediate filament network in simple glandular epithelial cells predominantly consists of heterotypic complexes of cytokeratin 8 (K8) and cytokeratin 18 (K18). In contrast to other cytokeratins, K8 and K18 are persistently expressed during malignant transformation, but changes in cell morphology are accompanied by alterations in the intermediate filament network. To study molecular changes, K8 and K18 were purified from surgically removed colon cancer and normal epithelia tissues. Western blotting and amino acid sequencing revealed the presence of abundant K8 and K18 fragments, truncated at the N terminus, from cancerous, but not normal, epithelial cells. The fragmentation pattern indicates proteolysis mediated by several enzymes, including trypsin-like enzymes. The cancer-associated forms of K8 and K18 are specifically recognized by the human antibody, COU-1, cloned from the B cells of a cancer patient. We demonstrate that COU-1 recognizes a unique conformational epitope presented only by a complex between K8 and K18. The epitope is revealed after proteolytic removal of the head domain of either K8 or K18. A large panel of recombinant K8 and K18 fragments, deleted N- or C-terminally, allowed for the localization of the COU-1 epitope to the N-terminal part of the rod domains. Using surface plasmon resonance, the affinity of COU-1 for this epitope was determined to be 10(9) x m(-1), i.e. more than 2 orders of magnitude higher than for intact heterotypic K8/K18 complexes. The cellular distribution of truncated K8/K18 heterotypic complexes in viable adenocarcinomas cells was probed using COU-1 showing small fibrillar structures distinct from those of intact K8/K18 complexes. Previously we demonstrated the binding and subsequent internalization of recombinant Fab COU-1 to live cancer cells. We have thus characterized a cancer neoepitope recognized by the humoral immune system. The results have biological as well as clinical implications.

Topics: Adenocarcinoma; Amino Acid Sequence; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Blotting, Western; Dose-Response Relationship, Drug; Electrophoresis, Polyacrylamide Gel; Enzyme-Linked Immunosorbent Assay; Epitopes; Gene Deletion; Humans; Immunoglobulin Fab Fragments; Keratins; Microscopy, Confocal; Models, Biological; Molecular Sequence Data; Protein Binding; Protein Structure, Tertiary; Recombinant Proteins; Surface Plasmon Resonance; Temperature; Tumor Cells, Cultured

Intermediate filaments are known as cytoskeletal elements. Recently, additional vimentin expression has been reported in some carcinomas; however, the function of such expression remains unclear. We studied the intracellular distribution of low-molecular weight cytokeratin and vimentin by immunohistochemistry in 17 vimentin-positive gastric carcinomas using confocal laser scanning microscopy. All materials were formalin-fixed and paraffin-embedded. Low-molecular weight cytokeratin expression showed a membranous pattern with a prominent deposition just below the cytoplasmic membrane in both tubular and solid components of the carcinomas. This unique membranous deposition was frequently absent in diffuse components. On the other hand, vimentin expression showed a fibrillary pattern in all components and also showed a unique basal distribution in the tubular components. We also recognized an aggregate pattern of the intermediate filament expression in diffuse components. We conclude that the significance of vimentin expression in carcinoma cells cannot be explained as a simple substitution for low-molecular weight cytokeratin because the distribution of vimentin and low-molecular weight cytokeratin is different.

Topics: Adenocarcinoma; Humans; Immunohistochemistry; Intermediate Filaments; Keratins; Microscopy, Confocal; Stomach Neoplasms; Vimentin

Due to more efficient chemotherapy protocols, the number of second and even third primary carcinomas is steadily increasing. To denominate the possible origin of a carcinoma, different markers are available as an aid, e.g. hormones, proteins and lipoproteins, secretion products and cytoskeletal proteins. Cytokeratins (CKs) have gained new popularity; however, they have not been extensively evaluated in lung tumours. In our study we evaluated the staining patterns of CK polypeptides 4-8, 10, 13, 14, and 17-20 and high molecular weight (HMW) CK polypeptides in routinely processed primary lung carcinomas and lung metastases of diverse origin. As expected, immunohistochemical investigation gave no clear-cut results, but, with statistical analysis, lung adenocarcinomas could be separated from metastatic adenocarcinomas using CK 5 and 18 and HMW CK (specificity 92.5%, sensitivity 62.5%). The different origin of the metastases could often be detected using CK 18 and CK 20. Lung clear cell carcinomas and large cell carcinomas with clear cell areas could be distinguished from metastatic renal clear cell carcinomas by the CK 7 staining reaction. Squamous cell carcinomas of the lung and metastatic squamous cell carcinomas of the larynx, pharynx and oesophagus could not reliably be separated in part due to the few number of cases available. CK polypeptide typing is thus an additional aid in the differential diagnosis of lung carcinomas versus carcinomas metastatic to the lung.

Topics: Adenocarcinoma; Carcinoma, Squamous Cell; Diagnosis, Differential; Humans; Immunohistochemistry; Keratins; Lung; Lung Neoplasms

Topics: Adenocarcinoma; Carcinoma, Squamous Cell; DNA, Neoplasm; DNA, Viral; Female; Humans; In Situ Hybridization; Keratins; Papillomaviridae; Papillomavirus Infections; Polymerase Chain Reaction; Tumor Virus Infections; Uterine Cervical Dysplasia; Uterine Cervical Neoplasms

This study aims to determine if layering of extracellular matrix (ECM) can achieve a physiological basement membrane thickness of 8 microm and to assess the use of paraffin wax-embedded Transwell plates coupled with digital image analysis as a means of determining invasion by malignant cell lines. Layers of Matrigel, a sarcoma-derived ECM was built to a concentration of 7.4 microg/mm2 in the upper chamber of a Transwell plate invasion assay. Two cell lines from extrahepatic bile duct adenocarcinoma were tested in serum-free growth medium. Conditioned medium was added to the lower chamber to act as a chemoattractant. Following attachment, cells were incubated for 48 h and the Matrigel-coated insert cut from its holder and fixed in 10% unbuffered formalin saline. Each insert was bisected and processed to paraffin wax. Serial levels were stained by haematoxylin and eosin. A Kontron image analysis system was used to measure the mean thickness of Matrigel for each cell line and the degree of invasion was assessed by measuring the depth to which cells had degraded the Matrigel. A mean thickness of 8 microm was achieved using 5.0 microg/mm2 for the OCUCh-LM1 cell line and 7.4 microg/mm2 for the SKChA-1 cell line. No significant difference was seen in the ability of either cell line to degrade Matrigel. Immunocytochemistry for laminin and cytokeratin helped to identify ECM components and cells, respectively. In conclusion, digital image analysis of paraffin wax-embedded inserts can be used to determine the invasive capacity of various cell lines; immunocytochemistry may help to identify ECM components and cells; and the assay used to assess different cell lines and their ability to degrade Matrigel.

Topics: Adenocarcinoma; Bile Duct Neoplasms; Biomarkers; Collagen; Culture Media, Conditioned; Diffusion Chambers, Culture; Drug Combinations; Extracellular Matrix; Humans; Image Processing, Computer-Assisted; Keratins; Laminin; Neoplasm Invasiveness; Proteoglycans; Tumor Cells, Cultured

Topics: Adenocarcinoma; Biomarkers, Tumor; Diagnosis, Differential; Humans; Immunohistochemistry; Keratins; Male; Prostate; Prostatic Intraepithelial Neoplasia; Prostatic Neoplasms

Hybrid follicular carcinoma (FC) and papillary thyroid carcinoma (PTC) have not been previously well described. Consecutive cases of 29 FC, 12 Hurthle cell carcinomas (HC), 247 PTC and 13 Hurthle cell PTC (HPTC) were reviewed with special attention to the coarse (CC) and fine chromatin patterns (FIC), as well as to the presence of nuclear grooves, pseudoinclusions or optically clear appearance. Limited nuclear features of PTC (LNF-PTC) are defined as areas of tumor with FIC in addition to some other nuclear features, but insufficient for the diagnosis of PTC. Tumors with nuclei showing an admixture of CC and PTC or LNFPTC were submitted for immunostaining for cytokeratin 19, HBME and Ret/PTC. FC and HC contained areas of LNFPTC in 25 tumors and focal PTC in 3 tumors. None of these cases was associated with lymph node metastasis. Areas with CC were found in 54 PTC and 3 HPTC. The rates of vascular invasion and distant metastasis tended to be higher for PTC with areas of coarse chromatin pattern than for PTC without such areas; however, the difference was not statistically significant. Immunoreactivity for cytokeratin 19 and HBME was moderate to strong for PTC and focal areas of PTC or LNFPTC in FC without Hurthle cell changes. Ret/PTC immunostaining was positive in areas of LNFPTC or focal PTC in three FC. Focal PTC or areas of LNFPTC are frequently seen in FC. Likewise, areas of CC are often present in PTC. The presence of these focal areas does not appear to change the clinical behavior of the tumor and therefore does not warrant a change of nomenclature.

Topics: Adenocarcinoma; Adenocarcinoma, Follicular; Adenoma, Oxyphilic; Adult; Biomarkers, Tumor; Carcinoma, Papillary; Chromatin; Diagnosis, Differential; Female; Humans; Immunohistochemistry; Keratins; Male; Middle Aged; Oncogene Proteins, Fusion; Protein-Tyrosine Kinases; Retrospective Studies; Thyroid Neoplasms

The clinicopathologic features of a case of endometrioid adenocarcinoma arising from colonic endometriosis that clinically and histologically mimicked a primary colonic carcinoma are reported. The differential diagnostic features of the tumor leading to the correct diagnosis included associated endometriosis, a minor mucosal component, focal squamous differentiation, absence of dirty necrosis, low nuclear grade, absence of a colonic adenoma, and a CK7+/CK20-/CEA- immunophenotype.

Topics: Adenocarcinoma; Aged; Aged, 80 and over; Carcinoembryonic Antigen; Carcinoma, Endometrioid; Colonic Diseases; Colonic Neoplasms; Diagnosis, Differential; Endometriosis; Female; Humans; Immunohistochemistry; Intermediate Filament Proteins; Keratin-20; Keratin-7; Keratins

The origin of metastatic adenocarcinoma lesions can sometimes be difficult to diagnose. The objectives of our study were to establish the cytokeratin staining pattern of primary and metastatic lung and colorectal adenocarcinomas, and to determine if this helps to identify the site of origin of metastatic lesions. We reviewed a total of 102 tissue samples from patients in our tumour registry, with either primary or metastatic lung or colorectal adenocarcinoma. Tissue sections were stained for cytokeratin 7 and 20 and read as positive or negative for staining. Clinical and radiologic information was reviewed from computerised charts. The cytokeratin 7+/cytokeratin 20- pattern characterised 96% (29 out of 30) of primary and 95% (21 out of 22) of metastatic lung adenocarcinomas. All the primary (26), and 88% (21 out of 24) of metastatic colorectal adenocarcinomas stained cytokeratin 7-/cytokeratin 20+. Samples from a variety of metastatic sites were evaluated for cytokeratin 7 and 20 staining. Out of the 102 samples, in 95% (97 out of 102) of the cases, the cytokeratin 7 and cytokeratin 20 staining pattern characterised and differentiated between lung and colorectal adenocarcinoma. Primary and metastatic lung adenocarcinomas show a cytokeratin 7+/cytokeratin 20- staining pattern, while colorectal adenocarcinomas stain cytokeratin 7-/cytokeratin 20+. Cytokeratin staining is helpful in the diagnostic differentiation of metastatic lesions from these two common primaries, and assists in determining the site of origin of metastatic lesions.

Topics: Adenocarcinoma; Biopsy; Colorectal Neoplasms; Diagnosis, Differential; Humans; Immunoenzyme Techniques; Intermediate Filament Proteins; Keratin-20; Keratin-7; Keratins; Lung Neoplasms; Prognosis; Registries; Staining and Labeling

Determining the site of origin of metastatic adenocarcinoma lesions has obvious therapeutic and prognostic implications. Immunostaining for cytokeratin subtypes 7 and 20 is increasingly used to evaluate metastatic colorectal cancer lesions. We present the case of a patient with a history of colorectal cancer who subsequently developed an isolated metastatic lesion in the lung. As illustrated by our case, staining for cytokeratin subtypes can be helpful in determining the site of origin of metastatic lesions.

Topics: Adenocarcinoma; Aged; Cecal Neoplasms; Humans; Immunohistochemistry; Intermediate Filament Proteins; Keratin-20; Keratin-7; Keratins; Lung Neoplasms; Male; Neoplasms, Unknown Primary

p63, a homologue of the tumor suppressor gene p53, is expressed in embryonic, adult murine, and human basal squamous epithelium and encodes both transactivating and dominant negative transcript isoforms. Mouse embryos functionally deficient in p63 fail to replenish basal squamous epithelial cells, resulting in multiple defects that include absent genital squamous epithelium. This study investigated the expression of p63 in the human cervical transformation zone and early cervical neoplasia.. Tissue localization of p63 was determined by immunohistochemistry in a wide range of epithelia. A correlation was also made between p63 expression and squamous basal cell (keratin 14), endocervical columnar cell (mucicarmine), and cell-cycle specific (Ki-67) markers.. p63 expression by immunostaining delineated basal and parabasal cells of maturing ectocervical squamous mucosa, squamous metaplasia in the cervix, and basal and subcolumnar cells of the cervical transformation zone. In atrophic epithelia immunostaining for p63 was present in all cell strata. In early cervical neoplasia, p63 expression was inversely correlated with both squamous cell maturation and nonsquamous differentiation in CIN. This biomarker also identified basal cells in a subset of preinvasive cervical neoplasms with endocervical cell differentiation that were bcl-2 and keratin 14 negative.. In the lower female genital tract, p63 is preferentially expressed in immature cells of squamous lineage and is not linked to cell proliferation. The broader range of p63 expression relevant to keratin 14 and bcl-2 indicates that p63 may identify additional subsets of benign and neoplastic epithelial basal cells in the cervical transformation zone and may be useful in studying cell differentiation in the early stages of neoplastic change in this region.

Topics: Adenocarcinoma; Atrophy; Biomarkers, Tumor; Carcinoma in Situ; Cell Cycle; Cell Differentiation; Cervix Uteri; DNA-Binding Proteins; Epithelium; Female; Gene Expression; Genes, Tumor Suppressor; Humans; Keratin-14; Keratins; Ki-67 Antigen; Membrane Proteins; Phosphoproteins; Proto-Oncogene Proteins c-bcl-2; RNA, Messenger; Trans-Activators; Transcription Factors; Tumor Suppressor Proteins; Uterine Cervical Dysplasia; Uterine Cervical Neoplasms

Adenocarcinoma of the esophagus (ADCE) with Barrett's mucosa and adenocarcinoma of the cardia (ADCC) are often reported as a single pathological entity. In this study we have used strict anatomical-pathological criteria to distinguish between these two lesions and we have investigated their differences in TP53 mutations, MDM2 gene amplification, and cytokeratin expression. DNA was extracted from the tumor areas of formalin-fixed, paraffin-embedded sections in 26 ADCC and 28 ADCE patients. TP53 mutations were detected by temporal temperature gradient electrophoresis and identified by sequencing. MDM2 amplification was assessed by differential polymerase chain reaction. The expression of cytokeratins 4, 7, and 13 was examined by immunohistochemistry. In ADCC, the male to female ratio was 1.8:1, compared to 27:1 in ADCE. Five ADCC patients had a history of other neoplasms, compared to only one ADCE patient. The two types of tumor differed in the prevalence of TP53 mutations (31% in ADCC and 50% in ADCE) and of MDM2 gene amplification (19% in ADCC and 4% in ADCE), and in the pattern of expression of cytokeratin 7 (positive in 100% of ADCE and in 41% of ADCC) and cytokeratin 13 (positive in 81% of ADCE and in 36.5% of ADCC). ADCE and ADCC differ in their clinical characteristics, in the prevalence of TP53 mutations and MDM2 amplifications, and in the patterns of cytokeratin expression. These results support the notion that ADCC and ADCE are distinct pathological entities.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Cardia; Diagnosis, Differential; Esophageal Neoplasms; Female; Gastric Mucosa; Gene Amplification; Gene Expression Regulation, Neoplastic; Humans; Keratin-7; Keratins; Male; Middle Aged; Mutation; Nuclear Proteins; Proto-Oncogene Proteins; Proto-Oncogene Proteins c-mdm2; Stomach Neoplasms; Tumor Suppressor Protein p53

Immunohistochemistry provides an important indicator for differential diagnosis between pleural malignant mesothelioma and lung adenocarcinoma, which have complex therapeutic and medicolegal implications. To pinpoint a reliable, restricted panel of markers, the authors evaluated the efficacy of select commercial antibodies in a series of patients with confirmed clinicopathologic diagnosis of mesothelioma or lung adenocarcinoma with the aid of multiple logistic classification tables. Specimens of 46 mesotheliomas and 20 lung adenocarcinomas were examined with calretinin, thrombomodulin, cytokeratins (CKs) 5/6, and high-molecular weight CKs (indicators of mesothelioma), alongside MOC 31, Ber-EP4, and carcinoembryonic antigen (CEA; indicators of lung adenocarcinoma). Of the mesotheliomas, 40 of 46 (87%) were positive with calretinin, 29 of 46 (63%) with thrombomodulin, 40 of 46 (87%) with CKs 5/6, and 41 of 46 (89%) with high-weight CKs; five of 46 mesotheliomas (11%) were focally reactive with MOC 31, four of 46 (9%) with Ber-EP4, and two of 46 (4%) with CEA. Of the lung adenocarcinomas, 18 of 20 (90%) were positive with MOC 31, 20 of 20 (100%) with Ber-EP4, and 17 of 20 (85%) with CEA; and two of 20 (10%) were focally reactive with calretinin, one of 20 (5%) with thrombomodulin, none of 20 (0%) with CKs 5/6, and five of 20 (25%) with high-weight CKs. Multiple logistic modeling indicated two batteries of three antibodies permitting more than 98% overall accuracy: Ber-EP4 plus CKs 5/6 plus calretinin, and Ber-EP4 plus CKs 5/6 plus CEA.

Topics: Adenocarcinoma; Antibodies; Antigens, Neoplasm; Antigens, Surface; Biomarkers, Tumor; Calbindin 2; Carcinoembryonic Antigen; Diagnosis, Differential; Female; Humans; Immunohistochemistry; Keratins; Lung Neoplasms; Male; Mesothelioma; Regression Analysis; S100 Calcium Binding Protein G; Thrombomodulin

The long-term prognosis after surgical therapy for esophageal carcinoma depends on tumor stage and completeness of resection. Similarly to other epithelial tumors, the presence of micro deposits of neoplastic cells in the bone marrow may indicate residual disease and the potential for recurrence. This study assesses the prevalence of bone marrow-disseminated tumor cells in patients undergoing surgical resection for esophageal carcinoma. In addition, we investigated the agreement between immunohistochemical and molecular techniques for the detection of micrometastases in a subgroup of patients.. Between January 1998 and November 1999, forty-eight patients with adenocarcinoma of the esophagogastric junction (n = 29) or squamous cell carcinoma of the thoracic esophagus (n = 19) and no evidence of overt metastatic disease entered the study. An immunohistochemical assay (capable of detecting 1 carcinoma cell in 7 x 10(5) bone marrow cells) was used to test bone marrow obtained by flushing a resected rib or by needle aspiration either of the iliac crest or of a rib. A polymerase chain reaction (PCR) molecular technique was also used to identify bone marrow and peripheral blood epithelial cells.. Cytokeratin-positive cells were found in 79.1% of the bone marrow samples obtained from the rib, and in only 8% of the needle aspirates either from the iliac crest or from a contiguous rib: This difference is probably explained by the improved removal of metastatic cells with the flushing of the rib. Comparable results were obtained at a qualitative level by the PCR technique on bone marrow. In addition, PCR-positive results were found in 3 of 18 peripheral blood samples. There was no association with tumor type, neoadjuvant therapy, or lymph node status. Patients with a pT3 or pT4 tumor showed, at a borderline statistical level, a higher proportion of cytokeratin-positive cells in the flushed rib.. Bone marrow-disseminated tumor cells are present in the resected rib of a high proportion of patients undergoing esophagectomy for carcinoma, and immunohistochemistry seems to be the method of choice for their quantitative assessment. However, the prognostic and therapeutic implications of this finding need further investigation.

Topics: Adenocarcinoma; Adult; Aged; Base Sequence; Bone Marrow Examination; Bone Marrow Neoplasms; Carcinoma, Squamous Cell; Cardia; DNA Primers; Esophageal Neoplasms; Female; Humans; Immunohistochemistry; Keratins; Male; Middle Aged; Polymerase Chain Reaction; Prognosis; Stomach Neoplasms

Atypical cribriform lesions on prostate needle biopsy specimens are rare and difficult to diagnose. Of 574 high-grade prostatic intraepithelial neoplasia (PIN) lesions on needle biopsy seen at our institution over 75 months, we identified 23 consult cases in which the differential diagnosis was cribriform high-grade PIN versus infiltrating cribriform carcinoma. Prebiopsy prostate-specific antigen (PSA) averaged 6.5 ng/mL (range, 0.3 to 37.3). A positive digital rectal examination (DRE) was present in 12 of 22 (55%) patients for whom information was available. Ordinary high-grade PIN was present elsewhere in the biopsy specimens in 32% of cases. The following architectural features of cribriform glands were evaluated: number (mean, 5; range, 1 to 21); largest size (mean, 0.5 mm; range, 0.1 to 1 mm); necrosis (14%); detached cribriform fragments (18%); stromal fibrosis (18%); and bilaterality (22%). Cytologically, there was cellular maturation toward the center of the cribriform glands (45%); identifiable basal cells on hematoxylin and eosin sections (36%); marked nuclear atypia (9%); and mitoses (23%). Nucleoli were not visible in 18% of cases, small in 36%, and prominent in 45%. With a mean follow-up of 13.8 months for those without progression (25.9 months' overall follow-up), a repeat biopsy diagnosis of cancer was seen in 10 of 22 men [by report: Gleason score (Gs) 4 (n = 1); Gs 6 (n = 3); Gs 7 (n = 4); Gs 9 (n = 2); three biopsy specimens showed ductal features]. An additional two men developed bone metastases without biopsy. Overall, 12 of 22 (55%) patients had cancer on follow-up (one patient lost to follow-up). Four clinicopathologic findings predicted carcinoma on follow-up: positive DRE (p = 0.02); positive transrectal ultrasound (p = 0.02); bilateral atypical cribriform glands (p = 0.02); and detached cribriform glands (p = 0.04).

Topics: Adenocarcinoma; Aged; Aged, 80 and over; Biopsy, Needle; Humans; Immunohistochemistry; Keratins; Male; Middle Aged; Prostate; Prostate-Specific Antigen; Prostatic Intraepithelial Neoplasia; Prostatic Neoplasms

Topics: Adenocarcinoma; Carcinoma, Transitional Cell; Diagnosis, Differential; Humans; Intermediate Filament Proteins; Keratin-20; Keratin-7; Keratins; Male; Prostatic Neoplasms

Fractalkine (CX3CL1) is synthesized as a type I transmembrane protein. Its unique CX(3)C chemokine domain is attached to a 241-amino acid mucin stalk, a 19-amino acid transmembrane domain, and a 37-amino acid intracellular domain of unknown function. A soluble form of fractalkine can be generated by proteolytic cleavage at the base of the mucin stalk. Novel monoclonal and polyclonal antibodies that specifically recognize only the amino- or carboxyl-terminal ends of the human fractalkine molecule have revealed that epithelial cells are the predominant cell type expressing transmembrane forms of fractalkine in human skin, the tonsil, and the large intestine. Using these specific anti-fractalkine reagents we do not detect high-level expression of fractalkine on endothelial cells in normal or inflamed colon samples obtained from patients with Crohn's disease or ulcerative colitis. In contrast to previous reports we do not detect fractalkine expression by Langerhans cells or immature dendritic cells in mucosal-associated lymphoid tissues in vivo. We show that the reagent used in previous studies, an anti-fractalkine N-terminal peptide antisera, cross-reacts with human CD84. Finally we discuss potential roles for fractalkine in constitutive leukocyte trafficking based on its observed pattern of expression in epithelia.

Topics: Adenocarcinoma; Animals; Antibodies; Antibody Specificity; Antigens, CD; Cell Line; Chemokine CX3CL1; Chemokines, CX3C; Chemokines, CXC; CHO Cells; Colon; Colorectal Neoplasms; Cricetinae; Cross Reactions; Epidermis; Epithelial Cells; Humans; Inflammatory Bowel Diseases; Keratins; Membrane Glycoproteins; Membrane Proteins; Palatine Tonsil; Peptides; Protein Isoforms; Signaling Lymphocytic Activation Molecule Family; Tumor Cells, Cultured

The CD40 antigen is expressed by antigen-presenting cells, many kinds of epithelium, and carcinomas. As signaling through CD40 modulates the differentiation state of CD40-expressing cells, we wanted to investigate whether benign or malignant prostate epithelium expressed CD40.. Twenty-two paraffin-embedded and 10 snap-frozen human prostate tissue samples were analyzed by immunohistologic methods, using the basal cell-specific markers, high molecular weight cytokeratin (HMWCK) and keratin-14 (K14), and the luminal cell marker, low molecular weight cytokeratin (LMWCK), together with CD40. Fresh prostate tissue was cultured in vitro and analyzed by immunocytofluorescence.. The pattern of CD40 expression was continuous on basal epithelial cells of normal and hyperplastic prostate glands but discontinuous in glands that featured prostatic intraepithelial neoplasia. Coexpression of CD40 with the basal cell-specific cytokeratins, HMWCK and K14, was confirmed by double labeling. In contrast, glandular epithelial cells in prostate adenocarcinoma did not express CD40 or these cytokeratins. A luminal cell phenotype defined as CAM5.2-positive and HMWCK-negative K14-negative was identified among primary epithelial cells cultured in vitro. Most of the cultured cells (more than 99%) were also CD40-negative.. Together, our results support the hypothesis that CD40 expression correlates with the basal cell phenotype, which is lost upon malignant transformation of the prostate. Hence, CD40 may be useful diagnostically to distinguish benign from malignant prostate lesions in biopsy material.

Topics: Adenocarcinoma; Biomarkers, Tumor; CD40 Antigens; Humans; Immunohistochemistry; Keratins; Male; Prostatic Hyperplasia; Prostatic Intraepithelial Neoplasia; Prostatic Neoplasms

To determine whether Brenner tumors and transitional cell carcinomas (TCCs) of the ovary are urothelial in type, the immunoprofiles of 14 Brenner tumors, including three malignant examples, and eight ovarian TCCs were compared with those of Walthard nests, urothelium, 12 urinary bladder TCCs and 17 ovarian adenocarcinomas (serous, endometrioid, mucinous, and undifferentiated type). The immunohistochemical stains used included those for cytokeratins CKs 5/6, CK7, CK8, CK13, and CK20, vimentin, CA125, and the specific urothelial differentiation marker uroplakin III. CK7 and CK8 were broadly expressed in most tumors of ovary and bladder examined, while vimentin was focally present in some ovarian TCCs and adenocarcinomas. As in normal and neoplastic bladder urothelium, urothelial markers, including uroplakin III, CK13, and CK20, were detected in the epithelial nests of Brenner tumors. Brenner tumor cells also expressed uroplakins Ia and II. CA125 was observed focally in some Brenner tumors. In contrast, TCCs of the ovary and Walthard nests lacked uroplakins and were essentially negative for CK20 and CK13 but quite strongly expressed CA125. This immunophenotype closely resembled that found in ovarian adenocarcinomas. Thus, it appears that the only true urothelial-type ovarian neoplasm is the Brenner tumor, whereas ovarian TCC most likely represents a poorly differentiated adenocarcinoma with a morphologic transitional cell pattern. These results may explain the controversies as expressed in the recent literature concerning TCC of the ovary and establish its place among the ovarian adenocarcinomas of müllerian type.

Topics: Adenocarcinoma; Brenner Tumor; Carcinoma, Transitional Cell; Cell Transformation, Neoplastic; Female; Humans; Keratins; Membrane Glycoproteins; Ovarian Cysts; Ovarian Neoplasms; Urinary Bladder Neoplasms; Uroplakin III; Urothelium

Several aspects of sweat gland carcinomas (incidence, classification, diagnosis, and behavior) have not been definitively clarified and need to be studied further.. The clinicopathologic findings of a large series of sweat gland carcinomas, collected during a period of 15 years, are presented.. Sixty sweat gland carcinomas (41 porocarcinomas, 3 syringomatous carcinomas, 8 ductal carcinomas, 5 adenoid cystic carcinomas, and 3 mucinous carcinomas) were analyzed histologically and immunohistochemically.. Porocarcinomas were composed of eosinophilic and clear atypical cells arranged in solid-cystic lobular masses. These tumors were divided into 2 subgroups: horizontal porocarcinomas, showing a prominent intraepidermal component, and nodular porocarcinomas, which demonstrated predominant nodular growth. Syringomatous carcinomas presented keratinizing and nonkeratinizing cysts, dilated tubules (sometimes with a "tadpole" appearance), small neoplastic ducts, solid islands, and cellular cords. Ductal carcinomas were characterized by a prominent formation of tubules, solid islands, and cellular cords. Adenoid cystic carcinomas presented a characteristic pattern, showing basaloid monomorphous cells with moderately atypical nuclei, arranged in cribriform or solid islands and in tubular structures. Mucinous carcinomas were composed of moderately atypical cells with eosinophilic vacuolated cytoplasm, forming solid and cystic islands floating in large mucin pools. Immunohistochemically, cytokeratin was found in neoplastic cells in all cases, carcinoembryonic antigen was detected in 73% of cases, and actin-positive (myoepithelial) cells were not found.. Although numerous studies have been published in recent years, the histologic features, histogenesis, and classification of sweat gland carcinomas still remain controversial and need to be clarified by further studies.

Topics: Acrospiroma; Actins; Adenocarcinoma; Adenocarcinoma, Mucinous; Adenoma, Sweat Gland; Adult; Aged; Aged, 80 and over; Carcinoembryonic Antigen; Carcinoma, Adenoid Cystic; Child; Female; Humans; Immunoenzyme Techniques; Keratins; Male; Middle Aged; Neoplasm Recurrence, Local; Sweat Gland Neoplasms; Sweat Glands

Routine microscopy provides only a 2-dimensional view of the complex 3-dimensional structure that makes up human tissue. Three-dimensional microscopic image reconstruction has not been described previously for prostate cancer.. To develop a simple method of computerized 3-dimensional image reconstruction and to demonstrate its applicability to the study of prostatic adenocarcinoma.. Serial sections were cut from archival paraffin-embedded prostate specimens, immunostained using antikeratin CAM5.2, and digitally imaged. Computer image-rendering software was used to produce 3-dimensional image reconstructions of prostate cancer of varying Gleason grades, normal prostate, and prostatic intraepithelial neoplasia.. The rendering system proved easy to use and provided good-quality 3-dimensional images of most specimens. Normal prostate glands formed irregular fusiform structures branching off central tubular ducts. Prostatic intraepithelial neoplasia showed external contours similar to those of normal glands, but with a markedly complex internal arrangement of branching lumens. Gleason grade 3 carcinoma was found to consist of a complex array of interconnecting tubules rather than the apparently separate glands seen in 2 dimensions on routine light microscopy. Gleason grade 4 carcinoma demonstrated a characteristic form of glandular fusion that was readily visualized by optically sectioning and rotating the reconstructed images.. Computerized 3-dimensional microscopic imaging holds great promise as an investigational tool. By revealing the structural relationships of the various Gleason grades of prostate cancer, this method could be used to refine diagnostic and grading criteria for this common tumor.

Topics: Adenocarcinoma; Biomarkers; Humans; Imaging, Three-Dimensional; Immunohistochemistry; Keratins; Male; Microtomy; Paraffin Embedding; Prostatic Intraepithelial Neoplasia; Prostatic Neoplasms

We assessed the association of vascular endothelial growth factor (VEGF) and nm23 expression with occult micrometastasis in lung cancer. As destination sites for micrometastasis, we scrutinized lymph node (LN) and bone marrow (BM) specimens. For LN, 122 stage I patients who had received curative operations were studied. As regards BM, 203 patients in stage I - IV who underwent operations were registered. Immunohistochemical anti-cytokeratin staining was used to detect microdissemination of cancer cells. The VEGF and the nm23 expression at the primary sites were immunohistochemically studied in 285 cases in total. The percentages of the patients with microdissemination were 28.7% for LN and 42.4% for BM. The outcome for the patients with LN or BM microdissemination was significantly worse than that for patients without it. The increased VEGF and the decreased nm23 expression within primary tumors were significantly associated with LN and BM microdissemination. The results indicate possible value of using these biological markers to predict the risk of systemic micrometastasis in non-small cell lung cancer.

Topics: Adenocarcinoma; Aged; Biomarkers, Tumor; Bone Marrow; Carcinoma, Adenosquamous; Carcinoma, Non-Small-Cell Lung; Carcinoma, Squamous Cell; Endothelial Growth Factors; Female; Humans; Immunohistochemistry; Keratins; Lung Neoplasms; Lymph Nodes; Lymphatic Metastasis; Lymphokines; Male; Middle Aged; Monomeric GTP-Binding Proteins; Neoplasm Metastasis; Neoplasm Staging; NM23 Nucleoside Diphosphate Kinases; Nucleoside-Diphosphate Kinase; Predictive Value of Tests; Sensitivity and Specificity; Transcription Factors; Vascular Endothelial Growth Factor A; Vascular Endothelial Growth Factors

Lung adenocarcinomas are heterogeneous clinically and histologically. Expression of the mucin genes was analyzed as a molecular marker of glandular cytodifferentiation in primary lung adenocarcinomas. Expression was correlated with histopathologic subtypes of World Health Organization classification with the aim of investigating the histogenesis of primary lung adenocarcinomas. Thirty-four primary lung adenocarcinomas were examined by in situ hybridization for mucin gene expression (MUC1-4, MUC5AC, MUC5B, MUC6-7) and by immunohistochemistry for MUC5AC and MUC5B apomucin expression. Mucinous bronchioloalveolar carcinoma (BAC) had a homogeneous pattern of mucin gene expression different from those of other types of lung adenocarcinoma, involving secreted mucins (MUC5AC, MUC5B, and MUC6) and membrane-bound mucins (MUC1, MUC3, and MUC4). Non-BAC adenocarcinoma and mucinous BAC aberrantly expressed mucin genes MUC3, and MUC3 and MUC6, respectively, which are undetectable in normal fetal and adult lung. Our results show the particular phenotype of mucin gene expression in mucinous type of BACs and the heterogeneous expression of respiratory and nonrespiratory mucins in the other types. This finding supports the theory of a common progenitor cell with the potential of multicellular differentiation. From a practical point of view, the aberrant expression of MUC3 and MUC6 could serve as a diagnostic marker in the management of the mucinous type of bronchioloalveolar carcinomas. HUM PATHOL 32:274-281.

Topics: Adenocarcinoma; Adenocarcinoma, Bronchiolo-Alveolar; Adult; Aged; Female; Gene Expression; Histocytochemistry; Humans; Immunohistochemistry; In Situ Hybridization; Keratins; Lung Neoplasms; Male; Middle Aged; Mucins; RNA, Messenger

Accurate tumour classification is critical for meaningful epidemiological studies in the assessment of cancer incidence rates and trends. Differentiating primary gastric carcinoma from oesophageal carcinoma can be difficult, especially when tumours are large and involve both the oesophagus and stomach. Furthermore, adenocarcinomas of both organs typically are of intestinal histological type and arise in a background of intestinal metaplasia. Consequently, histological markers that reliably distinguish Barrett's-related oesophageal adenocarcinoma from gastric adenocarcinoma would be useful. Cytokeratins (CK)7 and 20 are cytoplasmic structural proteins with restricted expression that help to determine the origin of many epithelial tumours including those of the gastrointestinal tract. The aim of this study was to determine the utility of co-ordinate CK7 and 20 expression in the distinction of Barrett's-related oesophageal adenocarcinoma from gastric adenocarcinoma arising in a background of intestinal metaplasia.. CK7 and 20 immunostaining was performed on randomly selected surgical resection specimens from patients with Barrett's-related oesophageal adenocarcinoma (n = 30) and intestinal type gastric adenocarcinoma (n = 14) arising in a background of intestinal metaplasia. A CK7+ CK20- immunophenotype was demonstrated in 27 of 30 (90%) patients with Barrett's-related oesophageal adenocarcinoma and only three of 14 (21%) gastric adenocarcinomas. The sensitivity, specificity and positive predictive value of a CK7+/20- immunophenotype for a diagnosis of Barrett's-related oesophageal adenocarcinoma was 90%, 79%, and 90%, respectively.. A CK7+/20- tumour immunophenotype is associated with Barrett's-related oesophageal adenocarcinoma and may be useful in accurate tumour classification, thus facilitating improving epidemiological evaluation of tumours at the oesophagogastric junction.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Barrett Esophagus; Biomarkers, Tumor; Esophageal Neoplasms; Female; Humans; Immunohistochemistry; Intermediate Filament Proteins; Keratin-20; Keratin-7; Keratins; Male; Metaplasia; Middle Aged; Observer Variation; Predictive Value of Tests; Sensitivity and Specificity; Stomach Neoplasms

The goal was to investigate the prognostic value of various molecular markers like CEA, Cyclin D1, Bcl-2, c-Myc, p53, p21ras, Ki-67, CD44, Factor VIII-related antigen, cytokeratin-19, adenoma antigen, and prolactin in patients with Dukes B and Dukes C colorectal adenocarcinoma.. These molecular markers were localized immunohistochemically in nonmalignant (n = 36) and malignant (n = 98) diseases of the colorectum. Data were analyzed statistically using the SPSS software program. The patients with colorectal cancer were followed for a period of five years or their death within that period.. The expression of carcinoembryonic antigen, Cyclin D1, Bcl-2, CD44, cytokeratin-19 and prolactin was significantly higher in malignant diseases (P < 0.05), whereas, p21ras was found to be significantly higher in nonmalignant diseases (P = 0.002) as compared with their respective counterparts. Besides Dukes stage, multivariate analysis indicated a significantly reduced relapse-free survival in patients expressing CD44 and cytokeratin-19 (P < 0.005). Similarly, besides Dukes stage, multivariate analysis indicated a significantly poor overall survival in patients expressing CD44, cytokeratin-19 and prolactin (P < 0.01). In patients with Dukes B disease, only cytokeratin-19 and CD44 expression attained statistical significance (P < 0.05), whereas in patients with Dukes C disease, CD44, p21ras- and c-Myc expression attained statistical significance (P < 0.018). Also, a multivariate analysis in relation to treatment given was performed using CD44 and cytokeratin-19.. Besides Dukes stage, multivariate analysis of all the studied molecular markers showed that patients expressing CD44 and cytokeratin-19 had a significantly reduced relapse-free and poor overall survival. Moreover, patients expressing both these markers (CD44 and cytokeratin-19) had the lowest significant relative risk for developing recurrence than patients with both markers negative when treated with surgery followed by adjuvant chemotherapy as compared with patients treated with surgery alone. Thus, in patients with colorectal cancer, immunohistochemical localization of CD44 and cytokeratin-19 may be included as a part of routine pathologic evaluation along with conventional prognostic factors.

Topics: Adenocarcinoma; Adult; Biomarkers, Tumor; Colorectal Neoplasms; Female; Humans; Hyaluronan Receptors; Immunohistochemistry; Keratins; Male; Multivariate Analysis; Neoplasm Metastasis; Neoplasm Proteins; Neoplasm Recurrence, Local; Neoplasm Staging; Prognosis; Retrospective Studies; Survival Analysis

Basal cell adenoma is a benign epithelial neoplasm with a uniform histologic appearance dominated by basaloid cells. Those cells may be distributed in various arrangements as solid, trabecular, tubular and membranous. Canalicular adenoma is also a benign neoplasm composed by columnar cells arranged in branching and interconnecting cords of single or double cell thick rows. There is some disagreement among investigators about whether canalicular adenoma should be included within the basal cell adenoma histologic spectrum. In the present study we compared the expression of cytokeratins (CK), vimentin and muscle-specific actin, utilizing immunohistochemical technique, in three cases diagnosed as basal cell adenomas predominantly of the solid type, and three cases of canalicular adenomas. The results obtained showed a distinct immunoprofile for both neoplasms. Solid areas of basal cell adenomas did not stain for any of the tested antibodies; only when there was tubular differentiation, those structures expressed CKs 7, 8, 14, and 19 in luminal cells and vimentin in non-luminal cells. On the other hand, canalicular adenomas strongly expressed CKs 7 and 13. The panel of antibodies utilized supports the separation of the two entities.

Topics: Actins; Adenocarcinoma; Adenoma; Humans; Immunohistochemistry; Keratin-7; Keratins; Neoplasm Proteins; Salivary Gland Neoplasms; Vimentin

We studied reactivity of cytokeratins (CK) 7, 17, and 20 in 64 pancreaticobiliary adenocarcinomas to examine the effect of different cut-point thresholds on "positive" results, compare ampulla of Vater and pancreas adenocarcinomas, and provide additional experience with CK17 reactivity. Almost all neoplasms had extensive CK7 reactivity. The number of CK20-positive cases decreased from 29 (45%; any stained cells) to 19 (30%; > 25% staining) to 14 (22%; > 50% staining) with an increasing threshold of reactive cells. Similar shifts in the distribution of CK7 and CK20 reactivity occurred when different thresholds of reactivity were used for a positive result. There were no differences in CK7 or CK20 reactivity in pancreas only, ampulla only, and neoplasms involving both sites. Of 64 adenocarcinomas, 29 (45%) had no or single-cell CK17 reactivity, and 19 (30%) had reactivity in more than 50% of neoplastic cells. Ampulla of Vater and pancreas adenocarcinomas have similar CK immunophenotypes that cannot assist in distinguishing ampullary from pancreatic neoplasms on endoscopically procured tissue. CK17 staining occurs in approximately 50% of pancreaticobiliary adenocarcinomas and is usually patchy. Single antibody staining results, especially CK7 and CK20 coordinate reactivity, are influenced by the reactivity threshold used.

Topics: Adenocarcinoma; Ampulla of Vater; Biomarkers, Tumor; Cell Count; Common Bile Duct Neoplasms; Humans; Immunohistochemistry; Intermediate Filament Proteins; Keratin-20; Keratin-7; Keratins; Pancreatic Neoplasms

The canine prostate has often been proposed as a model for abnormal growth of the human gland. Hyperplasia of the prostate is common in aging men and has been estimated to be present in 100% of old intact dogs. While prostatic carcinoma is common in older men it appears to be rare in dogs and unlike the disease in humans it occurs with relatively high frequency in castrated animals. Since basal cells are thought to be key participants in normal and abnormal growth of the human gland, we used immunohistochemistry to investigate the role that they may play in canine prostatic development, the evolution of hyperplasia and carcinoma, and the effects of sex hormones on these cells.. Prostate specimens were obtained at autopsy from seven sexually immature dogs, autopsy and biopsy samples from 14 sexually mature intact animals, from four castrates, and from 19 dogs with prostatic carcinoma. In addition, we also studied the prostates from two intact dogs treated with 5 alpha-dihydrotestosterone (DHT) for 6 months and two castrated dogs that were subsequently treated with 5 alpha-androstane-3 alpha diol and estradiol-17 alpha as well as specimens from two sexually ablated animals given DHT for 2 weeks. All specimens were immunostained for high molecular weight cytokeratin (HMC), Pancytokeratin, androgen receptor (AR), and the proliferative marker KI-67.. We find that basal cells are the major proliferative cell type in the neonatal and adult canine prostate and that the expression of HMC staining, which defines these cells, may be regulated by androgens. In the adult gland, ductal basal cells formed a contiguous layer whereas those lining acini were discontinuous. Populations of both basal cell types were variably AR positive but while HMC immunostaining was abolished in acinar cells following long-term castration, staining remained in ductal cell counterparts. Paralleling the histological development of hyperplasia, the acinar basal cell population increased with age and were the major cell type that expressed KI-67. In contrast, ductal basal cell populations did not expand in the prostates of older dogs and were seldom positively stained for KI-67. The numbers of HMC and KI-67-stained acinar basal cells were dramatically increased in the prostates of intact dogs treated with DHT when compared with glands of untreated controls. This was not the case with ductal basal cells. Androgens given alone or together with estrogen to castrated dogs induced widespread HMC and KI-67 immunostaining in both populations of basal cells. In addition, our results indicate that the majority of canine prostatic carcinomas likely arise exclusively from ductal epithelium. Only one of the 19 cases of carcinoma contained cells that expressed AR which suggests that androgens may not be required for the initiation or progression of these cancers.. Our findings indicate that two biologically distinct populations of basal cells may exist in the canine prostate. In this regard the age-related expansion of proliferating acinar basal cell populations, probably mediated by sex steroids, is a key factor in the pathogenesis of canine prostatic hyperplasia. Additionally we find that prostatic carcinoma in the dog likely arises from ductal cells. Taken together these findings may indicate that canine acinar basal cells and ductal epithelium have separate susceptibilities to factors that promote hyperplastic or neoplastic development. Prostate 47:149-163, 2001.

Topics: Adenocarcinoma; Androstane-3,17-diol; Animals; Cell Division; Dihydrotestosterone; Disease Models, Animal; Dog Diseases; Dogs; Estradiol; Gonadal Steroid Hormones; Immunohistochemistry; Keratins; Ki-67 Antigen; Male; Orchiectomy; Prostate; Prostatic Hyperplasia; Prostatic Neoplasms; Receptors, Androgen

histological features of metastasis are not always specific of the origin. The usefulness of cytokeratin 7 and 20 (CK7 and CK20) in cerebral metastases from an adenocarcinoma was studied in a series of 78 patients.. metastases from lung adenocarcinoma showed a CK7+/CK20- pattern in 79% of cases, CK7+/CK20+ in 19% and CK7-/CK20- in 2%. When observed, positivity for cytokeratin 20 was generally focal or weak. Breast adenocarcinoma metastases were CK7+/CK20- in 71% of cases and CK7-/CK20- in 29%. Less differentiated tumours were usually negative for both cytokeratins. Metastases by colonic adenocarcinoma were CK7-/CK20+ in 100% of cases. Cytokeratins 7 and 20 are useful to distinguish lung from colonic metastatic carcinoma. In case of double positivity, a more intense CK7 expression is rather suggestive of a lung origin.. these results might modify paraclinic investigations in search of the primitive tumor.

Topics: Adenocarcinoma; Brain Neoplasms; Breast Neoplasms; Colonic Neoplasms; Diagnosis, Differential; Humans; Intermediate Filament Proteins; Keratin-20; Keratin-7; Keratins; Lung Neoplasms

The distinction between pleural epithelial mesothelioma and peripheral lung adenocarcinoma involving the pleura is still an important diagnostic problem for surgical pathologists. The aim of our study was to identify the most specific and sensitive markers for the positive identification of mesothelioma to select a limited, appropriate panel of antibodies to differentiate between mesothelioma and adenocarcinoma. Forty-two cases of epithelial mesotheliomas and 23 cases of pulmonary adenocarcinomas were stained with the following antibodies: anticalretinin, antithrombomodulin, anti-CD44H, and monoclonal antibody HBME-1. We also studied the value of other markers in current use: cytokeratins AE1/AE3 and CAM5.2, epithelial membrane antigen (EMA), carcinoembryonic antigen (CEA), Ber-EP4, B72.3, and CD15. Of the mesotheliomas, 42 stained for calretinin, 39 (92.8%) for thrombomodulin, 42 stained for CD44H, and 41 (97.6%) stained for HBME-1. Among negative markers, 4 (9.5%) mesothelioma cases stained for CEA, 5 (11.9%) stained for Ber-EP4, 6 (14.2%) stained for B72.3, and 2 (4.7%) stained for CD15. Of the lung adenocarcinomas, 2 (8.7%) cases showed reactivity for calretinin, 5 (21.7%) for thrombomodulin, 13 (56.5%) for CD44H, all for HBME-1, 22 (95.6%) for CEA, 22 (95.6%) for Ber-EP4, 8 (34.7%) for B72.3, and all for CD15. In conclusion, calretinin and thrombomodulin were the most specific positive mesothelial markers, whereas CD44H and HBME-1 showed high sensitivity but very low specificity. Among negative markers, we advocate the use of CEA and CD15 which were the most specific in differentiating mesotheliomas from adenocarcinomas.

Topics: Adenocarcinoma; Antibodies, Monoclonal; Biomarkers, Tumor; Calbindin 2; Carcinoembryonic Antigen; Diagnosis, Differential; Humans; Hyaluronan Receptors; Immunohistochemistry; Keratins; Lewis X Antigen; Lung Neoplasms; Mesothelioma; Mucin-1; Pleural Neoplasms; S100 Calcium Binding Protein G; Thrombomodulin

Although numerous studies have shown that nm23-H1 gene product expression is inversely related to metastatic potential in some cancers, the expression in lymph nodes has not been studied in detail. An analysis of nm23-H1 gene product expression in mediastinal lymph nodes from lung cancer patients is reported.. One hundred and thirty-four, randomly selected lymph nodes (63 with positive pathological lymph node status) from 39 surgically treated lung cancer patients were examined. Expression of nm23-H1 gene product was determined using specific monoclonal antibodies. Metastatic cancer cells were highlighted using anti-cytokeratin antibody.. Expression of nm23-H1 gene product in patients with less and more than 50% nodes-positive was 12/23 (52.2%) and 15/16 (93.8%) cases, respectively. Immunohistochemical studies with cytokeratin revealed micrometastasis in 6/39 (15.4%) patients and 9/71 (12.7%) nodes previously reported as cancer negative. Expression of nm23-H1 gene product in micrometastasis and metastasis-positive nodes was 5/9 (55.6%) and 55/63 (87.3%), respectively. We also found nm23-H1 gene product expression in germinal center cells. However, we found no relationship between expression of nm23-H1 gene product in germinal center cells and extent of metastasis.. Our study demonstrates a positive relationship between expression of nm23-H1 gene product and extent of metastasis in mediastinal lymph nodes from lung cancer patients. Our data for normal germinal center cells suggests that nm23-H1 gene product expression does not play a specific biological role in suppressing tumor metastasis in lung cancer.

Topics: Adenocarcinoma; Carcinoma, Squamous Cell; Humans; Immunohistochemistry; Keratins; Lung Neoplasms; Lymph Nodes; Lymphatic Metastasis; Mediastinum; Monomeric GTP-Binding Proteins; NM23 Nucleoside Diphosphate Kinases; Nucleoside-Diphosphate Kinase; Transcription Factors

In cytological preparations, reactive mesothelial cells (RMC) in serous effusions are sometimes difficult to distinguish from adenocarcinoma cells (AC). RMC and AC can be distinguished by lectin-binding patterns, but the pattern of binding of lectins to normal mesothelium is not well defined. We investigated the expression of cytoskeletal filaments, cytokeratin (CK) and vimentin (VM), and the cell surface binding pattern of 10 lectins (HPA, SBA, ABA, DSA, PNA, RCA-I, UEA-I, LTA, WGA and ConA) in the serosa of 48 adenocarcinoma specimens. We also investigated the usefulness of six lectins (HPA, SBA, RCA-I, UEA-I, LTA and WGA) in identification of RMC and AC in 16 serous effusions. DSA reactivity was significantly higher (P < 0.05) in static mesothelial cells (SMC) than in RMC. Reactivity for LTA and ConA was significantly lower (P < 0.05) in SMC than in RMC. Anti-CK and anti-VM immunoreactivity was always positive in RMC and almost negative in SMC. In serous effusions, HPA, SBA and UEA-I binding was evident in 100, 88 and 81% of AC, respectively. Little to no binding of HPA, SBA or UEA-I was detected in RMC. Our results suggest that the morphological differences between SMC and RMC are likely to be due to differences in cytoskeletal composition, with accompanying changes in cell-surface lectin-binding patterns. HPA, SBA and UEA-I are likely to be useful markers for identification of RMC and AC in cytology.

Topics: Adenocarcinoma; Ascites; Binding Sites; Biomarkers; Cytoskeleton; Epithelium; Gastrointestinal Neoplasms; Humans; Immunohistochemistry; Keratins; Lectins; Lung Neoplasms; Pleural Effusion; Serous Membrane; Vimentin

The distribution of cytokeratins (CKs) and vimentin in the normal genital tract of calves and cows at different stages of the oestrous cycle and in epithelial tumours of the tract was studied immunohistochemically. Few differences in CK and vimentin immunolabelling were detected in relation to age or stage of the oestrous cycle. Coexpression of CKs in simple epithelia and in basal cells of stratified epithelia was detected in the oviduct and endocervix; this coexpression was different from that previously described in women. The demonstration of CKs but not vimentin in the neoplastic cells of a serous superficial ovarian papilloma suggested an origin from the ovarian surface epithelium, while the coexpression of CKs and vimentin in serous papillary and mucinous cystadenomas pointed to a possible origin from the rete ovarii. Studies on three uterine adenocarcinomas and the ovarian metastases from two of these showed an endometrial-CK phenotype. The intermediate filament profile of normal endometrium, conserved in uterine adenocarcinomas and their ovarian metastases, may be useful in discriminating between ovarian metastases from endometrial carcinomas and those originating from primary carcinomas in other organs.

Topics: Adenocarcinoma; Age Factors; Animals; Antibodies, Monoclonal; Cattle; Cattle Diseases; Cystadenoma; Estrus; Female; Genitalia, Female; Immunoenzyme Techniques; Keratins; Ovarian Neoplasms; Ovary; Oviducts; Papilloma; Uterine Neoplasms; Uterus; Vimentin

Pathologic factors of predictive value for carcinoma ex pleomorphic adenoma (CXPA), an aggressive salivary gland malignancy, are poorly defined. Because residual mixed tumor may be relatively inconspicuous and various carcinoma subtypes are encountered, misdiagnosis is common. To describe the pathologic features and identify potential prognostic factors, we retrospectively examined 73 cases of CXPA of the major salivary glands treated at Mayo Clinic. Paraffin section immunostaining for keratins (AE1/AE3, CK7, CK20), epithelial membrane antigen, carcinoembryonic antigen, vimentin, actin, S-100 protein, glial fibrillary acidic protein, and p53 and c-erbB-2 oncoproteins was performed in 69 cases. DNA content and proliferation indices were determined by digital image analysis of Feulgen- and MIB-I-stained sections, retrospectively. Survival was calculated by the Kaplan-Meier method, and prognostic variables were analyzed with the log-rank test. The carcinoma component was predominant in 82% of tumors. Adenocarcinoma not otherwise specified (31 cases) and salivary duct carcinoma (24 cases) were the most frequent histologic subtypes. Sixty-two tumors were high grade (Broders 3 or 4). Residual mixed tumor was extensively hyalinized in 54 cases. Pathologic features significantly associated with overall survival included pathologic stage (P =.009), tumor size (P =.012), grade (P =.005), proportion of carcinoma (P =.004), extent of invasion (P =.002), and proliferation index of carcinoma (P =.03). Of 4 patients with intracapsular (noninvasive) carcinoma, none had an adverse outcome. The immunohistochemical profile of CXPA included positive staining reactions in the malignant component for AE1/AE3 in 97% of cases, CK7 in 94%, epithelial membrane antigen in 86%, carcinoembryonic antigen in 75%, vimentin in 52%, and S-100 protein in 29%. Expression of p53 and c-erbB-2 oncoproteins was detected in 41% and 30% of the carcinomas, respectively, but neither was associated with decreased survival. High-grade salivary adenocarcinoma that is difficult to classify should raise the suspicion of possible CXPA. Intracapsular carcinoma has a benign clinical course. Significant prognostic factors in CXPA include tumor stage, grade, proportion of carcinoma, extent of invasion, and proliferation index.

Topics: Actins; Adenocarcinoma; Adenoma; Adult; Aged; Carcinoembryonic Antigen; Cell Division; DNA, Neoplasm; Female; Glial Fibrillary Acidic Protein; Humans; Keratins; Male; Middle Aged; Mucin-1; Neoplasm Invasiveness; Prognosis; Receptor, ErbB-2; Retrospective Studies; S100 Proteins; Salivary Ducts; Salivary Gland Neoplasms; Survival Rate; Tumor Suppressor Protein p53; Vimentin

To clarify whether intraglandular necrotic debris (IND) is a diagnostic clue to noninvasive high-grade neoplasia or invasive neoplasia of the stomach, we reviewed 135 gastric biopsy specimens and 55 surgical materials. Intraglandular necrotic debris is defined as an eosinophilic material with necrotic epithelial fragments within the lumen of a dilated atypical gland. Using the Vienna classification, the incidence of IND in category 4 (noninvasive high-grade neoplasia) and category 5 (invasive neoplasia) was significantly higher than that of category 1 (negative for neoplasia/dysplasia), category 2 (indefinite for neoplasia/dysplasia), and category 3 (noninvasive low-grade neoplasia). The incidence of IND was much higher in category 5 than in category 4 in biopsy specimens. In addition, cases with IND in category 4 in biopsy specimens turned out to be either carcinoma in situ or invasive carcinoma in the surgical specimens. According to the histologic classification of surgically removed invasive carcinoma, moderately differentiated adenocarcinoma showed the highest incidence of IND. Intraglandular necrotic debris was not found in either signet-ring cell carcinoma or mucinous adenocarcinoma. Our results indicate that IND in biopsy specimens is a diagnostic clue to noninvasive high-grade neoplasia or invasive carcinoma, and the origin of IND may be associated with necrotic atypical epithelium.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Biomarkers; Biopsy; Female; Gastric Mucosa; Humans; Immunoenzyme Techniques; Keratins; Male; Middle Aged; Necrosis; Neoplasm Invasiveness; Stomach Neoplasms

We present a case of synchronous breast and colon carcinoma in a pleural effusion, to our knowledge the first such reported case in the English-language literature. The patient was a 55-yr-old white female with known metastatic breast and colon carcinoma who developed a malignant pleural effusion which demonstrated two strikingly different populations of malignant cells by immunohistochemical study of cell block material. One cell population demonstrated a cytokeratin (CK)7+/CK20-/ER+ phenotype, while the other demonstrated a CK7-/CK20+/ER- phenotype, consistent with breast and colon origin, respectively. An immunohistochemical survey of archival breast and colon primary and metastatic carcinomas confirmed the established CK7+/CK20- phenotype of breast and CK7-/CK20+ phenotype of colon primary carcinomas, and the maintenance of this phenotype in metastases thereof. A survey of benign and malignant mesothelial lesions confirmed the absence of staining for estrogen receptor, but showed 6/10 cases weakly positive for CK20, which has not been described in other published series. This unusual case graphically illustrates the utility of cytokeratin subset immunohistochemistry in effusion cytology.

Topics: Adenocarcinoma; Breast Neoplasms; Carcinoma, Ductal, Breast; Colonic Neoplasms; Fatal Outcome; Female; Humans; Immunoenzyme Techniques; Intermediate Filament Proteins; Keratin-20; Keratin-7; Keratins; Middle Aged; Pleural Effusion, Malignant

Topics: Adenocarcinoma; Biopsy; Breast Neoplasms; CA-19-9 Antigen; Female; Gastric Mucosa; Gastroscopy; Humans; Immunohistochemistry; Keratins; Middle Aged; Mucin-1; Stomach Neoplasms

A large percentage of cases of perianal Paget disease are associated with an internal cancer, most commonly rectal adenocarcinoma. Immunostains for cytokeratin 7, cytokeratin 20, and gross cystic disease fluid protein 15 are useful in identifying cases associated with rectal adenocarcinoma. The Paget cells and rectal adenocarcinoma cells of these lesions typically have a cytokeratin 7(+)/cytokeratin 20(+)/gross cystic disease fluid protein 15(-) immunophenotype. It is not known whether rectal adenocarcinoma unassociated with perianal Paget disease has the same cytokeratin profile as rectal adenocarcinoma associated with perianal Paget disease.. To evaluate the immunohistochemical cytokeratin 7 and 20 profile of resected rectal adenocarcinoma unassociated with perianal Paget disease as well as that of normal anal glands from hemorrhoidectomy specimens.. We performed immunohistochemistry for cytokeratins 7 and 20 on tissues from 30 cases of rectal adenocarcinoma unassociated with perianal Paget disease and 12 hemorrhoidectomy specimens from 12 cases with normal anal glands. We defined positive staining as any immunoreactivity within the neoplastic cells.. Twenty-six of 30 cases of rectal adenocarcinoma (87%) had a cytokeratin 7(-)/cytokeratin 20(+) immunophenotype, similar to the immunophenotype of cases of nonrectal large intestine adenocarcinoma. In 4 cases (13%), neoplastic cells coexpressed cytokeratins 7 and 20. Anal glands stained strongly for cytokeratin 7 but were negative for cytokeratin 20 in all cases, and the anal transitional zone mucosa had a similar immunophenotype.. Rectal adenocarcinoma unassociated with perianal Paget disease has a cytokeratin profile similar to that of nonrectal large intestine adenocarcinoma. These data suggest that rectal adenocarcinoma unassociated with perianal Paget disease has a different cytokeratin profile than rectal adenocarcinoma associated with perianal Paget disease.

Topics: Adenocarcinoma; Anal Canal; Colonic Neoplasms; Hemorrhoids; Humans; Immunohistochemistry; Intermediate Filament Proteins; Keratin-20; Keratin-7; Keratins; Paget Disease, Extramammary; Rectal Neoplasms

We report the case of a 78-year-old man who developed a breast mass 12 months after hormonal therapy for palliation of prostatic adenocarcinoma. On histologic and immunohistochemical examination, the breast tumor revealed a unique collision tumor composed of metastatic prostatic adenocarcinoma and solid papillary breast carcinoma.

Topics: Adenocarcinoma; Aged; Alkaline Phosphatase; Breast Neoplasms, Male; Carcinoma, Papillary; Humans; Immunohistochemistry; Keratins; Male; Mastectomy, Radical; Neoplasms, Multiple Primary; Prostate-Specific Antigen; Prostatic Neoplasms; Receptors, Androgen; Receptors, Estrogen; Receptors, Progesterone

We investigated whether a panel of antibodies including WT1 could separate pancreaticobiliary and ovarian carcinomas by staining 64 pancreaticobiliary adenocarcinomas, 41 ovarian serous carcinomas, and 12 primary ovarian mucinous neoplasms with WT1, cytokeratin (CK) 17, CK20, carcinoembryonic antigen (CEA), and CA-125. Moderate or strong intensity reactivity in more than 25% of cells was a positive result. Of the ovarian serous carcinomas, 38 (93%) were WT1 reactive and 22 (54%) WT1 positive, 9 (22%) had CK20 reactivity, and 3 (7%) were CK20 positive in fewer than 50% of cells. All were CK17 or CEA nonreactive. Of the ovarian mucinous neoplasms, all were WT1 and CK17 nonreactive and 11 (92%) were CEA reactive, 8 (67%) CEA positive, 10 (83%) CK20 reactive, and 6 (50%) CK20 positive. Of the pancreaticobiliary adenocarcinomas, 19 (30%) were CK20 positive, 27 (42%) CK17 positive, and 52 (81%) CEA positive. All were WT1 nonreactive. A panel including WT1, CK17, CK20, and CEA is useful to distinguish pancreaticobiliary and ovarian serous carcinomas. Extensive CK17 reactivity is supportive of a pancreaticobiliary adenocarcinoma when the differential diagnosis includes ovarian mucinous neoplasm. None of the antibodies positively identified ovarian mucinous neoplasms.

Topics: Adenocarcinoma; Adenocarcinoma, Mucinous; Antibodies; Biliary Tract Neoplasms; CA-125 Antigen; Carcinoembryonic Antigen; Cystadenocarcinoma; Diagnosis, Differential; DNA-Binding Proteins; Female; Humans; Immunohistochemistry; Intermediate Filament Proteins; Keratin-20; Keratins; Ovarian Neoplasms; Pancreatic Neoplasms; Transcription Factors; WT1 Proteins

To identify the most accurate and useful panel to diagnose mesothelioma, we immunostained sections from 112 mesotheliomas, 18 adenocarcinomas, and 11 reactive pleural specimens with 13 antibodies. Positive results for mesotheliomas, adenocarcinomas, and reactive pleura, respectively, were CAM5.2, 111, 18, and 11; vimentin, 30, 3, and 3; HBME-1, 75, 10, and 8; thrombomodulin, 31, 2, and 2; calretinin, 43, 6, and 11; and CD44H, 68, 10, and 4. Positive results for adenocarcinoma markers in mesotheliomas and adenocarcinomas, respectively, were carcinoembryonic antigen, 1 and 15; LeuM1, 7 and 9; and Ber-EP4, 5 and 12. All reactive pleura were negative. Positive results for markers to help distinguish mesothelioma from reactive pleura in mesotheliomas, adenocarcinomas, and reactive pleura, respectively, were epithelial membrane antigen, 76, 17, and 6; p53, 78, 16, and 9; P-170 glycoprotein, 37, 4, and 2; and platelet-derived growth factor receptor beta, 31, 1, and 2. The differential diagnosis of mesothelioma from adenocarcinoma is based on negative markers. Individual mesothelial markers are of low sensitivity and specificity for mesothelioma. However, diagnostic accuracy is improved by the use of antibody panels. To date there are no antibodies that help distinguish mesothelioma from reactive pleura.

Topics: Adenocarcinoma; Antigens, Surface; ATP Binding Cassette Transporter, Subfamily B; Biomarkers; Biomarkers, Tumor; Calbindin 2; Carcinoembryonic Antigen; Diagnosis, Differential; Glycoproteins; Humans; Hyaluronan Receptors; Immunohistochemistry; Keratins; Lewis X Antigen; Mesothelioma; Mucin-1; Neoplasm Metastasis; Peritoneal Neoplasms; Pleural Neoplasms; Receptor, Platelet-Derived Growth Factor beta; S100 Calcium Binding Protein G; Thrombomodulin; Tumor Suppressor Protein p53; Vimentin

The canine prostate has often been proposed as a model for abnormal growth of the human gland. Hyperplasia of the prostate is common in aging men and has been estimated to be present in 100% of old intact dogs. While prostatic carcinoma is common in older men, it appears to be rare in dogs and unlike the disease in humans, it occurs with relatively high frequency in castrated animals. Since basal cells are thought to be key participants in normal and abnormal growth of the human gland, we used immunohistochemistry to investigate the role that they may play in canine prostatic development, the evolution of hyperplasia and carcinoma, and the effects of sex hormones on these cells.. Prostate specimens were obtained at autopsy from seven sexually immature dogs, autopsy and biopsy samples from 14 sexually mature intact animals, from four castrates, and from19 dogs with prostatic carcinoma. In addition, we also studied the prostates from two intact dogs treated with 5alpha-dihydrotestosterone (DHT) for 6 months and two castrated dogs that were subsequently treated with 5alpha-androstane-3alpha diol and estradiol-17alpha, as well as specimens from two sexually ablated animals given DHT for 2 weeks. All specimens were immunostained for high molecular weight cytokeratin (HMC), pancytokeratin, androgen receptor (AR), and the proliferative marker KI-67.. We find that basal cells are the major proliferative cell type in the neonatal and adult canine prostate and that the expression of HMC staining, which defines these cells, may be regulated by androgens. In the adult gland, ductal basal cells formed a contiguous layer, whereas those lining acini were discontinuous. Populations of both basal cell types were variably AR positive, but while HMC immunostaining was abolished in acinar cells following long-term castration, staining remained in ductal cell counterparts. Paralleling the histological development of hyperplasia, the acinar basal cell population increased with age and were the major cell type that expressed KI-67. In contrast, ductal basal cell populations did not expand in the prostates of older dogs and were seldom positively stained for KI-67. The numbers of HMC and KI-67-stained acinar basal cells were dramatically increased in the prostates of intact dogs treated with DHT when compared with glands of untreated controls. This was not the case with ductal basal cells. Androgens given alone or together with estrogen to castrated dogs induced widespread HMC and KI-67 immunostaining in both populations of basal cells. In addition, our results indicate that the majority of canine prostatic carcinomas likely arise exclusively from ductal epithelium. Only one of the 19 cases of carcinoma contained cells that expressed AR, which suggests that androgens may not be required for the initiation or progression of these cancers.. Our findings indicate that two biologically distinct populations of basal cells may exist in the canine prostate. In this regard, the age-related expansion of proliferating acinar basal cell populations, probably mediated by sex steroids, is a key factor in the pathogenesis of canine prostatic hyperplasia. Additionally, we find that prostatic carcinoma in the dog likely arises from ductal cells. Taken together, these findings may indicate that canine acinar basal cells and ductal epithelium have separate susceptibilities to factors that promote hyperplastic or neoplastic development.

Topics: Adenocarcinoma; Androstane-3,17-diol; Animals; Cell Division; Dihydrotestosterone; Disease Models, Animal; Dog Diseases; Dogs; Estradiol; Gonadal Steroid Hormones; Immunohistochemistry; Keratins; Ki-67 Antigen; Male; Orchiectomy; Prostate; Prostatic Hyperplasia; Prostatic Neoplasms; Receptors, Androgen

Topics: Adenocarcinoma; Biopsy; Breast Neoplasms; Carcinoembryonic Antigen; Eyelid Neoplasms; Fatal Outcome; Female; Humans; Keratins; Middle Aged; Mucin-1; Skin Neoplasms

Based on the fact that pancreatic carcinoma is still associated with poor outcome, the aim of the study was to determine frequency of early tumor cell dissemination using immunohistology in lymph nodes classified as tumor-free by conventional histopathology.. Fifteen patients with ductal pancreatic carcinoma and 10 patients with carcinoma of the papilla of Vater underwent radical tumor resection (resection status R0, tumor staging pTxpN0M0). In total, 229 lymph nodes classified as tumor-free by histopathology were investigated for disseminated tumor cells using antibodies against cytokeratin and CA19-9. As control, 81 lymph nodes obtained from patients with chronic pancreatitis were analyzed.. In 55 of 229 lymph nodes (26.3%), cytokeratin-positive, disseminated tumor cells were detected. Cytokeratin-positive cells were found in at least one resected lymph node of each patient with ductal carcinoma of the pancreatic head (100%), whereas in patients with carcinoma of the papilla of Vater, no disseminated tumor cells were detected using the antibody against cytokeratin. Similarly, there was no detection of tumor cells (false-positive) in patients with chronic pancreatitis. In contrast, CA19-9 antigen was detectable in resected lymph nodes of each of the 25 carcinoma patients (pancreatic carcinoma and carcinoma of the papilla of Vater). Interestingly, 52 of 81 lymph nodes (64.2%) from the control group (chronic pancreatitis) were false-positive.. Detection of disseminated tumor cells in lymph nodes using an antibody against cytokeratin is specific and suitable while use of an antibody against CA19-9 is not recommendable because of the high rate of false-positive results. The results may indicate that ductal pancreatic carcinoma generates early dissemination of tumor cells into lymph nodes. This may be one explanation for the poor outcome of this carcinoma compared with that of the carcinoma of the papilla of Vater (14 versus 48 months P < 0.05).

Topics: Adenocarcinoma; Adult; Aged; Ampulla of Vater; Biomarkers, Tumor; CA-19-9 Antigen; Carcinoma; Chronic Disease; Common Bile Duct Neoplasms; Female; Humans; Immunohistochemistry; Keratins; Lymph Nodes; Lymphatic Metastasis; Male; Middle Aged; Neoplasm Staging; Pancreatic Neoplasms; Pancreatitis; Predictive Value of Tests; Prognosis

We report herein a case of a collision tumor composed of high-grade urothelial carcinoma and a Gleason grade 3+4 prostate adenocarcinoma metastasizing to the same lymph node. After the patient underwent cystoprostatectomy for known urothelial carcinoma, he was incidentally discovered to have a second primary prostate tumor. Lymph node examination revealed that one node appeared to have metastatic foci from both primary tumors. The presence of 2 tumor types colliding in the same lymph node was confirmed using immunohistochemical stains, including monoclonal carcinoembryonic antigen, prostate-specific antigen, prostatic acid phosphatase, cytokeratins 7 and 20, and CD57. We also stained both primary tumors with the same panel as an internal control. Although 2 similar collision tumors have been reported in the literature in the past, neither used a battery of immunohistochemical stains to definitively distinguish one tumor from the other. Herein, we review the literature on urothelial and prostate collision tumors and some of the special stains used to distinguish them.

Topics: Acid Phosphatase; Adenocarcinoma; Aged; Carcinoma, Transitional Cell; CD57 Antigens; Humans; Immunohistochemistry; Intermediate Filament Proteins; Keratin-20; Keratin-7; Keratins; Lymph Nodes; Lymphatic Metastasis; Male; Neoplasms, Second Primary; Prostate; Prostate-Specific Antigen; Prostatic Neoplasms; Urinary Bladder Neoplasms

To examine the expression of the p63 protein in normal, preneoplastic, and neoplastic human prostatic tissue. The p63 gene, a member of the p53 gene family, is expressed in the basal epithelial cells of multiple organs. Irregularities in p63 expression have been associated with epithelial carcinogenesis.. We performed immunohistochemistry with an anti-p63 antibody on specimens from radical prostatectomies, prostate needle biopsies, and metastatic prostate adenocarcinoma. We analyzed p63 expression in regions of normal prostate, benign prostatic hyperplasia, proliferative inflammatory atrophy (PIA), high-grade intraepithelial neoplasia, and adenocarcinoma.. Basal epithelial cells in normal, benign prostatic hyperplasia, and high-grade intraepithelial neoplasia tissue stained intensely for the p63 polypeptide, but the vast majority of adenocarcinoma specimens from 233 patients-66 (94%) of 70 radical prostatectomies, 132 (89%) of 148 prostate needle biopsies, and 14 (93%) of 15 metastases-did not. In tumors in which the adenocarcinoma cells were positive, the staining intensity was weak and occurred in less than 1% of the cells. Tumors that stained positive for p63 were more likely to be high grade than those that did not (P <0.0001). Basal cells in PIA expressed p63, but these cells were sparsely distributed relative to the basal cells in the normal glands. Luminal cells in PIA were, in general, negative for p63.. In contrast to normal and preneoplastic prostatic tissue, the vast majority of prostate adenocarcinomas do not express p63. Therefore, p63 immunohistochemistry represents a potential novel adjuvant method for facilitating the pathologic diagnosis of prostate cancer in prostate needle biopsies. The selective expression of p63 in normal basal cells, coupled with the finding that p63 null mice fail to develop prostates, provides strong evidence that the basal cells represent prostatic epithelial stem cells. In addition, these findings suggest that p63 may protect prostatic epithelial cells against neoplastic transformation and support the hypothesis that intermediately differentiated cells in the luminal epithelium of PIA are the targets of neoplastic transformation in the prostate.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Biopsy, Needle; Bone Neoplasms; Cell Differentiation; DNA-Binding Proteins; Epithelium; Genes, Tumor Suppressor; Humans; Immunohistochemistry; Keratins; Lymphatic Metastasis; Male; Membrane Proteins; Middle Aged; Phosphoproteins; Precancerous Conditions; Prostate; Prostatic Hyperplasia; Prostatic Neoplasms; Stem Cells; Trans-Activators; Transcription Factors; Tumor Suppressor Proteins

Lymph node analysis is essential for staging gastrointestinal (GI) neoplasms. Our group has conducted several studies of intraoperative lymphatic mapping and sentinel lymphadenectomy (LM/SL) for the staging of GI neoplasms. LM is performed following injection of 0.5-1 ml of isosulfan blue dye, and blue-stained sentinel lymph nodes (SLNs) are analyzed by hematoxylin and eosin (H&E) staining, multiple sectioning, and cytokeratin immunohistochemistry. In feasibility trials, LM identified at least one SLN in 121 of 126 patients. Of the 58 cases with nodal metastasis, 50 (89%) had at least one positive SLN and 24 (42%) had nodal metastasis only in the SLN. In 25 cases, tumor deposits were identified by multiple sectioning (n = 8) or immunohistochemistry (n = 17) only. In 10 cases (8%), LM identified aberrant lymphatic drainage that altered the extent of the lymphadenectomy. Our cumulative experience indicates that focused analysis of the SLNs draining GI neoplasms can increase the detection of micrometastases and may improve selection of patients for adjuvant treatment.

Topics: Adenocarcinoma; Gastrointestinal Neoplasms; Humans; Immunohistochemistry; Intraoperative Care; Keratins; Lymph Nodes; Lymphatic Metastasis; Neoplasm Staging; Rosaniline Dyes; Sentinel Lymph Node Biopsy

Endocervicosis is a rare condition, being one of the triad of non-neoplastic secondary mullerian lesions. This report describes a primary vaginal adenocarcinoma arising in endocervicosis. Histologic examination showed a mucin-secreting adenocarcinoma admixed with benign mucin-containing endocervical-type glands with a transition from dysplastic glands to obvious adenocarcinoma. There were bilateral groin lymph node metastases at presentation and the tumor recurred locally 9 and 12 months after treatment. This is the second reported case of vaginal endocervicosis and the first documented report of adenocarcinoma arising in endocervicosis at any site.

Topics: Adenocarcinoma; Biopsy; CA-125 Antigen; Carcinoembryonic Antigen; Cervix Uteri; Endometrium; Female; Humans; Keratins; Lymph Node Excision; Magnetic Resonance Imaging; Middle Aged; Mucins; Neoplasm Recurrence, Local; Tomography, X-Ray Computed; Vaginal Neoplasms; Vaginal Smears

The distinction of a primary lung carcinoma from a metastatic lesion is important, because the treatment and prognosis differ for patients with these malignancies. Such a distinction can be difficult because of overlapping cytologic features. It has been shown that antibodies to thyroid transcription factor 1 (TTF-1) and PE-10 are fairly specific markers for primary lung tumors in histologic specimens. TTF-1 regulates the expression of surfactant protein production, and PE-10 is a monoclonal antibody against components of human surfactant proteins. The combination of cytokeratin 7 (CK7) and cytokeratin 20 (CK20) immunoprofiling has been helpful in the identification of the primary site of origin of lung tumors.. In the current study, the authors evaluated the utility of TTF-1 and PE-10 immunostaining and also compared the staining with expression of CK7 and CK20 in the discrimination between primary lung tumors and metastatic lesions in 55 specimens from fine-needle aspiration (FNA) biopsies of the lung. Formalin fixed, paraffin embedded cell blocks from 35 primary lung tumors (16 adenocarcinomas, 8 squamous cell carcinomas, 6 large cell undifferentiated carcinomas, and 5 small cell carcinomas) and 20 metastatic carcinomas (6 breast lesions, 6 colon lesions, 3 urinary bladder lesions, 2 kidney lesions, 1 biliary tract lesion, 1 endometrial lesion, and 1 thyroid lesion) were immunostained with monoclonal antibodies to TTF-1, PE-10, CK7, and CK 20. Positive immunostaining for CK7, CK20, and PE-10 was based on cytoplasmic staining, whereas TTF-1 positive staining was based on nuclear staining of the neoplastic cells.. Positive immunostaining with TTF-1 and PE-10 was noted in six primary lung tumors (17%). One metastatic lesion (5%) and two metastatic lesions (10%) were positive for TTF-1 and PE-10, respectively. The CK7 positive/CK20 negative immunophenotype was noted in 30 primary lung tumors (86%) and in 11 metastatic lesions (55%). The CK7 negative/CK20 negative immunophenotype was seen in four metastatic lesions and in the remaining five primary lung tumors. The CK7 negative/CK20 positive and CK7 positive/CK20 positive immunophenotypes were seen in two and three metastatic lesions, respectively, but in none of the primary lung tumors. When a CK7 positive/CK20 negative adenocarcinoma also demonstrated either TTF-1 positive or PE-10 positive staining, it was likely that the adenocarcinoma was of pulmonary origin (P < 0.035; Fisher exact test). The specificity of such a combination for discriminating between primary and metastatic adenocarcinomas was 94%.. The results suggest that TTF-1, PE-10, or CK7/CK20 alone did not distinguish reliably between primary pulmonary tumors carcinomas and metastatic neoplasms of the lung in FNA biopsy specimens because of low sensitivity and specificity. The use of a panel of antibodies that includes CK7/CK20, TTF-1, and PE-10 may be helpful in discriminating between primary and metastatic adenocarcinomas of the lung. An adenocarcinoma is likely a primary lung tumor when it is of the CK7 positive/CK20 negative phenotype and demonstrates either TTF-1 positive or PE-10 positive staining.

Topics: Adenocarcinoma; Biomarkers, Tumor; Biopsy, Needle; Carcinoma, Large Cell; Carcinoma, Small Cell; Carcinoma, Squamous Cell; Humans; Immunohistochemistry; Intermediate Filament Proteins; Keratin-20; Keratin-7; Keratins; Lung Neoplasms; Neoplasm Metastasis; Nuclear Proteins; Predictive Value of Tests; Pulmonary Surfactants; Sensitivity and Specificity; Thyroid Gland; Thyroid Nuclear Factor 1; Transcription Factors

We sought to determine the critical diameter of a peripheral non-small cell lung cancer tumor less than which no evidence of nodal micrometastasis is present.. Samples of 3081 lymph nodes from 181 patients with stage I peripheral lung cancer (155 with adenocarcinoma and 26 with squamous cell carcinoma) who had undergone complete resection with systematic lymphadenectomy were used in the study. In the samples immunohistochemical staining for cytokeratin was performed. The expression of vascular endothelial growth factor (VEGF) at primary sites was also immunohistochemically assessed.. Nodal micrometastasis was detected in 44 patients. The mean tumor sizes were 2.2 +/- 1.3 cm (range, 1.0-7.0 cm) in nodal micrometastasis-positive adenocarcinoma, 2.1 +/- 0.9 cm (range, 0.5-6.0 cm) in nodal micrometastasis-negative adenocarcinoma, 4.8 +/- 2.3 cm (range, 2.2-10.0 cm) in nodal micrometastasis-positive squamous cell carcinoma, and 3.2 +/- 2.1 cm (range, 0-9.0 cm) in nodal micrometastasis-negative squamous cell carcinoma. The tumor size in the nodal micrometastasis-positive group tended to be greater than that in the nodal micrometastasis-negative group in squamous cell carcinomas, but there was no significant difference in adenocarcinomas. Nodal micrometastasis was not found in patients with squamous cell carcinoma of 2.0 cm or less in diameter. However, nodal micrometastasis was found in 20% (19/95) of the patients with adenocarcinoma of 1.1 to 2.0 cm in diameter and even in 4 of 11 patients with adenocarcinoma of 1.0 cm or less. Among the patients with nodal micrometastasis, survival of patients with vascular endothelial growth factor overexpression was worse than that of patients without it. The survival of patients with nodal micrometastasis without vascular endothelial growth factor overexpression was comparable with that of patients without nodal micrometastasis.. A limited surgical intervention without lymphadenectomy is validated for squamous cell carcinoma of 2.0 cm or less without pleural involvement. In adenocarcinoma the tumor size itself is not a reliable guide for nodal micrometastasis status. In patients with nodal micrometastasis with vascular endothelial growth factor overexpression, the risk of systemic disease should be considered.

Topics: Adenocarcinoma; Carcinoma, Non-Small-Cell Lung; Carcinoma, Squamous Cell; Endothelial Growth Factors; Female; Follow-Up Studies; Humans; Keratins; Lung Neoplasms; Lymph Node Excision; Lymph Nodes; Lymphatic Metastasis; Lymphokines; Male; Middle Aged; Protein Isoforms; Time Factors; Vascular Endothelial Growth Factor A; Vascular Endothelial Growth Factors

The human monoclonal antibody SC-1 was isolated from a patient with a diffuse-type adenocarcinoma of the stomach using somatic cell hybridization. The immunoglobulin (Ig)M antibody reacts specifically with diffuse- (70%) and intestinal-type (25%) gastric adenocarcinoma and induces apoptosis in vitro and in vivo. When used in clinical trials with stomach carcinoma patients, significant apoptotic and regressive effects in primary tumors have been observed with the antibody SC-1. The SC-1 receptor is a new 82 kd membrane-bound isoform of glycosylphosphatidylinositol (GPI)-linked CD55 (decay-accelerating factor, DAF). CD55 is known to protect cells from lysis through autologous complement and is coexpressed with the ubiquitously distributed 70 kd isoform. The SC-1-specific CD55 isoform is up-regulated shortly after antibody binding, followed by an internalization of the antibody/receptor-complex, whereas the membranous expression of wild-type CD55 remains unchanged. The apoptotic process is marked by cleavage of cytokeratin 18, indicating the involvement of caspase-6 in the apoptotic process. In contrast to other apoptotic pathways, a cleavage of poly(ADP-ribose)polymerase (PARP) is not observed. The expression of the cell-cycle regulator c-myc becomes up-regulated, whereas expression of topoisomerase IIalpha is down-regulated. Induction of apoptosis leads to an increase in the internal Ca(2+) concentration, which is not necessary for the apoptotic process but for the transport of newly synthesized SC-1-specific CD55 isoform to the membrane.

Topics: Adenocarcinoma; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antineoplastic Agents; Apoptosis; Calcium; Caspase 3; Caspase 6; Caspase Inhibitors; CD55 Antigens; Cell Membrane; Cytoplasm; Flow Cytometry; HeLa Cells; Humans; Keratins; Poly(ADP-ribose) Polymerases; Stomach Neoplasms

Cancer presumably arises from stem cells, preserved in an undifferentiated status since fetal development, or from a dedifferentiation of mature cells that return into a fetal phenotype with the potential for proliferation and renewal. Dedifferentiation in this context could represent a transient phase, passed through by cells, before they switch to redifferentiation, metaplasia or neoplasia. Cytokeratin-7 (CK7) is present in fetal, largely absent in normal adult, and transiently neoexpressed in metaplastic and neoplastic epithelial cells of the stomach according to previous observations. CK7 neoexpression in the stomach could, hence, define a fetal-like, dedifferentiated, cellular phenotype during the development of metaplasia and neoplasia. To test this hypothesis, we investigated CK7 expressions in fetal stomachs, non-neoplastic control stomachs, and neoplastic stomachs exhibiting metaplasia, intraepithelial neoplasia, and early cancer. Proliferation and beta-catenin expression of CK7-positive cells were also evaluated. The chronology of CK7 expression was studied during the experimental gastritis-cancer sequence in Mongolian gerbils. Our results show that metaplastic and neoplastic changes in the gastritis-cancer sequence are related to dedifferentiated epithelial cells which are defined by CK7 expression and can phenotypically be linked to fetal cells at the start of gastric pit development. The dedifferentiated cells exhibit a low proliferation and beta-catenin accumulation, similar to stem cells. Thus, the "stem cell" and "dedifferentiation" hypotheses for cancer origin could complement one another, and dedifferentiation-redifferentiation processes might be decisive for carcinogenesis in the stomach.

Topics: Adenocarcinoma; Adolescent; Adult; Aged; Aged, 80 and over; Animals; Carcinoma in Situ; Cell Transformation, Neoplastic; Child; Disease Models, Animal; Epithelial Cells; Female; Fetus; Gastric Mucosa; Gastritis; Gerbillinae; Gestational Age; Helicobacter Infections; Helicobacter pylori; Humans; Keratin-7; Keratins; Male; Metaplasia; Middle Aged; Stomach; Stomach Neoplasms

Mesonephric (wolffian) neoplasms of the female genital tract are infrequent and found in sites where embryonic remnants of wolffian origin are usually detected, such as the uterine cervix, broad ligament, mesosalpinx, and ovary. Their diagnosis is difficult because of the absence of specific immunohistochemical markers for mesonephric derivatives. We present the first report of adenocarcinoma of mesonephric type arising as a purely myometrial mass without endometrial or cervical involvement in the uterine corpus of a 33-year-old woman. The tumor showed a combination of patterns, with retiform areas, ductal foci, and small tubules with eosinophilic secretion, which merged with solid sheets of cells with a sarcomatoid appearance. Immunohistochemically, neoplastic cells were diffusely positive for cytokeratin 7, epithelial membrane antigen, and CD15 and focally positive for BerEP4 and vimentin. A hitherto unreported feature was the positivity for CD10 in neoplastic cells, which was also present in a large number of control tissues obtained from male mesonephric derivatives and female mesonephric remnants and tumors. Furthermore, CD10 was negative in controls from müllerian epithelia of the female genital tract and in their corresponding tumors. Therefore, the expression of CD10 by mesonephric remnants may be useful in establishing the diagnosis of tumors with mesonephric differentiation.

Topics: Adenocarcinoma; Adult; Antigens, Neoplasm; Antigens, Surface; Biomarkers, Tumor; Cell Differentiation; Female; Humans; Hysterectomy; Immunohistochemistry; Keratin-7; Keratins; Lewis X Antigen; Mesonephroma; Mesonephros; Mucin-1; Neprilysin; Radiotherapy, Adjuvant; Treatment Outcome; Uterine Neoplasms; Vimentin

p63 is a p53-related DNA-binding protein that helps regulate differentiation and proliferation in epithelial progenitor cells. Its expression has never been evaluated in the human gastrointestinal tract. The aim of this study was to evaluate the expression of p63 in the esophagus and related metaplastic and neoplastic disorders to gain insight into the pathogenesis of these processes. Of particular interest was the expression of p63 in Barrett esophagus (BE) and in BE-associated multilayered epithelium. Multilayered epithelium has been postulated to represent an early precursor to the development of BE primarily because it shares morphologic and immunophenotypic features of both squamous and columnar epithelium, and has been shown prospectively to be highly associated with BE. Routinely processed mucosal biopsy or resection specimens that contained normal esophageal squamous epithelium (n = 20), squamous dysplasia (n = 4), squamous cell carcinoma (n = 7), BE (n = 10), BE-associated multilayered epithelium (n = 13), esophageal mucosal gland ducts (n = 10), BE-associated dysplasia (n = 12), and BE-associated adenocarcinoma (n = 7) were immunostained for p63 to determine the extent and location of staining. p63 staining was compared with the staining patterns observed for p53, Ki 67 (proliferation marker), and cytokeratins (CKs) 13 (squamous marker), 14 (basal squamous marker), 8/18 (columnar marker), and 19 (basal/columnar marker). Expression of p63 messenger RNA (mRNA) isoforms was also analyzed by reverse-transcription polymerase chain reaction of freshly isolated tissues. In the normal esophagus, p63 was expressed in the basal and suprabasal layers of the squamous epithelium and in basal cells that line the mucosal gland ducts but was negative in all other epithelia of the gastrointestinal tract, including the stomach, small intestine, and colon. Similarly, p63 was not expressed in BE, but it, was present in the basal layer of multilayered epithelium in 9 of 13 cases (69%). p63-positive cells in multilayered epithelium and in the mucosal gland duct epithelium were positive for CK8/18 (100%) and CK13 (67% and 30%, respectively) and negative for CK14 (0%), in contrast to p63-positive cells in squamous epithelium, which were positive for CK14 and CK13 (100%) but negative for CK8/18. In neoplastic tissues, p63 was diffusely expressed in all cases of esophageal squamous cell dysplasia and carcinoma but was negative in all cases of esophageal and colorectal ad

Topics: Adenocarcinoma; Barrett Esophagus; Carcinoma, Squamous Cell; Digestive System; DNA-Binding Proteins; Epithelium; Esophageal Diseases; Esophageal Neoplasms; Esophagus; Genes, Tumor Suppressor; Humans; Immunohistochemistry; Keratins; Ki-67 Antigen; Membrane Proteins; Metaplasia; Phosphoproteins; Protein Isoforms; Retrospective Studies; RNA, Messenger; Trans-Activators; Transcription Factors; Transcription, Genetic; Tumor Suppressor Protein p53; Tumor Suppressor Proteins

Topics: Adenocarcinoma; Aged; Aqueous Humor; Biomarkers, Tumor; Carcinoembryonic Antigen; Cytological Techniques; Eye Neoplasms; Humans; Immunoenzyme Techniques; Immunophenotyping; Keratins; Lung Neoplasms; Male; Syndrome; Tomography, X-Ray Computed; Uveitis; Vitreous Body

This prospective study aimed to evaluate the detection of micrometastases in bone marrow of patients with suspected pancreatic and ampullary cancer and to determine their predictive value on overall survival.. Between December 1997 and December 1998, 35 patients (19 male, 42-77 years) with suspected pancreatic and ampullary cancer underwent diagnostic laparoscopy as a final staging procedure before exploration. Bone marrow was aspirated from the iliac crest at the beginning of laparoscopy. Mononuclear cells were isolated and stained using the specific monoclonal antibody CAM 5.2.. Cytokeratin-positive cells were detected in 12/35 (34%) of all patients. In the 31 patients with a final diagnosis of carcinoma, a positive staining was found in 10/31 (32%) of the bone marrow aspirates. After a median follow-up of 17 months (2-24), 15/31 (48%) patients had died: 7/10 (70%) with and 8/21 (38%) without micrometastases (* P<0.04). All four patients who turned out to have chronic pancreatitis were alive without malignancy. In two of these four patients, distinct cytokeratin-positive cells were seen.. Micrometastases in bone marrow of patients with the final diagnosis pancreatic or ampullary carcinoma seem to predict a significantly shorter survival. However, clinical use of cytokeratin markers cannot be recommended at present, because false-positive staining was found.

Topics: Adenocarcinoma; Adult; Aged; Biomarkers; Biomarkers, Tumor; Bone Marrow Cells; Bone Marrow Neoplasms; Common Bile Duct Neoplasms; Female; Humans; Immunohistochemistry; Inhalation; Keratins; Laparoscopy; Male; Middle Aged; Neoplasm Staging; Pancreatic Neoplasms; Prospective Studies; Survival Analysis

Cribriform areas are common features of both adenoid cystic carcinoma and polymorphous low-grade adenocarcinoma. Both are malignant salivary gland tumors that share similar histologic patterns, but with marked distinct clinical behavior. This study was undertaken to improve the accuracy of the histopathology diagnostic process, using an immunohistochemical panel to differentiate adenoid cystic carcinoma from polymorphous low-grade adenocarcinoma, with special concern to the common cribriform areas shared by these tumors. Three-microm serial sections of these tumors were submitted to the streptavidin-biotin peroxidase immunotechnique against the monoclonal antibodies anticytokeratins 7, 8, 14 and 19, and anti-integrins beta1, beta3, and beta4. In the neoplastic lobules of adenoid cystic carcinoma cribriform type, the spaces were mainly surrounded by cells negative for the cytokeratins and integrins studied. In the solid type of adenoid cystic carcinoma, the microcystic areas were caused by spaces lined by neoplastic luminal cells positive for cytokeratins and presenting integrins concentrated in the apical pole of these cells. The cribriform areas of polymorphous low-grade adenocarcinoma were composed of cords of luminal cells, positive for cytokeratins and showing integrins disposed in a bipolar pattern. We concluded that cribriform areas of adenoid cystic carcinoma and polymorphous low-grade adenocarcinoma are histologically similar, although not identical. Indeed, their cellular composition is distinct and can be distinguishable from one another by the proteins of the cytoskeleton, by the integrins, or both.

Topics: Adenocarcinoma; Biomarkers, Tumor; Carcinoma, Adenoid Cystic; Diagnosis, Differential; Humans; Immunoenzyme Techniques; Integrins; Keratins; Salivary Gland Neoplasms

Immunohistochemistry is a useful method in the differential diagnosis between pleural mesotheliomas and metastatic adenocarcinomas to the pleura. Cytokeratin (CK) 5-6 is one of the most specific mesothelioma-associated antibodies. Cytokeratin 20 and CK7 have been used successfully in studies determining primary location of adenocarcinomas from metastases. In the current study, the value of these CKs in differential diagnosis of malignant pleural lesions was examined.. Ninety-three autopsy-verified cases (14 mesotheliomas and 79 adenocarcinomas including 42 primary lung tumors and 37 adenocarcinomas metastatic to the pleura) were stained on CK20, CK7, and CK5-6 with commercially available primary antibodies. The staining was conducted in an automated immunohistochemical system. The results were analyzed statistically at different positivity thresholds: 10% and 0%.. None of the mesotheliomas stained positively for CK20 at the 10% positivity level, but 3 cases showed focal positivity in < 10% of the tumor cells. Eighty-six percent (12 of 14) of these tumors were CK7+ and 64% (9 of 14) were CK5-6+. None of the mesotheliomas expressed the CK20+/7- pattern. Lung adenocarcinomas, both primary and metastatic, and breast carcinomas were very similar to mesotheliomas with regard to expression of CK20 and CK7 but differed significantly with regard to expression of CK5-6. Conversely, gastrointestinal adenocarcinomas and pancreaticobiliary tumors expressed CK20 positivity in a high proportion, 86% (13 of 15) and 77% (7 of 9), respectively. The gastrointestinal tumors stained positively for CK7 in only 20% (3 of 15) of cases and differed significantly from the other adenocarcinomas in this aspect. The CK20+/7- pattern was typical for gastrointestinal tumors.. Adding CK20 and CK7 to the panel of antibodies in the differential diagnosis of pleural mesothelioma versus metastatic adenocarcinomas is useful because diffuse CK20 positivity seems to be an indicator of metastasis. Furthermore, CK7 negativity most often is associated with metastases, and the CK20+/7- pattern, typical of colorectal adenocarcinomas, is absent in pleural mesotheliomas.

Topics: Adenocarcinoma; Autopsy; Biomarkers, Tumor; Diagnosis, Differential; Gene Expression Regulation, Neoplastic; Humans; Immunohistochemistry; Intermediate Filament Proteins; Keratin-20; Keratin-7; Keratins; Lung Neoplasms; Mesothelioma; Neoplasm Metastasis; Pleural Neoplasms; Sensitivity and Specificity

Within normal human prostate epithelium, basal and luminal cells can be discriminated by their expression of keratins (K). While basal cells express K5/14, luminal cells show expression of K8/18 and an intermediate cell population can be identified by co-expression of K5/18. Prostate cancer is predominantly composed of luminal and neuroendocrine cells, while a minority of cells have a basal phenotype. In order to distinguish between basal and intermediate cells, and to assess the effects of androgen deprivation on prostate cancer, 56 human prostate cancer metastases and three cancer cell lines were characterized using antibodies to K5, K14, K18, and the neuroendocrine marker chromogranin A (ChA). The staining was performed on paraffin tissue and visualized by the avidin-biotin-peroxidase complex method. Protein expression was quantified as the number of positive cells in 20 high power fields (HPF; 400x). Keratin expression in the prostate cancer cell lines LNCaP, DU145, and PC3 was analysed by immunofluorescence with triple staining and confocal laser scanning microscopy. Prostate cancer metastases were consistently positive for K18 and negative for K14, irrespective of hormonal therapy. K5 expression was displayed in 28.9% of the tumours without treatment, in 75% after androgen deprivation, and in 57.1% of hormone-escaped prostate carcinomas. After androgen deprivation, the number of K5-expressing cells increased significantly. While androgen-dependent prostate cancer showed a median of 0 cells/20 HPF (range 0-50), regressed tumours displayed 22.5 (range 0-65) and hormone-escaped tumours 7.5 (range 0-361) positive cells/20 HPF. Expression of ChA was observed in 47.4% of the androgen-dependent tumours. The number of neuroendocrine cells was not significantly affected in regressed or hormone-escaped disease. The androgen-dependent cell line LNCaP stained for K18, while the androgen-independent lines DU145 and PC3 both expressed K5 and 18. Expression of K5 in the absence of K14 identifies the existence of an intermediate cell population in prostate carcinoma. Accumulation of intermediate cells in regressed and hormone-escaped prostate cancer indicates that for their survival, these cells are androgen-independent.

Topics: Adenocarcinoma; Biomarkers, Tumor; Chromogranin A; Chromogranins; Humans; Immunoenzyme Techniques; Keratin-5; Keratins; Male; Neoplasm Proteins; Prostatic Neoplasms; Tumor Cells, Cultured

To estimate the utility of thyroid transcription factor-1 (TTF-1) and the combined cytokeratin 7 (CK7) and 20 (CK20) immunoprofile as a marker for identifying the primary site of metastatic adenocarcinoma in effusions of the serous cavity.. Formalin-fixed, paraffin-embedded cell block specimens of pleural and peritonealfluid diagnosed as metastatic adenocarcinomas with known sites of origin were used for TTF-1, CK7 and CK20 immunohistochemistry. The primary sites of these cases were lung (16 cases), ovary (15), stomach (9), colon (8) and breast (8) and were confirmed by radiologic and/or histologic evaluation.. The lung adenocarcinomas showed TTF-1 positivity in 81% (13/16) of cases. All nonpulmonary adenocarcinomas lacked TTF-1 staining. The CK7-/CK20+ immunophenotype was seen in 63% of colonic adenocarcinomas and not seen in lung, ovary, stomach or breast adenocarcinomas. The CK7+/CK20- immunophenotype was seen in 100%, 88% and 87% of cases that originated in the lung, breast and ovary, respectively.. TTF-7 immunostaining is useful in the differentiation between pulmonary and nonpulmonary origin of adenocarcinomas in malignant effusions. The combination of CK7-/CK20+ immunostaining is useful in identifying colon adenocarcinomas.

Topics: Adenocarcinoma; Ascitic Fluid; Biomarkers; Female; Humans; Immunoenzyme Techniques; Intermediate Filament Proteins; Keratin-20; Keratin-7; Keratins; Male; Neoplasms, Unknown Primary; Nuclear Proteins; Pleural Effusion, Malignant; Thyroid Nuclear Factor 1; Transcription Factors

To study the distinctive clinicopathologic and immunohistochemical difference between ovarian metastatic carcinomas and primary ovarian carcinomas.. The clinical and pathological features of 27 cases of ovarian metastatic carcinomas (gastric carcinomas 12 cases, colon carcinomas 11 cases, others 4 cases) obtained from our department were reviewed. Immunostainings for CK (AE1/AE3), CK7, CK20, CEA, vimentin, nm23 were performed with SP staining methods.. On gross examination, metastasis from gastric adenocarcinoma were usually bilateral, while solid (11/12) and metastases from colonic adenocarcinoma were more often unilateral and cystic (7/11). Microscopically, metastases from gastric adenocarcinoma revealed signet ring cells or poorly differentiated adenocarcinomas (12/12), whereas metastases from colonic adenocarcinomas showed similar morphology of endometrioid adenocarcinoma (8/11). The majority of ovarian metastases of gastric carcinoma (7/12) and colon carcinoma (8/11) were CK20 positive. In particular, CK20 was invariably expressed in colon cancer metastases. Most of the ovarian metastatic carcinomas from the gastrointestinal tract failed to react with immunostaining of CK7. A combined use of CEA, vimentin and nm23 had made a correct classification for 11/12 cases of the gastric carcinoma, 10/11 cases of the colonic cancer.. CK7 and CK20 have been proved to be useful antibodies in distinguishing between metastatic carcinomas and primary carcinomas of the ovary. Combined use of a panel of antibodies can give more significant results.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Breast Neoplasms; Carcinoembryonic Antigen; Carcinoma, Endometrioid; Carcinoma, Signet Ring Cell; Colonic Neoplasms; Diagnosis, Differential; Female; Follow-Up Studies; Genes, Tumor Suppressor; Humans; Intermediate Filament Proteins; Keratin-20; Keratin-7; Keratins; Middle Aged; NM23 Nucleoside Diphosphate Kinases; Nucleoside-Diphosphate Kinase; Ovarian Neoplasms; Stomach Neoplasms; Vimentin

A 60-year-old man underwent radical prostatectomy for biopsy-proved adenocarcinoma of the prostate. Histologic examination of the entirely embedded prostatectomy specimen revealed extensive ordinary adenocarcinoma, Gleason's grade 3 + 3 = 6, involving both sides of the gland, and extending into extraprostatic soft tissue at the left base. Adjacent to the carcinoma, and separately, extensive high-grade prostatic intraepithelial neoplasia (PIN) was identified, much of which showed bland nuclei and abundant xanthomatous cytoplasm, identical morphologically to that seen in foamy gland prostate carcinoma. However, unlike foamy gland carcinoma, the foamy glands in the current patient were large, showed papillary infolding, and were associated with a discontinuous layer of basal cells, demonstrated by immunostaining for high-molecular weight cytokeratin. No invasive foamy gland carcinoma was identified in the prostatectomy specimen. Immunostains for Ki-67 showed an increased proliferation rate in foamy high-grade PIN glands when compared with adjacent benign glands. Review of additional outside biopsy material revealed foamy gland high-grade PIN on four of seven needle cores, two of which showed no carcinoma. This patient demonstrates a new subtype of high-grade PIN that is difficult to recognize on needle biopsy. It is important to distinguish foamy gland high-grade PIN from its infiltrating counterpart, and it is critical to recognize because of the association of high-grade PIN with prostate carcinoma.

Topics: Adenocarcinoma; Biopsy, Needle; Humans; Keratins; Male; Middle Aged; Neoplasms, Multiple Primary; Prostate; Prostatectomy; Prostatic Intraepithelial Neoplasia; Prostatic Neoplasms; Staining and Labeling

The use of somatic cell hybrids has led to an increased understanding of the 'negative' regulation of cellular phenotype. Using somatic cell hybrids constructed between human breast cells that represent differing stages of malignancy but also display differing phenotypes from the same tissue, we present experimental results suggesting that luminal epithelial characteristics are controlled by repressive mechanisms. Fusion of HBL 100 cells, non-tumorigenic and characteristic of the basal cell lineage, with MCF-7 or MDA-MB-468 malignant breast cancer cells, characteristic of the luminal lineage, resulted in hybrid cells that displayed the phenotype of the HBL 100 cells. Using representational difference analysis, a panel of genes whose expression was repressed in the hybrid between HBL 100 and MDA-MB-468 was identified. This analysis revealed markers of luminal epithelial cells to be repressed, including Ep-CAM, cytokeratin 19 and E-cadherin. These markers were found to be coordinately re-expressed in variant hybrid cells indicating that the observed repression is reversible. Integrin (alpha)(v)(beta)(3) expression was found to be in mutual exclusivity to the luminal epithelial markers, thereby revealing a bidirectional 'switch' in the pattern of gene expression in this system. Finally, the expression of Ep-CAM was found to be lost in heterokaryons produced by fusion of HBL 100 and MCF-7 or MDA-MB-468 cells suggesting that the extinction of this gene in hybrid cells is the consequence of a trans-acting factor(s) synthesized by the HBL 100 cells. These data suggest that a number of markers of luminal cell differentiation in the mammary gland can be controlled through negative mechanisms and that such control of phenotype is highly coordinated.

Topics: Adenocarcinoma; Antigens, Neoplasm; Biological Factors; Biomarkers; Breast; Breast Neoplasms; Cadherins; Cell Adhesion Molecules; Cell Differentiation; Cell Fusion; Cell Lineage; Cell Nucleus; Cytoplasm; Epistasis, Genetic; Epithelial Cell Adhesion Molecule; Epithelial Cells; Female; Gene Expression Regulation; Gene Silencing; Humans; Hybrid Cells; Keratins; Neoplasm Proteins; Neoplasms, Hormone-Dependent; Phenotype; Tumor Cells, Cultured

Basal cell adenocarcinoma is a recently recognized entity among malignant tumors of the salivary glands. This entity has not received enough attention among ophthalmologists and ophthalmic pathologists. We recommend that basal cell adenocarcinoma be included in the differential diagnosis of lacrimal gland tumors.. Case report.. In 1988 a lacrimal gland tumor was incompletely removed from the left orbit of a 36-year-old woman and diagnosed as "solid basaloid adenoid cystic carcinoma". Soon after, an exenteration of the orbit was performed. In 1998, upon review of the initial histopathology, the diagnosis of solid adenoid cystic carcinoma was changed to basal cell adenocarcinoma. RESULTS AND MAIN OUTCOME MEASURE: The pathologic findings included nests of basaloid cells with minimal atypia and incomplete palisading around the periphery. The cells were of two types. The first type were large, pale cells with round or oval nuclei, scanty cytoplasm, and ill-defined borders. The other type were smaller cells with hyperchromatic nuclei situated mainly near the periphery of the nests. There was no necrosis or perineural invasion. Mitotic figures were present. Cysts within the nests showed Alcian blue negative contents. Immunohistochemistry showed a positive reaction to cytokeratin and a negative reaction with smooth muscle actin (SMA).. The Alcian blue negative stain, the negative reaction to SMA, and the fact that the patient is still alive 10 years after exenteration favored the diagnosis of basal cell adenocarcinoma. It is essential to differentiate a basal cell adenocarcinoma of the lacrimal gland from the solid basaloid type of adenoid cystic carcinoma, because the former has a better prognosis. Patients with basal cell adenocarcinomas of the lacrimal gland should be closely monitored for local recurrences because this tumor has the tendency to show perineural invasion.

Topics: Adenocarcinoma; Adult; Biomarkers, Tumor; Diagnosis, Differential; Eye Neoplasms; Female; Humans; Immunoenzyme Techniques; Keratins; Lacrimal Apparatus Diseases; Mucin-1; S100 Proteins; Tomography, X-Ray Computed

Primary adenocarcinoma of the seminal vesicles is an extremely rare neoplasm. Because prompt diagnosis and treatment are associated with improved long-term survival, accurate recognition of this neoplasm is important, particularly when evaluating limited biopsy material. Immunohistochemistry can be used to rule out neoplasms that commonly invade the seminal vesicles, such as prostatic adenocarcinoma. Previous reports have shown that seminal vesicle adenocarcinoma (SVCA) is negative for prostate-specific antigen (PSA) and prostate-specific acid phosphatase (PAP); however, little else is known of its immunophenotype. Consequently, we evaluated the utility of cancer antigen 125 (CA-125) and cytokeratin (CK) subsets 7 and 20 for distinguishing SVCA from other neoplasms that enter the differential diagnosis. Four cases of SVCA-three cases of bladder adenocarcinoma and a rare case of adenocarcinoma arising in a mullerian duct cyst-were immunostained for CA-125, CK7, and CK20. Three of four cases of SVCA were CA-125 positive and CK7 positive. All four cases were CK20 negative. All bladder adenocarcinomas and the mullerian duct cyst adenocarcinoma were CK7 positive and negative for CA-125 and CK20. In addition, CA-125 immunostaining was performed in neoplasms that commonly invade the seminal vesicles, including prostatic adenocarcinoma (n = 40), bladder transitional cell carcinoma (n = 32), and rectal adenocarcinoma (n = 10), and all were negative for this antigen. In conclusion, the present study has shown that the CK7-positive, CK20-negative, CA-125-positive, PSA/PAP-negative immunophenotype of papillary SVCA is unique and can be used in conjunction with histomorphology to distinguish it from other tumors that enter the differential diagnosis, including prostatic adenocarcinoma (CA-125 negative, PSA/PAP positive), bladder transitional cell carcinoma (CK20 positive, CA-125 negative), rectal adenocarcinoma (CA-125 negative, CK7 negative, CK20 positive), bladder adenocarcinoma (CA-125 negative), and adenocarcinoma arising in a mullerian duct cyst (CA-125 negative).

Topics: Adenocarcinoma; Biomarkers, Tumor; CA-125 Antigen; Carcinoma, Transitional Cell; Cysts; Diagnosis, Differential; Genital Neoplasms, Male; Humans; Immunoenzyme Techniques; Intermediate Filament Proteins; Keratin-20; Keratin-7; Keratins; Male; Mullerian Ducts; Prostatic Neoplasms; Rectal Neoplasms; Seminal Vesicles; Urinary Bladder Neoplasms

The T1, N0, M0 subset of stage I lung adenocarcinoma is a tumor that has a 5-year disease-free survival rate of 66% to 85%. To date, there has not been a rigorous immunohistochemically detected lymph node micrometastasis study composed of patients with identical stage and type of tumors, and in which standard histologic features were incorporated into multivariate analyses. We immunohistochemically examined the peribronchial and mediastinal lymph nodes from 80 consecutively accrued patients with T1, N0, M0 adenocarcinomas and bronchioloalveolar carcinomas unselected for distant metastasis, and an additional 39 patients with similar stage and type neoplasms who were selected for their development of metastases to evaluate the prevalence of micrometastases, their association with distant metastases, and their relationship with other pathologic prognostic features. All slides were stained with keratin AE1/3. Micrometastases were confirmed with Ber-Ep4. Three immunohistochemically detected lymph node micrometastases were identified in three of 80 consecutively accrued patients (4%). These three positive stains constituted 0.5% of the 573 stains required to immunohistochemically screen all of the lymph node blocks from these patients. Among the 39 patients who were selected because they developed distant metastases, three immunohistochemically detected lymph node micrometastases from three patients were identified, which constituted 8% of patients in this group and 1% of the 280 stains required to screen all of these patients' lymph nodes. Small vessel invasion, maximum tumor dimension, and immunohistochemically detected lymph node micrometastases were independently associated with metastases on multivariate analysis. Among patients who developed metastases, there was no significant difference in the disease-free survival rate between those with and those without immunohistochemically detected lymph node micrometastases. Given the low sensitivity in terms of the number of immunohistochemical stains performed, and the prognostic significance of standard histologic features, the use of immunohistochemical screening lymph nodes from all patients with T1, N0, M0 adenocarcinomas is questionable.

Topics: Adenocarcinoma; Adenocarcinoma, Bronchiolo-Alveolar; Antigens, Surface; Biomarkers, Tumor; Bronchi; Humans; Immunohistochemistry; Keratins; Lung Neoplasms; Lymph Nodes; Lymphatic Metastasis; Mediastinum; Neoplasm Staging; Proportional Hazards Models

Until recently, the standard approach of most laboratories in distinguishing epithelioid pleural mesothelioma from metastatic adenocarcinoma has been a negative result from a panel of adenocarcinoma-associated antibodies. However, several "mesothelium-associated" antibodies have been proposed as useful in this situation, and we have applied four of these putative mesothelioma markers--thrombomodulin, cytokeratin 5/6, calretinin, and CD44H--to a series of 61 epithelioid pleural mesotheliomas and 63 metastatic adenocarcinomas with known primary sites (lung = 19; breast = 21; ovary = 6; colon = 10; kidney = 4; uterus, epididymis, pancreas = 1 case each). Of the mesotheliomas, 55 of 61 (90%) stained for thrombomodulin, 56 of 61 (92%) for cytokeratin 5/6, 47 of 51 cases (92%) were positive for calretinin, and 39 of 43 (91%) were positive for CD44H. Of the metastatic adenocarcinomas, 12 of 63 (19%) cases were positive for thrombomodulin, 9 of 63 (14%) were positive for CK5/6, and 27 of 60 (45%) were positive for CD44H. With calretinin, only 1 case of 59 (2%) showed positive nuclear staining. All four antibodies stained reactive mesothelium; thrombomodulin also stained endothelium; and CD44H variably stained lymphocytes, macrophages, and fibroblasts. We conclude that all four antibodies show high sensitivity for epithelioid mesothelioma, but only calretinin (98%), cytokeratin 5/6 (86%), and thrombomodulin (81%) show sufficient specificity for practical use in this situation.

Topics: Adenocarcinoma; Antibodies, Neoplasm; Antigens, Neoplasm; Calbindin 2; Diagnosis, Differential; Humans; Hyaluronan Receptors; Immunoenzyme Techniques; Keratins; Mesothelioma; Pleural Neoplasms; S100 Calcium Binding Protein G; Sensitivity and Specificity; Thrombomodulin

We studied the expression of cytokeratin (CK)-7 and CK-20 in prostate adenocarcinoma and urothelial carcinoma and evaluated their usefulness for distinguishing high-grade forms of these tumors. We examined prostate adenocarcinoma in 59 radical prostatectomy specimens and in 10 autopsy specimens showing metastatic disease, and urothelial carcinoma of the bladder in 28 cystectomy specimens. Immunohistochemical staining for CK-7, CK-20, and prostate-specific antigen (PSA) was performed on paraffin sections. For prostate adenocarcinoma, 5 cases had only CK-7 positivity, 5 had only CK-20 focal positivity, 1 stained for both markers, and 48 were negative for both. PSA was positive in all but 1 poorly differentiated prostatic carcinoma. In the autopsy cases, PSA was expressed in the prostate and the metastatic tumors in most cases; few cases were focally positive for CK-7 or CK-20, but none was positive for both markers. For the urothelial tumors, CK-7 was the sole positive marker in 6 cases, and CK-20 in 1 case; 17 cases were positive for both, and 4 were negative for both. All urothelial carcinomas were PSA negative. Although PSA is useful for differentiating prostatic from urothelial carcinoma, CK-7 and CK-20 are helpful when both are positive, supporting the diagnosis of urothelial carcinoma. However, if only 1 marker is positive or both are negative, these markers have limited usefulness for distinguishing these carcinomas.

Topics: Adenocarcinoma; Carcinoma, Transitional Cell; Humans; Immunoenzyme Techniques; Intermediate Filament Proteins; Keratin-20; Keratin-7; Keratins; Male; Prostate-Specific Antigen; Prostatic Neoplasms; Urinary Bladder Neoplasms

Anti-CEA, anti-vimentin, CAM5.2, BerEp4, Leu-M1 and anti-EMA were applied to effusions from 36 mesotheliomas, 53 adenocarcinomas and 24 reactive mesothelial proliferations. Stepwise logistic regression analysis selected three criteria of major importance for distinguishing between adenocarcinoma and mesothelioma: BerEp4, CEA and EMA accentuated at the cell membrane (mEMA), these three being of similar diagnostic value. The pattern BerEp4-, CEA- and mEMA+ was fully predictive for mesothelioma (sensitivity 47%), whereas the opposite pattern was fully predictive for adenocarcinoma (sensitivity 80%). Only EMA seemed to distinguish between mesotheliosis and mesothelioma. Comparison of reactivity in cytological and histological material from the same mesotheliomas showed similar staining frequencies for CEA and CAM5.2, with some random variation for Leu-M1 and EMA, whereas vimentin and BerEp4 reactivity was more frequent in cytological specimens.

Topics: Adenocarcinoma; Antibodies, Monoclonal; Antibodies, Neoplasm; Antibody Specificity; Antigens, Neoplasm; Antigens, Surface; Biomarkers; Biomarkers, Tumor; Carcinoembryonic Antigen; Diagnosis, Differential; Epithelium; Humans; Hyperplasia; Immunoenzyme Techniques; Keratins; Lewis X Antigen; Logistic Models; Lung Neoplasms; Mesothelioma; Mucin-1; Neoplasm Proteins; Pleural Effusion, Malignant; Sensitivity and Specificity; Vimentin

Hale's colloidal iron staining of 8 chromophobe cell carcinomas (CCC) was compared with that of non-chromophobe renal cell carcinomas (RCC), renal oncocytomas, and renal adenomas. Six non-chromophobe RCC showing diffuse and moderate cytoplasmic staining contained extensive areas with translucent cytoplasm as observed in CCC. Seventeen of 25 conventional RCC of the clear cell variant (randomly chosen from 130 cases), 21 of 26 RCC with areas of chromophilic cytoplasm, and 16 of 20 papillary RCC, 7 of 14 adenomas and 14 of 16 oncocytomas displayed focal areas with mild to moderate staining of the cytoplasm. Hale's colloidal iron staining was partially reduced by digestion with neuramidase but not with hyaluronidase. This positive staining demonstrated glycoproteins containing sialylated glycoconjugates, probably a type of acid epithelial mucin. We suggest that there is a spectrum of mucin-like changes in typical CCC representing RCC with extensive and marked "mucin-like changes". The eosinophilic variant of CCC and some RCC with extensive chromophobe cell features represent renal neoplasms with moderate changes. The other RCC, oncocytomas and papillary renal neoplasms with mild to moderate staining with Hale's colloidal iron represent renal neoplasms with focal mucin-like changes. RCC with extensive chromophobe cell features may pose a differential diagnostic problem with CCC.

Topics: Adenocarcinoma; Adenoma; Adenoma, Oxyphilic; Carcinoma, Renal Cell; Diagnosis, Differential; Humans; Immunoenzyme Techniques; Iron; Keratins; Kidney Neoplasms; Mucin-1; Neoplasm Proteins; Neuraminidase; Vimentin

Despite the similarity in clinical appearance, there is a significant difference in the prognosis between primary extramammary Paget's disease (EPD) and the pagetoid spread of underlying regional internal malignancy (secondary EPD, pagetoid phenomenon). Fifteen cases of primary EPD (11 carcinoma in situ and four invasive carcinoma), seven cases of secondary EPD (five colorectal adenocarcinoma and two urothelial carcinoma), and six cases of anal canal carcinoma were retrieved and analysed immunohistochemically using six kinds of monoclonal anticytokeratin antibodies. No expression of cytokeratins 1, 5, 10, 13 and 14 was observed in any cases examined in this study. All 15 cases of primary EPD had the immunophenotype cytokeratin (CK)7+/CK20-. CK20 expression was diffusely positive in six cases of secondary pagetoid spread (two urothelial carcinoma and four colorectal adenocarcinoma), and focally in one case (a colorectal adenocarcinoma). In anal canal carcinoma, three of six cases showed CK20 diffuse expression and the remaining three cases expressed CK20 focally. CK7 expression was observed in three of six cases of anal canal carcinoma and in two of five cases of secondary EPD associated with colorectal adenocarcinoma. The combination of CK7 and CK20 demonstrates these to be useful markers in distinguishing 'primary' EPD from a pagetoid spread of extracutaneous malignancies. Namely, immunophenotypes other than CK7+/CK20- in Paget cells suggest underlying regional internal malignancy.

Topics: Adenocarcinoma; Anus Neoplasms; Biomarkers, Tumor; Carcinoma, Transitional Cell; Colorectal Neoplasms; Diagnosis, Differential; Humans; Immunoenzyme Techniques; Intermediate Filament Proteins; Keratin-20; Keratin-7; Keratins; Neoplasm Proteins; Paget Disease, Extramammary

Patients with metastatic renal and colon carcinoma have a very poor prognosis. In many cases, the tumor recurs after surgical excision and chemotherapy. Therefore, it might be beneficial for cancer patients to induce an immune attack against the tumor by inserting a cytokine gene into the tumor cells. Here, two different techniques for isolation of single tumor cells were compared. An enzymatic solution was superior to an EDTA/DTT isolation solution for establishing tumor primary cultures. In total, 18 primary cell cultures could be established from 68 patients with colon and renal cell carcinoma. Cells were further characterized concerning fibroblast contamination, cell proliferation and HLA-typing. These primary tumor cells might be of value for cytokine gene transfer and in vaccination protocols for cancer patients.

Topics: Adenocarcinoma; Antigens, Neoplasm; Carcinoma, Renal Cell; Cell Culture Techniques; Cell Division; Cell Separation; Clone Cells; Colonic Neoplasms; Cytokines; Electroporation; HLA Antigens; Humans; Keratins; Kidney Neoplasms; Neoplasm Metastasis; Recombinant Fusion Proteins; Transfection; Tumor Cells, Cultured

We report a case of intestinal hepatoid adenocarcinoma, confirmed by albumin m-RNA in situ hybridization, with subsequent metastatic spread to the liver in a male with a long-standing history of ulcerative colitis. This novel finding strongly suggests that ulcerative colitis can lead not only to conventional adenocarcinomas but also to hepatoid adenocarcinoma and highlights the mimicry of hepatocellular carcinoma by metastatic hepatoid adenocarcinoma liver nodules.

Topics: Adenocarcinoma; Adult; Albumins; Biomarkers, Tumor; Carcinoembryonic Antigen; Carcinoma, Hepatocellular; Colitis, Ulcerative; Colonic Polyps; Follow-Up Studies; Humans; In Situ Hybridization; Keratins; Liver Neoplasms; Lymphatic Metastasis; Male; Mucin-1; Rectal Neoplasms; RNA, Messenger

Serum pyridinoline cross-linked carboxy-terminal telopeptide of type I collagen (ICTP) is a metabolite of type I collagen comprising 90% or more of organic substances in bone. Its usefulness as a marker of bone metastasis from malignant tumors is expected.. We measured ICTP to evaluate its clinical usefulness for diagnosis of bone metastasis in 140 patients with lung cancer. For comparison, serum carcinoembryonic antigen (CEA), cytokeratin 19 fragment (CYFRA 21-1), gastrin-releasing peptide precursor (ProGRP), alkaline phosphatase and calcium were simultaneously measured. ICTP was measured by double-antibody radioimmunoassay.. ICTP was significantly higher in patients with bone metastasis from lung cancer than in the group without bone metastasis, patients with other pulmonary diseases or healthy control subjects and showed excellent sensitivity and specificity, indicating that this marker is highly useful for complementary diagnosis of bone metastasis from lung cancer. Moreover, the survival duration was significantly shorter in the ICTP-positive group than in the ICTP-negative group, suggesting that ICTP can be a prognostic factor in lung cancer.. It is suggested that measurement of ICTP is worthwhile as a serological diagnostic method of bone metastasis from lung cancer. Moreover, since repeated measurements are possible, this measure was considered very helpful in complementary diagnosis of bone metastasis and also as a standard to determine the timing of examinations such as bone scintigraphy.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Alkaline Phosphatase; Antigens, Neoplasm; Biomarkers; Biomarkers, Tumor; Bone Neoplasms; Calcium; Carcinoembryonic Antigen; Carcinoma, Large Cell; Carcinoma, Small Cell; Carcinoma, Squamous Cell; Collagen; Collagen Type I; Female; Gastrointestinal Hormones; Humans; Keratin-19; Keratins; Lung; Lung Diseases; Lung Neoplasms; Male; Middle Aged; Peptide Fragments; Peptides; Prognosis; Recombinant Proteins; Sensitivity and Specificity; Survival Rate

An autopsy case of carcinosarcoma of the liver in an 84-year-old man is described. The 14 x 6-cm solid tumor was located in the hilus to the left lobe and was grayish-white with some translucent areas. Histologically, the tumor consisted of an intimate mixture of adenocarcinomatous and chondrosarcomatous elements with transitional areas in between. Immunohistochemically, cells of the adenocarcinomatous elements were positive for cytokeratin but negative for S100 protein, whereas cells of the chondrosarcomatous elements showed the reverse staining pattern. Cells of transitional areas were positive for both cytokeratin and S100 protein. Most previously reported cases of carcinosarcoma of the liver have involved elderly men and have had a poor prognosis. The findings of the present case support the view that carcinosarcomas represent carcinomas that develop a sarcomatous element via metaplasia of the epithelial element.

Topics: Adenocarcinoma; Aged; Aged, 80 and over; Autopsy; Carcinosarcoma; Chondrosarcoma; Humans; Immunohistochemistry; Keratins; Liver Neoplasms; Male; S100 Proteins

Topics: Adenocarcinoma; Breast Neoplasms; Chemotherapy, Adjuvant; Female; Humans; Keratins; Lymphatic Metastasis; Neoplasm Seeding; Stress, Mechanical

Urethral adenomatous polyps with prostatic epithelium (also known as benign prostatic epithelial polyps [BPEPs]) are a documented cause of hematuria, dysuria, and hematospermia, conditions that may prompt cytologic evaluation of urine.. The urine cytologic test findings in 5 cases of biopsy-proven BPEPs and in 1 case of prostatic ductal adenocarcinoma (PDA) that presented as a urethral polyp were retrospectively evaluated. Immunocytochemical stain for prostate-specific antigen (PSA), prostatic acid phosphatase (PAP), and high-molecular-weight cytokeratin (34betaE12) were used in evaluation of the lesions.. In 4 of 5 cases of BPEPs, clusters of bland columnar cells with uniform, oval nuclei were seen. Positive immunostaining for PSA and PAP confirmed the prostatic origin of the clusters in 2 cases. One urine sample contained abundant goblet cells and extracellular mucin, consistent with intestinal metaplasia coexisting in the bladder biopsy specimen. The urine sample in the fifth case of BPEPs contained no columnar cells. The last case had multiple urine cytologic evaluations that demonstrated PSA-positive, malignant-appearing clusters of columnar cells. A biopsy specimen of the polyps was described as a high-grade prostatic intraepithelial neoplasm in adenomatous polyp. However, in this patient, PDA was diagnosed on transurethral resection of the prostate specimen 4 years after the initial urine cytologic test.. Benign prostatic epithelial polyps should be considered in the differential diagnosis of clusters of columnar cells in urine cytologic testing. Cells with malignant nuclear features should instigate a careful search for a (prostatic) neoplasm, which may present as urethral polyps (e.g., PDA). Stains for PSA or PAP are useful adjuncts in differential diagnosis of this condition.

Topics: Acid Phosphatase; Adenocarcinoma; Adenomatous Polyps; Adult; Aged; Diagnosis, Differential; Humans; Keratins; Male; Middle Aged; Prostate-Specific Antigen; Prostatic Neoplasms; Urethral Neoplasms; Urine

Investigation of the histopathological changes in prostatectomy specimens of patients with prostate cancer after high intensity focused ultrasound (HIFU) and identification of immunohistochemical markers for tissue damage after HIFU treatment.. Nine patients diagnosed with adenocarcinoma of the prostate underwent unilateral HIFU treatment seven to 12 days before radical prostatectomy. The prostatectomy specimens were analysed histologically. Immunohistochemical staining and electron microscopy were performed to characterise more subtle phenotypic changes.. All prostatectomy specimens revealed well circumscribed HIFU lesions at the dorsal side of the prostate lobe treated. Most epithelial glands in the centre of the HIFU lesions revealed signs of necrosis. Glands without apparently necrotic features were also situated in the HIFU lesions, raising the question of whether lethal destruction had occurred. This epithelium reacted with antibodies to pancytokeratin, prostate specific antigen (PSA), and Ki67, but did not express cytokeratin 8, which is indicative of severe cellular damage. Ultrastructural examination revealed disintegration of cellular membranes and cytoplasmic organelles consistent with cell necrosis. HIFU treatment was incomplete at the ventral, lateral, and dorsal sides of the prostate lobe treated.. HIFU treatment induces a spectrum of morphological changes ranging from apparent light microscopic necrosis to more subtle ultrastructural cell damage. All HIFU lesions are marked by loss of cytokeratin 8. HIFU does not affect the whole area treated, leaving vital tissue at the ventral, lateral, and dorsal sides of the prostate.

Topics: Adenocarcinoma; Aged; Biomarkers, Tumor; Humans; Keratins; Male; Middle Aged; Necrosis; Neoplasm Proteins; Prostate; Prostatectomy; Prostatic Neoplasms; Ultrasonic Therapy

The aim of this case report was to evaluate the impact of immunohistochemical markers in diagnosing the primary site of adenocarcinoma in the abdominopelvic region.. Surgicopathologic data were obtained from laparotomy and necropsy. Paraffin-embedded tissue from the ovary and jejunum was stained with hematoxylin and eosin, as well as with immunohistochemical stains for cytokeratin 20 and cytokeratin 7.. A 53-year-old African American woman underwent an emergency laparotomy due to small bowel obstruction. During the operation, in addition to a complex adnexal mass as the cause of obstruction, a small solid jejunal tumor was also identified. Pathologic evaluation of the two sites demonstrated an infiltrating moderately to poorly differentiated adenocarcinoma with mucinous features. The malignant cells from both intestinal and ovarian sites showed immunoreactivity for cytokeratin 20 and revealed negative staining for cytokeratin 7. These results confirmed the diagnosis of intestinal primary with ovarian metastasis, which was initially misdiagnosed as an ovarian primary.. Given the potential difficulty in determining the primary site of these tumors, immunohistochemistry proved to be a useful tool in reaching the correct diagnosis.

Topics: Adenocarcinoma; Biomarkers, Tumor; Diagnosis, Differential; Female; Humans; Immunohistochemistry; Intermediate Filament Proteins; Intestinal Obstruction; Jejunal Neoplasms; Keratin-20; Keratin-7; Keratins; Middle Aged; Ovarian Neoplasms

We evaluated the cytokeratin profile of intrahepatic cholangiocarcinoma with respect to its histological classification and intrahepatic location (peripheral vs. hilar), and compared its profile with that of a variety of metastatic adenocarcinomas in liver.. Expression of cytokeratins 7, 8, 18, 19 and 20 was immunohistochemically examined in intrahepatic cholangiocarcinoma (n = 77) and metastatic adenocarcinoma in liver (21 colorectal, 14 gastric, three gallbladder and three pancreatic cancers). Materials were autopsy or surgical specimens. Cytokeratins 7, 8, 18 and 19 were expressed in 75 (97%), 75 (97%), 59 (77%) and 71 (92%) cases of intrahepatic cholangiocarcinoma, respectively. Moderate and extensive expression of cytokeratin 18 was more frequent in the peripheral than in the hilar type. Moderate and extensive expression of cytokeratin 19 was seen in almost all cases of well-differentiated intrahepatic cholangiocarcinomas, while expression was decreased relatively in the moderately and decreased more in the poorly differentiated cases. While cytokeratin 20 was not found in non-neoplastic biliary epithelia or in well-differentiated intrahepatic cholangiocarcinomas, this cytokeratin was occasionally detectable in moderately and poorly differentiated intrahepatic cholangiocarcinomas and its expression was more frequent in the hilar type. Cytokeratin 20 expression was observed in 17 (81%) of metastatic adenocarcinomas in liver from colorectal regions, to a lesser degree in those from gastric regions, and was rare in those from gallbladder and pancreatic regions; cytokeratin 7 showed a reverse expression pattern in these metastatic adenocarcinomas in liver. The profile of cytokeratins 7 and 20 of metastatic colorectal and gastric carcinomas differed from that for intrahepatic cholangiocarcinomas, while that of metastatic gallbladder and pancreatic carcinoma was similar to that for intrahepatic cholangiocarcinomas. Moreover, cytokeratin 18 and 19 expression was significantly infrequent in metastatic gastric carcinomas than in intrahepatic cholangiocarcinomas and metastatic colorectal carcinomas.. The combined immunostaining of cytokeratins 7, 18, 19 and 20 is useful for the characterization of intrahepatic cholangiocarcinomas with respect to histological subtypes and intrahepatic location. It helps to differentiate intrahepatic cholangiocarcinoma from metastatic adenocarcinomas in liver and from colorectal and gastric regions; it also indicates the primary focus metastatic adenocarcinomas in livers.

Topics: Adenocarcinoma; Biomarkers; Cholangiocarcinoma; Colorectal Neoplasms; Gallbladder Neoplasms; Humans; Immunohistochemistry; Keratins; Liver Neoplasms; Pancreatic Neoplasms; Stomach Neoplasms

Calretinin (CR) is a Ca(2+)-binding protein (CaBP) of the EF-hand family expressed in a cell-type-specific manner and thought to act as a Ca(2+) buffer. Based upon previous studies, CR can undergo Ca(2+)-induced conformational changes, suggesting that it may also belong to the subfamily of Ca(2+)-sensor proteins that are characterized by their ability to interact with target ligands. To elucidate the role of CR, we used the undifferentiated colon adenocarcinoma cell line WiDr, which expresses significant amounts of CR. It has been shown previously that combined treatment with an inducer of differentiation sodium butyrate (NaBt) and a cell growth inhibitor hexamethylene bisacetamide (HMBA) or treatment with CR antisense oligonucleotides is down-regulating CR in parallel with a decrease of cell growth, suggesting a possible involvement of CR in maintaining the undifferentiated phenotype of WiDr cells. Furthermore, CR is absent from normal colon cells and from well-differentiated colon adenocarcinoma cell lines (e.g., Caco-2). Since members of the EF-hand family of proteins are interacting with cytoskeletal components, we investigated the possible association of CR with the cytoskeleton in WiDr cells. With double immunofluorescence stainings and immunoprecipitation experiments, we show close association of CR with intermediate filaments or microtubules in WiDr cells. Treatment with NaBt either disrupted or strongly diminished this interaction, respectively. The same effect was observed after elevation of [Ca(2+)](i) by applying the ionophore A-23187. These data suggest that CR may contribute to the transformation of enterocytes by interfering with the differentiation process, i.e., acting at both levels: cell shape dynamics and mitosis.

Topics: Adenocarcinoma; Butyrates; Calbindin 2; Calcimycin; Colonic Neoplasms; Humans; Intermediate Filaments; Ionophores; Keratins; Microtubules; S100 Calcium Binding Protein G; Tubulin; Tumor Cells, Cultured

Fine-needle aspiration of prostatic carcinoma usually yields an acinar carcinoma that is immunoreactive for prostatic-specific antigen (PSA) and prostatic acid phosphatase (PAP). We report on two FNAs of metastatic sarcomatoid prostatic carcinoma that were PSA- and PAP-negative. Our methods included a review of the medical records and pathology results. Both cases presented with elevated serum PSA levels and prostate needle biopsies with Gleason score 8 and 9 tumors, respectively. Both cases developed retroperitoneal/pelvic lymphadenopathy, and fine-needle aspirations were performed. These showed high-grade, sarcomatoid tumors with marked anisonucleosis. Immunocytochemical staining for PSA and PAP was negative in both cases. Clinical and radiologic evaluation failed to reveal any other potential primary sites. Metastatic, sarcomatoid, PSA- and PAP-negative prostatic carcinoma is a rare diagnosis of exclusion that should be considered in the characteristic clinical setting.

Topics: Acid Phosphatase; Adenocarcinoma; Antineoplastic Agents, Hormonal; Antineoplastic Combined Chemotherapy Protocols; Biopsy, Needle; Carcinoembryonic Antigen; Flutamide; Humans; Immunohistochemistry; Keratins; Leuprolide; Lymph Nodes; Lymphatic Metastasis; Male; Middle Aged; Prostate-Specific Antigen; Prostatic Neoplasms; Sarcoma

An elevation of melatonin secretion parallel to an enhanced production of macrophage-derived biopterin was observed in female F344 Fischer rats bearing passage 2 serial transplants derived from a malignant mammary tumor induced by 7,12-dimethylbenz[a]anthracene (DMBA). As opposed to that both parameters were depressed at passage 12. These results indicate the presence of divergent immunoneuroendocrine interactions during different phases of tumor growth. Since these biochemical events must have their common origin in changes taking place within these tumor transplants the current histopathological study was initiated. The primary tumor used for serial transplantation was a moderately differentiated adenocarcinoma of the mammary gland showing cytokeratin-positive epithelial components located in the inner epithelial tubule layer. In addition, bland-looking round or elongated actin-positive myoepithelial cells were detected which apart from epithelial cells are known to constitute the main cellular components of the mammary ductal system which resemble smooth muscle cells both morphologically and functionally. The tumor of passage 1 showed glandular tubules, lined by an inner epithelial layer, and many nests of clear, bland-looking actin-positive myoepithelial cells lying around tubules as well as in the stroma between actin-negative epithelial elements. The tumor of passage 2 used for transplantation consisted of a chaotic mixture of epithelial carcinomatous cells, forming a few irregular small tubules or solid nests, and, predominantly, of elongated plump or spindle-shaped, "myoid" atypical myoepithelial cells with a strong actin-positive reaction and some of these cells showed a focal vimentin expression. The tumor was characterized as a carcinosarcoma. At passage 12 epithelial cells were not identified. The tumor displayed features of a pleomorphic sarcoma consisting mainly of giant cells with bizarre nuclei being cytokeratin- and desmin-negative, weakly vimentin-positive but strongly actin-positive. These results indicate that DMBA-induced mammary tumor cells in female F344 Fischer rats undergo dramatic morphological changes during serial transplantation characterized by a total loss of malignant epithelial (carcinomatous) cells and the emergence and subsequent predominance of malignant (sarcomatous) mesenchymal cells. It appears that these sarcomatous cells develop out of myoepithelial cells since atypical myoepithelial cells with a strong actin-posit

Topics: 9,10-Dimethyl-1,2-benzanthracene; Actins; Adenocarcinoma; Animals; Disease Models, Animal; Epithelium; Female; Humans; Immunohistochemistry; Keratins; Kinetics; Mammary Neoplasms, Experimental; Melatonin; Neoplasm Transplantation; Rats; Rats, Inbred F344

The nuclear matrix-intermediate filament complex (NM-IF) is a protein scaffold which spans the whole cell, and several lines of evidence suggest that this structural frame represents also a functional unit, which could be involved in the epigenetic control of cancer development. Here we report the characterization by high resolution two-dimensional gel electrophoresis and Western blot analysis of the NM-IF complex isolated from prostate cancer (PCa); tumor-associated proteins were identified by comparing the electrophoretic patterns with those of normal human prostate (NHP). Extensive changes in the expression of both the NM and IF proteins occur; they are, however, related in a different way to tumor progression. Poorly differentiated PCa (Gleason score 8-9) shows a strong down regulation of several constitutive cytokeratins (CKs 8, 18, and 19); their expression significantly (P < 0.05) decreases with respect to both NHP and benign prostatic hyperplasia (BPH) and, more interestingly, also with respect to moderately (Gleason score 6-7) and well (Gleason score 4-5) differentiated tumors. Moreover, we have identified a tumor-associated species which is present in all of the tumors examined, systematically absent in NHP and occurs only in a few samples of BPH; this polypeptide, of M(r) 48,000 and pI 6.0, represent a proteolytic fragment of CK8. At variance with these continuing alterations in the expression, the NM proteins undergo stepwise changes correlating with the level of differentiation. The development of less differentiated tumors is characterized by the appearance of several new proteins and by the decrease in the expression of others. Six proteins were found to be expressed with a frequency equal to one in poorly differentiated tumor, namely in all the samples of tumor examined, while in moderately and well differentiated tumors the frequency is less than one, and decreases with increasing the level of differentiation. When tumors of increasing Gleason score are compared with NHP a dramatic increase in the complexity of the protein patterns is observed, indicating that tumor dedifferentiation results in a considerable increase in the phenotypic diversity. These results suggest that tumor progression can be characterized using an appropriate subset of tumor-associated NM proteins.

Topics: Adenocarcinoma; Aged; Antigens, Nuclear; Cell Differentiation; Disease Progression; Electrophoresis, Gel, Two-Dimensional; Gene Expression Regulation, Neoplastic; Humans; Isoelectric Focusing; Keratins; Macromolecular Substances; Male; Middle Aged; Neoplasm Proteins; Nuclear Proteins; Phenotype; Prostatic Hyperplasia; Prostatic Neoplasms; Protein Isoforms; Subtraction Technique

Metastases to the eyelids are rare. They may appear as diffuse swellings, nodules or ulcerations. Most often they correspond to the dissemination of a breast adenocarcinoma. An 83 year old woman is reported with mammary adenocarcinoma metastasizing to the eyelids.

Topics: Adenocarcinoma; Aged; Aged, 80 and over; Apolipoproteins; Apolipoproteins D; Biomarkers; Breast Neoplasms; Carcinoembryonic Antigen; Carrier Proteins; Eyelid Neoplasms; Female; Glycoproteins; Humans; Immunohistochemistry; Keratins; Membrane Transport Proteins; Mucin-1

Colon signet ring cell adenocarcinomas are uncommon, high-grade neoplasms. Given their rarity, the question of primary colon or metastatic gastric adenocarcinoma frequently arises when signet ring cell carcinoma is seen in a colonoscopic biopsy or in biopsies procured from other regions of the body. A second related question regarding colon and gastric signet ring cell carcinomas is their immunophenotypic similarities with the glandular form of adenocarcinoma in each site. We studied the immunohistochemical phenotype of 14 colonic signet ring cell adenocarcinomas and compared them with immunophenotype of 27 gastric signet ring cell adenocarcinomas. We also compared the immunophenotype of the 27 gastric signet ring cell with the immunophenotype of 19 gastric gland-forming adenocarcinomas, and the immunophenotype of the 14 colonic signet ring cell adenocarcinomas to the immunophenotype of 20 colonic gland-forming adenocarcinomas to identify staining differences in the neoplastic cells of the two architectures. Antibodies studied were cytokeratins 7, 17, 19, and 20, CA 19-9, CA-125. estrogen receptor, and gross cystic disease fluid protein 15. Sixty-four percent of colon signet ring cell adenocarcinomas had either no staining or focal staining with cytokeratin 7 compared with diffuse staining in 63% of gastric signet ring cell adenocarcinomas (P = 0.016). Seventy-two percent of colon signet ring cell adenocarcinomas had diffuse staining with cytokeratin 20 compared with no or focal staining in 50% of gastric signet ring cell adenocarcinomas (P = 0.019). Fifty-seven percent of the colon signet ring cell adenocarcinomas had a cytokeratin 7 (-)/cytokeratin 20 (+) staining pattern compared with 11% of gastric signet ring cell adenocarcinomas (P = 0.004). Forty-four percent of gastric signet ring cell adenocarcinomas had a cytokeratin 7 (+)/cytokeratin 20 (-) pattern, compared with none of the colon signet ring cell adenocarcinomas (P = 0.004). The staining distribution of the antibody battery was similar in colon signet ring cell and colon glandular adenocarcinoma and gastric signet ring cell and gastric glandular adenocarcinomas. When signet ring cell adenocarcinoma is encountered in a colon biopsy, a colon primary is supported if the neoplastic cells have a cytokeratin 7 (-)/cytokeratin 20 (+) staining pattern, and a gastric primary is supported if they have a cytokeratin 7 (+)/cytokeratin 20 (-) staining pattern. The signet ring morphology at each site had an

Topics: Adenocarcinoma; Apolipoproteins; Apolipoproteins D; CA-125 Antigen; CA-19-9 Antigen; Carcinoma, Signet Ring Cell; Carrier Proteins; Colonic Neoplasms; Glycoproteins; Humans; Immunohistochemistry; Immunophenotyping; Keratins; Membrane Transport Proteins; Receptors, Estrogen; Stomach Neoplasms

A panel of antibodies composed of the cytokeratins (CKs), vimentin, and actin was applied to 114 minor salivary gland tumors to evaluate its diagnostic value. The results revealed that luminal cells of intercalated duct-like structures, such as those seen in pleomorphic adenoma, basal cell adenoma, adenoid cystic carcinoma, and epithelial-myoepithelial carcinoma, expressed CKs 7, 8, 14, and 19. The outer cells of these structures exhibited vimentin or vimentin plus muscle-specific actin, but rarely CK14, which is seen particularly in pleomorphic adenoma, in the tubular type of basal cell adenoma, and seldom in the tubular type of adenoid cystic carcinoma. Modified myoepithelial cells of pleomorphic adenoma and myoepithelioma exhibited a variable immunoprofile. CKs 7 and 8 were also observed in acinar cell adenocarcinoma and polymorphous low-grade adenocarcinoma with vimentin in the latter. CK13 was expressed only by canalicular adenoma and mucoepidermoid carcinoma cells. This study showed that the panel of antibodies employed is effective in distinguishing among salivary gland tumors.

Topics: Actins; Adenocarcinoma; Adenoma; Adenoma, Pleomorphic; Carcinoma; Carcinoma, Acinar Cell; Carcinoma, Adenoid Cystic; Carcinoma, Mucoepidermoid; Immunohistochemistry; Keratins; Myoepithelioma; Salivary Gland Neoplasms; Vimentin

Carcinoma that has metastasized to the central nervous system (CNS) poses a particular clinical problem regarding confirmation of the diagnosis and subsequent management. Prior to excision, thorough evaluation for coexisting systemic disease is essential, but current imaging techniques are limited by their spatial resolution and under-stage many patients. We evaluated the potential utility of bone-marrow evaluation for micrometastatic cells in patients with CNS metastasis. Bone-marrow aspirates were examined for cytokeratin-positive cells in 12 consecutive patients who presented with symptomatic space-occupying lesions of the CNS. These patients had previously undergone surgical excision of either gastrointestinal or breast cancers. All twelve had micrometastases in their bone marrow at the time of presentation with the CNS disease and all had a fatal outcome within 13 months. In nine of the 12 patients, bone-marrow micrometastases were the only evidence for systemic spread. Three patients had elevated serum tumour markers and two of these had radiologically detectable recurrence elsewhere. Bone-marrow micrometastases indicate concurrent systemic involvement and a poor prognosis. The results suggest that bone-marrow evaluation for systemic spread is a useful diagnostic adjunct and should be performed before considering diagnostic biopsy or excision.

Topics: Adenocarcinoma; Biomarkers, Tumor; Bone Marrow Examination; Bone Marrow Neoplasms; Brain; Brain Neoplasms; Breast Neoplasms; Carcinoma; Carcinoma, Ductal, Breast; Female; Flow Cytometry; Gastrointestinal Neoplasms; Humans; Immunohistochemistry; Keratins; Neoplasm Staging; Predictive Value of Tests; Prospective Studies; Tomography, X-Ray Computed

The histologic classification of pulmonary neoplasms can have important implications regarding appropriate management of patients. Although the histologic classification of lung tumors is predominantly based on morphology, ancillary studies such as immunohistochemistry can be used in difficult cases, and the diagnosis of large cell neuroendocrine carcinoma requires confirmation of neuroendocrine differentiation by immunohistochemistry or electron microscopy. We immunostained 142 lung tumors for B72.3, keratin 34betaE12, keratin 7, keratin 14, keratin 17, synaptophysin, and chromogranin to determine the utility of neuroendocrine markers and epithelial markers in the differential diagnosis. Among neuroendocrine carcinomas (small cell carcinoma and large cell neuroendocrine carcinoma), 84% (37 of 44) were chromogranin positive, 64% (21 of 36 small cell, 6 of 6 large cell neuroendocrine) were synaptophysin positive, 5% (2 of 43) were keratin 34betaE12 positive, 9% (4 of 44) were keratin 7 positive, and 5% (2 of 37) of small cell carcinomas and 50% (3 of 6) of large cell neuroendocrine carcinomas were B72.3 positive. Among non-neuroendocrine carcinomas, 5% (5 of 98) were chromogranin positive, 3% (3 of 96) were synaptophysin positive, and 97% (95 of 98) were positive for either keratin 34betaE12 or keratin 7 and 99% (97 of 98) were positive for either keratin 34betaE12, keratin 7 or B72.3. An antibody panel consisting of keratin 7, keratin 34betaE12, chromogranin, and synaptophysin separated 132 of 141 tumors (94%) into distinct groups. We conclude that immunostaining with both neuroendocrine markers and epithelial markers can be useful in the differential diagnosis of lung neoplasms.

Topics: Adenocarcinoma; Adenocarcinoma, Bronchiolo-Alveolar; Biomarkers, Tumor; Carcinoma, Large Cell; Carcinoma, Non-Small-Cell Lung; Carcinoma, Small Cell; Carcinoma, Squamous Cell; Chromogranins; Diagnosis, Differential; Humans; Immunohistochemistry; Keratins; Lung Neoplasms; Pilot Projects; Synaptophysin

Two cases of bilateral radiation pneumonitis associated with unilateral thoracic irradiation against lung cancer are described. Both patients died of respiratory failure and autopsy was performed. Histologically, bilateral diffuse alveolar damage was demonstrated in both cases, associated with marked organization of hyaline membrane in one case (case 1). In addition, numerous hyperplastic type II pneumocytes which strongly expressed cytokeratins 8, 18 and 19 were observed. In both patients' sera, antibodies against cytokeratin 8, 18 and 19 were demonstrated by a Western immunoblot. The possible association between autoantibodies to cytokeratins and diffuse alveolar damage observed in patients with bilateral radiation pneumonitis are discussed.

Topics: Adenocarcinoma; Aged; Autoantibodies; Blotting, Western; Fatal Outcome; Humans; Keratins; Lung Neoplasms; Male; Pulmonary Alveoli; Radiation Pneumonitis; Sarcoma, Small Cell

Over one third of patients with stage II colonic adenocarcinoma experience tumor recurrence. Because effective adjuvant therapy is now available, it is important to identify subsets of patients at higher risk for relapse who may benefit from early treatment. Immunohistochemistry has been used to detect microscopic metastases in histologically uninvolved mesenteric lymph nodes, but the prognostic significance of minimal nodal involvement has not been established.. Hematoxylin and eosin (H&E)-stained recuts of 900 mesenteric lymph nodes from 55 patients (range, 2-47; mean, 16.4 nodes per case) with resected pT3 or pT4, N0, M0 (TNM stage II) colonic adenocarcinomas were re-examined for the presence of metastases and then stained immunohistochemically for keratin using the AE1:AE3 antibody. Twenty-seven patients did not experience recurrence of tumor within 5 years following resection (no evidence of disease [NED]); 28 patients relapsed during the same time frame. Lymph nodes from 10 patients having colonic resections for nonneoplastic disorders also were stained as controls. Keratin-positive cells and cell clusters were quantified in the lymph nodes, and comparisons were made between patients with and without tumor relapse.. In the relapse group, four patients had positive nodes already identified on the H&E-stained recuts and had to be excluded from further analysis. Sixteen additional patients had keratin-positive cells; thus, 16 of 24 (67%) had micrometastases. In the NED group, one patient had a positive node on H&E staining and 22 additional patients had keratin-positive cells, so 22 of 26 (84%) patients had micrometastases. In the patients who had micrometastases, there was a mean of 3.5 and 4.6 positive nodes in the relapse and NED groups, respectively, and a mean of 11.3 and 12.4 keratin-positive cells or clusters in the relapse and NED groups, respectively. No keratin-positive cells were found in the 1 to 21 (mean, 9.1) nodes per case studied in the control patients.. Micrometastases to histologically uninvolved mesenteric lymph nodes commonly are detected in patients with pT3 or pT4 colonic adenocarcinomas on recuts stained immunohistochemically for keratin. Nodal micrometastases detected by immunohistochemical staining are not useful for identifying stage II patients at higher risk for relapse.

Topics: Adenocarcinoma; Colonic Neoplasms; Coloring Agents; Disease Progression; Eosine Yellowish-(YS); Female; Hematoxylin; Humans; Immunohistochemistry; Keratins; Lymphatic Metastasis; Male; Mesentery; Neoplasm Recurrence, Local; Neoplasm Staging; Recurrence; Risk Factors

Prostate tissue and lesions obtained by needle biopsy may be scant and not survive cutting into the block; this study examined the efficacy of destaining hematoxylin and eosin-stained sections and restaining the slides using immunohistochemistry with high-molecular weight cytokeratin (high-molecular weight cytokeratin). We identified 105 prostate needle biopsies referred to Johns Hopkins Hospital in an 18-month period (January 1997-June 1998) that had been destained and restained for high molecular weight cytokeratin. The slides were reviewed for the Johns Hopkins Hospital diagnosis (benign, malignant, or equivocal), which had factored in the immunohistochemistry results, and for immunohistochemistry staining quality (optimal, suboptimal, stain failed, or lesion fell off). We obtained data on 96 cases from the referring institutions about the fixative and glass slides used for processing the needle biopsy. In 58% of cases, destaining and restaining with high-molecular weight cytokeratin allowed a definitive benign or malignant diagnosis to be made; in 79% of these cases, the staining was optimal. In only 13% of cases the diagnosis remained equivocal; of these, the stain worked optimally in only 36%. In 19% of cases, the stain failed. In 9% of cases, the lesion fell off; in all 7 cases with available data the tissue had been cut on non-charged slides. All but 3 cases were received in 10% neutral buffered formalin. There was no correlation between the use of charged (plus or lysine coated) or non-charged slides and the staining quality. Furthermore, in 12 instances, we received more than 1 specimen from the same referring institution, and in 6 of these instances there was variable staining in the different cases from the same institution. Destaining hematoxylin and eosin-stained slides and restaining for high-molecular weight cytokeratin is a useful technique that in the majority of cases enables a definitive diagnosis to be made. Tissue may survive the procedure better if originally cut on charged slides, but staining quality is no different for charged or non-charged slides.

Topics: Adenocarcinoma; Biopsy, Needle; Evaluation Studies as Topic; Humans; Immunoenzyme Techniques; Keratins; Male; Molecular Weight; Prostatic Neoplasms; Reproducibility of Results; Staining and Labeling

Primary adenocarcinoma of the urinary tract are uncommon. But secondary involvement of pyelocalyceal system by metastasis of colorectal origin is rare. We report a case of late rectal metastasis with renal pelvis growth presenting as a pyonephrosis. This study emphasizes the relevance of cytokeratin 7 and 20 immunostaining in such differential diagnosis.

Topics: Adenocarcinoma; Aged; Diagnosis, Differential; Humans; Immunohistochemistry; Intermediate Filament Proteins; Keratin-20; Keratin-7; Keratins; Kidney Neoplasms; Male; Rectal Neoplasms

The aim of the study was to assess diagnosis value of tumor markers for differential diagnosis between mesothelioma and other pleural tumors.. Prospective study of 85 patients attending our hospital with malignant pleural effusion. The diagnostic approach involved routine pleurocentesis followed by pleural needle. When precise diagnosis was not achieved, thoracoscopy with pleural biopsies was performed. Carcinoembryonic antigen (CEA), hyaluronic acid, tissue polypeptide antigen and cyfra 21 to 1 were measured in serum and pleural fluid.. By using receiver operating characteristics curves and area under curves, the best diagnostic characteristics were obtained with pleural and serum CEA concentrations. The area under the curve was larger for pleural ACE than for serum ACE. The sensitivity and specificity of a pleural CEA level exceeding 3 ng/mL for ruling out the diagnosis of mesothelioma were 100% and 77%, respectively.. A CEA level above 3 ng/mL in pleural fluid eliminated the diagnosis of mesothelioma, whereas the other markers were not sufficiently discriminant. However, despite a negative predictive value of 100% at a cutoff of 3 ng/mL, CEA assay in pleural fluid only avoids a small number of diagnostic thoracoscopies.

Topics: Adenocarcinoma; Aged; Antigens, Neoplasm; Area Under Curve; Biomarkers, Tumor; Carcinoembryonic Antigen; Carcinoma, Small Cell; Carcinoma, Squamous Cell; Diagnosis, Differential; Female; Humans; Hyaluronic Acid; Keratin-19; Keratins; Lung Neoplasms; Male; Mesothelioma; Middle Aged; Pleural Effusion; Pleural Neoplasms; Prospective Studies; ROC Curve; Sensitivity and Specificity; Tissue Polypeptide Antigen

Expression of laminin-5 alpha3, beta3 and gamma2 protein subunits was investigated in colorectal adenocarcinomas using immunostaining and confocal microscopy. The laminin-5 heterotrimer was found in basement membranes and as extracellular deposits in tumor stroma. In contrast to the alpha3 subunit, which was under-expressed, the gamma2 and beta3 subunits were detected in the cytoplasm of carcinoma cells dissociating (budding) from neoplastic tubules, suggestive of focal alterations in laminin-5 assembly and secretion. Laminin-5 gamma2 or beta3 subunit-reactive budding carcinoma cells expressed cytokeratins but not vimentin; they did not proliferate and were not apoptotic. Furthermore, expression of laminin-5 gamma2 and beta3 subunits in budding cells was associated with focal under-expression of the E-cadherin-beta-catenin complex. Results from xenograft experiments showed that budding activity in colorectal adenocarcinomas could be suppressed when these tumors grew at ectopic s.c. sites in nude mice. In vitro, cultured colon carcinoma cells, but not adenoma-derived tumor cells, shared the laminin-5 phenotype expressed by carcinoma cells in vivo. Using colon carcinoma cell lines implanted orthotopically and invading the cecum of nude mice, the laminin-5-associated budding was restored, indicating that this phenotype is not only determined by tumor cell properties but also dependent on the tissue micro-environment. Our results indicate that both laminin-5 alpha3 subunit expression and cell-cell cohesiveness are altered in budding carcinoma cells, which we consider to be actively invading. We propose that the local tissue micro-environment contributes to these events.

Topics: Adenocarcinoma; Animals; beta Catenin; Cadherins; Cell Communication; Colorectal Neoplasms; Cytoskeletal Proteins; Disease Models, Animal; Gene Expression Regulation, Neoplastic; HT29 Cells; Humans; In Situ Nick-End Labeling; Keratins; Ki-67 Antigen; Laminin; Mice; Mice, Nude; Neoplasm Transplantation; Phenotype; RNA, Messenger; Stromal Cells; Trans-Activators; Tumor Cells, Cultured; Vimentin

A small composite esophageal carcinoma measuring 1.5 x 1.4 x 1.0 cm is described. The tumor had a polypoid elevation with a superficial extension. Histologic examination revealed invasion of the submucosal layer and multidirectional differentiation, including neuroendocrine, squamous, ciliated glandular, and sarcomatous components. The neuroendocrine component was strongly positive for chromogranin and formed the bulk of the polypoid tumor. The squamous cell carcinoma exhibited a superficial extension. The adenocarcinoma was located in a small region of the tumor and contained ciliated glandular cells. The spindle cell sarcomatous component, which was positive for alpha-smooth muscle actin and negative for cytokeratin, exhibited no specific mesenchymal differentiation. Each component was found in 60%, 10%, 5%, and 25% of the tumor, respectively. Cases of small composite esophageal carcinoma containing various carcinomatous and sarcomatous components are extremely rare.

Topics: Actins; Adenocarcinoma; Carcinoma, Neuroendocrine; Carcinoma, Squamous Cell; Carcinosarcoma; Cell Differentiation; Chromogranins; Esophageal Neoplasms; Humans; Immunohistochemistry; Keratins; Male; Middle Aged; Muscle, Smooth

Staining of prostatic basal cells for the expression of high-molecular-weight cytokeratin has been suggested as a way of distinguishing benign from malignant prostate glands. We evaluated the utility of high-molecular-weight cytokeratin in the diagnosis of malignancy in prostate specimens obtained in various ways.. Prostate tissues obtained from needle biopsies, transurethral resections, and total prostatectomies were immunostained with monoclonal antibody 34betaE12, an antibody directed against high-molecular-weight cytokeratins.. Antiserum to high-molecular-weight cytokeratin only stained the basal cells in normal glands in 3 (12%) of 25 specimens obtained by transurethral resection. Other antigens, such as the alternate 10-nm filament protein vimentin, were unaffected and were detected in 100% of these specimens. However, keratin antigenicity in transurethral biopsies could be restored in these specimens by antigen retrieval in a low pH citrate buffer using a microwave heat technique. Keratin staining in needle biopsies and total prostatectomies was unaffected.. In summary, our results indicate the technique of transurethral resection results in a specific loss of keratin antigenicity. This limits the utility of anticytokeratin 34betaE12 in interpreting transurethral resections without the application of antigen retrieval.

Topics: Adenocarcinoma; Antibodies, Monoclonal; Biopsy, Needle; Diagnosis, Differential; Humans; Immunohistochemistry; Keratins; Male; Molecular Weight; Prostate; Prostatectomy; Prostatic Neoplasms; Transurethral Resection of Prostate

The monoclonal antibody M30 recognizes a neoepitope of cytokeratin 18 produced during apoptosis. It is reactive in formalin-fixed, paraffin-embedded tissue and has great potential in the study of apoptosis in clinical and experimental material.. To compare the results of M30 immunoexpression with a more established technique of demonstrating apoptosis in tissue sections, in situ end-labeling. A secondary objective was to compare the results with immunoexpression of the proliferation-associated antigen Ki-67.. Retrospective analysis of adenomas and adenocarcinomas of the large intestine.. Immunohistochemistry for M30 and Ki-67, and in situ end-labeling. Formalin-fixed, paraffin-embedded tissue was used.. The number of cells positive for M30, Ki-67, and in situ end-labeling, expressed as a proportion of the total number of cells counted.. A strong positive correlation was found between in situ end-labeling and expression of M30, although the counts were widely scattered around the regression line. Counts of Ki-67 were strongly correlated with both M30 expression and in situ end-labeling. Immunoexpression of M30 was generally easier to interpret than in situ end-labeling, and the procedures for M30 immunohistochemistry were technically less exacting.. These findings support the application of M30 immunoreactivity in the study of apoptosis.

Topics: Adenocarcinoma; Adenoma; Antibodies, Monoclonal; Apoptosis; Immunohistochemistry; In Situ Nick-End Labeling; Intestinal Neoplasms; Intestine, Large; Keratins; Ki-67 Antigen; Statistics as Topic

The predictive value of lymph node micrometastasis, detected by immunohistochemical or genetic methods, is well appreciated in terms of prognosis. However, a major problem is high false-positive rates, because most methods focus on cytokeratin, which is a component not only of carcinoma but also normal epithelial and nonepithelial cells. Mutant allele-specific amplification (MASA) can detect DNAs derived from cancer cells itself, reportedly with high sensitivity. It was, therefore, used with nested-PCR using p53 or K-ras mutation for analysis of lymph node micrometastasis in non-small cell lung carcinoma (NSCLC) patients in the present study, in comparison with the immunohistochemical method using an anti-cytokeratin reagent for the same samples. Lymph nodes from 31 NSCLC patients with p53 and K-ras mutated tumors (30 and 1, respectively) staged as pathological (p)-T1-4 N0-1 and M0 were examined. Genetic and immunohistochemical methods demonstrated positive reactions in 34 (15%) and 61 (27%) of 229 lymph nodes, respectively (9 cases, 29%, and 24 cases, 77%). The concordance with the two methods was 77%, but 13 (39%) of 34 genetically positive lymph nodes could not be detected by immunohistochemistry (IHC). Of 22 cases with p-N0 disease, 6 (27%) were genetically positive in hilar and/or mediastinal lymph nodes, and 4 (67%) of them died after cancer relapse. In contrast, none of the patients without micrometastasis died of cancer (P < 0.001, log rank analysis). Of the same p-N0 patients, 17 (77%) were positive by IHC, and 4 (24%) of them died of cancer, whereas 5 negative patients did not suffer cancer relapse. Survival did not significantly differ between cases positive and negative (P = 0.246) by IHC. According to the g-N (N factor restaged by a genetic method), patients with g-N1 and g-N2 disease had a shorter survival than those with g-N0 disease (P = 0.042 and P < 0.001, respectively). However, no significant difference was observed with grading by IHC. Thus, detection of micrometastasis in regional lymph nodes with the MASA method, in other words with a carcinoma-specific marker, is of greater prognostic significance for early stage NSCLC patients than immunohistochemical results. This approach should facilitate selection of patients for whom postoperative adjuvant chemotherapy should be performed.

Topics: Adenocarcinoma; Adult; Aged; Alleles; Carcinoma, Squamous Cell; Female; Humans; Immunohistochemistry; Keratins; Lung Neoplasms; Lymph Nodes; Lymphatic Metastasis; Male; Middle Aged; Mutation; Nucleic Acid Amplification Techniques; Polymerase Chain Reaction; Prognosis; Survival Analysis

Female urethral adenocarcinoma is extremely rare and more than one tissue of origin has been suggested other than the Skene's gland. Immunohistochemistry with cytokeratins (CK) 7 and 20 is used to define the origin of the tumor.. A 72-year-old woman presented with a 2-cm polypoid tumor at the external urethral meatus and bleeding. Wide local excision and bilateral inguinal lymphadenectomy were performed. Postoperative convalescence was uneventful. It was a poorly differentiated mucinous adenocarcinoma without direct urothelial involvement. There were focal areas of intestinal metaplasia. The tumor cells were positive for CK 7 and 20 and negative for prostate-specific antigen.. This case provides supportive evidence that mucinous urethral adenocarcinoma may arise from malignant transformation of urethritis glandularis.

Topics: Adenocarcinoma; Aged; Biomarkers, Tumor; Female; Humans; Immunohistochemistry; Intermediate Filament Proteins; Keratin-20; Keratin-7; Keratins; Urethral Neoplasms; Urethritis

The tumor suppressor p53 transcriptionally regulates a large number of target genes that may affect cell growth and cell death pathways. To better understand the role of p53 loss in tumorigenesis, we have developed a mouse mammary cancer model, the Wnt-1 TG/p53 model. Wnt-1 transgenic females that are p53-/- develop mammary adenocarcinomas that arise sooner, grow faster, appear more anaplastic, and have higher levels of chromosomal instability than their Wnt-1 transgenic p53+/+ counterparts. In this study, we used several assays to determine whether the presence or absence of p53 affects gene expression patterns in the mammary adenocarcinomas. Most of the differentially expressed genes are increased in p53+/+ tumors and many of these represent known target genes of p53 (p21WAF/C1P1, cyclin G1, alpha smooth muscle actin, and cytokeratin 19). Some of these genes (cytokeratin 19, alpha smooth muscle actin, and kappa casein) represent mammary gland differentiation markers which may contribute to the inhibited tumor progression and are consistent with the more differentiated histopathology observed in the p53+/+ tumors. Several differentially expressed genes are growth regulatory in function (p21, c-kit, and cyclin B1) and their altered expression levels correlate well with the differing growth properties of the p53+/+ and p53-/- tumors. Thus, while tumors can arise and progress in the presence of functioning wild type p53, p53 may directly or indirectly regulate expression of an array of genes that facilitate differentiation and inhibit proliferation, contributing to a more differentiated, slow growing, and genomically stable phenotype.

Topics: Actins; Adenocarcinoma; Animals; Blotting, Western; Caseins; Cell Division; Cyclin B; Cyclin B1; Cyclin G; Cyclin G1; Cyclin-Dependent Kinase Inhibitor p21; Cyclins; Female; Gene Deletion; Gene Expression Regulation, Neoplastic; Immunohistochemistry; Incidence; Keratins; Mammary Neoplasms, Animal; Mice; Neoplasm Proteins; Nuclease Protection Assays; Oligonucleotide Array Sequence Analysis; Polymerase Chain Reaction; Proto-Oncogene Proteins; RNA, Neoplasm; Tumor Suppressor Protein p53; Wnt Proteins; Wnt1 Protein; Zebrafish Proteins

We established and characterized a human hilar bile duct carcinoma (HBDC) cell line from cells isolated from the ascites of a 75-year-old Japanese woman. Histopathological findings were confirmed to be poorly differentiated adenocarcinoma (pat BsrlCm according to the Japanese Society of Biliary Surgery General rules for surgical and pathological studies on cancer of the biliary tract, 4th edn.). Using a semi-agarose method, a daughter-cell strain was also established. Both the cell line and the strain were transplanted into scid or nude mice with a 100% inoculation rate. The population doubling times of the cell line and the strain were 32.25 and 35.78 h, respectively. The cell line and strain strongly expressed human epithelial antigen (HEA)-125 and cytokeratin (CK)-19 but did not express desmin and partly expressed vimentin. High values tumor markers (carbohydrate antigen [CA19-9], Span-1, KMO-1) were detected in culture supernatants from both the cell line and the cell strain and the concentrations paralleled the patient's serum data. DNA analysis revealed that the cell strain was diploid, whereas the cell line was aneuploid, with a DNA index (DI) of 0.85. Chromosomal analysis of the cell line and the strain revealed a range of numerical abnormalities (76-93 and 74-88, respectively) as well as structural abnormalities. The establishment of this HBDC cell line and strain may provide some benefit for fundamental biological research.

Topics: Adenocarcinoma; Aged; Animals; Antigens, Surface; Bile Duct Neoplasms; Biomarkers, Tumor; Female; Flow Cytometry; Humans; Immunohistochemistry; Keratins; Mice; Mice, Nude; Mice, SCID; Middle Aged; Tumor Cells, Cultured

A clinicopathological study of 10 patients with pleomorphic carcinoma of the lung.. Histopathological and immunohistochemical staining for keratin, vimentin, Mac387, desmin, actin and S-100 protein were used for this study.. Pleomorphic carcinoma of the lung was found to often occur in males above 50 years of age and with clinical symptoms including cough, expectoration, haemoptysis and chest pain. The most frequent microscopic diagnosis was squamous cell carcinoma, and adenocarcinoma, accompanied by spindle and giant cells. The epithelial component of pleomorphic carcinoma of the lung displayed positivity for keratin and the spindle cells displayed positivity for vimentin. In some cases the neoplastic epithelial component and spindle cells showed positive expression of both keratin and vimentin.. Pleomorphic carcinoma of the lung may display various histopathological changes making it easy to be misdiagnosed as carcinosarcoma. Understanding its pathogenesis and histopathology is important for the diagnosis and differential diagnosis.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Carcinoma; Carcinoma, Giant Cell; Carcinoma, Large Cell; Carcinoma, Squamous Cell; Carcinosarcoma; Diagnosis, Differential; Female; Follow-Up Studies; Humans; Keratins; Lung Neoplasms; Male; Middle Aged; Pneumonectomy; Vimentin

Metastatic adenocarcinoma in the liver with an unidentified primary tumor site is a common clinical problem. Pathologists often are asked to identify the primary tumor site. The histologic picture itself usually is not helpful, because the histology may be similar in the metastases of tumors with different primary localizations. Immunohistochemistry can be helpful, but the previously recommended antibody panels are too complicated for everyday use.. A simple immunohistochemical algorithm with two monoclonal cytokeratin (CK) antibodies, CK20 and CK7, was tested on 93 autopsy cases of adenocarcinomas metastatic to the liver. Sections of the liver metastases were stained automatically and evaluated as negative (no staining), focally positive, or diffusely positive. Statistical comparison of the staining results for a single antibody was calculated as an odds ratio.. Thirty-six of 93 (39%) metastases proved to be CK20 positive (+). In this group, the CK20+/CK7 negative (-) pattern was highly characteristic for colorectal localization of the primary tumor, having been observed 17 of 21 of the cases (81%). The CK20+/CK7+ pattern of the metastatic liver adenocarcinomas was highly suggestive of primary localization in the pancreas or biliary tract (11 of 14 cases; 79%). Exclusion of the tumors originating in the stomach raised these values to 94% and 92%, respectively. The statistically calculated predicted probability of primary tumor site being in the colon or rectum for CK20+/CK7- metastasis was 78,41%, the probability of a primary tumor being located in the pancreas or biliary tract was 74,85%, if calculated for the whole study group.. The tested simple algorithm proved to be useful in CK20 positive (+) cases, predicting a primary tumor localization in the colon, rectum, pancreas, or biliary tract with high accuracy. The CK20- group was too heterogeneous to be classified adequately by these two antibodies.

Topics: Adenocarcinoma; Algorithms; Colorectal Neoplasms; Female; Gallbladder Neoplasms; Humans; Immunohistochemistry; Intermediate Filament Proteins; Keratin-20; Keratin-7; Keratins; Liver Neoplasms; Male; Neoplasms, Unknown Primary; Pancreatic Neoplasms; Retrospective Studies; Stomach Neoplasms

Topics: Adenocarcinoma; Aged; Endometrial Neoplasms; Female; Granuloma, Foreign-Body; Histiocytes; Humans; Keratins; Peritoneal Diseases

Immunohistochemistry with antibodies for high-molecular-weight cytokeratin labels basal cells and is used as an ancillary study in diagnosing prostate carcinoma, which reportedly lacks expression of high-molecular-weight cytokeratin. A recent report questioned the specificity of this marker, describing immunopositivity for high-molecular-weight cytokeratin in a small series of metastatic prostate cancer. We have also noted rare cases of prostate lesions on biopsy with typical histological features of adenocarcinoma showing immunopositivity for high-molecular-weight cytokeratin, either in tumor cells or in patchy cells with the morphology of basal cells. In some of these cases, it was difficult to distinguish cancer from out-pouching of high-grade prostatic intraepithelial neoplasia. To investigate whether prostate cancer cells express high-molecular-weight cytokeratin, we studied 100 cases of metastatic prostate carcinoma and 10 cases of prostate cancer invading the seminal vesicles from surgical specimens. Metastatic sites included regional lymph nodes (n = 67), bone (n = 19), and miscellaneous (n = 14). Cases with any positivity for high-molecular-weight cytokeratin antibody (34betaE12) were verified as being of prostatic origin with immunohistochemistry for prostate-specific antigen and prostate-specific acid phosphatase. Only four cases were detected positive for high-molecular-weight cytokeratin. In two cases (one metastasis, one seminal vesicle invasion) there was weakly diffuse positivity above background level. Two metastases in lymph nodes showed scattered strong staining of clusters of tumor cells, which represented <0.2% of tumor cells in the metastatic deposits. These positive cells did not have the morphology of basal cells. We conclude that prostate cancer, even high grade, only rarely expresses high-molecular-weight cytokeratin. This marker remains a very useful adjunct in the diagnosis of prostate cancer.

Topics: Acid Phosphatase; Adenocarcinoma; Biomarkers, Tumor; Humans; Immunoenzyme Techniques; Keratins; Male; Molecular Weight; Neoplasm Metastasis; Prostate-Specific Antigen; Prostatic Neoplasms; Seminal Vesicles

Micrometastases within bone marrow indicate a poor prognosis. We prospectively examined micrometastases in patients undergoing resection of esophagogastric cancers for (1) prevalence in rib marrow; (2) comparative detection rates in rib and iliac crest marrow; (3) responsiveness to neoadjuvant therapy; and (4) viability and tumorigenicity.. In 50 consecutive patients, marrow was obtained before manipulation of the primary tumor. Micrometastatic cells were detected by staining contaminant cytokeratin-18-positive cells. Viability and tumorigenicity were determined by culture and xenograft.. Micrometastases were detected in rib marrow from 88% of patients (44 of 50). When bilateral iliac crest marrow was also obtained, micrometastases were found in 15% (4 of 27) compared with 89% (24 of 27) for ribs (P < 0.001). Detection rates were independent of histological type or nodal status and were similar in patients with and without neoadjuvant therapy. Metastatic cells were cultured from rib marrow of 5 of 7 patients and were tumorigenic in nude mice.. Most patients undergoing resection of esophagogastric malignancies have micrometastases in rib marrow. Detection rates based on iliac crest marrow are underestimates. Hematogenous spread of metastatic cells is independent of histological type or nodal status. The metastatic cells are viable, tumorigenic, and resistant to neoadjuvant therapy.

Topics: Adenocarcinoma; Animals; Bone Marrow; Carcinoma, Squamous Cell; Esophageal Neoplasms; Esophagogastric Junction; Flow Cytometry; Humans; Ilium; Keratins; Mice; Mice, Nude; Neoplasm Metastasis; Neoplasm Staging; Prospective Studies; Ribs; Stomach Neoplasms; Transplantation, Heterologous

To clarify the correlation between multidirectional differentiation and aggressiveness of endometrial adenocarcinomas, we assessed both proliferative activities (PA) using Ki-67 expression and squamous and/or endocrine differentiation. We divided 51 adenocarcinomas into 22 adenocarcinomas with typical squamous differentiation (>/=10% of tumor cells, typical SQ) classified into 10 adenoacanthomas (AA) and 12 adenosquamous carcinomas (AS), 17 adenocarcinomas with focal squamous differentiation (<10% of tumor cells), and 12 typical adenocarcinomas without morphological squamous differentiation (pure AC), according to the new WHO classification. Paraffin-embedded sections were stained using monoclonal antibodies against high-molecular-weight keratins (HMWK) to recognize squamous cells, chromogranin A to recognize endocrine cells, and Ki-67 antigen to recognize proliferating cells. Both AA and AS exhibited lower PA than pure AC. Typical SQ exhibited lower PA than pure AC. This difference was also significant after selecting only grade 1 or stage I/II cases. AA exhibited lower PA than AS and also after selecting only grade 1 or stage I/II cases. PA of adenocarcinoma with the expression of HMWK in >/=30% of tumor cells was lower than those without HMWK. PA of adenocarcinoma with the expression of chromogranin A in >/=10% of tumor cells was lower than those without chromogranin A. These differences were also significant after selecting only grade 1 or stage I/II cases. Squamous and/or endocrine differentiation is a good marker for a reduction of PA. Endometrial adenocarcinomas with multidirectional differentiation exhibited lower PA and were likely to be more mature than those with monodirectional differentiation.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Carcinoma, Adenosquamous; Cell Transformation, Neoplastic; Chromogranin A; Chromogranins; Endometrial Neoplasms; Female; Humans; Immunohistochemistry; Keratins; Ki-67 Antigen; Metaplasia; Middle Aged; Neoplasm Invasiveness

This study was designed to identify a difference in immunostaining that might help to distinguish between primary and metastatic liver neoplasms.. We examined immunohistochemical expression of cytokeratins (CKs) 7, 8, 19, and 20 in 12 intrahepatic cholangiocarcinomas (ICCs; 9 of the mass-forming and 3 of the infiltrating type), 25 metastatic colorectal carcinomas (MCCs), and 7 metastatic gastric carcinomas (MGCs) of the liver.. CKs 7 and 19 were expressed in all ICCs of infiltrating type, while each was seen in 7/9 (77.8%) of mass-forming type. CK 7-positive/CK 20-negative was seen in 9/12 (75.0%) of ICCs and in none of the 25 MCCs, while CK 7-negative/CK 20-positive was seen in 1/12 (8.3%) of ICCs and 20/25 (80.0%) of MCCs. No differences were observed between MGCs and ICCs.. These results suggest that immunohistochemical staining for both CKs 7 and 20 is useful for the differential diagnosis of ICCs and MCCs, whereas phenotypic expression of CKs appears to be different between mass-forming and infiltrating types of ICCs.

Topics: Adenocarcinoma; Bile Duct Neoplasms; Bile Ducts, Intrahepatic; Cholangiocarcinoma; Humans; Immunohistochemistry; Keratins; Liver Neoplasms; Staining and Labeling

Lymph node metastasis is a well known feature of poor prognosis in patients with esophageal adenocarcinoma and squamous cell carcinoma. However, a significant proportion of apparently lymph node negative patients die early of metastatic disease. The aim of this study was to determine the prevalence and prognostic significance of occult lymph node metastasis in patients with esophageal adenocarcinoma and squamous cell carcinoma.. Lymph node sections from esophagectomy specimens of 78 patients with lymph node negative esophageal carcinoma (49 patients with adenocarcinoma and 29 with squamous cell carcinoma) were cut serially, it toto, and immunostained with the cytokeratin antibody AE1/AE3 and evaluated for occult lymph node metastasis. The results were correlated with the clinical and pathologic features and with patient survival.. Fifteen of 49 patients (31%) with adenocarcinoma and 5 of 29 patients (17%) with squamous cell carcinoma had occult lymph node metastasis detected by cytokeratin staining. In the adenocarcinoma patients, the presence of occult lymph node metastasis showed a significant correlation with increasing depth of invasion, but was not associated significantly with any other clinical or pathologic feature. In the squamous cell carcinoma patients, the presence of occult lymph node metastasis did not correlate significantly with any clinical or pathologic parameter, except that patients with occult lymph node metastasis were more likely to have received preoperative chemotherapy or radiation therapy. Occult lymph node metastasis did not correlate with poorer survival rates in patients with either adenocarcinoma (Cox proportional hazards ratio: 1.42; P - 0.46) or squamous cell carcinoma (Cox proportional hazards ratio: 0.86; P = 0.90).. Occult lymph node metastasis is not an independent poor prognostic feature in esophageal adenocarcinoma or squamous cell carcinoma. Therefore, the authors do not recommend extensive lymph node sectioning with keratin immunostaining for prognostication of patients with these malignancies.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Biomarkers, Tumor; Carcinoma, Squamous Cell; Esophageal Neoplasms; Female; Humans; Immunohistochemistry; Keratins; Lymphatic Metastasis; Male; Middle Aged; Prognosis; Proportional Hazards Models

The purpose of this study was to examine the ultrastructural and immunohistochemical characteristics of basal cell adenocarcinoma.. Three cases of basal cell adenocarcinoma of the salivary glands were studied by means of light microscopy, electron microscopy, and immunohistochemistry.. Some of the architectural tumor patterns encountered were solid, some were trabecular, and some were mixed. Ultrastructurally, solid areas were composed of nonluminal cells, some of which contained tonofilaments and well-formed desmosomes; tubulo-trabecular areas differentiated into both luminal and nonluminal cells. Both growth patterns were associated with the formation of excess basal lamina, marginally and between nonluminal cells. Myofilaments were infrequent in nonluminal cells of solid or trabecular areas. Cytokeratin (AE1/AE3) stained all 3 tumors, more peripherally in the solid pattern and usually centrally in the trabecular areas; vimentin stained all 3 tumors diffusely; smooth muscle actin (IA4) stained all 3 tumors but was mainly confined to peripheral tumor cells in both the solid and the trabecular growth patterns; epithelial membrane antigen and carcinoembryonic antigen stained 1 of the 3 tumors, predominantly in the luminal cells; p53 oncoprotein was focally positive in 2 of the 3 tumors; Ki-67 stained less than 5% of the tumor cells in all cases; and c-erb-B2 was uniformly negative in all cases. Staining patterns of cytokeratin and actin varied with the architecture of the tumor.. Neither ultrastructural characteristics nor immunohistochemistry findings appear to distinguish basal cell adenocarcinoma from basal cell adenoma.

Topics: Actins; Adenocarcinoma; Antigens, Neoplasm; Diagnosis, Differential; Humans; Immunohistochemistry; Keratins; S100 Proteins; Salivary Gland Neoplasms; Vimentin

Dimethylbenzanthracene (DMBA) induces pancreatic adenocarcinomas in rats 9 months after carcinogen exposure, with precursor lesions (tubular complexes) developing 1 month after initiation of treatment. Because previous studies have suggested an acinar cell of origin for these tumors, we investigated the expression pattern of ductal, acinar, and islet cell markers in these cancers to gain insight into their phenotype and cell of origin. Pancreatic neoplasms were induced in rats by implantation of DMBA into the head of the pancreas. Lesions studied included 10 early tubular complexes (DMBA for 2 weeks), 8 tubular complexes (DMBA for 1 month), and 10 adenocarcinomas (DMBA for 9 months). Normal rat pancreas served as a control. For comparison, 5 human ductal adenocarcinomas were also evaluated. Immunohistochemistry with ductal (keratin, cytokeratin 19, cytokeratin 20), acinar (chymotrypsin), and islet (chromogranin A) cell markers was performed to analyze the tissues. Rat tubular complexes and adenocarcinomas revealed strong expression of keratin, cytokeratin 19, and cytokeratin 20 in the cytoplasm of all neoplastic cells, absence of chymotrypsin, and rare immunoreactivity to chromogranin A. Human adenocarcinomas showed strong expression of keratin and cytokeratin 19 in all neoplastic cells, expression of cytokeratin 20 in 5-20% of cells, and absence of chymotrypsin and chromogranin A. Pancreatic adenocarcinomas induced by DMBA in rats express markers consistent with a ductal phenotype, as observed in human tumors. Ductal marker expression in early tumor stages suggests a ductal cell of origin.

Topics: 9,10-Dimethyl-1,2-benzanthracene; Adenocarcinoma; Aged; Animals; Biomarkers, Tumor; Chromogranin A; Chromogranins; Chymotrypsin; Female; Humans; Immunohistochemistry; Intermediate Filament Proteins; Keratin-20; Keratins; Male; Pancreas; Pancreatic Neoplasms; Precancerous Conditions; Rats; Rats, Sprague-Dawley

The present study was designed to clarify the mechanism by which some lung cancer cell lines can produce cytokeratin 19 (CK19) fragment and others cannot. We hypothesized that some lung cancer cell lines which cannot release CK19 express an incomplete sequence of CK19 mRNA. Expression of mRNA was evaluated by RT-PCR using several primer pairs for CK19. CK19 in the culture supernatant was measured by an immuno-radiometric assay. CK19 protein synthesis was evaluated by Western immunoblot and immunohistochemistry. Among 16 lung cancer cell lines, 7 released significant amounts of CK19 in the supernatant. In some cell lines, expression of CK19 mRNA was observed only in some combinations of primers, suggesting that incomplete mRNA was expressed. 3'-RACE analysis detected amplified products of a shorter size compared with normal amplified products in cell lines which expressed incomplete CK19 mRNA, suggesting that 3'-ends of mRNA for CK19 were deleted. Results of Western immunoblot and immuno-histochemical staining using anti-human CK19 monoclonal antibody completely correlated with the results on CK19 levels in culture supernatants as well as with complete expression of mRNA. We conclude that levels of CK19 closely relate to the expression of complete mRNA for CK19.

Topics: Adenocarcinoma; Carcinoma, Small Cell; Carcinoma, Squamous Cell; DNA Primers; Gene Expression Regulation, Neoplastic; Humans; Keratins; Lung Neoplasms; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Transcription, Genetic; Tumor Cells, Cultured

To provide cytospins as a means of external quality assurance (EQA), while maintaining antigen expression integrity and achieving uniformity of material for all participating laboratories.. Cells were collected from two adenocarcinoma and one reactive pleural effusion specimens. Lymphoid cells were also collected through aspiration of a resected tonsil specimen. All cells were collected in Hanks balanced salt solution (HBSS); cytospins were made and fixed in methanol or acetone alone or protected using a layer of 10% polyethylene glycol (PEG) in 50% methanol. Two laboratories participated (RGHT and UCL).. Cytokeratin expression detected using either CAM5.2 or AE1/AE3 antibodies was sensitive to temperature. Without PEG, unacceptable or negative staining was seen within six weeks of preparation. LCA was not sensitive to temperature, with good staining scores being achieved after eight weeks following preparation.. It is possible to send alcohol fixed, air dried cytospins to laboratories participating as part of an EQA scheme for immunocytology. Some antigens will require protection from temperature variations during transit. A layer of 10% PEG in 50% methanol, allowed to air dry, is suitable for this purpose. Participating laboratories will only have to remove this layer using methanol before their localisation technique for assessment.

Topics: Adenocarcinoma; Cell Separation; Cytodiagnosis; Ethanol; Humans; Immunoenzyme Techniques; Keratins; Neoplasm Proteins; Pleural Effusion; Polyethylene Glycols; Quality Assurance, Health Care; Tissue Preservation

Because of the widespread use of keratin 34 beta E-12 to assist in the distinction between benign acini and malignant glands, the lack of immunoreactivity of benign prostatic acini are important issues. We studied midprostate whole-mount sections from 21 low-volume adenocarcinoma radical prostatectomy specimens with keratin 34 beta E-12. We marked out benign 0.25-cm2 areas in the peripheral and transition zones and counted the number of small acini immunoreactive with keratin 34 beta E-12 to a total of 50 acini within each area. Small benign acini from nonatrophic peripheral zone lobules of 3 prostate specimens were examined by electron microscopy. The median number of immunoreactive acini in each region was 49. The nonreactive acini were always the most peripheral acini in a lobule, a small cluster of outpouched acini furthest from a large duct, or the terminal end of a large duct. More proximal acini had a discontinuous pattern of immunoreactivity. Electron microscopy showed occasional acini with luminal cells abutting the basement membrane, without the interposition of basal cell cytoplasm, and other acini with extremely attenuated basal cell cytoplasmic processes containing sparse bundles of intermediate filaments. The basal cell layer becomes attenuated toward the periphery of some lobules and duct outpouchings, producing nonreactive acini adjacent to discontinuously reactive acini.

Topics: Adenocarcinoma; Epithelial Cells; Humans; Immunoenzyme Techniques; Keratins; Male; Microscopy, Electron; Prostate; Prostatectomy; Prostatic Neoplasms

To determine the rate of diagnostic uncertainty in rendering diagnoses on prostate needle biopsies and to examine pathology practice variables that influence that rate.. Anatomic pathology departments participating in the College of American Pathologists Q-Probes laboratory quality improvement program retrospectively reviewed their last 50 consecutive prostate needle biopsy diagnoses. For each diagnosis, participants provided information concerning patients' prostate-specific antigen levels; number, locations, and laterality of biopsy specimens; number of tissue levels examined; performance of high-molecular-weight cytokeratin immunoperoxidase staining; and acquisition of consultations from general pathologists or experts in prostate pathology. Characteristics of pathology practices included yearly surgical and prostate needle biopsy caseloads, number of pathologists rendering biopsy diagnoses, use of standard descriptive checklists, access to patients' prostate-specific antigen and digital rectal examination results, percentages of prostate needle biopsies routinely submitted for internal consultations, and presence of departmental experts in prostate pathology.. Three hundred thirty-two public and private institutions located in the United States (n = 318), Canada (n = 6), Australia (n = 5), United Kingdom (n = 2), and Guam (n = 1).. The rate of diagnostic uncertainty in prostate needle biopsy diagnoses.. Participants submitted diagnoses on a total of 15 753 prostate needle biopsy cases, of which 33.4% were adenocarcinoma; 55.5% were benign; 3.9% were carcinoma in situ, prostatic intraepithelial neoplasia, or both; and 7.1% were diagnostically uncertain. The median rate of diagnostic uncertainty was 6%, ranging from 0 at the 10th percentile to 14% at the 90th percentile of all participating laboratories. Performing high-molecular-weight cytokeratin immunoperoxidase staining resolved diagnostic uncertainty in 68% of cases in which it was performed, and obtaining intradepartmental and extradepartmental consultations resolved diagnostic uncertainty in 70% to 87% of cases for which they were obtained. Knowledge of patients' prostate-specific antigen results and examining multiple biopsy cores had marginal effects on the rate of uncertainty. Thoroughness of prostate gland sampling and examination of multiple tissue block levels were not associated with the aggregate rate of diagnostic uncertainty. We found no particular pathology departmental practices or institutional demographic characteristics associated with institutional rates of diagnostic uncertainty.. Use of high-molecular-weight cytokeratin immunoperoxidase staining and obtaining intradepartmental and extradepartmental consultations may be effective in reducing diagnostic uncertainty in prostate biopsies.

Topics: Adenocarcinoma; Biopsy, Needle; Carcinoma in Situ; Humans; Immunoenzyme Techniques; Keratins; Male; Palpation; Pathology; Prostate-Specific Antigen; Prostatic Intraepithelial Neoplasia; Prostatic Neoplasms; Quality Control; Rectum; Sensitivity and Specificity

In order to characterize the cellular component of the polymorphous low-grade adenocarcinoma (PLGA) of the salivary gland, a morphological and immunohistochemical study was carried out. Thirty cases of PLGA were studied by light microscopy and immunohistochemistry and five cases by transmission electron microscopy (TEM). The expression of cytokeratins (CKs) 7,8,10,13,14,18,19, vimentin and muscle-specific actin (MSA) was investigated through the streptavidin-biotin method. The majority of tumor cells stained for vimentin, CKs 8, 18 and 7. CK 14 was positive in most cells of the papillary and trabecular sub-types. Although the expression of CKs 8,18 and 14 varied among the tumors sub-types, a straight relationship between each histologic pattern and the CK expression could not be delineated. MSA was reactive in only three tumors while CKs 10 and 13 were not detected in any tumor studied. The absence of MSA and the expression of CKs 8,18 and 7, in most of the tumor cells, lead to the hypothesis that myoepithelial cells are not the major cellular component of the PLGA. TEM revealed cells exhibiting microvilli and variable amounts of secretory granules, some of them suggesting an excretory activity. The presence of CKs 8,18 and 7, added to the secretory granules, indicates that PLGA originates from cells located at the acinar-intercalated duct junction.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Biotin; Cytoplasmic Granules; Female; Humans; Immunohistochemistry; Keratins; Male; Microscopy, Electron; Microvilli; Middle Aged; Neoplasm Proteins; Salivary Gland Neoplasms; Streptavidin; Vimentin

Minimal residual disease in patients with operable pancreatic carcinoma is frequently missed by current noninvasive tumour staging. We applied an immunocytochemical cytokeratin assay that allows identification of individual pancreatic carcinoma cells disseminated to bone marrow. Prior to therapy, bone marrow was aspirated from the upper iliac crest of 48 patients with ductal adenocarcinoma of the pancreas at various disease stages and an age-matched control group of 33 noncarcinoma patients. Tumor cells in cytologic bone marrow preparations were detected with monoclonal antibodies (mAbs) CK2, KL1, and A45-B/B3 to epithelial cytokeratins (CK) using the alkaline phosphatase antialkaline phosphatase method. CK-positive cells were found in 14 (48.4%) of 31 cancer patients treated with curative intent and in 10 (58.8%) of 18 patients with extended disease. The overall frequency of these cells was 1 to 83 per 5x10(5) mononuclear cells with no significant differences between patients at different tumor stages and lymph node involvement. After a median follow-up of 22.8 months (range 3-48 months), 6 (40.0%) of 15 patients who underwent complete surgical resection but had tumor cells in bone marrow presented with distant metastasis and 7 (46.7%) had local relapse compared to none of 12 corresponding patients without such cells (p<0.05). Univariate survival analyses revealed that the presence of CK-positive cells was predictive of reduced overall survival. In conclusion, anticytokeratin mAbs are reliable probes for the immunocytochemical detection of single pancreatic cancer cells disseminated to bone marrow. Thus the described technique may help identify patients with pancreatic cancer and at potentially high risk of early metastatic relapse. The results promise to be of important assistance for determining prognosis and the consequences in therapy of early stage pancreatic cancer.

Topics: Adenocarcinoma; Antibodies, Monoclonal; Bone Marrow Neoplasms; Female; Humans; Immunohistochemistry; Keratins; Male; Middle Aged; Pancreatic Neoplasms; Prognosis; Prospective Studies

The detection of cytokeratin-positive bone marrow cells has been considered a prognostic factor in numerous malignant tumors. We investigated whether this was also valid for localized prostate cancer. Bone marrow aspirates were taken prior to radical prostatectomy from 169 consecutive patients with pT1/2 pN0 G1-3 adenocarcinoma of the prostate. The immunocytochemical detection of cytokeratin no. 18 (CK 18)-positive cells using monoclonal antibody CK 2 was interpreted as micrometastasis. Repeat marrow aspirations were performed at 6 months postoperatively and once a year thereafter. The patients were re-examined over a period of at least 10 and a maximum of 72 months (median 32 months). An increase in prostate specific antigen >/=0.5 ng/ml was considered a biochemical "relapse". One hundred and fifty-four patients had evaluable bone marrow aspirates, of which 74.7% were CK 18-negative and 25.3% positive. The latency period for biochemical relapse was 1481 days (median) in the CK 18-negative group and 1106 days (median) in the CK 18-positive group. This difference was not statistically significant. The CK 18-positive aspirates (n = 39) showed one positive cell in 20 cases, two positive cells in 8 and three or more positive cells in 11 cases. The preoperative number of cells had no statistically significant effect upon the onset of biochemical relapse. Only patients with three or more CK 18-positive cells tended to have a poorer prognosis. One hundred and thirteen patients had evaluable bone marrow aspirates pre- and postoperatively. Postoperative persistence or occurrence of CK 18-positive cells did not affect the outcome of the disease. The detection of CK 18-positive cells in bone marrow does not influence the prognosis of patients with localized prostate cancer within a period of 32 months (median). Solely a subgroup of patients showing a large preoperative number of CK 18-positive cells seems to tend to an unfavorable course of the disease. Thus, further studies are necessary aiming at a more detailed characterization of these cells.

Topics: Adenocarcinoma; Aged; Bone Marrow Examination; Bone Marrow Neoplasms; Disease-Free Survival; Epithelial Cells; Humans; Keratins; Male; Middle Aged; Prognosis; Prostate-Specific Antigen; Prostatectomy; Prostatic Neoplasms; Recurrence

Fifty patients with adenocarcinoma of the lung were enrolled in this study, including 20 patients with recurrence and 30 patients without recurrence 1 year after surgery. Serial serum levels of cytokeratin fragment 19 (CYFRA 21-1) and carcinoembryonic antigen (CEA) were measured before the operation and 1 week, 1 month, 3 months, 6 months, 9 months, and 12 months after surgery for the early detection of recurrence. The results revealed that the mean serum values of either CYFRA 21-1 or CEA were significantly higher until 9 and 12 months after surgery in the 20 patients with recurrent adenocarcinoma compared with the 30 patients without recurrent adenocarcinoma. We conclude that CYFRA 21-1 is not a better marker than CEA for early prediction of adenocarcinoma. We conclude that CYFRA 21-1 is not a better marker than CEA for early prediction of adenocarcinoma recurrence in lung.

Topics: Adenocarcinoma; Adult; Aged; Antigens, Neoplasm; Biomarkers, Tumor; Carcinoembryonic Antigen; Female; Humans; Keratin-19; Keratins; Lung Neoplasms; Male; Middle Aged; Neoplasm Recurrence, Local; Prognosis; Prospective Studies

To discriminate between adenocarcinomas that are primary to the ovary and metastatic to the ovary, especially of colonic and breast origin, by immunohistochemistry, using stepwise discriminant analysis or a decision tree.. 312 routinely processed, formalin fixed tissue specimens were used. The tumours were divided into a learning set (n = 159), composed of primary tumours of ovary, breast, and colon, and a test set, comprising 134 metastases from these sites and an additional 19 primary ovarian carcinomas. The immunohistochemical panel was composed of antibodies against cytokeratin 7 (CK7) and 20 (CK20), CA125, vimentin, carcinoembryonic antigen (CEA), gross cystic disease fluid protein-15 (GCDFP-15), and the oestrogen receptor (ER). The staining results of the tumours were expressed as the product of the staining intensity and the percentage of positive tumour cells. Analyses were first performed on the learning set and then evaluated on the test set.. Although the immunostaining patterns showed a considerable overlap between the three types of adenocarcinoma, the breast carcinomas were typically positive for GCDFP-15 and often for ER, and negative for vimentin. Ovarian carcinomas were always positive for CK7 and to a lesser extent for CA125. Colonic carcinomas showed prominent positivity for CEA and CK20, while no staining was seen for ER and vimentin. In discriminant analysis, six antibodies (alpha CK7, alpha CK20, alpha CA125, alpha CEA, alpha ER, and alpha GCDFP-15) appeared to be necessary for optimal classification: 89% of the learning set and 82% of the test set were classified correctly. In the decision tree, only four antibodies (alpha CK7, alpha CEA, alpha ER, and alpha GCDFP-15) were used to obtain a correct classification score of 89% for the learning set and 84% for the test set.. Using a semiquantitative assessment of the immunostaining results by a restricted panel of six antibodies with stepwise discriminant analysis, 80-90% of the adenocarcinomas of colon, breast, and ovary can be correctly classified. Discriminant analysis is computer aided and therefore an easy method and for each case a probability value of the classification result is obtained. The intuitive decision tree method provides a slightly better result, requires only four antibodies, and offers a more practical method for the surgical pathologist.

Topics: Adenocarcinoma; Apolipoproteins; Apolipoproteins D; Biomarkers, Tumor; Breast Neoplasms; CA-125 Antigen; Carcinoembryonic Antigen; Carrier Proteins; Colonic Neoplasms; Decision Trees; Diagnosis, Differential; Discriminant Analysis; Female; Glycoproteins; Humans; Immunohistochemistry; Intermediate Filament Proteins; Keratin-20; Keratin-7; Keratins; Membrane Transport Proteins; Ovarian Neoplasms; Receptors, Estrogen; Vimentin

We have previously shown that human breast carcinoma cells demonstrating an interconverted phenotype, where keratin (epithelial marker) and vimentin (mesenchymal marker) intermediate filaments are both expressed, have an increased ability to invade a basement membrane matrix in vitro. This increase in invasive potential has been demonstrated in MDA-MB-231 cells, which constitutively express keratins and vimentin, and in MCF-7 cells transfected with the mouse vimentin gene (MoVi). However, vimentin expression alone is not sufficient to confer the complete metastatic phenotype in MoVi cells, as determined by orthotopic administration. Thus, in the present study, differential display analysis was utilized to identify genes that are associated with the invasive and/or metastatic phenotype of several human breast cancer cell lines. Forty-four of 84 PCR fragments were differentially expressed as assessed by Northern hybridization analysis of RNA isolated from MCF-7, MoVi, and MB-231 cell lines. Polyadenylated RNA from a panel of poorly invasive, invasive/non-metastatic, and invasive/metastatic breast carcinoma cell lines was used to differentiate between cell-specific gene expression and genes associated with the invasive and/or metastatic phenotype(s). We observed that lysyl oxidase and a zinc finger transcription factor were expressed only in the invasive and/or metastatic cell lines; whereas, a thiol-specific antioxidant and a heterochromatin protein were down-regulated in these cells. In contrast, tissue factor was expressed only in breast carcinoma cell lines having the highest invasive potential. These results suggest that specific genes involved in breast cancer invasion and metastasis can be separated by differential display methodology to elucidate the molecular basis of tumor cell progression.

Topics: Adenocarcinoma; Animals; Biomarkers, Tumor; Blotting, Northern; Breast Neoplasms; Chromobox Protein Homolog 5; Chromosomal Proteins, Non-Histone; DNA-Binding Proteins; DNA, Complementary; Expressed Sequence Tags; Female; Gene Expression Regulation, Neoplastic; Homeodomain Proteins; Humans; Keratins; Mice; Mice, Nude; Neoplasm Invasiveness; Neoplasm Metastasis; Neoplasm Proteins; Neoplasm Transplantation; Phenotype; Polymerase Chain Reaction; Protein-Lysine 6-Oxidase; Repressor Proteins; Subtraction Technique; Transcription Factors; Tumor Cells, Cultured; Vimentin; Zinc Finger E-box-Binding Homeobox 1; Zinc Fingers

The technetium Tc 99m-labeled monoclonal antibody MAb-170 was designed for diagnostic use in patients with gynecologic adenocarcinoma. Our investigation was initiated to verify its usefulness for radioimmunoscintigraphy of ovarian tumors.. Most of the 82 patients participating in this study underwent immunoscintigraphy before first-look surgery.. Radioimmunoscintigraphy recognized 36 of 41 patients with adenocarcinoma of the ovaries, corresponding to an overall sensitivity of 88%. Specificity was 90% (38/42). The calculation of accuracy gave a result of 89% (74/83). Of 110 known lesions, 92 were visualized successfully; thus the local-regional sensitivity was 84%. Of 160 benign tumor sites, 154 showed no evidence of tracer accumulation, corresponding to a local-regional specificity of 96%. The smallest lesion visualized was an adenocarcinoma of the corpus uteri with a diameter of 1.5 cm.. The monoclonal antibody MAb-170 is a promising radiopharmaceutical for immunoscintigraphy of ovarian adenocarcinoma.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Antibodies, Monoclonal; Antigens, Neoplasm; Female; Humans; Immunologic Techniques; Keratins; Middle Aged; Ovarian Neoplasms; Radionuclide Imaging; Sensitivity and Specificity; Technetium

The morphology, cell growth, antigenic expression and tumorigenicity of cell subpopulations from the A549 lung adenocarcinoma isolated by Percoll gradient separation have been analysed. Four subpopulations were obtained (subpopulations A, B, C and D). Immunocytochemical analysis of several antigens was performed with monoclonal antibodies (MAbs): MUC1 mucin (C595, HMFG1 and HMFG2), MUC5B (PANH2); gp230 (PANH4); carbohydrate antigens including sialyl Lewis x (KM93), Tn antigen (83D4), Lewis y (C14); 5, 6, 8, 17 and 19 cytokeratins and p53. The cell population D tended to form cell aggregates that piled up on the monolayer similar to overgrowth cultures of the A549 parental cell line, whereas A, B and C cell subpopulations formed well spread monolayers. Both parental A549 and subpopulation D secreted abundant mucus. The topographic distribution and secretion production were correlated with tumorigenic assays since only subpopulation D grew in nude mice exhibiting reduced latency period; these characteristics correlated with the fast growth of the subpopulation D in vitro. Immunocytochemical analysis demonstrated that subpopulation D showed greater expression of MUC1 mucin and carbohydrate antigens such as Tn antigen, sialyl Lewis x and Lewis y and less expression of cytokeratins, p53, MUC5B and gp230; conversely, subpopulations A, B and C showed the opposite antigenic profile. Our results illustrate heterogeneity in the A549 cell line; subpopulations A, B and C retained characteristics of more differentiated adenocarcinoma while subpopulation D displayed features of a less differentiated tumor line.

Topics: Adenocarcinoma; Animals; Antibodies, Monoclonal; Cell Separation; Humans; Immunohistochemistry; Keratins; Lung Neoplasms; Mice; Mice, Nude; Neoplasm Transplantation; Oligosaccharides; Phenotype; Sialyl Lewis X Antigen; Time Factors; Tumor Cells, Cultured; Tumor Suppressor Protein p53

Dissemination of single tumor cells to the bone marrow is a common event in cancer. The clinical significance of cytokeratin-positive cells detected in the bone marrow of cancer patients is still a matter of debate. In gastric cancer, overexpression of the receptor (uPAR or CD87) for the serine protease urokinase-type plasminogen activator (uPA) in disseminated cancer cells indicates shorter survival of cancer patients. A new immunofluorescence approach, applying confocal laser scanning microscopy, is introduced to locate CD87 antigen in cytokeratin-positive tumor cells and to quantify the CD87 antigen by consecutive scanning. At first, cytokeratin 8/18/19-positive carcinoma cells are identified at excitation wavelength 488 nm using monoclonal antibody A45B/B3 to the cytokeratins and goat anti-mouse IgG labeled with the fluorochrome Alexa488. Next, CD87 in tumor cells is identified by chicken antibody HU277 to the uPA-receptor and goat anti-chicken IgY labeled with fluorochrome Alexa568 (excitation wavelength 568 nm) and the fluorescence signal quantified on a single cell basis using fluorescently labeled latex beads as the fluorescence reference. From 16 patients with gastric or esophageal carcinoma, bone marrow aspirates were obtained, stained for cytokeratins and CD87 and then subjected to laser scanning fluorescence microscopy. Three of six gastric cancer patients had tumor cells present in the bone marrow of which 2 stained for CD87. Three of ten esophageal carcinoma patients had tumor cells in the bone marrow, all three samples stained for CD87. CD87-positive tumor cells were also dissected from stained bone marrow aspirates by laser microdissection microscope to allow analysis of single cells at the gene level.

Topics: Adenocarcinoma; Adult; Aged; Bone Marrow Examination; Bone Marrow Neoplasms; Carcinoma, Squamous Cell; Esophageal Neoplasms; Fluorescent Antibody Technique, Indirect; Humans; Immunohistochemistry; Keratins; Microscopy, Confocal; Middle Aged; Plasminogen Activators; Predictive Value of Tests; Receptors, Cell Surface; Receptors, Urokinase Plasminogen Activator; Sensitivity and Specificity; Stomach Neoplasms; Tumor Cells, Cultured

Tumor-associated antigens may be expressed as surface glycoproteins. These molecules undergo qualitative and quantitative modifications during cell differentiation and malignant transformation. During malignant transformation, incomplete glycosylation is common, and certain glycosylation pathways are preferred. These antigens might help distinguish between ovarian and colonic adenocarcinomas in the primary and metastatic lesions. Different cytokeratins have been proposed as relatively organ-specific antigens.. We used monoclonal antibodies against T1, Tn, sialosyl-Tn, B72.3, CA125, carcinoembryonic antigen, and cytokeratins 7 and 20 to detect tumor-associated glycoproteins and keratin proteins in ovarian and colonic carcinomas.. CA125, carcinoembryonic antigen, and cytokeratins 7 and 20 can distinguish between colonic and serous or endometrioid adenocarcinomas of the ovary in both primary and metastatic lesions. Mucinous ovarian adenocarcinomas differed in that they express carcinoembryonic antigen and cytokeratins 7 and 20 and weakly express CA125. The other glycoprotein antigens were equally expressed by ovarian and colonic adenocarcinomas and therefore were of no use in distinguishing between these 2 entities.. A panel of monoclonal antibodies against cytokeratins 7 and 20 antigens, CA125, and carcinoembryonic antigen is useful in differentiating serous and endometrioid adenocarcinomas of the ovary from colonic adenocarcinomas. Mucinous ovarian adenocarcinomas cannot be distinguished from colonic adenocarcinomas using immunohistochemistry.

Topics: Adenocarcinoma; Antibodies, Monoclonal; CA-125 Antigen; Carcinoembryonic Antigen; Colonic Neoplasms; Diagnosis, Differential; Female; Humans; Immunoenzyme Techniques; Keratins; Ovarian Neoplasms

Nephrogenic Adenoma (NA) is a rare lesion of the urinary tract, considered a metaplastic response to chronic inflammation, trauma or immunosuppression.. We report two cases of NA arising in the urinary bladder of patients with previous history of recurrent urinary tract infections due to neuropsychiatric disease. Pathological examination of the lesions, resected by transurethral (TUR) management, revealed a papillary proliferation of tubules and cysts lined by cuboidal to low-columnar cells without atypia. Immunohistochemistry showed positivity for Cam 5.2, CK7 and EMA. MIB 1 count demonstrated a positivity in 12/200 cells in case 1 and < 2/200 in case 2. No expression of nuclear p53 was evident.. NA is a benign unusual neoplasm which might be misdiagnosed as clear cell adenocarcinoma of the bladder or prostatic adenocarcinoma. Its recognition is important because it is a benign lesion cured by a conservative resection and no additional therapy is generally required.

Topics: Adenocarcinoma; Adenocarcinoma, Clear Cell; Adenoma; Antigens, Nuclear; Biomarkers, Tumor; Calbindin 2; Carcinoma in Situ; Carcinoma, Transitional Cell; Diagnosis, Differential; Epithelial Cells; Female; Humans; Immunophenotyping; Keratins; Ki-67 Antigen; Male; Metaplasia; Middle Aged; Mucin-1; Neoplasm Proteins; Neoplasms, Multiple Primary; Nuclear Proteins; Prostatic Neoplasms; Protein Isoforms; S100 Calcium Binding Protein G; Urinary Bladder Neoplasms

Carcinomas of salivary gland ducts are described in five cats. The typical histological pattern was the formation of large cell aggregates resembling dilated ducts, often with central necrosis and a looping pattern. All tumours were labelled with antibody to cytokeratins (CKs) 5, 6, 8, 14, 17 and 19. Labelling of tumour cells with CK14 suggested basal cell differentiation. All tumours stained with Jack bean (Canavalia ensiformis) agglutinin (Con A); this is a feature of normal salivary gland ducts but is seen in other salivary gland tumours. Staining of tumour cells at the luminal surface of ductal structures with wheat germ (Triticum vulgaris) agglutinin (WGA) in the cat tumours was similar to that seen in ducts of normal cat salivary glands but occurs in other cat tumours. Other immunohistochemical staining results were unremarkable. 1999 Harcourt Publishers Ltd.

Topics: Adenocarcinoma; Animals; Biomarkers, Tumor; Cat Diseases; Cats; Female; Immunoenzyme Techniques; Keratins; Male; Salivary Ducts; Salivary Gland Neoplasms

Intraoperative pathologic examination of the sentinel lymph node (SLN) draining a primary breast carcinoma allows an SLN-positive patient to undergo complete axillary lymphadenectomy as part of the same surgical procedure. However, the optimal technique for rapid SLN assessment has not been determined. We reviewed our results with imprint cytology (IC) and frozen section (FS) examination of SLNs from 278 patients. Compared with H&E-stained paraffin sections, IC and FS had an overall accuracy of 93.2%. The false-reassurance rate (false-negative results/all negative results) was 8.4%. It correctly identified 98% of macrometastases but only 28% of micrometastases. There were no false-positive results. Compared with paraffin-section cytokeratin immunohistochemistry results, the IC-FS false-reassurance rate increased to 25.8%. The false-reassurance rate decreased with smaller primary tumor size (T1 vs T2/3) and ductal type, smaller diameter of the SLN (< or = 2.0 cm), and greater pathologist experience. IC combined with 2-level FS reliably identifies SLN macrometastases but commonly fails to detect SLN micrometastases. If SLN micrometastasis is used to determine the need for further lymphadenectomy, more sensitive intraoperative methods will be needed to avoid a second operation.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Biopsy, Needle; Breast Neoplasms; Female; Frozen Sections; Humans; Intraoperative Period; Keratins; Lymph Nodes; Lymphatic Metastasis; Middle Aged; Neoplasm Staging; Reproducibility of Results

It has been reported that cytokeratin 8 (CK8) is expressed in all non-small-cell lung cancers (NSCLC). We hypothesized that antigenic changes of CK8 may occur in some NSCLC cell lines. To prove this, Western immunoblot analysis using anti-human CK8 monoclonal antibodies as well as immunohistological staining of CK8 were performed in NSCLC cell lines. As a result, CK8 which had a higher molecular weight than recombinant CK8 was demonstrated in two of eight NSCLC cell lines. In addition, this CK8 contained antigenic epitopes of CA19-9. This CK8 with higher molecular weight, may have played a role in the process of invasion or metastasis of NSCLC.

Topics: Adenocarcinoma; Animals; Blotting, Western; CA-19-9 Antigen; Carcinoma, Non-Small-Cell Lung; Carcinoma, Squamous Cell; Carrier Proteins; Humans; Immunohistochemistry; Keratins; Lung Neoplasms; Molecular Weight; Neoplasm Proteins; Rabbits; Tumor Cells, Cultured

Hybrid tumours of the salivary gland are rare neoplasms that have been described only in the parotid and palate. Their recognition is important particularly when the component tumours have different biological behaviours. The occurrence of a submandibular hybrid tumour has not been reported.. We describe a case of a 36-year-old woman with a hybrid carcinoma composed of salivary duct adenocarcinoma and adenoid cystic carcinoma of the right submandibular gland. There was no evidence of a pre-existing or concurrent pleomorphic adenoma. The presence of the two components was verified by differential immunohistochemical staining using a panel of cytokeratin, vimentin, smooth muscle actin and S100. The patient subsequently developed metastases to the pelvis, lumbar, vertebra and wrist. The clinical course in this patient was consistent with the behaviour of the salivary duct adenocarcinoma component.. The histogenesis of hybrid tumours is largely unknown, but in this case it may represent diverging differentiation of luminal tumour cells. Because some histological features of different salivary gland tumours overlap, immunohistochemistry is a valuable tool especially when used to delineate the components of a hybrid tumour.

Topics: Actins; Adenocarcinoma; Adult; Carcinoma, Adenoid Cystic; Female; Humans; Immunohistochemistry; Keratins; Neoplasms, Multiple Primary; S100 Proteins; Submandibular Gland Neoplasms; Vimentin

Cytokeratin (CK) immunohistochemistry revealed changes in the CK19 immunoreactivity in human gastrointestinal epithelium during embryonic and fetal development. These changes were particularly marked in the jejunum and ileum. CK19 immunoreactivity was strong up to the 11th week of pregnancy, but was absent between weeks 12 and 17, and reappeared weakly from week 18 to week 24. This temporal pattern correlated with that of cell proliferation investigated by immunohistochemical detection of proliferating cell nuclear antigen. Marked CK expression was associated with a low proliferative rate and vice versa. To test whether these results were relevant to the assessment of intestinal metaplasia and the risk of malignant transformation with poor cell differentiation, adenomas and adenocarcinomas of the colon, intestinal metaplasia of the stomach, and two types of gastric carcinoma were also examined by CK19 immunohistochemistry. Substantial CK19 immunoreactivity was found in well-differentiated cancers and low-grade dysplasias with low cell proliferation, whereas only weak CK19 immunoreactivity was found in poorly differentiated carcinomas and high-grade dysplasias with a high proliferation rate.

Topics: Adenocarcinoma; Aging; Cell Differentiation; Cell Division; Colonic Neoplasms; Gastric Mucosa; Gastrointestinal Neoplasms; Humans; Ileum; Immunohistochemistry; Jejunum; Keratins; Proliferating Cell Nuclear Antigen; Reference Values; Stomach; Stomach Neoplasms

Metastatic adenocarcinomas of unknown primary site are a common clinical problem. Invasive ductal carcinomas of the breast and some special types of invasive breast carcinoma are common sources of metastases. Immunohistochemical algorithms, such as a combination of cytokeratins 20 and 7, can be helpful in this situation. Detailed phenotyping of the different types and subtypes of primary invasive carcinomas and their metastases is an essential prerequisite for a successful search for an unknown primary tumor. A series of 123 primary invasive breast adenocarcinomas of special type and of 27 lymph node metastases was analyzed. Sections of selected blocks were stained with two monoclonal cytokeratin antibodies (CK20 and CK7) and evaluated as negative (no staining), focally positive or diffusely positive. Of the 123 carcinomas, 113 (92%) proved to be CK20 negative. Three of 82 (4%) invasive lobular carcinomas, three of 11 (27%) mucinous carcinomas, one of 10 (10%) tubular carcinomas, and one invasive papillary carcinoma stained diffusely with CK20. Additionally, a tubulolobular carcinoma and a medullary carcinoma showed focal CK20 positivity. One hundred twenty (98%) of the 123 tumors were CK7 positive, five of them only focally. One of the four solid invasive lobular carcinomas, one medually carcinoma, and one invasive papillary carcinoma were completely negative for CK7. Only two cases, one mucinous and one invasive papillary carcinoma, exhibited the CK20(+)/CK7(-) ("colorectal") pattern. One of the lymph node metastases was CK20(+); another was CK7(-). Like their ductal counterparts, invasive breast carcinomas of special type are usually CK20(-)/CK7(+); they generally retain this phenotype in their metastases. However, there are CK20-positive special-type breast carcinomas that can be confused with gastrointestinal or pancreaticobiliary carcinoma in metastases, especially if they are mucinous or invasive lobular.

Topics: Adenocarcinoma; Adenocarcinoma, Mucinous; Breast Neoplasms; Carcinoma, Medullary; Female; Humans; Immunohistochemistry; Intermediate Filament Proteins; Keratin-20; Keratin-7; Keratins; Neoplasm Invasiveness; Tissue Distribution

We report a series of 41 ovarian metastases from colorectal adenocarcinomas. The patients'mean age was 57.1 years at the time the metastasis was discovered, and 55.8 years at the time the primary carcinoma was found. The diagnosis of the primary tumour was anterior to the metastasis in 25 cases (mean interval 21 months), simultaneous in 13 and posterior in 3 others. The metastases formed cystic and solid masses with a mean weight of 330 g. The endometrioid architectural type was the most frequent, either pure (71%, 29/41) or associated with a mucinous component (17%, 7/41). Pure mucinous or other architectural types were rare. The endometrioid type was characterized by glands with a garland pattern, and intraluminal dirty tumoral necrosis. Immunohistochemistry helped to distinguish the metastases of endometrioid type from serous or endometrioid primary ovarian carcinoma; 71% of the former were CK7(-)/CK20(+), and 100% of the latter had the reverse profile CK7(+)/CK20(-).

Topics: Adenocarcinoma; Adolescent; Adult; Aged; Aged, 80 and over; Biomarkers, Tumor; Carcinoma, Endometrioid; Colorectal Neoplasms; Diagnosis, Differential; Female; Follow-Up Studies; Humans; Keratins; Middle Aged; Ovarian Neoplasms; Time Factors

Topics: Adenocarcinoma; Carcinoma, Squamous Cell; Female; Humans; Keratins; Uterine Cervical Neoplasms

Neural invasion is known to be one of the aggressive characteristics of pancreatic adenocarcinoma. However, there have been no systematic studies on intraoperative examination of neural invasion of pancreatic carcinomas after wide dissection of the retroperitoneum, particularly at the surgical margin.. We performed intraoperative immunostaining on the frozen sections of several excised plexus specimens, using peroxidase-labeled anti-cytokeratin 19 antibody in 17 cases of resectable pancreatic carcinoma. Postoperatively, we also tried to detect occult micrometastasis by direct sequencing of the K-ras gene in the same samples.. Intraoperative staining for cytokeratin 19 was positive in 4 of 17 (23.5%) cases. Patients with margin-positive neural invasion had significantly worse prognosis than patients who were margin negative (P < 0.05). One patient had micrometastasis in the nerve plexus, revealed by K-ras mutation, whereas neither cytokeratin 19 staining nor postoperative pathological investigation detected involvement of the analyzed portion. In the four patients margin-positive for cytokeratin 19 staining, the diagnosis of neural invasion by cytokeratin 19 staining was in agreement with the K-ras gene analysis.. Intraoperative staining for cytokeratin 19 is useful for detecting pancreatic cancer involvement of the neural plexus margin. The results can be also utilized as a prognostic indicator during the follow-up period.

Topics: Adenocarcinoma; Aged; Base Sequence; Female; Humans; Immunohistochemistry; Intraoperative Period; Keratins; Male; Middle Aged; Mutation; Neoplasm Invasiveness; Nervous System; Nervous System Neoplasms; Pancreatic Neoplasms; Prognosis; Proto-Oncogene Proteins p21(ras); Staining and Labeling

Recently, cytokeratins (CK) were studied as tumor markers for many carcinomas. In lung cancer they appeared to be useful in distinguishing primary from secondary tumors, in histological typing as well as in evaluating patient's prognosis. However, the results have yet to be conclusive. In this study, expression of CK7, CK10/13, CK18, CK19, CK20 was investigated in a group of 72 surgically resected specimens of lung including 31 adenocarcinomas, 30 squamous cell carcinomas and 11 neuroendocrine carcinomas. Cytokeratin immunophenotypes were analyzed in comparison to histological characteristics of tumors, TNM stages and patients survival.. CK7, CK10/13 and CK18 can be used in distinguishing the lung adenocarcinomas from the lung squamous cell carcinomas: CK7(+), CK10/13(-), CK18(+) for adenocarcinomas; CK7(-), CK10/13(+), CK18(-) for squamous cell carcinomas. Relatively higher CK7 and CK18 immunostaining rates of the squamous cell carcinomas with high keratinization, with high percentage of dead cells and with late stages of disease suggested their prognostic significance but it was not confirmed when comparing different survival groups. Both adenocarcinomas and squamous cell carcinomas were stained strongly with antibody against CK19 (90.3% and 86.7% respectively) but much less with anti-CK20 antibody (9.7% and 3.3% respectively). In general, neuroendocrine tumors of the lung were non-reactive for these cytokeratins except CK18, among them all carcinoid tumors expressed CK18 abundantly.

Topics: Adenocarcinoma; Adult; Aged; Biomarkers, Tumor; Carcinoma, Squamous Cell; Diagnosis, Differential; Female; Humans; Immunohistochemistry; Keratins; Lung Neoplasms; Male; Middle Aged; Molecular Weight; Neuroendocrine Tumors

Patients with solitary rectal ulcer syndrome (SRUS) frequently present with a mass that can be misinterpreted as cancer. In contrast, the occurrence and characteristics of SRUS-like histopathology produced by underlying malignancy have not been reported in detail. We report seven patients whose rectal mass that was induced by infiltrating carcinoma showed only histopathologic changes of SRUS on initial mucosal biopsy specimens. Carcinoma was evident in subsequent specimens after one to five repeat biopsies with delay in diagnosis from 1 week to 18 months in six patients. In one patient, infiltrating carcinoma was suggested on the first biopsy specimen by immunohistochemistry for cytokeratin. Three of the patients had primary rectal adenocarcinoma, two had metastatic carcinoma from stomach or ovary, and two had direct invasion of anal squamous cell carcinoma or prostatic adenocarcinoma. We conclude that the histopathology of SRUS may occasionally represent a characteristic but nonspecific mucosal reactive change to a deeper seated malignancy. The terminology "solitary rectal ulcer syndrome/mucosal prolapse changes" with a cautionary note may be useful for reporting biopsy results to emphasize the possibility of underlying primary or metastatic malignancy in the differential diagnosis.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Biopsy; Carcinoma, Squamous Cell; Diagnosis, Differential; Female; Follow-Up Studies; Humans; Immunohistochemistry; Keratins; Male; Middle Aged; Proctoscopy; Prostate-Specific Antigen; Rectal Diseases; Rectal Neoplasms; Rectal Prolapse; Retrospective Studies; Ulcer

Little is known about the factors regulating epithelial ovarian cancer cell growth. This is due, in large part, to the difficulty in obtaining and culturing human ovarian cells for relevant in vitro studies. We recently developed a method for culturing epithelial carcinoma cells derived from fresh, untreated epithelial ovarian cancer specimens. The cell populations are free of fibroblasts and reflect the primary tumor as determined by chromosomal analysis. In this study we report on the cells' growth in serum-free medium and their secretion of CA-125, a glycoprotein marker for ovarian cancer. Furthermore we characterize the insulin-like growth factor (IGF) system in these primary ovarian carcinoma cell cultures. The cells secrete IGF peptides and IGF-binding proteins, possess specific type I IGF receptors, and respond to exogenous IGFs. The culture system reported here provides the basis for further study and manipulation of the IGF system as well as other regulators of epithelial ovarian cancer. Greater understanding of the cellular and molecular mediators of primary human ovarian cancer cell growth may translate into relevant clinical interventions.

Topics: Adenocarcinoma; CA-125 Antigen; Cell Division; Culture Media, Conditioned; Culture Media, Serum-Free; Female; Humans; Insulin-Like Growth Factor Binding Proteins; Keratins; Ovarian Neoplasms; Receptor, IGF Type 1; RNA, Messenger; RNA, Neoplasm; Somatomedins; Tumor Cells, Cultured; Vimentin

Perianal Paget's disease is rare, and its relationship to an associated internal regional cancer has been ill defined. We analyzed the histologic and immunohistochemical features of perianal Paget's disease in 11 patients to determine the frequency and relationship of associated regional internal carcinoma and to gain insight into its histogenesis. Of five patients with documented rectal adenocarcinoma, it was discovered synchronously with the Paget's disease in four and, subsequently, in one. Paget's cells of signet ring type predominated in four cases. Intraepithelial glands with intraluminal dirty necrosis were present in four cases. The immunophenotype in four cases studied was cytokeratin (CK)7+/CK20+/gross cystic disease fluid protein- (GCDFP) in both the intraepithelial Paget's cells and the invasive rectal adenocarcinoma. Six patients did not have documented rectal carcinoma. The Paget's cells in four were CK7+/CK20-/GCDFP15+. Three of these had purely intraepithelial Paget's disease, and invasive or metastatic disease developed in none after wide local excision. Bilateral inguinal lymph node metastases developed in the fourth patient, and the patient died 8 months after diagnosis of Paget's disease. In two patients, the Paget's cells were CK7+/CK20+/GCDFP15-. Recurrent intraepithelial perianal Paget's disease developed in one patient at 7 months; the patient was alive without disease at 24 months, and the other patient had several intraepithelial recurrences of perianal Paget's disease, and, subsequently, a large perianal tumor of uncertain cell type developed at 108 months, which led to the patient's death. We conclude that there are two types of perianal Paget's disease. One type has endodermal differentiation with gastrointestinal-type glands containing intraluminal dirty necrosis, numerous signet ring cells, CK20 positivity, and GCDFP15 negativity. Such cases are especially likely to be associated with synchronous or metachronous rectal adenocarcinoma. The other type is a primary cutaneous intraepithelial neoplasm in which the Paget's cells display sweat gland differentiation, including GCDFP15 positivity; it generally lacks gastrointestinal-type glands, intraluminal dirty necrosis, and CK20 positivity. The CK7 is a sensitive, albeit nonspecific, marker for Paget's cells.

Topics: Adenocarcinoma; Aged; Aged, 80 and over; Female; Humans; Immunohistochemistry; Intermediate Filament Proteins; Keratin-20; Keratin-7; Keratins; Male; Middle Aged; Paget Disease, Extramammary; Rectal Neoplasms

Adenocarcinomas may arise primarily from the urinary bladder, but secondary involvement from adenocarcinomas arising in adjacent organs is more common. In the present study we tried to differentiate primary urinary bladder adenocarcinomas from adenocarcinomas arising from the surrounding organs, based on their antigen profiles in routinely processed, paraffin-embedded tissue specimens. We analysed the staining results using stepwise linear discriminant analysis.. We investigated the usefulness of a panel of antibodies against cytokeratin 7, E48, cytokeratin 20, PSA, PSAP, CEA, vimentin, OC125 and HER-2/neu, to discriminate primary bladder adenocarcinoma from adenocarcinomas arising from the prostate, urachus, colon, cervix, ovary and endometrium. In the differential diagnosis with urinary bladder adenocarcinoma, an overall correct classification was reached for 77% and 81% of urachal and colonic carcinomas, respectively, using CEA, for 93% of prostatic adenocarcinomas using PSA, for 82% and 70% of cervical and ovarian adenocarcinomas, respectively, using OC125, and for 91% of endometrial adenocarcinomas using vimentin. Adding other antibodies did not improve the classification results for any of these differential diagnoses.. For the surgical pathologist, a panel of antibodies consisting of CEA, PSA, OC125 and vimentin is helpful to differentiate primary urinary bladder adenocarcinomas from adenocarcinomas originating from prostate and endometrium, less helpful in differentiation with urachal carcinoma, and not helpful in differentiation with colonic, cervical and ovarian carcinoma.

Topics: Abdominal Neoplasms; Acid Phosphatase; Adenocarcinoma; Antibodies, Monoclonal; Antibody Specificity; CA-125 Antigen; Carcinoembryonic Antigen; Carcinoma, Papillary; Cell Adhesion Molecules; Diagnosis, Differential; Endometrial Neoplasms; Female; Glycoproteins; GPI-Linked Proteins; Humans; Immunohistochemistry; Intermediate Filament Proteins; Keratin-20; Keratin-7; Keratins; Male; Neoplasms, Unknown Primary; Ovarian Neoplasms; Prostate; Prostate-Specific Antigen; Receptor, ErbB-2; Urachus; Urinary Bladder Neoplasms; Uterine Cervical Neoplasms; Vimentin

Undifferentiated carcinomas with osteoclast-like giant cells are rare pancreatic and periampulary neoplasms that morphologically mimic giant cell tumor of bone. Despite numerous publications based primarily on single case reports, the terminology, histogenesis, and biologic behavior of these tumors remain controversial.. The authors studied one periampullary and nine pancreatic neoplasms of this type. Immunohistochemistry was performed on nine of the cases and clinical follow-up data was obtained in eight.. The neoplasms were large (average 9 cm), partially or completely multicystic, and hemorrhagic. Histologically, they were composed predominantly of ovoid or spindle-shaped bland mononuclear cells and evenly spaced osteoclast-like giant cells. However, three neoplasms had foci in which the nuclear pleomorphism of the mononuclear cells approached that observed in anaplastic spindle and giant cell carcinomas. Other histologic features included phagocytosis of the mononuclear cells by the osteoclast-like giant cells (in 7 of 10 cases), osteoid or bone formation (in 3 of 10 cases), and chondroid differentiation (in 1 of 10 cases). Four neoplasms had foci of conventional adenocarcinoma and two arose in preexisting mucinous cystic neoplasms of the pancreas. The mononuclear cells were positive for epithelial markers in six of nine tumors tested (cytokeratins AE-1, AE-3, Cam 5.2, and/or epithelial membrane antigen). They were negative for the histiocytic markers (CD-68, lysozyme) in all nine cases tested. In contrast, the osteoclast-like giant cells were positive for CD-68 in all nine cases, positive for lysozyme in four cases, and negative for cytokeratins (AE-1, AE-3, and Cam 5.2) in all nine cases. p53 stained the mononuclear tumor cells in three cases and MIB-1 stained the mononuclear tumor cells in four cases, but the osteoclast-like giant cells did not stain with either antibody in all nine cases tested. Most of the patients died of disease within 1 year of diagnosis; only 1 patient was alive and disease free 14 years after surgical excision.. The association of these tumors with conventional adenocarcinoma or mucinous cystic neoplasms, the histologic features, and the immunohistochemical profile supports an epithelial phenotype for the mononuclear cells and a reactive histiocytic lineage for the nonneoplastic osteoclast-like giant cells. These neoplasms, which are better classified as undifferentiated carcinomas, follow an aggressive clinical course; most patients die of disease within 1 year.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Ampulla of Vater; Antigens, CD; Antigens, Differentiation, Myelomonocytic; Biomarkers, Tumor; Carcinoma; Common Bile Duct Neoplasms; Female; Giant Cells; Humans; Immunohistochemistry; Keratins; Macrophages; Male; Middle Aged; Osteoclasts; Pancreatic Neoplasms; Tumor Suppressor Protein p53

We have seen in consultation a variant of atrophy, which is frequently confused with well-differentiated adenocarcinoma of the prostate. We have designated this entity as partial atrophy to distinguish it from its more common counterpart of fully developed atrophy. Partial atrophy is defined as benign prostate glands with relatively scant cytoplasm, yet the glands are not fully atrophic in that they do not appear basophilic at low magnification. Fifty-one cases of partial atrophy were identified (4 from Johns Hopkins Hospital, 47 from consultation). Within the partial atrophy focus, irregular (crinkled) nuclei were frequent in 23.5% and occasionally present in 33.3% of cases. Visible nucleoli were frequent in 25.4% of cases. Basal cells were not identifiable in 27.4% of cases or were hard to identify in 35.3% of cases. No intraluminal crystalloids or blue-tinged mucinous secretion was identified in partial atrophy. Adenocarcinoma or glands suspicious for cancer were present in other cores in 15.6% of cases. More fully developed atrophy was present in simultaneously obtained needle cores in 35.3% of cases. In the cases in which regular atrophy was the only coexisting condition, it was present within one 10x field from the partial atrophy in 22.2%, farther than one 10x field from the partial atrophy in 11.1%, and present in the same gland as the partial atrophy in 66.7%. Partial atrophy may be confused with low-grade adenocarcinoma because of the focus of crowded glands, irregular nuclei, and visible nucleoli. Clues for recognizing partial atrophy include relatively scant cytoplasm, distinct crinkled nuclei, pale cytoplasm similar to adjacent, more recognizably benign glands, and association with more fully developed benign atrophy.

Topics: Adenocarcinoma; Aged; Aged, 80 and over; Atrophy; Biopsy, Needle; Diagnosis, Differential; Humans; Immunohistochemistry; Keratins; Male; Middle Aged; Pathology, Surgical; Prostate; Prostatic Neoplasms

Villin (V) is a glycoprotein of microvilli associated with rootlet formation. Most colonic adenocarcinomas have a V positive (+), cytokeratin (CK) 20 (+), CK7-negative (-) immunophenotype; most lung adenocarcinomas have a CK20(-), CK7(+) immunophenotype. The reports of villin immunoreactivity in lung adenocarcinoma range from 6% to 68% in studies using various fixations and varied anti-villin antibodies. Some lung adenocarcinomas have microvilli with rootlets leading to possible diagnostic confusion with metastatic colonic adenocarcinoma to lung. Nine primary lung adenocarcinomas with rootlets on ultrastructure (including four bronchioloalveolar carcinomas [BAC]), four metastatic lung adenocarcinomas with rootlets, nine metastatic colon adenocarcinomas to lung, and 10 randomly selected lung adenocarcinomas without rootlets (including five BAC), were immunostained with monoclonal antibodies to villin (1D2C3), CK7 (OV-TL12/30), and CK20 (Ks20.8) using a streptavidin peroxidase technique with heat-induced epitope retrieval. All primary lung adenocarcinomas with rootlets were CK7(+) CK20(-), and six of nine (67%) were V(+). Cytoplasmic villin positivity occurred in a diffuse--five of nine (56%), focal--two of nine (22%), or brush border pattern--two of nine (22%). Two of four metastatic lung adenocarcinomas with rootlets were V(+). One metastatic lung adenocarcinoma had a CK7(+), CK20(+), V(-) phenotype. All metastatic colonic adenocarcinomas were V(+), CK20(+), CK7(-), and 1 of 10 (10%) lung adenocarcinomas without rootlets was V(+), and all 10 were CK20(-), and CK7(+). In summary, villin positivity is more common in lung adenocarcinoma with rootlets (67%) than those without rootlets (10%). AU primary lung adenocarcinomas were CK7(+), CK20(-). The combination of villin, CK 7, and CK 20 is helpful in differentiating metastatic colon adenocarcinoma from lung adenocarcinoma with rootlets.

Topics: Adenocarcinoma; Biomarkers, Tumor; Calcium-Binding Proteins; Carrier Proteins; Colonic Neoplasms; Humans; Immunohistochemistry; Intermediate Filament Proteins; Keratin-20; Keratin-7; Keratins; Lung Neoplasms; Microfilament Proteins; Microscopy, Electron; Microvilli

Lipocortin 1 (annexin I) is a calcium- and phospholipid-binding annexin protein which can be externalised from cells despite the lack of a signal sequence. To determine its cellular distribution lipocortin 1 in A549 human lung adenocarcinoma cells was localised by light- and electron-microscopic immunocytochemistry and by cell fractionation and western blotting. Lipocortin 1 immunoreactivity is concentrated in prominent patches associated with the plasma membrane. The intensity of these patches varied with the confluence and duration of the culture and was not detectably diminished by an EDTA wash before fixation. Tubulin and cytokeratin 8 were colocalized with lipocortin 1 in the patches. Within the cells lipocortin 1 was distributed throughout the cytoplasm. Electron microscopy revealed prominent immunoreactivity along the plasma membrane with occasional large clusters of gold particles in contact with the membrane surface of the cells; within the cytoplasm the membrane of some vesicle/vacuole structures and some small electron-dense bodies was immunoreactive, but no immunogold particles were associated with the multilamellar bodies. Subcellular fractionation, extraction and western blotting showed that lipocortin 1 in the membrane pellet was present as two distinct fractions; one, intimately associated with the lipid bilayer, which behaved like an integral membrane protein and one loosely attached which behaved like a peripheral membrane protein. The results show that a substantial amounts of lipocortin 1 is concentrated in focal structures associated with and immediately beneath the plasma membrane. These might form part of the mechanism by which lipocortin 1 is released from the cells.

Topics: Adenocarcinoma; Annexin A1; Biological Transport; Blotting, Western; Cell Compartmentation; Cell Membrane; Cytochalasin D; Cytoplasm; Cytoskeleton; Fluorescent Antibody Technique; Humans; Keratins; Lung Neoplasms; Membrane Proteins; Microscopy, Immunoelectron; Microtubules; Nucleic Acid Synthesis Inhibitors; Tubulin; Tumor Cells, Cultured

The aim of this study was to investigate certain genes for their suitability as molecular markers for detection of breast carcinoma cells using the reverse transcriptase-polymerase chain reaction (RT-PCR). RNA was prepared from MCF-7 breast carcinoma cells and peripheral blood leucocytes of healthy female volunteers. This RNA was screened for mRNA of MUC1, cytokeratin 19 (CK19) and CD44 (exons 8-11) by RT-PCR and the results validated by Southern blots. Variable degrees of expression of MUC1 and CD44 (exons 8-11) were detected in normal peripheral blood, rendering these genes non-specific for epithelial cells and therefore unsuitable for use as markers to detect breast carcinoma cells. Although CK19 mRNA was apparently specific, it was deemed unsuitable for use as a marker of breast cancer cells in light of its limited sensitivity. Furthermore, an attempt at using nested primers to increase sensitivity resulted in CK19 mRNA being detected after two amplification rounds in blood from healthy volunteers.

Topics: Adenocarcinoma; Adolescent; Adult; Biomarkers, Tumor; Blotting, Southern; Breast Neoplasms; DNA Primers; Female; Humans; Hyaluronan Receptors; Keratins; Middle Aged; Mucin-1; Polymerase Chain Reaction; RNA, Messenger; RNA, Neoplasm; Sensitivity and Specificity; Tumor Cells, Cultured

Expression of KAI1, a tumor metastasis suppressor gene, was studied with different fixatives in frozen and paraffin-embedded sections of human and rat prostate carcinoma cell lines and human prostate lesions by immunohistochemistry. Immunoreactivity of the membrane antigen in cell lines was associated with known expression levels in these lines and the fixative used. Formalin and paraformaldehyde helped maintain the immunoreactivity of cells. In human prostate, frozen sections revealed diffuse reactivity of the antigen in normal and neoplastic tissues while paraffin-embedded tissues usually showed focal reactivity, although more than 50% of cases with normal epithelium and adenocarcinomas were reactive. In some cases, pretreatment with trypsin enhanced immunoreactivity. Benign prostatic hyperplasia (BPH) showed the most intense diffuse immunoreactivity, which suggested enhanced expression. Prostatic intraepithelial neoplasia (PIN) also often expressed high levels of KAI1. Three of five metastases were reactive but two primaries and their metastases were not. Lymphocytes in primary carcinomas and lymphocytes and germinal center cells in lymph nodes were immunoreactive, while adjacent primary or metastatic prostate adenocarcinoma epithelium was not immunoreactive. Although paraffin-embedded human tissues were not optimal for determining levels of expression of KAI1, they did show immunoreactivity that could have prognostic value and showed the specific cytoplasmic localization of the protein in cells.

Topics: Adenocarcinoma; Animals; Antigens, CD; Frozen Sections; Humans; Immunohistochemistry; Kangai-1 Protein; Keratins; Male; Membrane Glycoproteins; Paraffin Embedding; Prostate; Prostatic Hyperplasia; Prostatic Intraepithelial Neoplasia; Prostatic Neoplasms; Proto-Oncogene Proteins; Rats; Tumor Cells, Cultured

To discriminate adenocarcinoma metastases originating from either colon or ovary, a panel of immunohistochemical markers was evaluated. For this purpose, paraffin sections from 157 primary and metastatic colonic and ovarian carcinomas were immunostained. These cases were divided into a learning group of 46 colonic and 54 ovarian carcinomas and a test group of 29 colonic and 28 ovarian carcinomas, including all metastatic tumors, among which were five with unknown primary site at the time of testing. The sections were immunostained with antibodies against carcinoembryonic antigen (CEA), cytokeratin 7 (CK7), cytokeratin 20 (CK20), CA125, vimentin, and CA19.9. Staining results were expressed as the product of staining intensity and percentage of positive tumor cells. Stepwise discriminant analysis was applied on the learning set to obtain a classification function for both tumors. The validity of the classification function was evaluated using the test set. There was considerable overlap in immunostaining for both tumor types, but colonic carcinomas were typically positive for CEA and CK20 and negative for CK7 and CA125. Ovarian carcinomas were typically positive for CK7 and CA125 and negative for CEA and CK20. In discriminant analysis, the best combination of markers appeared to be CK7 and CEA. Only one sample of the test group (2%) was misclassified. Taking learning and test groups together, 136 of the 157 samples (87%) were correctly classified with high posterior probability (PP > .8). However, from the 28 mucinous ovarian carcinomas, only 19 (68%) could correctly be classified with high PP. When excluding the nonmucinous ovarian carcinomas from the analysis, overall 87 of 103 (84.5%) of the samples were correctly classified (PP > .8) with a combination of CEA, CK7, and also vimentin. From the 28 mucinous ovarian carcinomas, only two (7%) were misclassified, and four could not be classified with sufficient certainty. In neither analysis did CK20, CA125, or CA19.9 emerge as discriminatory parameters. Based on the same data, an intuitive flow chart was constructed with which 129 of 157 cases could be classified (only one falsely) without further statistical analysis. The five metastases with an at first unknown primary could, according to the follow-up, all be classified correctly with high PP. Most ovarian carcinomas, including the mucinous ones, can be discriminated with high probability from colonic carcinomas using a panel of three antibodies directed

Topics: Adenocarcinoma; Biomarkers, Tumor; CA-125 Antigen; CA-19-9 Antigen; Carcinoembryonic Antigen; Cell Count; Colonic Neoplasms; Decision Trees; Diagnosis, Differential; Discriminant Analysis; Female; Humans; Immunoenzyme Techniques; Immunohistochemistry; Intermediate Filament Proteins; Keratin-20; Keratin-7; Keratins; Neoplasms, Unknown Primary; Ovarian Neoplasms; Retrospective Studies; Vimentin

A wide variety of architectural patterns of adenocarcinoma may be seen in the prostate. We have recently encountered a hitherto-undescribed pattern of growth characterized by intraluminal ball-like clusters of cancer cells reminiscent of renal glomeruli, which we refer to as prostatic adenocarcinoma with glomeruloid features. To define the architectural features, frequency, and distribution of prostatic adenocarcinoma with glomeruloid features, we reviewed 202 totally embedded radical prostatectomy specimens obtained between October 1992 and April 1994 from the files of the Mayo Clinic. This series was supplemented by 100 consecutive needle biopsies with prostatic cancer from January to February 1996. Prostatic adenocarcinoma with glomeruloid features was characterized by round to oval epithelial tufts growing within malignant acini, often supported by a fibrovascular core. The epithelial cells were sometimes arranged in semicircular concentric rows separated by clefted spaces. In the radical prostatectomy specimens, nine cases (4.5%) had glomeruloid features. The glomeruloid pattern constituted 5% to 20% of each cancer (mean, 8.33%) and was usually located at the apex or in the peripheral zone of the prostate. Seven cases were associated with a high Gleason score (7 or 8), one with a score of 6, and one with a score of 5. All cases were associated with high-grade prostatic intraepithelial neoplasia and extensive perineural invasion. Pathological stages included T2c (three cases), T3b (four cases), and T3c (two cases); one of the T3b cases had lymph node metastases (N1). Three (3%) of 100 consecutive routine needle biopsy specimens with cancer showed glomeruloid features, and this pattern constituted 5% to 10% of each cancer (mean, 6.7%). The Gleason score was 6 for two cases and 8 for one case. Two cases were associated with high-grade prostatic intraepithelial neoplasia, and one case had perineural invasion. Glomeruloid features were not observed in any benign or premalignant lesions, including hyperplasia and intraepithelial neoplasia. Glomeruloid structures in the prostate represent an uncommon but distinctive pattern of growth that is specific for malignancy. Glomeruloid features may be a useful diagnostic clue for malignancy, particularly in some challenging needle biopsy specimens. This pattern of growth is usually seen in high-grade adenocarcinoma, often with extraprostatic extension. Further investigations are required to determine its independen

Topics: Adenocarcinoma; Aged; Humans; Immunohistochemistry; Keratins; Male; Middle Aged; Mucins; Neoplasm Staging; Prognosis; Prostatic Intraepithelial Neoplasia; Prostatic Neoplasms

Differential diagnosis of adenocarcinoma from other proliferative conditions in the prostate is often problematic. Immunohistochemistry using an antibody (34 beta E12) to high molecular weight cytokeratin, specifically present in basal cells of the prostate, could clearly demonstrate the presence or absence of these cells in the proliferating glands and thus provide an important clue in cancer diagnosis.. To examine the utility of immunostaining using 34 beta E12, we examined 88 equivocal lesions. Twenty lesions with apparently benign and malignant features were added as controls. We compared the morphologic features of these lesions with their immunoreactivities toward 34 beta E12 on a personal computer display following storage on the MICROPHOT-FXA system.. Proliferating glands in all 20 benign lesions had 34 beta E12-reactive basal cells, but none of the malignant lesions did. The equivocal lesions were categorized on morphologic grounds into 2 groups: possibly benign and possibly malignant. Forty-five (51.1%) of the 88 equivocal lesions, were positive for 34 beta E12. These included 35 of the 45 (77.8%) possibly benign lesions and 10 of the 43 (23.3%) possibly malignant lesions. Among the equivocal lesions, 10 considered possibly benign on morphologic grounds showed negative reactivities, and 10 considered possibly malignant showed positive reactivities. Even through comparison on the computer display, no difference in morphology could be discovered between the negative and positive lesions in either group.. Immunohistochemical procedures using 34 beta E12 are indispensable in the diagnosis of equivocal prostate lesions.

Topics: Adenocarcinoma; Aged; Aged, 80 and over; Antibodies, Monoclonal; Diagnosis, Differential; Evaluation Studies as Topic; Humans; Immunohistochemistry; Keratins; Male; Middle Aged; Molecular Weight; Prostatic Neoplasms

To report a case of metastasis to the iris from endometrial carcinoma.. Case report. A 67-year-old woman with a history of endometrial carcinoma and local recurrence after surgery presented 11 months later with two yellow-pink nodules on the iris of the right eye.. Systemic medical evaluation demonstrated no other metastases. The iris tumors were removed surgically, and histology demonstrated adenocarcinoma consistent with endometrial carcinoma.. Endometrial carcinoma can metastasize to the iris. This possibility should be considered because the frequency of endometrial carcinoma is increasing.

Topics: Adenocarcinoma; Aged; Anterior Chamber; Endometrial Neoplasms; Female; Humans; Immunoenzyme Techniques; Iris Neoplasms; Keratins; Ultrasonography

The clinical and pathological features of carcinomas of the pancreas with DNA replication errors (RER+) have not been characterized. Eighty-two xenografted carcinomas of the pancreas were screened for DNA replication errors using polymerase chain reaction amplification of microsatellite markers. Cases with microsatellite instability in at least two markers of a minimum of five tested were considered RER+. RER status was correlated with histological appearance, karyotype of the carcinomas when available, K-ras mutational status, and patient outcome. Three (3.7%) of the eighty-two carcinomas were RER+. In contrast to typical gland-forming adenocarcinomas of the pancreas, all three RER+ carcinomas were poorly differentiated and had expanding borders and a prominent syncytial growth pattern. Neither a Crohn's-like lymphoid infiltrate nor extracellular mucin production were prominent. Ductal adenocarcinomas of the pancreas typically contain a mutant K-ras gene, yet all three RER+ carcinomas had wild-type K-ras. One of the three RER+ carcinomas was karyotyped and showed a near diploid pattern. All three of the RER+ tumors were removed via Whipple resection. One of the three patients is free of disease 16 months after pancreaticoduodenectomy, one is alive and free of tumor at 52 months but developed two colon carcinomas during this period, and the third died of pancreatic cancer at 4 months. None of the three patients had a family history of colorectal carcinoma. A review of the K-ras wild-type carcinomas in a previously characterized series of pancreatic carcinomas with known K-ras mutational status identified two additional cancers with poor differentiation, a syncytial growth pattern, and pushing borders. Both of the cancers were diploid and both patients were longterm survivors (over 5 years). The inclusion of such patients in previous prognostic studies of pancreas cancer may explain the failure of histological grade to be a predictor of prognosis. These data suggest that DNA replication errors occur in a small percentage of resected carcinomas of the pancreas and that wild-type K-ras gene status and a medullary phenotype characterized by poor differentiation, and expanding pattern of invasion, and syncytial growth should suggest the possibility of DNA replication errors in carcinomas of the pancreas.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; DNA Replication; DNA, Neoplasm; Female; Genes, ras; Humans; Immunohistochemistry; Karyotyping; Keratins; Male; Microsatellite Repeats; Middle Aged; Pancreatic Neoplasms

Peripheral pulmonary adenocarcinomas (PPAs) often demonstrate a bronchioloalveolar component, with or without glandular differentiation. PPAs can be nondescript, mucinous, or show features of Type II pneumocytes. Particularly, mucinous lung carcinomas can resemble gastrointestinal metastases. Previous reports suggested that patterns of keratins 7 (K7) and 20 (K20) differ in pulmonary tumors versus enteric metastases. These studies, however, often failed to specify the precise morphotypes of PPA. Thus, we undertook this evaluation of PPAs with different histologic images. Thirty-nine cases were retrieved from institutional files; all were confirmed as primary tumors by clinicopathologic and radiographic review. Cases were classified as Type I (mucinous) bronchioloalveolar carcinoma (BAC1); Type II (nonmucinous) bronchioloalveolar carcinoma (BAC2); conventional PPA with BAC1-like areas (PPA1); or conventional PPA with BAC2-like foci (PPA2). Immunostains were performed for K7, K20, carcinoembryonic antigen, CA19-9, tumor-associated glycoprotein-72, surfactant apoprotein-A, and the c-erbB-2 peptide. BAC1 and PPA1 failed to express surfactant apoprotein-A, and BAC2 also consistently lacked K20, whereas 28% of PPA2 lesions were labeled for K20. All of the other determinants, however, were seen in variable proportions in each subgroup of PPA. Primary BAC1 and PPA1 resembled enteric adenocarcinomas immunophenotypically; on the other hand, BAC2 demonstrated a pattern of protein expression similar to that of Type II pneumocytes. PPA2s are a diverse group of neoplasms, and a subset of PPA2 does show K20 reactivity, as would be expected in metastatic enteric carcinomas. Thus, immunohistochemical data on PPAs must be interpreted carefully and only in clinicopathologic context. With respect specifically to primary pulmonary mucinous tumors, there still seems to be no uniformly reliably marker that will always allow the exclusion of metastatic enteric tumors.

Topics: Adenocarcinoma; Antigens, Neoplasm; Biomarkers, Tumor; CA-19-9 Antigen; Carcinoembryonic Antigen; Diagnosis, Differential; Glycoproteins; Humans; Immunoenzyme Techniques; Keratins; Lung Neoplasms

The diagnosis of polymorphous low-grade adenocarcinoma (PLGA) of salivary glands remains difficult for general surgical pathologists. In an effort to understand the morphological heterogeneity of these neoplasms and facilitate their recognition we reviewed the architectural patterns, cell differentiation and immunohistochemical features of 17 case of PLGA.. There were 11 females and six males with a mean age of 58 years. Twelve tumours were located in the palate, two in the posterior third of the tongue, and one each in the upper lip, buccal mucosa and retromolar triangle. Two patients presented with neck metastases. The mean tumour size was 20 mm (range 6-50 mm). The tumour cells were arranged in five architectural patterns: tubules and small duct-like structures; cords and trabeculae; solid nests; cribriform areas and papillae. Twelve (71%) cases were composed of a combination of tubules and small duct-like structures, cords and trabeculae, and solid nests. Cribriform areas with pseudoluminal spaces were seen in six (35%) cases. A focal papillary pattern was evident in three cases and constituted 40% of the tumour in one. Perineural invasion was seen in 13 cases (76%). All cases studied were positive for CAM5.2, 34BE12, vimentin and S100 protein and showed overexpression of bcl-2 protein. Rb protein was present in 13 cases whereas p53 expression was absent in all cases. The average proliferation index (PI) was 7% (range 1-17%). Three patients developed local recurrences with cervical lymph node metastases but no patient died as result of tumour. No morphological features were found to be prognostic for the development of local recurrences or lymph nodes metastases.. PLGA is a distinctive neoplasm of salivary glands formed by luminal and nonluminal tumour cells with limited patterns of architectural differentiation. The relative proportion of these cells seems to play a significant role in the morphogenesis of these tumours. The overexpression of the bcl-2 protein and the low PI suggest that inhibition of programmed cell death may be involved in the oncogenesis of PLGA.

Topics: Adenocarcinoma; Adult; Aged; Biomarkers, Tumor; Cell Differentiation; Cyclin D1; Female; Humans; Immunohistochemistry; Keratins; Male; Middle Aged; Proto-Oncogene Proteins c-bcl-2; Retinoblastoma Protein; S100 Proteins; Salivary Gland Neoplasms; Salivary Glands, Minor

An extremely rare case of epithelial-myoepithelial carcinoma (EMC) of a lobar bronchus in a 47-year-old female is reported. Grossly, the tumor formed a polypoid mass obstructing the bronchial lumen. Microscopically, it was composed of two cellular types--epithelial cells with eosinophilic cytoplasm and clear myoepithelial cells. Numerous tubules formed by an inner epithelial and outer myoepithelial layer were found. Focally, the tumor showed solid growth of clear cells. Prominent hyalinization of the stroma was found. The nature of the cells was confirmed by positive expression of cytokeratins and epithelial membrane antigen in epithelial cells and vimentin and smooth muscle actin in myoepithelial cells. Differential diagnosis of EMC includes a broad spectrum of salivary gland-type tumors. Furthermore, metastases of clear cell carcinoma of the kidney or thyroid, clear cell ("sugar") tumor of the lung, glandular form of carcinoid, bronchioalveolar adenocarcinoma with myoepithelial cells and pulmonary adenosquamous carcinoma with amyloid-like stroma must be distinguished from EMC. The tumor has neither recurred nor metastasised, a fact supporting the current opinion, that EMC is a tumor of low grade malignancy.

Topics: Actins; Adenocarcinoma; Bronchial Neoplasms; Carcinoma; Diagnosis, Differential; Female; Humans; Immunoenzyme Techniques; Keratins; Kidney Neoplasms; Lung Neoplasms; Middle Aged; Salivary Gland Neoplasms; Thyroid Neoplasms

The aim of the present study was to evaluate the clinical usefulness of the cytokeratin tumor marker M3/M21 as a screening marker for ovarian cancer, as a predictive marker in patients with adnexal masses and as a prognostic factor in women with ovarian cancer. To determine the specificity of the M3/M21 test, we investigated M3/M21 serum levels in several benign conditions. This retrospective study comprises 37 patients with ovarian cancer FIGO stages Ia to III. Sera of patients with benign cysts, endometriosis, pelvic inflammatory disease, inflammatory bowel disease and liver cirrhosis were evaluated in 90, 10, 38, 10 and 20 cases, respectively. With a sensitivity of 57% and a specificity of 95%, M3/M21 is not suitable as a screening marker for ovarian cancer. Although M3/M21 is able to discriminate between ovarian cancer and benign adnexal tumors (univariate logistic regression, p = 0.0003), M3/M21 does not provide information additional to CA 125. M3/M21 serum levels are elevated in several benign conditions such as liver cirrhosis and inflammatory bowel disease. In ovarian cancer patients, elevated M3/M21 serum levels prior to therapy were associated with poor overall and disease-free survival (log-rank test, p = 0.03; log-rank test, p = 0.01, respectively). M3/M21, while obviously not suitable for screening or differential diagnosis of adnexal masses, could be useful as an additional prognostic factor in ovarian cancer patients.

Topics: Adenocarcinoma; Adult; Aged; Biomarkers, Tumor; Carcinoma; Endometriosis; Epitopes; Evaluation Studies as Topic; Female; Humans; Keratins; Middle Aged; Ovarian Diseases; Ovarian Neoplasms; Pelvic Inflammatory Disease; Retrospective Studies

Undifferentiated carcinomas and osteoclast-like giant cell tumours of the pancreas commonly contain foci of neoplastic ductal glands. To test the hypothesis that undifferentiated carcinomas and osteoclast-like giant cell tumours have a ductal origin, the immunocytochemical cytokeratin pattern and the frequency and type of Ki-ras mutations at colon 12 were studied in a series of 17 undifferentiated carcinomas and two osteoclast-like giant cell tumours. The cytokeratin features of undifferentiated carcinomas and osteoclast-like giant cell tumours were compared with those found in 10 ductal adenocarcinomas, 20 acinar cell carcinomas, 25 neuroendocrine tumours, and 15 solid-pseudopapillary tumours. All undifferentiated carcinomas and osteoclast-like giant cell tumours stained with at least one cytokeratin antibody, and 13/19 of them with antibodies against cytokeratins 7, 8, 18, and 19. The latter cytokeratins were expressed in all ductal adenocarcinomas, but only in 15/20 acinar cell carcinomas, 2/25 neuroendocrine tumours, and 1/15 solid-pseudopapillary tumours. In addition to cytokeratin, 15/19 undifferentiated carcinomas/osteoclast-like giant cell tumours were positive for vimentin. Ki-ras mutations at codon 12 were found in 10 undifferentiated carcinomas and one osteoclast-like giant cell tumour from which DNA could be successfully amplified. The Ki-ras mutation patterns were analysed in six tumours and corresponded to those typical of ductal adenocarcinomas. In tumours with ductal and anaplastic components, both components revealed identical mutation patterns. From these findings, it is concluded that both undifferentiated carcinomas and osteoclast-like giant cell tumours belong to the pancreatic tumours that show a ductal phenotype. Since undifferentiated carcinomas and osteoclast-like giant cell tumours share the same cytokeratin and Ki-ras features, they are probably derived from the same cell lineage.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Carcinoma; Female; Genes, ras; Giant Cell Tumors; Humans; Immunoenzyme Techniques; Intermediate Filaments; Keratins; Male; Middle Aged; Mutation; Neoplasm Proteins; Pancreatic Neoplasms; Polymorphism, Restriction Fragment Length

Topics: Adenocarcinoma; Biomarkers, Tumor; Biopsy; Diagnosis, Differential; Humans; Immunoenzyme Techniques; Keratins; Male; Prostate; Prostatic Neoplasms

After initial regression in response to androgen deprivation, most prostate cancers develop resistance to endocrine therapy. Identification of cellular and molecular changes occurring during endocrine therapy-induced regression and subsequent hormone insensitivity may point to mechanisms underlying the transition to hormone-independent prostate cancer. A series of untreated (n = 24), regressed (n = 15), and endocrine therapy-resistant (n = 10) prostatic adenocarcinomas were analyzed using immunohistochemistry with regard to cytokeratin 5 and 18, androgen receptor (AR), and epidermal growth factor receptor (EGF-R) expression in tumor cells. Using semiquantitative reverse transcription-polymerase chain reaction, the amount of AR mRNA also was determined. In regressed and therapy-resistant prostate cancers, an increase in cytokeratin 5-positive tumor cells was noted when compared with untreated carcinomas. Similarly, the proportion of EGF-R-positive tumor cells increased in the treated cases, whereas the proportion of AR-positive tumor cells dropped in regressed carcinomas and increased in hormone-refractory cancers. In the latter group, an eightfold higher level of AR mRNA was observed when compared with the other cases. Changes in the proportion of cytokeratin 5 and EGF-R-positive tumor cells suggests that during androgen deprivation an enlarged subpopulation of tumor cells with combined features of basal and secretory phenotypes arises. The increased proportion of AR-positive tumor cells during the transition from the regression phase to the hormone escape phase points to an important role of AR overexpression in this process.

Topics: Adenocarcinoma; ErbB Receptors; Humans; Immunoenzyme Techniques; Keratins; Male; Phenotype; Polymerase Chain Reaction; Prostatic Neoplasms; Receptors, Androgen; RNA, Messenger

The immunohistochemical diagnosis of mesothelioma is commonly made by using a battery of antibodies that reacts with lung adenocarcinomas but not with epithelial mesotheliomas. Only recently have markers that are often expressed in mesotheliomas but not in adenocarcinomas been recognized. Some of these markers, however, require frozen tissue sections, whereas others are not commercially available, or their value remains controversial. In a recent publication, it was suggested that immunostaining for cytokeratin 5/6 could assist in distinguishing epithelial mesothelioma from lung adenocarcinoma. To determine the practical value of cytokeratin 5/6 immunostaining in the diagnosis of mesothelioma, 40 formalin-fixed, paraffin-embedded epithelial pleural mesotheliomas, 30 pulmonary adenocarcinomas, 93 nonpulmonary adenocarcinomas, 15 squamous carcinomas of the lung, 5 large cell undifferentiated carcinomas of the lung, and 12 metastatic transitional cell carcinomas to the lung were stained with the same antibody, which was obtained from a commercial source. Cytokeratin 5/6 reactivity was observed in all 40 mesotheliomas, but there was none in any of the 30 pulmonary adenocarcinomas. Focal or weak reactivity was observed in 14 of 93 nonpulmonary adenocarcinomas (10 of 30 ovarian, 2 of 10 endometrial, 1 of 18 breast, I of 7 thyroid, 0 of 10 kidney, 0 of 10 colonic, and 0 of 8 prostatic). All 15 squamous carcinomas of the lung, 6 of 12 transitional cell carcinomas metastatic to the lung, and 3 of 5 large cell undifferentiated carcinomas of the lung expressed cytokeratin 5/6. It is concluded that cytokeratin 5/6 immunostaining is not only useful in separating epithelial pleural mesotheliomas from pulmonary adenocarcinomas but also can assist in distinguishing epithelial mesotheliomas from nonpulmonary adenocarcinomas metastatic to the pleura.

Topics: Adenocarcinoma; Biomarkers, Tumor; Carcinoma, Non-Small-Cell Lung; Carcinoma, Squamous Cell; Carcinoma, Transitional Cell; Diagnosis, Differential; Epithelial Cells; Evaluation Studies as Topic; Female; Humans; Immunoenzyme Techniques; Keratins; Lung Neoplasms; Male; Mesothelioma; Pleural Neoplasms; Retrospective Studies

Topics: Adenocarcinoma; Antibodies, Monoclonal; Biopsy, Needle; Diagnosis, Differential; Humans; Keratins; Male; Precancerous Conditions; Prostate; Prostatic Hyperplasia; Prostatic Neoplasms

The immunohistochemical localization and expression of 1,25-dihydroxyvitamin D3 receptors (VDR) has been investigated in normal human cervical tissue (n = 15) and in cervical carcinomas (n = 23). VDR immunoreactivity (monoclonal antibody 9A7gamma) was compared with the staining patterns of transglutaminase K, cytokeratin 10 and Ki-67 in these tumours. Moderate to strong nuclear immunoreactivity for VDR was detected in almost all cervical carcinomas analysed. VDR staining was homogeneous, with no visual differences between individual tumour cells. Some 60% of normal cervical tissues revealed weak immunoreactivity for VDR. In normal cervical tissue, nuclear VDR staining was confined to the lower cervical layers, predominantly to the basal cell layer. Both the intensity of VDR immunostaining and the number of VDR-positive cells were up-regulated in cervical carcinomas compared with normal cervical tissue. No visual correlation was found for the coexpression of VDR with markers of proliferation and differentiation. Our findings indicate that: (1) cervical tissue may be a new target organ for therapeutically applied vitamin D analogues; (2) VDR is up-regulated at the protein level in cervical carcinomas compared with normal cervical tissue; (3) up-regulation of VDR in cervical carcinoma is induced not exclusively by alterations in epithelial differentiation or proliferation, but by different, unknown mechanisms; and (4) calcitriol and new vitamin D analogues exerting fewer calcaemic side-effects may be promising new drugs for the treatment or chemoprevention of metastasizing cervical carcinomas as well as of cervical precancerous lesions.

Topics: Adenocarcinoma; Carcinoma, Squamous Cell; Cell Nucleus; Cervix Uteri; Female; Humans; Immunohistochemistry; Keratins; Ki-67 Antigen; Receptors, Calcitriol; Transglutaminases; Uterine Cervical Neoplasms

Two human cancer cell lines were established from metastatic lesions of an adenocarcinoma (RAL) and a squamous cell (CAEP) carcinoma of the lung. The clinical histories of the patients from whom the cell lines were derived are reported. The lines were maintained in continuous culture with doubling times of 65 (RAL) and 50 (CAEP) hours. The RAL and CAEP cell lines, whose morphology and ultrastructural features are presented, showed extensively rearranged karyotypes with modal number of 85 (RAL) and 98 (CAEP). In particular, chromosome 2 pentasomy and several clonal markers were evident in the RAL cells, whereas a telomeric deletion of chromosome 1, del (1)(q32), was observed in the CAEP cells. The morphologic data were confirmed by high expression of specific antigens for each histotype. A marked positivity of the neuron-specific enolase (NSE) levels was evident by immunoenzymatic assays in the cell lines cytosol with respect to those present in the respective patient's sera. No amplification or rearrangements were evident in the CMYC, LMYC, NMYC, INT-2, ERBB2, HRAS, KRAS, MOS, HST-1 genes by Southern blotting analysis in each cell line. Point mutations in exon 1 of KRAS and in exon 7 of TP53 were evident by polymerase chain reaction (PCR)-DNA sequencing in the RAL cell line, whereas no alterations were present in the HRAS and RB genes. The four genes studied did not show point mutations in the CAEP cell line. The RAL cell line was resistant to all the drugs tested, whereas the CAEP cells were sensitive to vinblastine. These cell lines may represent useful experimental models to investigate lung cancer biology and anticancer drug response.

Topics: Adenocarcinoma; Aged; Biomarkers, Tumor; Carcinoembryonic Antigen; Carcinoma, Squamous Cell; Female; Genetic Markers; Humans; Karyotyping; Keratins; Lung Neoplasms; Male; Middle Aged; Phosphopyruvate Hydratase; Tumor Cells, Cultured

The identification of basal cells by the basal-cell-specific anti-cytokeratin antibody 34 beta E12 has been shown to be useful in the diagnosis of prostate carcinoma. To determine the usefulness of 34 beta E12 in prostate biopsies we examined formalin-fixed needle biopsy specimens. In a 17-month period 796 prostate needle biopsies obtained from 293 patients were evaluated on hematoxylin and eosin stains; all 796 biopsy specimens were immunostained as well. Immunostaining with 34 beta E12 reduced the rate of equivocal cases from 5.1% to 1.0% and additionally offered a means of quality assurance by confirming the diagnoses of 61 prostate carcinomas made on the basis of biopsy specimens.

Topics: Adenocarcinoma; Adult; Aged; Antibodies, Monoclonal; Antibody Specificity; Basement Membrane; Diagnosis, Differential; Humans; Immunoenzyme Techniques; Keratins; Male; Middle Aged; Precancerous Conditions; Prostate; Prostatic Hyperplasia; Prostatic Intraepithelial Neoplasia; Prostatic Neoplasms; Sensitivity and Specificity

Cytokeratins are epithelial markers whose expression is not lost during malignant transformation. The level of soluble cytokeratin fragment 19 was measured with an enzyme immunoassay method developed by Boehringer Mannheim (Enzymum-test CYFRA 21-1) in the serum of 200 male and 50 female patients with NSCLC (Non Small Cell Lung Cancer) lung cancer (120 planocellulare and 80 adenocarcinoma in males; 22 planocellulare and 28 adenocarcinoma in females). The comparative group comprised 50 young healthy males and 50 females without any clinical proof for malignancy or any other lung disease. The aim of this investigation was to find out if any possible statistical difference exists in the serum level of CYFRA 21-1 between patients with lung cancer and healthy controls, and also between different types of lung cancers. The mean value of serum CYFRA 21-1 in NSCLC (6.25 ng/ml) was significantly higher than in healthy controls (1.26 ng/ml) (p < 0.001). Sensitivity for CYFRA 21-1 (using 3.3 ng/ml, a cut-off value corresponding to a 98% specificity for healthy controls) in NSCLC was 60.5%. Positive CYFRA 21-1 levels were significantly higher in patient with carcinoma planocellulare (66.2%) than in adenocarcinoma (52.1%). CYFRA 21-1 levels were significantly different between squamous cell carcinoma (6.52 ng/ml) and adenocarcinoma (5.86 ng/ml) (p < 0.05). Our results indicate that CYFRA 21-1 may be a useful tumor marker in NSCLC, especially in carcinoma planocellulare. CYFRA 21-1 may also be useful in identification of the preoperative stages of diseases and the postoperative monitoring of NSCLC.

Topics: Adenocarcinoma; Antigens, Neoplasm; Biomarkers, Tumor; Carcinoma, Non-Small-Cell Lung; Carcinoma, Squamous Cell; Female; Humans; Immunoenzyme Techniques; Keratin-19; Keratins; Lung Neoplasms; Male; Sensitivity and Specificity

To study the differentiation of epithelial tissues within their histological context, and to identify hypothetically, on the basis of keratin pattern, the putative tissue origin of a (metastatic) carcinoma.. Using well characterised monoclonal antibodies against individual keratins 7, 8, 18, and 19, which are predominantly found in columnar epithelia, and keratins 4, 10, 13, and 14, predominantly expressed in (non)-keratinising squamous epithelia, the keratin patterns for a series of 45 squamous cell carcinomas and 44 adenocarcinomas originating from various epithelial tissues were characterised.. The predominant keratins in all adenocarcinomas proved to be 8, 18, and 19. In addition, these keratins were also abundantly present in squamous cell carcinomas of the lung, cervix, and rectum and, to a lesser extent, of the larynx, oesophagus, and tongue, but not in those of the vulva and skin. Keratins 4, 10, 13, and 14 were present in almost all squamous cell carcinomas, but also focally in some of the adenocarcinomas studied.. There is a limited differential expression of distinctive keratin filaments between squamous cell carcinomas and adenocarcinomas. Apparently, squamous cell carcinomas that originate from columnar epithelium by squamous metaplasia gain the keratins of squamous cells but retain the keratins of columnar epithelial cells. However, the simultaneous expression of two of three squamous keratins (4, 10, and 13) identifies a squamous cell carcinoma, and thus might be useful in solving differential diagnostic problems.

Topics: Adenocarcinoma; Antibodies, Monoclonal; Biomarkers, Tumor; Carcinoma, Squamous Cell; Cell Differentiation; Diagnosis, Differential; Humans; Immunoenzyme Techniques; Keratins; Neoplasm Proteins

Prostatic epithelium basically consists of secretory-luminal, basal and endocrine-paracrine cells. Immunohistochemical procedures are frequently used for showing the cells reflecting different differentiations. In this study, 40 prostatic tissue specimens submitted to the Department of Pathology of Inönü University, Research Hospital, between 1991 and 1996 were examined. Half of the cases were diagnosed as cancer and the other half had various benign lesions. Of the cases 22.5% (n = 9) were needle biopsy material whereas the remainder, 47.5% (n = 19), were from prostatectomy and 30% (n = 12) were transurethral resection of the prostate (TURP) specimens. High molecular weight anti-cytokeratin antibodies (HMW anti-cytokeratin) stained basal cells both in all normal prostatic tissue and benign prostatic lesions, but in the majority of cancers (70%, n = 14) negative immunoreactivity was seen. Nevertheless, in some of the cancer cases (30%, n = 6) basal cell anti-cytokeratin staining was shown. Negative immunoreactivity with HMW anti-cytokeratin is important in distinguishing between malignant and benign lesions, whereas positive staining is not every time in favour of benign lesions. With the usage of prostate specific antigen (PSA) it was seen that all of the malignant and benign prostatic lesions stained positively. Basal cells in hyperplastic glands were not stained with this stain. Irregular, and in some areas, intense (PSA) immunoreactivity is present in precancerous and malignant lesions. Endocrine cells, which are represented with Chromogranin-A (Chr-A) immunoreactivity and reflecting neuroendocrine differentiation, are present in 75% (n = 15) of benign lesions and in 50% (n = 10) of cancer cases. It was thought that the lesser number of these cells in neoplastic lesions in comparison to the non-tumoral lesions is correlated with the disorder of mechanism that regulates the cell growth. Both in neoplastic and non-tumoral tissues the prostatic epithelial cells showed the three markers, namely HMW anti-cytokeratin, PSA, and Chr-A, which may reflect the multidirectional differentiation of these cells from a pluripotent origin.

Topics: Adenocarcinoma; Biomarkers, Tumor; Biopsy, Needle; Cell Division; Chromogranin A; Chromogranins; Diagnosis, Differential; Epitopes; Humans; Keratins; Male; Prostate-Specific Antigen; Prostatectomy; Prostatic Diseases; Prostatic Hyperplasia; Prostatic Neoplasms

To set the serum cut-off value of CYFRA21-1 in lung cancer patients in china, and to evaluate the clinical usefulness of CYFRA21-1 as a new tumor marker of lung cancer.. CYFRA21-1 levels were measured with two monoclonal antibodies (Ks19.1 and BM19.21) in the serum of 72 patients with lung cancer, 50 patients with benign lung diseases and 33 post-therapy lung cancer patients. To set the cut-off value, ROC curve was use.. (1) Serum concentrations of CYFRA21-1 in patients with lung cancer were significantly higher than those with benign lung diseases (P < 0.001). CYFRA21-1 levels in patients with squamous cell carcinoma were significantly higher than those in patients with any other subtypes. The more advanced the clinical stages, the higher the levels of CYFRA21-1. (2) If the threshold of CYFRA21-1 was set at 5.5 micrograms/L, its sensitivity and specificity for lung cancer were 63% and 94%, respectively. The sensitivity for squamous cell carcinoma was 78%, which was the highest among all the pathological subtypes. (3) The sensitivity of CYFRA21-1 in non-small cell lung cancer increased with the advancement of clinical stages. (4) CYFRA21-1 could be a good index in monitoring patient's condition and predicting prognosis for lung cancer. (5) When CYFRA21-1 was used as a screening index for lung cancer, the threshold of CYFRA21-1 should be set at the upper left corner of the receiver operating characteristic curve of stage I-II. The value of CYFRA21-1 in early diagnosis for non-small cell lung cancer was found limited.. CYFRA21-1 is a sensitive and specific tumor marker of non-small cell lung cancer, especially of squamous cell carcinoma.

Topics: Adenocarcinoma; Adult; Aged; Antigens, Neoplasm; Biomarkers, Tumor; Carcinoma, Non-Small-Cell Lung; Carcinoma, Small Cell; Carcinoma, Squamous Cell; Female; Humans; Keratin-19; Keratins; Lung Neoplasms; Male; Middle Aged; Neoplasm Staging

The aim of the present study was to investigate whether trivariate FCM analysis, for the simultaneous detection of two different CK subtypes in combination with DNA content, can be applied to paraffin embedded samples of different types of non-small cell lung cancer in order to evaluate the cell cycle of individual sublines. Single cell suspensions were prepared from 50 microm thick paraffin sections of 22 lung carcinomas by pepsin digestion and immunostained with CK-antibodies which were chosen to distinguish glandular differentiation (adenocarcinomas) and squamous differentiation. There was a good correlation between the immunocytochemical results of the different CK antibodies in tissue sections and in the corresponding single cell suspensions. Gating for CK-positivity revealed a higher S-phase fraction as compared to the ungated cell population. The tumor cells in adenocarcinoma cases were specifically recognized by CK7 antibodies, while well-differentiated squamous cell carcinomas were specifically stained for CK14 and/or CK17. In poorly differentiated squamous cell carcinomas simultaneous expression of CK7 and CK17 was detected in a subpopulation of the tumor cells, next to cells positive for CK7 or CK17 alone. The trivariate FCM analysis allowed the separate estimation of ploidy status and cell cycle parameters in the three different cell populations of these, apparently (phenotypically) heterogeneous, malignancies.

Topics: Adenocarcinoma; Antibodies; Carcinoma, Squamous Cell; Cell Cycle; DNA, Neoplasm; Flow Cytometry; Frozen Sections; Humans; Immunoenzyme Techniques; Keratins; Lung Neoplasms; Paraffin Embedding

Anticytokeratin antibody 34 beta E12 is advocated as an immunohistochemical stain for discriminating benign and malignant lesions of the prostate. Positive staining with 34 beta E12 is said to identify benign lesions, whereas negative staining is said to help substantiate a diagnosis of carcinoma. It is further claimed that 34 beta E12 does not stain prostate carcinoma. The studies leading to these conclusions used hematoxylin-eosin-stained sections of primary prostate lesions as controls. Although the cytokeratin content of a few cell lines of metastatic prostate carcinoma has been investigated, the 34 beta E12 immunohistochemical staining of metastatic prostate carcinoma has not been evaluated. If 34 beta E12 positivity is present only in benign prostate cells, then metastatic prostate carcinoma cells should be uniformly negative with this stain. In 14 cases of moderate and high-grade prostate cancer with metastases to lymph nodes, we found 34 beta E12 positivity in 6 (43%) of 14 metastases and in 7 (54%) of 13 primary tumors. Our findings of 34 beta E12 staining in primary and metastatic moderately and poorly differentiated prostate carcinoma differ from those reported in the literature for well-differentiated prostate carcinoma. We urge caution in the use and interpretation of 34 beta E12 staining for the diagnosis of primary and metastatic prostate carcinoma.

Topics: Adenocarcinoma; Biomarkers, Tumor; Formaldehyde; Humans; Keratins; Lymphatic Metastasis; Male; Prostatic Neoplasms; Staining and Labeling; Tissue Fixation

In a previous study, the authors used a variety of anticytokeratin monoclonal antibodies to show that a large proportion of lung tumors cytologically diagnosed as squamous cell carcinoma contain cells expressing simple epithelial cytokeratins, suggesting that these tumors have their origin in adenocarcinoma. These findings raised the possibility that cytokeratin (CK) typing might have a diagnostic capacity not attainable by standard histopathology. The aim of the current study was to assess the value of CK typing for this purpose by determining the correlation between the diagnosis of lung tumors based on CK typing and the survival rate of the patients.. Paraffin embedded tissue sections of 66 nonsmall cell lung carcinoma (NSCLC) specimens were examined. These included 18 adenocarcinomas, 32 squamous cell carcinomas, and 16 undifferentiated carcinomas, all diagnosed surgically and histopathologically, and further classified as either Stage I or II. CK typing was performed using the streptavidin-biotin-peroxidase method, employing the following anti-CK monoclonal antibodies: Ks.B.17 (which reacts with CK 18), A3-3 (which reacts with CK 13), and E5-9 (which reacts with CK 10).. Comparison between the 5-year survival rates (5 ysr) of patients with different NSCLC indicated that all types of Stage II tumors had a much poorer prognosis than Stage I tumors. Differences found in the 5 ysr among patients with different types of Stage I tumors were not statistically significant (adenocarcinomas, 33% 5 ysr; squamous cell carcinomas, 59% 5 ysr; undifferentiated carcinomas, 36% 5 ysr; all diagnosed by conventional histopathology). Similarly, no significant differences were noted in 5 ysr between patients with tumors stained positively or negatively with monoclonal antibodies A3-3 or E5-9 (anti-CK 13 and anti-CK 10, respectively). In contrast, highly significant differences (P = 0.002) were found in the 5 ysr between patients with Stage I tumors positively or negatively stained with monoclonal antibody Ks.B.17 (23% vs. 75% 5 ysr, respectively) regardless of the histologic types of tumors. Especially informative was a combination of immunohistochemical and histologic diagnoses, with best survival rates (87% 5 ysr) in Ks.B.17 negative tumors histologically diagnosed as Stage I squamous cell carcinomas and worst survival rates (14% 5 ysr) in Ks.B.17 positive tumors diagnosed as adenocarcinomas.. The current study showed that CK 18 typing of lung tumors can provide a more accurate diagnosis and therefore facilitate the planning of more suitable therapeutic approaches.

Topics: Adenocarcinoma; Aged; Carcinoma; Carcinoma, Non-Small-Cell Lung; Carcinoma, Squamous Cell; Female; Gene Expression Regulation, Neoplastic; Humans; Immunoenzyme Techniques; Keratins; Lung Neoplasms; Male; Middle Aged; Neoplasm Staging; Predictive Value of Tests; Prognosis; Retrospective Studies; Survival Analysis

We previously reported that a transgenic mouse line containing the fetal globin promoter linked to the SV40 T antigen (T Ag) viral oncogene (Ggamma/T-15) resulted in prostate tumors. In this study, we further explored tumor origin, frequency, invasiveness, androgen sensitivity, and gene expression pattern. T Ag was detected in adult but not fetal and neonatal prostates, suggesting a role for androgens in tumor progression. However, castration shortly after prostate morphogenesis did not prevent tumor development, suggesting an androgen-independent phenotype. Tumors originated within ventral or dorsal prostate lobes and involved intraepithelial neoplasia, rapid growth in the pelvic region, and metastasis to lymph nodes and distant sites. In addition, the primary cancers could be propagated in nude mice or nontransgenic mice. Seventy-five percent of hemizygous and 100% of homozygous transgenic males developed prostate tumors, suggesting a T Ag dosage effect. Biochemical characterization of advanced tumors revealed markers of both neuroendocrine and epithelial phenotypes; markers of terminal differentiation are lost early in tumorigenesis. Tumor suppressor genes (p53 and Rb), normally bound to T Ag, were up-regulated; bcl-2 proto-oncogene, which prevents apoptosis, was slightly up-regulated. Myc, a stimulus to cell cycle progression, was unchanged. We propose the Ggamma/T-15 transgenic line as a model of highly aggressive androgen-independent metastatic prostate carcinoma with features similar to end-stage prostate cancer in humans.

Topics: Adenocarcinoma; Androgens; Animals; Antigens, Polyomavirus Transforming; Chromogranin A; Chromogranins; Gene Expression Regulation, Developmental; Gene Expression Regulation, Neoplastic; Genes, bcl-2; Genes, myc; Genes, p53; Genes, Retinoblastoma; Keratins; Male; Mice; Mice, Transgenic; Neoplasm Metastasis; Orchiectomy; Precancerous Conditions; Prostatic Neoplasms; Proto-Oncogene Mas; RNA, Messenger; Time Factors

Adenocarcinomas of the prostate with attenuated cytoplasm (i.e., atrophic features) have not been studied formally and represent a diagnostic dilemma to the surgical pathologist. Forty-four cases of adenocarcinoma with atrophic features seen at the Johns Hopkins Medical Institutions were reviewed. Forty-two cases were seen on needle biopsy, and two were from transurethral resection specimens. Neoplastic atrophic glands were characterized by cells with a paucity of cytoplasm, such that the nuclei occupied almost the entire cell height. Atrophic cancers were defined as cancers with atrophic glands constituting > or = 50% of the tumor. Ony two of 44 patients whose prostatic adenocarcinoma showed atrophic features were on hormone therapy at the time of biopsy. Forty-one cases had an infiltrative pattern of growth. Thirty-nine cases were Gleason grade 3 + 3 = 6. Nuclear size was increased in 39 cases, and macronucleoli were noted in 21 cases. The most useful criteria to establish a diagnosis of adenocarcinoma were (1) an infiltrative pattern of growth, (2) the presence of macronucleoli, (3) increased nuclear size, and (4) the presence of adjacent, nonatrophic cancer.

Topics: Adenocarcinoma; Aged; Biopsy, Needle; Cell Nucleolus; Cell Nucleus; Cytoplasm; Humans; Immunohistochemistry; Keratins; Male; Middle Aged; Prostatic Neoplasms

The aim of this study was to evaluate the diagnostic value of three tumour markers, squamous cell carcinoma (SCC) antigen, carcinoembryonic antigen (CEA) and CYFRA 21.1, in lung cancer using a Bayesian analysis to obtain the predictive values for different pretest probabilities or prevalences. A cross-sectional study included 94 patients with lung cancer, 40 with benign lung disease, and 40 healthy controls. SCC antigen and CEA were measured in blood samples by microparticle enzyme immunoassay (MEIA), and CYFRA by enzyme-linked immunosorbent assay (ELISA). The results of tumour marker determinations were expressed as percentiles, and showed significantly higher levels in the cancer group than in the two control groups. Taking the 95th percentile of benign lung diseases as the cut-off point (specificity 95%), the following sensitivities were found: SCC 41%, CEA 31% and CYFRA 79%. After a Bayesian analysis, the best results for the three tumour markers were found in prevalences of 30-40%. The highest incremental gain was obtained by CYFRA (at prevalence of 36%, positive and negative predictive value approximately 90%). The three tumour markers were included in a stepwise regression analysis to predict lung cancer, and CYFRA was the only selected variable. We conclude that CYFRA 21.1 may be a useful marker in lung cancer when there is an intermediate pretest probability of disease.

Topics: Adenocarcinoma; Aged; Antigens, Neoplasm; Bayes Theorem; Biomarkers, Tumor; Carcinoembryonic Antigen; Carcinoma, Small Cell; Carcinoma, Squamous Cell; Cross-Sectional Studies; Enzyme-Linked Immunosorbent Assay; Female; Humans; Immunoenzyme Techniques; Keratin-19; Keratins; Logistic Models; Lung Diseases; Lung Neoplasms; Male; Middle Aged; Predictive Value of Tests; ROC Curve; Sensitivity and Specificity; Serpins

Hemidesmosomes (HDs) mediate adhesion of epithelial cells to the extracellular matrix and have morphological associations with intermediate-size filaments (IFs). Hemidesmosomal molecular components including HD1, the two bullous pemphigoid antigens, and the integrin alpha 6 beta 4 have been identified in HDs of stratified and complex epithelium. In this study, we report that HT29-Fu cells, a human colonic tumor cell line, express two hemidesmosomal components (HD1, alpha 6 beta 4) associated in an adhesion structure termed type II HDs. Immunofluorescence studies showed a colocalization of HD1 and alpha 6 beta 4 in basal patches between actin stress fibers. Using cytochalasin B or vinblastine, two drugs which disrupt the cytoskeleton, we demonstrate that the redistribution of HD1 was probably induced by the reorganization of the basal cytokeratin network. We also show that in vitro HD1 binds to polymerized cytokeratin intermediate filaments; this suggests that HD1 in intestinal epithelial cells functions as a linker protein connecting cytokeratin filaments to the basal plasma membrane, probably through the beta 4 subunit of the integrin alpha 6 beta 4.

Topics: Actins; Adenocarcinoma; Cell Adhesion; Cell Differentiation; Cell Polarity; Colonic Neoplasms; Cytochalasin B; Cytoskeleton; Gene Expression Regulation, Neoplastic; Homeodomain Proteins; Humans; Intermediate Filament Proteins; Intermediate Filaments; Keratins; Neoplasm Proteins; Organelles; Tumor Cells, Cultured; Vinblastine

Phenotypic expression of keratin polypeptides is known to be dependent on various factors, one of which is malignant transformation. In this study, we compared the pattern of expression of keratin polypeptides between control and malignant gastric tissues by employing different morphological and biochemical techniques. The results indicated preferential decrease of acidic keratin polypeptides in malignant gastric tissues. The nonmalignant gastric tissues expressed four keratin polypeptides-two acidic and two basic-whereas in the gastric adenocarcinomas expression of only two basic polypeptides was observed. Marked variation of keratin expression between the control and malignant gastric tissues not only highlights its clinical value as a support to diagnosis but also elucidates the underlying changes due to malignant transformation.

Topics: Adenocarcinoma; Adult; Gastric Mucosa; Gene Expression Regulation, Neoplastic; Humans; Keratins; Neoplasm Proteins; Peptide Biosynthesis; Peptides; Stomach Diseases; Stomach Neoplasms

Primary prostatic duct adenocarcinoma, initially labeled as endometrioid carcinoma of the prostate, is a rare neoplasm that displays exophytic growth into the prostatic urethra with involvement of prostatic ducts. Because this tumour arises from preexisting epithelia, there is a possibility that a remnant basal epithelium may be seen in association with these tumours. If this hypothesis is correct, then prostatic duct adenocarcinoma may possibly be mistaken for high-grade prostatic intraepithelial neoplasia (PIN) on needle biopsies. The distribution of basal cells in this tumour has not been described previously. Nine cases of prostatic duct adenocarcinoma and prostatic adenocarcinoma with focal ductal differentiation were studied immunohistochemically with antibodies specifying cytokeratin 34 beta E12, prostate-specific antigen (PSA), and prostatic acid phosphatase (PAP). All cases were positive for PSA and PAP. In some areas of the tumour in eight cases there was a continuous and discontinuous layer of basal cells surrounding islands of carcinoma. This was found with cribriform, comedo, solid, and papillary components of ductal type adenocarcinoma. It is necessary to be aware of the presence of basal cells in association with primary prostatic duct adenocarcinoma. Differentiation of high-grade PIN from this lesion should depend on complex architectural characteristics and Cytologic features rather than presence of a basal cell layer. This finding confirms that the solid, cribriform, papillary, and comedo components initially grow intraluminally within ducts before invasion into surrounding stroma occurs.

Topics: Acid Phosphatase; Adenocarcinoma; Aged; Aged, 80 and over; Carcinoma, Endometrioid; Epithelium; Humans; Keratins; Male; Middle Aged; Prostate-Specific Antigen; Prostatic Neoplasms

To elevate the diagnostic value of the serum cytokeratin 19 fragment (CYFRA 21-1) and compare it with carcinoembryonic antigen (CEA) and tissue polypeptide antigen (TPA) in bronchogenic carcinoma, the sera of 161 patients (58 with benign pulmonary disease and 103 with bronchogenic carcinoma) was investigated using immunoradiometric assay. Sensitivities for CYFRA 21-1, CEA and TPA (using 3.5 ng ml-1, 5.0 ng ml-1, 110 U l-1, respectively, cut-off values corresponding to a 95% specificity for benign pulmonary disease) in bronchogenic carcinoma were 64, 47 and 61%, respectively. Positive CYFRA 21-1 levels were identified in 75% of patients with squamous cell carcinoma (n = 36), in 67% with adenocarcinoma (n = 45), in 17% with large cell carcinoma (n = 6), and in 50% with small cell lung cancer (SCLC) (n = 16). However, CYFRA 21-1 levels were not significantly different between squamous cell carcinoma and the other histological types. The sensitivity of the combined measurement of CYFRA 21-1 with any other tumour marker was significantly higher than that of CYFRA 21-1 measurement alone. Elevated CYFRA 21-1 levels were observed in 44% of Stages I and II (n = 18) and 72% of Stage III and IV (n = 69) patients with non-small cell lung cancer (P < 0.05). A significant inter-marker correlation was observed between CYFRA 21-1 and TPA (n = 103, r = 0.448, P < 0.0001). Twenty-one patients were monitored by CYFRA 21-1, and significantly different changes in progressive patients (P = 0.0058) and regressive patients (P = 0.016) were obtained. These results indicate that CYFRA 21-1 may be not only a sensitive tumour marker in the diagnosis of bronchogenic carcinoma, but also a useful marker for the monitoring of bronchogenic carcinoma.

Topics: Adenocarcinoma; Adolescent; Adult; Aged; Aged, 80 and over; Antigens, Neoplasm; Biomarkers, Tumor; Carcinoembryonic Antigen; Carcinoma, Bronchogenic; Carcinoma, Large Cell; Carcinoma, Small Cell; Carcinoma, Squamous Cell; Female; Humans; Immunoradiometric Assay; Keratin-19; Keratins; Lung Diseases; Lung Neoplasms; Male; Middle Aged; Sensitivity and Specificity; Tissue Polypeptide Antigen

Our knowledge about the nature and biological activity of tumor cells residing in the prostate gland after radical radiotherapy (RRT) is limited.. In the present study, residual tumor in core biopsies taken from 37 patients after an average of 6.8 years follow-up after radiation, were investigated with immunohistochemistry for the biochemical markers prostate-specific antigen (PSA), prostatic acid phosphatase (PAP), and the epithelial marker, cytokeratin 8 (CK8).. Tumor cells were cytokeratin-positive in 33 of 34 evaluable specimens (97%). PSA and PAP were expressed in the tumor cells in 94% (34/36) and 81% (30/37) of cases, respectively. No significant correlation was observed between PSA/PAP expression and tumor grade after treatment. Endocrine treatment administered in addition to RRT in 12 of the 37 patients did not affect the expression of PSA or PAP. The expression of both biochemical markers was reduced after radiotherapy in 10 of the 12 cases for which pre- and post-treatment specimens were available.. Tumor cells retain their epithelial characteristics immunohistochemically after radiation, though their morphology sometimes suggests an altered phenotype after treatment. PSA and PAP reactivity was demonstrated in tumor cells nearly 7 years after radiotherapy, which indicates that these cells maintain their biochemical integrity and protein synthesis to a certain extent. Furthermore, endocrine treatment did not abolish PSA or PAP expression in the tumor cells. Whether PSA and PAP immunoexpression provides independent prognostic information needs to be further investigated.

Topics: Acid Phosphatase; Adenocarcinoma; Humans; Immunohistochemistry; Keratins; Male; Neoplasm, Residual; Prostate; Prostate-Specific Antigen; Prostatic Neoplasms

The co-expression of vimentin and keratin-type intermediate filaments in the same cell was often reported to correlate with increased invasiveness and a more aggressive tumorigenic phenotype. To address the possible physiological relevance of these observations, we transfected simple keratins (K8 and 18) either individually, or in combination, into a tumorigenic but non-metastatic pancreatic adenocarcinoma that expresses vimentin but no keratins. Expression of K8 resulted in the stabilization of endogenous K19 in these cells, and formation of keratin filaments containing K8 and K19. Transfection of K18 yielded unstable K18 protein, but K18 could be stabilized when K8 was co-expressed in the same cells. Clones expressing K18 alone, or together with K8, displayed a reduced ability to grow in soft agar and decreased motility when compared to control, or K8/19 expressing cells. Moreover, K18 expressing cells were dramatically inhibited in their ability to form tumors when injected into syngeneic animals. The extent of suppression in the tumorigenicity of these cells correlated with the level of K18 expressed by these cells. The results show that K18 expression in cells may result in the suppression of the motile and tumorigenic abilities of this adenocarcinoma.

Topics: Adenocarcinoma; Animals; Cell Division; Cell Movement; Gene Expression Regulation, Neoplastic; Keratins; Neoplasms, Experimental; Pancreatic Neoplasms; Rats; Transfection; Tumor Cells, Cultured

We report an 85-year-old man with squamous cell carcinoma on the right pinna. Two years after the excision of the lesion, metastatic foci were found extending from the right retromandibular to the mastoid region and into the parapharyngeal space. Histopathologically, the primary tumor showed interconnecting nests of atypical cells invading into the dermis from multiple epidermal and infundibular foci. The tumor had both squamous and glandular differentiation. A peculiar finding was the presence of decapitation secretion in the glandular foci. To our knowledge, definite apocrine differentiation in squamous cell carcinoma has not previously been reported.

Topics: Adenocarcinoma; Aged; Aged, 80 and over; Apocrine Glands; Carcinoembryonic Antigen; Carcinoma, Squamous Cell; Cell Differentiation; Ear Neoplasms; Ear, External; Head and Neck Neoplasms; Humans; Keratins; Male; Mastoid; Neoplasm Invasiveness; Pharyngeal Neoplasms; Skin Neoplasms; Skull Neoplasms

Occult dissemination of tumor cells mainly determines the prognosis of patients with primary prostate cancer. The effect of androgen deprivation on micrometastatic tumor cells in these patients is currently unknown. We therefore used an immunocytochemical assay with monoclonal antibodies (MAbs) directed against epithelial cytoskeleton proteins (i.e., cytokeratins) to monitor the concentration of isolated tumor cells in the bone marrow of 36 prostate cancer patients (stage C), who underwent hormonal androgen deprivation with Flutamide and Leuprorelin acetate. Tumor cells in cytologic bone marrow preparations were detected using an assay that employed the MAb CK2 directed against cytokeratin (CK) 18 and the alkaline anti-alkaline phosphatase staining method. Prior to therapy, we detected between 1 and 38 CK-positive cells per sample of 2 x 10(6) nucleated cells in 21 patients, while the remaining 15 patients displayed tumor-free marrow samples. There was no significant correlation between the concentration of CK-positive cells and the volume of hypo-echogenic lesions as an indicator of the primary tumor volume or the serum level of prostate-specific antigen (PSA). After androgen deprivation, 20 of the 21 initially positive patients either became negative (n = 16) or showed at least a reduction in the concentration of CK-positive cells (n = 4). Moreover, only 2 of the 15 patients with negative pre-treatment findings became positive. All of the 7 patients with remaining tumor cells in the bone marrow after therapy showed no detectable amounts of PSA in their serum. Our findings suggest that serum PSA concentration is no indicator of micrometastatic disease in bone marrow. Neoadjuvant androgen deprivation appears to eliminate disseminated CK-positive tumor cells present in bone marrow, a preferred site of overt metastasis in prostate cancer patients.

Topics: Adenocarcinoma; Androgen Antagonists; Antineoplastic Agents, Hormonal; Antineoplastic Combined Chemotherapy Protocols; Bone Marrow; Bone Neoplasms; Chemotherapy, Adjuvant; Combined Modality Therapy; Disease-Free Survival; Flutamide; Follow-Up Studies; Humans; Keratins; Leuprolide; Male; Neoplasm Proteins; Prognosis; Prostatectomy; Prostatic Neoplasms; Treatment Outcome; Ultrasonography

We report a 50-year-old man with a history of malignant pleural mesothelioma diagnosed 1 year previously and treated with pneumonectomy and radiotherapy who presented with an erythematous eruption on the left chest wall. A skin biopsy showed a proliferation of malignant epithelioid cells lining irregular clefts in the dermis. Some groups of cells were observed filling vascular lumina. Immunohistochemically, the tumor cells expressed cytokeratins (with antibodies AE1/AE3, MNF 116, and CAM 5.2), and epithelial membrane antigen (EMA), and were negative with Ulex europaeus (UE) and for carcinoembryonic antigen (CEA), CD34, CD15 (with LeuM1 antibody), and factor VIII-related antigen (FVIIIra). The histologic features and immunohistochemical profile were comparable to those observed in the primary pleural mesothelioma. This is the first reported case in which malignant mesothelioma metastatic to the skin presented as "inflammatory carcinoma." Although a very uncommon presentation, mesothelioma should be considered in the differential diagnosis of erythematous eruptions on the chest.

Topics: Adenocarcinoma; Antigens, CD34; Carcinoembryonic Antigen; Diagnosis, Differential; Humans; Immunohistochemistry; Keratins; Lewis X Antigen; Male; Mesothelioma; Middle Aged; Mucin-1; Pleural Neoplasms; Skin Neoplasms; Thorax; von Willebrand Factor

To identify a sensitive marker for extramammary Paget's disease and to identify histochemical and immunohistochemical features that suggest occult pelvic cancer in patients with extramammary Paget's disease, we retrieved all cases between 1983 and 1992 with a Standardized Nomenclature of Medicine code of extramammary Paget's disease in the Vanderbilt University Medical Center (Nashville, Tenn) surgical pathology archives. All were stained for alcian blue/dPAS (periodic acid-Schiff), mucicarmine, AE1/AE3, cytokeratin (CAM 5.2), cytokeratin (CK) 7, CK 20, carcinoembryonic antigen (CEA), orthokeratin, prostate-specific antigen, and S-100. Sixteen cases (2 men, 14 women) were retrieved. Two had pelvic malignancies: one rectal adenocarcinoma and one transitional carcinoma. Only CK7 marked all cases. Mucins were sensitive but focal, a potential problem in small biopsy specimens. The transitional tumor had a unique staining profile (CEA- and mucin-negative). CK20 strongly marked Paget cells associated with rectal cancer; its presence suggests a large bowel lesion but is not specific. No case expressed prostate-specific antigen; its presence in a man suggests prostatic carcinoma.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Alcian Blue; Antiporters; Apolipoproteins; Apolipoproteins D; Biomarkers; Biopsy; Carcinoembryonic Antigen; Carcinoma, Transitional Cell; Carmine; Carrier Proteins; Coloring Agents; Female; Glycoproteins; Histocytochemistry; Humans; Immunohistochemistry; Intermediate Filament Proteins; Keratin-20; Keratins; Male; Membrane Proteins; Membrane Transport Proteins; Middle Aged; Mucins; Paget Disease, Extramammary; Pelvic Neoplasms; Prostate-Specific Antigen; Retrospective Studies; S100 Proteins

Topics: Adenocarcinoma; Antigens, Neoplasm; Biomarkers, Tumor; Carcinoma, Small Cell; Carcinoma, Squamous Cell; Humans; Keratin-19; Keratins; Lung Neoplasms; Neoplasm Staging; Phosphopyruvate Hydratase

The expression of cytokeratins (CKs) in normal cervical epithelium, low grade squamous intraepithelial lesions (SIL), high grade SILs and squamous cell carcinoma (SCC) were analyzed using four different monoclonal antikeratin antibodies. In normal cervical epithelium, CK 18 showed strong immunoreactivity in basal and parabasal layers. CK 19 and 14 were expressed only in the basal layer while CK 13 was found selectively n the spinal cells. As the lesions progressed from low grade SIL to high grade SIL, immunoreactivity of CK 18, 19 and 14 in the basal cell compartment increased while the expression of CK 13 decreased. In SCC, as well-differentiated tumors showed decreased immunoreactivity for CK 18, 19 and 14 with CK 13 showing a strong and focal (localized) immunoreactivity. Undifferentiated carcinomas totally lacked CK 13 reactivity. Our findings therefore suggest that expression of CK 18, 19 and 14 may be directly related to tumor grade and CK 13 may be a marker of differentiation in cervical lesions.

Topics: Adenocarcinoma; Biomarkers, Tumor; Carcinoma, Squamous Cell; Female; Humans; Immunohistochemistry; Keratins; Uterine Cervical Dysplasia; Uterine Cervical Neoplasms

A case of heterotopic salivary gland adenocarcinoma (HSGA) in the right cervical region is presented. The carcinoma cells were positive for alpha-amylase, carcinoembryonic antigen, epithelial membrane antigen, cytokeratin as well as for expression of human salivary alpha-amylase messenger ribonucleic acid. The possibility of HSGA should be considered when an adenocarcinoma producing human salivary alpha-amylase is diagnosed away from sites where major and minor salivary glands normally are found.

Topics: Adenocarcinoma; Aged; alpha-Amylases; Carcinoembryonic Antigen; Choristoma; Diagnosis, Differential; Fatal Outcome; Head and Neck Neoplasms; Humans; Keratins; Male; Mucin-1; Neck; Neoplasms, Unknown Primary; RNA, Messenger; Salivary Gland Neoplasms; Salivary Glands

The diagnosis of metastatic adenocarcinoma to the brain of unknown primary is problematic, and the role of immunohistochemistry in identifying a source has not been fully characterized. Sixty-eight metastatic adenocarcinomas of the brain with known primaries were immunostained with antibodies to cytokeratin 7 (CK7), cytokeratin 20 (CK20), CAM 5.2, wide-spectrum keratin (WSK), gross cystic disease fluid protein-15 (GCDFP-15), glial fibrillary acidic protein (GFAP), estrogen receptor (ER), and progesterone receptor (PR). True positive staining was defined as CK7 in lung or breast; CK20 in gastrointestinal; and GCDFP-15, ER, and PR in breast carcinomas. CK7 immunoreactivity was present in all 27 lung carcinomas and 14 of 15 breast carcinomas with a sensitivity of 98% and specificity of 78%. CK20 stained 15 of 16 GI carcinomas with a sensitivity and specificity of 94%. None of the cytokeratins stained surrounding brain tissue. GCDFP-15, ER, and PR had sensitivities of 33%, 33%, and 87%, with specificities of 92%, 84%, and 28%, respectively. PR often stained nuclei of normal brain tissue and was accentuated in areas of necrosis or cautery artifact. CK7 and CK20 are highly sensitive and specific in patients with metastatic adenocarcinoma to the brain of unknown primary. GCDFP-15 and ER are relatively specific, but insensitive markers, and PR is nonspecific and difficult to interpret.

Topics: Adenocarcinoma; Apolipoproteins; Apolipoproteins D; Biomarkers, Tumor; Brain Neoplasms; Carrier Proteins; Glial Fibrillary Acidic Protein; Glycoproteins; Humans; Immunohistochemistry; Intermediate Filament Proteins; Keratin-20; Keratins; Membrane Transport Proteins; Neoplasms, Unknown Primary; Receptors, Estrogen; Receptors, Progesterone

We present one case of sarcomatoid chromophobe cell renal carcinoma with an indolent clinical course and assume that the carcinomatous component may affect the biologic behavior. The patient was a 61-year-old man who underwent right radical nephrectomy for a 11.2 cm tumor in the lower pole. The immunohistochemical findings demonstrate that EMA and cytokeratins 8 and 18 are useful markers for the sarcomatoid fraction, and the lectin study shows a loss of surface blood antigen. Chromophobe cell carcinoma may convert into sarcomatoid carcinoma. The existence of sarcomatoid renal cell carcinoma as a distinct entity should be re-considered.

Topics: Adenocarcinoma; Aged; Antigens, Surface; Biomarkers, Tumor; Humans; Immunohistochemistry; Keratins; Kidney Neoplasms; Lectins; Male; Mucin-1; Nephrectomy; Sarcoma

To develop a syngeneic transplantable system to study immunotherapeutic approaches for the treatment of prostate cancer, three cell lines were established from a heterogeneous 32 week tumor of the transgenic adenocarcinoma mouse prostate (TRAMP) model. TRAMP is a transgenic line of C57BL/6 mice harboring a construct comprised of the minimal -426/+28 rat probasin promoter driving prostate-specific epithelial expression of the SV40 large T antigen. TRAMP males develop histological prostatic intraepithelial neoplasia by 8-12 weeks of age that progress to adenocarcinoma with distant metastases by 24-30 weeks of age. The three cell lines (TRAMP-C1, TRAMP-C2, and TRAMP-C3) express cytokeratin, E-cadherin, and androgen receptor by immunohistochemical analysis and do not appear to have a mutated p53. Although TRAMP-C1 and TRAMP-C2 are tumorigenic when grafted into syngeneic C57BL/6 hosts, TRAMP-C3 grows readily in vitro but does not form tumors. The T antigen oncoprotein is not expressed by the cell lines in vitro or in vivo. The rationale for establishing multiple cell lines was to isolate cells representing various stages of cellular transformation and progression to androgen-independent metastatic disease that could be manipulated in vitro and, in combination with the TRAMP model, provide a system to investigate therapeutic interventions, such as immunotherapy prior to clinical trials.

Topics: Adenocarcinoma; Androgen-Binding Protein; Animals; Antigens, Viral, Tumor; Cadherins; Disease Progression; Keratins; Male; Mice; Mice, Inbred C57BL; Mice, Transgenic; Neoplasm Proteins; Prostatic Neoplasms; Receptors, Androgen; RNA, Messenger; Tumor Cells, Cultured; Tumor Stem Cell Assay; Tumor Suppressor Protein p53

Two histopathologic lesions are considered putative precursors of prostate cancer, but the supportive evidence for one (prostatic intraepithelial neoplasia, or PIN) is much greater than the other (atypical adenomatous hyperplasia, or AAH). High grade PIN is the most likely precursor of carcinoma, arising in the peripheral zone, but probably does not account for well-differentiated cancer arising in the transition zone. The biological significance of atypical adenomatous hyperplasia of the prostate (AAH) is inconclusive at the time. The histological and cytological features of AAH are intermediate between BPH and low grade carcinoma, suggesting that AAH may be a precursor of well differentiated transition; zone carcinoma. In the recent time new findings on morphogenetic aspects of normal and abnormal prostatic growth i.e. stem cell models are discussed and topics about grading and proliferative activities, frequency and histological changes associated with aging as well as clinical relevance of PIN and AAH. This paper reviews the results and discussion at the second international consultation meeting on PIN in Mayo Clinic, Rochester, Nov. 3-4 th. 1995, following the first international consultation meeting of AAH and PIN and origin of the prostatic carcinoma in Ancona, Sept. 11-12 th 1994.

Topics: Adenocarcinoma; Adult; Aged; Apoptosis; Biopsy; Carcinoma in Situ; Cell Differentiation; Cell Division; Cell Nucleus; Humans; Incidence; Keratins; Male; Middle Aged; Nucleolus Organizer Region; Prostatic Hyperplasia; Prostatic Neoplasms

This unusual case is that of a middle-aged man exhibiting a tumor diathesis including a basal cell adenocarcinoma with features of adenoid cystic carcinoma arising in minor salivary gland of lip in association with multiple primary malignant cylindromas of skin. The labial lesion showed invasive tubules, solid epithelial sheets and cribriform structures. It did not exhibit PAS positive juxta-tubular basement membrane material. The skin lesions all showed features of a highly infiltrative cylindromatous carcinoma with two cell types, peripheral palisading and prominent PAS positive juxta-tubular basement membrane material. Immunocytochemical studies of the lip lesion and one of the skin lesions showed similarities, including positive staining for high and low molecular weight keratins and S-100 with negative staining for CEA. The precious descriptions of tumor diatheses involving dermal cylindromas and dermal analogue tumors of salivary glands and the distinctions with the present study are noted. If benign and even malignant cylindromas were described in the literature to be associated with basal cell adenocarcinoma of the major salivary glands, our case is unique by its association with this rare malignant tumor in a minor salivary gland.

Topics: Adenocarcinoma; Adult; Carcinoma, Adenoid Cystic; Disease Susceptibility; Humans; Keratins; Lip; Male; S100 Proteins; Salivary Gland Neoplasms; Scalp; Skin Neoplasms

Mucin-producing Cowper's glands, which are situated in the urogenital diaphragm, can be sampled inadvertently by transurethral resection of the prostate and rarely by needle biopsy. Because they are small, closely packed glandular units, Cowper's glands can be misinterpreted as prostatic adenocarcinoma. A panel of immunoperoxidase and mucin stains performed on 10 Cowper's glands showed negative immunoreactivity for prostatic-specific antigen, prostatic alkaline phosphatase, S-100 protein, and carcinoembryonic antigen. Acini in nine of the 10 Cowper's glands were negative for high-molecular-weight cytokeratin K-903 (34beta E12). One case showed faint focal staining of cells around the periphery of acinar units. Smooth muscle actin consistently stained the periphery of acini in all cases. Ultrastructural examination of one Cowper's gland showed the presence of myoepithelial cells at the periphery of the acini. Contrary to previous reports, the acini were lined by a prominent secretory cell layer underlain by an attenuated myoepithelial cell layer. A negative stain for K-903. without additional immunohistochemical study on Cowper's glands taken during transurethral resection or needle biopsy, may substantiate an erroneous diagnosis of prostatic adenocarcinoma. This potential misdiagnosis of carcinoma can be averted if samples stain positive for mucin and smooth muscle actin and negative for prostate-specific antigen and prostatic alkaline phosphatase.

Topics: Actins; Adenocarcinoma; Adult; Aged; Aged, 80 and over; Alkaline Phosphatase; Biopsy, Needle; Bulbourethral Glands; Carcinoembryonic Antigen; Cell Division; Diagnosis, Differential; Humans; Immunohistochemistry; Keratins; Male; Microscopy, Electron; Middle Aged; Mucins; Prostate; Prostate-Specific Antigen; Prostatic Neoplasms; S100 Proteins

We report on a rare tumor of the lung characterized by its morphologic hepatoid features and alpha-fetoprotein production. This unusual neoplasm arose in the left lung of a 36-year-old man in whom clinical and radiologic examinations did not reveal any other tumor. The serum level of alpha-fetoprotein was measured at 6,090 ng/mL and was parallel to the evolution of the tumor. Despite treatment, the patient died 7 months after the diagnosis. The microscopic appearance of the tumor was the same as observed in hepatocarcinoma and hepatoid adenocarcinoma of the ovary or the stomach, with a tubular, papillary, or trabecular pattern. Periodic acid-Schiff-positive hyaline globules were numerous, and tumor cells showed immunohistologic positivity for alpha-fetoprotein and carcinoembryonic antigen. This lung adenocarcinoma was first described by Ishikura et al. in 1990 and was named hepatoid lung adenocarcinoma. Like the rare hepatoid carcinoma of the gallbladder, the pancreas, the ampulla of Vater, the renal pelvis, and the bladder, the exact histogenesis and the prognosis of this type of lung tumor are not yet known.

Topics: Adenocarcinoma; Adult; alpha-Fetoproteins; Carcinoma, Hepatocellular; Diagnosis, Differential; Humans; Immunohistochemistry; Keratins; Lung; Lung Neoplasms; Magnetic Resonance Imaging; Male; Mucin-1; Prognosis; Time Factors

Keratins 8 (K8) and 18 (K18) are major components of intermediate filaments (IFs) of simple epithelial cells and tumors derived from such cells. Structural cell changes during apoptosis are mediated by proteases of the caspase family. During apoptosis, K18 IFs reorganize into granular structures enriched for K18 phosphorylated on serine 53. K18, but not K8, generates a proteolytic fragment during drug- and UV light-induced apoptosis; this fragment comigrates with K18 cleaved in vitro by caspase-6, -3, and -7. K18 is cleaved by caspase-6 into NH2-terminal, 26-kD and COOH-terminal, 22-kD fragments; caspase-3 and -7 additionally cleave the 22-kD fragment into a 19-kD fragment. The cleavage site common for the three caspases was the sequence VEVD/A, located in the conserved L1-2 linker region of K18. The additional site for caspases-3 and -7 that is not cleaved efficiently by caspase-6 is located in the COOH-terminal tail domain of K18. Expression of K18 with alanine instead of serine at position 53 demonstrated that cleavage during apoptosis does not require phosphorylation of serine 53. However, K18 with a glutamate instead of aspartate at position 238 was resistant to proteolysis during apoptosis. Furthermore, this cleavage site mutant appears to cause keratin filament reorganization in stably transfected clones. The identification of the L1-2 caspase cleavage site, and the conservation of the same or very similar sites in multiple other intermediate filament proteins, suggests that the processing of IFs during apoptosis may be initiated by a similar caspase cleavage.

Topics: Adenocarcinoma; Animals; Apoptosis; Caspase 3; Caspase 6; Caspase 7; Caspases; Cysteine Endopeptidases; Endometrial Neoplasms; Enzyme Precursors; Epithelium; Female; Gene Expression; Humans; Intermediate Filaments; Keratins; Mice; Molecular Sequence Data; Mutagenesis; Peptide Mapping; Protein Structure, Tertiary; Sequence Homology, Amino Acid; Tumor Cells, Cultured

To better understand the mechanism(s) underlying lung cancer invasion and metastasis, a Transwell invasion chamber was used to select progressively more invasive cancer cell populations from a clonal cell line of human lung adenocarcinoma, CL1. Five sublines with progressive invasiveness, designated CL1-1, CL1-2, CL1-3, CL1-4, and CL1-5, were obtained through this in vitro selection process. Their invasive abilities through basement membrane matrix showed a 4- to 6-fold increase over that of the parental cells. Moreover, the sublines manifested an increase in their colony-forming ability on soft agar, tumorigenicity, and metastatic potency in severe combined immunodeficiency (SCID) mice. Examining the phenotypes of the cell lines revealed increased expression of 92 kD gelatinase and an increase in the cell population stained with anti-keratin-8 and -18 antibodies. Clonal isolation of anti-keratin-18-antibody-positive and -negative cell populations demonstrated a correlated enhancement of the invasiveness of these cells and their expression of keratin-18. These results support the notion that the metastatic behavior of lung cancer cells can be characterized with this in vitro system, and that the properties of these progressively invasive cancer cells can be clonally studied.

Topics: Adenocarcinoma; Carcinogenicity Tests; Cell Culture Techniques; Gelatinases; Humans; Keratins; Lung Neoplasms; Male; Microscopy, Electron; Middle Aged; Neoplasm Invasiveness; Tumor Cells, Cultured

Carcinosarcoma is a rare neoplasm that displays morphological features of both an adenocarcinoma and a sarcoma. The question is whether two tumors co-exist or whether the two morphological aspects represent sequential steps in tumor progression. We report a case of carcinosarcoma of the caecum in a young female. To characterize the two tumor cell populations and to gain insight into the pathogenesis of the lesion, we conducted immunohistochemical and ultrastructural analyses of the tumor. The biphasic aspect of the tumor showed an admixture of carcinoma and spindle-cell sarcomatoid areas. Both adenocarcinoma and sarcomatous cells were positive for cytokeratins. Vimentin was undetectable in the epithelial portion, but many of the sarcomatous cells stained for vimentin. Electron microscopic analyses of the sarcomatous portion revealed budding of "retroviral particles" from the rough endoplasmic reticulum cisternae. Our data support the contention that "carcinosarcoma" is a part of a single clinicopathological continuum with "spindle-cell carcinoma", the former being the biphasic expression of the neoplasia, the latter the monophasic expression; the presence of productive retroviral infection in the sarcomatous cells could constitute one of the additional support in tumor progression from the carcinomatous to the sarcomatous phase.

Topics: Adenocarcinoma; Adult; Biomarkers, Tumor; Carcinosarcoma; Cell Transformation, Neoplastic; Colonic Neoplasms; Disease Progression; Endoplasmic Reticulum, Rough; Fatal Outcome; Female; Humans; Keratins; Neoplasm Proteins; Organelles; Retroviridae; Sarcoma; Vimentin

Twenty cases of ovarian metastases derived from appendiceal adenocarcinomas were analyzed. The most common presentation was a pelvic mass. The appendiceal and ovarian tumors were diagnosed concurrently in 15 cases; in the remaining five, the ovarian tumors were diagnosed before the appendiceal tumor. The appendiceal adenocarcinomas demonstrated four morphologic patterns: 1) signet ring cell type, with or without glandular or goblet cell differentiation (14 cases); 2) mixed signet ring cell and intestinal type (two cases); 3) intestinal type (two cases); and 4) typical colorectal type (two cases). The ovarian tumors were bilateral in 16 cases and were histologically similar to the associated appendiceal tumor in each case. Ovarian metastases that demonstrate signet ring cell, glandular, and goblet cell differentiation mimic metastases from gastric adenocarcinoma. Those that are derived from well-differentiated mucinous appendiceal adenocarcinomas mimic primary ovarian mucinous tumors and metastases from the pancreas and biliary tract. Metastases of appendiceal adenocarcinomas of colorectal type simulate both metastatic colorectal carcinoma and primary ovarian endometrioid carcinomas. The appendiceal and ovarian tumors were immunophenotypically identical in each case. Approximately 50% of the appendiceal and ovarian tumors were positive for cytokeratin 7 (CK 7), and all were positive for cytokeratin 20 (CK 20). CK 20 positivity of the ovarian tumors is consistent with gastrointestinal origin; CK 7 positivity does not confirm ovarian origin, because appendiceal carcinomas are positive in 50% of cases. Metastatic appendiceal adenocarcinoma should be considered in the differential diagnosis of mucinous ovarian tumors with signet ring cell, goblet cell, or intestinal type differentiation, especially when these tumors are associated with extraovarian disease and are bilateral.

Topics: Adenocarcinoma; Adult; Aged; Appendiceal Neoplasms; Diagnosis, Differential; Female; Follow-Up Studies; Humans; Immunohistochemistry; Intermediate Filament Proteins; Keratin-20; Keratins; Middle Aged; Ovarian Neoplasms

High-grade prostatic intraepithelial neoplasia (HGPIN) is the most likely precursor proliferation of peripheral zone, moderately to poorly differentiated prostatic adenocarcinomas. The usual cell type of the epithelial lining of HGPIN is a glandular epithelial cell with characteristic nuclear abnormalities. Here we report nine cases of unusual types of HGPIN, including three cases of signet-ring cell HGPIN, one case of small cell neuroendocrine HGPIN, and five cases of HGPIN with distinctive mucinous features. The three examples of signet-ring cell PIN were all associated with an invasive primary signet-ring cell carcinoma of the prostate. The HGPIN assumed a classical tufted and micropapillary architectural growth pattern, with the constituent cells exhibiting a morphologic appearance identical to that of the invasive signet-ring cells. The intraepithelial and invasive signet-ring cells were mucin negative and were immunoreactive for prostate-specific antigen (PSA). A fourth case displayed a mixed intraepithelial glandular-small cell neoplastic proliferation, where intraepithelial small cells were histologically identical to surrounding invasive small cell carcinoma cells. The small cell HGPIN and invasive small cell carcinoma cells were positive for the neuroendocrine markers chromogranin, synaptophysin, and neuron-specific enolase. In five cases, mucinous distension of HGPIN glands, producing a flat pattern of the epithelial lining layer, comprised the third unusual pattern of HGPIN. These blue mucinous secretions were readily detected by hematoxylin and eosin staining and were composed of both neutral (periodic acid-Schiff-positive) and acidic (alcian blue-positive) mucins. Herein we document the existence of an intraepithelial proliferation of neoplastic cell types-small cell neuroendocrine and signet-ring cell-that are usually considered as stromal-invasive cells in the prostate. The presence of these rare prostatic cell types in both HGPIN and invasive carcinoma provides further support for a close relationship between HGPIN and invasive carcinoma of the prostate. All three unusual types of HGPIN-signet-ring cell, small cell neuroendocrine, and mucinous-are important to diagnostically recognize because of the strength of association of HGPIN with invasive carcinoma.

Topics: Adenocarcinoma; Aged; Aged, 80 and over; Chromogranins; Humans; Keratins; Male; Microscopy, Electron; Middle Aged; Neoplasms; Precancerous Conditions; Prostate-Specific Antigen; Prostatic Intraepithelial Neoplasia; Prostatic Neoplasms

Cytokeratins (CK) are one of the main families of intermediate filaments which make up the cytoskeleton. CK19 is strongly expressed by normal simple bronchial and respiratory epithelium as well as by their malignant counterpart. Although CK19 is a part of the cytoskeleton, a soluble fragment of this polypeptide can be released and assayed in the blood as CYFRA 21-1, new sensitive and valuable marker of non small cell lung cancer. In some cases, however, discrepancies between the serum level of CYFRA 21-1 and presence of tumor and its histological type have been observed. We studied immunohistochemically tissue localization of CK19 in tumors and non invaded lung parenchyma in a series of 34 patients surgically treated due to lung cancer. CK 19 was detected in cancer cells as well as in non neoplastic epithelium covering bronchial tree and alveolar surfaces. We found a different expression of CK19 in different histological type of tumors. The most intensive expression revealed squamous cell carcinomas and adenocarcinomas. Small cell cancer revealed poor expression of CK19. In non invaded parts of the resected lungs we found the strong expression of CK19 in the cytoplasm of regenerative II type pneumocytes occurring in large quantity in the cases of interstitial lung fibrosis concomitant with some tumors. We suggest it may be a cause of unexpectedly elevated serum levels of CYFRA 19-21 in some not oncological patients or patients with small cell lung cancer.

Topics: Adenocarcinoma; Adult; Aged; Antibodies, Monoclonal; Biomarkers, Tumor; Bronchi; Carcinoma, Large Cell; Carcinoma, Non-Small-Cell Lung; Carcinoma, Small Cell; Carcinoma, Squamous Cell; Cytoplasm; Epithelium; Female; Humans; Infant; Keratins; Lung Neoplasms; Male; Middle Aged; Neoplasm Proteins; Pulmonary Alveoli; Pulmonary Fibrosis

A study was made of the prognostic value of pretreatment measurements of tumour radiosensitivity (surviving fraction at 2 Gy, SF2) in 128 patients with stage I-III carcinomas of the uterine cervix undergoing radiotherapy. The median follow-up time was 47 months. In a univariate analysis stratifying patients according to the median value, radiosensitivity was a significant prognostic factor for overall survival, local control and metastasis-free survival. The 5-year survival rate for tumours with SF2 values below the median was 81% and was significantly greater than the rate of 51% for those with SF2 values above the median. In bivariate analyses, SF2 was shown to be independent of disease stage, tumour grade, patient age, colony-forming efficiency and tumour diameter. In a multivariate analysis, radiosensitivity was the most important variable and, after allowing for this, only stage was a significant independent predictor of treatment outcome. These data indicate that, in carcinoma of the cervix treated with radiotherapy, pretreatment tumour intrinsic radiosensitivity is an important prognostic parameter and contributes to prognosis independently of other established and putative parameters.

Topics: Adenocarcinoma; Adult; Age Factors; Aged; Carcinoma, Squamous Cell; Disease-Free Survival; Female; Humans; Immunohistochemistry; Keratins; Middle Aged; Multivariate Analysis; Neoplasm Recurrence, Local; Prognosis; Radiation Tolerance; Survival Rate; Time Factors; Treatment Outcome; Uterine Cervical Neoplasms

The present study describes a case of the recently discovered chromophobe cell carcinoma of the kidney. Additional findings that have not been previously reported are presented and the importance of the clinical and anatomopathological diagnosis of this tumor type is underscored.. The tumor presented in a 72-year-old female with symptoms and signs that were not distinct from those of other more common renal tumors. She underwent a right radical nephrectomy. Histopathological, immunohistochemical and ultrastructural studies were performed and the findings were compared with those reported in the literature.. The foregoing studies disclosed a chromophobe cell renal carcinoma, with some findings-chiefly ultrastructural-that have not been previously described.. Chromophobe cell renal carcinoma, a tumor type that has recently been identified, is the subject of several studies that have been conducted to permit its clinical and anatomopathological characterization. The present study describes some observations which, to our knowledge, have not been previously described elsewhere.

Topics: Adenocarcinoma; Aged; Biomarkers, Tumor; Female; Humans; Keratins; Kidney Neoplasms; Mucin-1; Neoplasm Proteins; Staining and Labeling

The human monoclonal antibody (MAb) AE6F4 is secreted by a human-human hybridoma line established from the in vitro immunization of normal human peripheral blood lymphocytes with the human lung adenocarcinoma cell line, A549. This MAb is strongly reactive to lung cancer tissues. In the previous study, the antigens recognized by the MAb AE6F4 were purified from A549 cells and identified as 14-3-3 protein and 31 kDa cytosolic phospholipase A2 (cPLA2). The MAb AE6F4 also binds two kinds of antigens (53 kDa and 40 kDa), which are not related to 14-3-3 protein or 31 kDa cPLA2, in the human breast adenocarcinoma cell line, MCF-7. We purified a 38 kDa antigen, which is a degradation product of 53 kDa antigen from breast adenocarcinoma MCF-7 cells using ion-exchange and hydroxyapatite column chromatography. Two partial amino acid sequences of the purified 38 kDa antigen showed 95-100% homology to human cytokeratin 8 (CK8). Two-dimensional gel electrophoresis and immunoblot analysis of intermediate filament fraction separated from MCF-7 cells demonstrated that the 53 kDa and 40 kDa antigens were CK8 and CK19, respectively. Antigenic determinants on CK8 and CK19 recognized by the MAb AE6F4 were resistant to sodium periodate treatment, although antigenic determinant on 31 kDa antigen (14-3-3 protein and(or) cPLA2) was sensitive to this treatment. These results suggest that the MAb AE6F4 reacts with both carbohydrate and peptide antigenic determinants.

Topics: Adenocarcinoma; Amino Acid Sequence; Antibodies, Monoclonal; Antigens; Carbohydrates; Epitopes; Humans; Hybridomas; Keratins; Molecular Sequence Data; Molecular Weight; Peptides; Tumor Cells, Cultured

The immunohistochemical diagnosis between epithelial mesothelioma and adenocarcinoma is currently based on the use of a panel of antibodies to adenocarcinoma-associated antigens and a few antibodies to mesothelial-associated antigens. Since the introduction of epitope retrieval methods, the sensitivity of many antibodies has been enhanced. Thus, a reevaluation of the mesothelioma/adenocarcinoma diagnostic panel becomes necessary. We studied 268 paraffin-embedded formalin-fixed tumor samples that included 57 epithelial mesotheliomas and 211 adenocarcinomas of various origins, comparing an extensive antibody panel with and without heat-induced epitope retrieval (HIER). Marked increase in the sensitivity of several antibodies, with no loss of specificity, was found when HIER was used. After statistical analysis, the antibodies to the epithelial glycoproteins carcinoembryonic antigen, BerEp4, and Bg8 emerged as the best discriminators between adenocarcinoma and epithelial mesothelioma within the entire panel. The mesothelium-associated antibodies, HBME-1, calretinin, and thrombomodulin were less sensitive and less specific than the former, although they were found to be useful on certain cases. Antibodies to cytokeratins and vimentin, although of minor diagnostic value in this context, may be helpful to evaluate the quality of antigen preservation. This study confirms the value of immunohistochemistry to accurately distinguish mesothelioma from adenocarcinoma when an antibody panel approach is used. The addition of heat-induced epitope retrieval methods increases the effectiveness of the procedure and is recommended for most of the antibody panel members.

Topics: Adenocarcinoma; Biomarkers, Tumor; Breast Neoplasms; Calbindin 2; Carcinoembryonic Antigen; Colorectal Neoplasms; Decision Trees; Diagnosis, Differential; Epitopes; Female; Hot Temperature; Humans; Immunohistochemistry; Keratins; Lung Neoplasms; Mesothelioma; Ovarian Neoplasms; Peritoneal Neoplasms; Pleural Neoplasms; Retrospective Studies; S100 Calcium Binding Protein G; Sensitivity and Specificity; Thrombomodulin; Vimentin

To cast light on the capacity of an ovarian adenocarcinoma to undergo irreversible cellular differentiation, we established clonal cell lines from cultured ovarian carcinoma cells treated with sodium butyrate and examined their phenotypic changes.. The poorly differentiated ovarian carcinoma cell line AMOC-2 was exposed to 2 mM sodium butyrate for 30 days, and clonal cell lines were established by a dilution plating technique.. Five clonal cell lines were established. One of them had a longer doubling time and lower plating efficiency than the parental clone, also demonstrating stronger expression of vimentin and 56 kD cytokeratin. This clone became columnar with pronounced polarity, formed gland-like structures when cultured in collagen gels, and exhibited no tumorigenicity, in contrast to the parental clone.. Sodium butyrate treatment of AMOC-2 cells can cause phenotypic changes reminiscent of maturation in the Müllerian duct, endocervix, and/or endometrium.

Topics: Adenocarcinoma; Animals; Blotting, Western; Butyrates; Butyric Acid; Cell Count; Cell Differentiation; Cell Division; Collagen; Culture Media; Female; Humans; Keratins; Mice; Mice, Nude; Neoplasm Transplantation; Ovarian Neoplasms; Time Factors; Tumor Cells, Cultured; Vimentin

We describe the case of a 73-year-old patient with gastric adenocarcinoma composed of histologically well differentiated glandular areas, extensive rhabdoid zones and regions depicting a transition between these two constituents. The rhabdoid component showed typical features such as abundant eosinophilic cytoplasm, eccentric nuclei, prominent nucleoli, intense positive immunohistochemical cytoplasmic reaction for vimentin and less evident immunohistochemical for cytokeratin and epithelial membrane antigen (EMA). Our findings strongly suggest that the rhabdoid areas probably represent a phenotypic variant of a gastric adenocarcinoma, otherwise fairly well differentiated, a combination that to the best of our knowledge has not been previously reported.

Topics: Actins; Adenocarcinoma; Aged; Carcinoembryonic Antigen; Cell Transformation, Neoplastic; Desmin; Female; Humans; Immunohistochemistry; Keratins; Mucin-1; Rhabdoid Tumor; Stomach Neoplasms; Vimentin

Eight cases of a distinctive histological variant of bowel cancer characterized by an anaplastic morphology were identified from 2,650 colonic malignancies (0.3%). The tumors were histologically composed of sheets of anaplastic tumor cells with frequent atypical mitoses, absence of gland formation, and mucicarmine and periodic acid-Schiff (PAS) negativity. Positive immunostaining for cytokeratin and vimentin was observed in eight cases and for epithelial membrane antigen in three; whereas carcinoembryonic antigen, alpha-fetoprotein, S-100 protein, HMB-45 antimelanoma antigen, leukocyte common antigen, and neuroendocrine markers were uniformly negative. Ultrastructural examination demonstrated intercellular tight junctions, focal surface microvilli, and apical terminal webs or long rootlets of microfilaments supporting a colonic derivation. At the time of diagnosis, metastases to regional lymph nodes were found in seven cases and to the liver in six. All patients in this study died of tumor within 9 months. This report emphasizes a poorly recognized variant of colonic carcinoma, characterized by a high degree of anaplasia and malignant behavior. The differential diagnosis for these lesions is discussed.

Topics: Adenocarcinoma; Aged; Biomarkers, Tumor; Carcinoma; Carcinoma, Large Cell; Colonic Neoplasms; Diagnosis, Differential; Humans; Immunoenzyme Techniques; Keratins; Liver Neoplasms; Lymphatic Metastasis; Male; Microvilli; Middle Aged; Mucin-1; Survival Analysis; Tight Junctions; Vimentin

Insulin-like growth factor (IGF)-binding proteins (IGFBPs) modulate the activity of IGFs. In vitro human prostate epithelial cells secrete IGFBP-2 and -3. In vivo IGFBP-2 is increased, and IGFBP-3 is decreased in the serum of patients with prostate cancer. Immunohistochemistry and in situ hybridization were performed to compare the expression of IGFBP-2 and -3 in vivo in prostate tissue containing benign epithelium, high grade prostate intraepithelial neoplasia (PIN), and adenocarcinoma. Immunoreactivity and messenger ribonucleic acid (mRNA) hybridization signals for IGFBP-2 and -3 were localized to epithelial cells. IGFBP-2 immunostaining intensity was significantly increased in PIN regions compared to that in normal epithelium and was further increased in malignant cells. IGFBP-2 mRNA was also significantly increased in PIN and cancer cells. IGFBP-3 immunoreactivity was significantly increased in PIN regions compared to normal epithelium; however, IGFBP-3 protein was significantly decreased in malignant cells. IGFBP-3 mRNA remained virtually unchanged in benign epithelium, PIN, and adenocarcinoma cells. These results demonstrate that increased IGFBP-2 protein in PIN and malignant cells is probably due to increased mRNA expression. However, levels of IGFBP-3 protein may be due to pre- and/or posttranslational mechanisms, including proteolysis. The changes in IGFBP-2 and -3 protein levels in prostatic tissue are in agreement with serum changes reported in patients with prostate cancer.

Topics: Adenocarcinoma; Aged; Epithelium; Humans; Immunohistochemistry; In Situ Hybridization; Insulin-Like Growth Factor Binding Protein 2; Insulin-Like Growth Factor Binding Protein 3; Keratins; Male; Middle Aged; Prostate; Prostate-Specific Antigen; Prostatic Intraepithelial Neoplasia; Prostatic Neoplasms; RNA, Messenger

Schistosomiasis remains one of the major public health problems of the tropics. Conservative estimates place the number of infected individuals at about 200 millions. In Egypt, carcinoma of the urinary bladder associated with schistosomiasis is the foremost oncologic problem, because of its high frequency and the late presentation of cases. A newly developed monoclonal antibody CK1K10 to keratinized grade 1 squamous cell carcinoma was used in a dot enzyme-linked immunosorbent assay (Dot ELISA) to test urine samples of 118 patients with bladder carcinoma, 291 patients with genitourinary pathology other than bladder carcinoma, in addition to 550 healthy controls. The overall sensitivity of the dot ELISA was 90% among 118 patients with bladder carcinoma. Twenty-seven of 33 transitional cell carcinoma cases (82%), 68 of the 71 squamous cell carcinoma cases (96%), 7 of 10 undifferentiated tumors cases (70%), and 4 of 4 adenocarcinoma were positive with this assay. The specificity was 90% in our sample population. A comparative study of diagnosis by cytology and dot ELISA was carried out in 57 patients with bladder carcinoma. Dot ELISA was found to be superior as a screening tool for high risk groups (P < .001 using chi-square test). Cytology detected 21% of transitional cell carcinoma, 68% of squamous cell carcinoma, 50% of adenocarcinoma, and 86% of undifferentiated tumors. The dot ELISA assay should be useful for screening high-risk groups because it does not require sophisticated equipment, is noninvasive, does not require highly trained staff, and can be performed in less than 30 minutes.

Topics: Adenocarcinoma; Antibodies, Monoclonal; Carcinoma, Squamous Cell; Carcinoma, Transitional Cell; Cytodiagnosis; Enzyme-Linked Immunosorbent Assay; Female; Humans; Keratins; Male; Pregnancy; Risk Factors; Sensitivity and Specificity; Urinary Bladder Neoplasms; Urine

Epstein-Barr virus (EBV)-associated gastric carcinomas have been reported from various regions of the world. Epstein-Barr virus appears to be pathogenetically related to some gastric carcinomas. To determine the incidence of EBV association with gastric carcinomas among Koreans, the authors have studied EBV genome expression in 89 consecutive patients with gastric carcinomas diagnosed at the Catholic University Hospitals in Seoul, Korea, using in situ hybridization (ISH) for EBV-encoded small RNAs (EBERs), and immunohistochemistry for EBV latent membrane proteins (LMP) and CD21 antigen on paraffin sections. Thirty-seven gastric specimens with benign ulcer disease were used controls. EBV-encoded small RNAs were expressed in tumor cell nuclei in 12 patients (13.5%). None of the controls or benign portions of the cases were positive. In the positive cases, all tumor cell nuclei were uniformly stained and the staining intensity was strong. Immunohistochemistry for LMP was positive in 3 of 12 EBERs positive patients and none of EBERs negative patients. EBV latent membrane proteins was localized only in the lymphoid cells infiltrating the tumor in two patients, and tumor cells as well as infiltrating lymphoid cells in one patient. These results indicate that the rate of EBV association with gastric carcinomas in Koreans is relatively high and comparable to other Far Eastern Asian regions. The expression pattern in EBV-associated gastric carcinomas is similar to those of nasopharyngeal carcinomas in which clonality analysis using specific probes to the tandem repeat region of EBV yielded single episomal bands suggesting that EBV infection in EBV-associated gastric carcinomas are also clonal and pathogenetically related to the neoplasm. However, the mechanism of tumorigenesis remains to be elucidated.

Topics: Adenocarcinoma; Adult; Aged; DNA, Viral; Female; Genes, Viral; Herpesviridae Infections; Herpesvirus 4, Human; Humans; Immunohistochemistry; In Situ Hybridization; Keratins; Korea; Male; Middle Aged; Receptors, Complement 3d; Retrospective Studies; RNA, Viral; Stomach Neoplasms; Tumor Virus Infections; Viral Matrix Proteins

Topics: Adenocarcinoma; Aged; Autoantigens; Biomarkers; Brain Neoplasms; Carcinoembryonic Antigen; Cerebellum; DNA-Binding Proteins; Gynecomastia; Humans; Immunoglobulins, Intravenous; Immunohistochemistry; Keratins; Male; Neoplasm Proteins; Neoplasms, Unknown Primary; Nerve Tissue Proteins; Paraneoplastic Syndromes; Plasma Exchange; Purkinje Cells

The MIB-1 monoclonal antibody is a marker of cycling cells and the PC10 monoclonal antibody is a marker of proliferating cell nuclear antigen in paraffin sections. This study was conducted to elucidate the difference in response to radiotherapy (RT) between cervical adenocarcinomas and squamous cell carcinomas, focusing on cell proliferation.. A total of 196 biopsy specimens taken from the cervical carcinomas of 14 consecutive patients with adenocarcinoma and 62 patients with squamous cell carcinoma before and after RT at doses of 9 and 27 Grays (Gy) were investigated for MIB-1 and PC10 immunoreactivities.. In adenocarcinomas, the mean MIB-1 labeling indices before and after RT at 9 and 27 Gy were 28%, 21%, and 26%, respectively, whereas the mean PC10 labeling indices were 15%, 13%, and 14%, respectively. In squamous cell carcinomas, the mean MIB-1 labeling indices before and after RT at 9 and 27 Gy were 38%, 53%, and 26%, respectively, and the mean PC10 labeling indices were 23%, 23%, and 11%, respectively.. Cervical adenocarcinomas have a lower cycling cell population and their indices show no change during RT. Squamous cell carcinomas have a higher cycling cell population and show a transient increase of the MIB-1 cycling cell population at 9 Gy of RT. These findings suggest a difference in response to RT between adenocarcinomas and squamous cell carcinomas.

Topics: Adenocarcinoma; Aged; Aged, 80 and over; Antibodies, Monoclonal; Antigens, Neoplasm; Biomarkers, Tumor; Carcinoma, Adenosquamous; Carcinoma, Endometrioid; Carcinoma, Squamous Cell; Cell Cycle; Cell Nucleus; Female; Humans; Keratins; Ki-67 Antigen; Neoplasm Proteins; Neoplasm Staging; Nuclear Proteins; Proliferating Cell Nuclear Antigen; Treatment Outcome; Uterine Cervical Neoplasms

The CYFRA 21-1, a newly developed sandwich enzyme-linked immunosorbent assay (ELISA), was used to measure soluble cytokeratin 19 fragment in serum that is expressed in simple epithelium and its malignant counterpart. The present study was designed to investigate whether CYFRA 21-1 is a sensitive and specific tumor marker for non-small cell lung cancer.. CYFRA 21-1 assay, using two specific monoclonal antibodies (KS 19.1 and BM 19.21) for cytokeratin 19, was measured in 312 serum samples, including 164 lung cancer, 118 benign pulmonary disease, and 30 healthy individuals. The sensitivity of CYFRA 21-1 was also compared with two other markers, carcinoembryonic antigen (CEA) and squamous cell carcinoma antigen (SCC), in 164 patients with lung cancer.. The median value of healthy individuals was 1.3 ng/mL (95th percentile 1.8). In patients with benign pulmonary diseases, the median was 1.5 ng/mL (95th percentile 2.9). There is no significant difference between sexes, smoking habit, and the subgroups of benign pulmonary disease, such as tuberculosis, pneumonia, or COPD. Using the cutoff value of 3.3 ng/mL, defined at 95% specificity for benign lung disease, the sensitivities of CYFRA 21-1 for squamous cell carcinoma (n=74), adenocarcinoma (n=54), undifferentiated large cell carcinoma (n=11), and small cell lung cancer (n=25) were 62%, 39%, 36%, and 20%, respectively. Despite the cell types, the sensitivities of CYFRA 21-1 in non-small cell lung cancer (NSCLC, n=169) were 51% (CEA 42%, SCC 20%). The sensitivity of CEA was significantly higher in patients with adenocarcinoma (58%) than other markers; while in patients with squamous cell carcinoma, CYFRA 21-1 assay has the highest sensitivity. The median level of CYFRA 21-1 in squamous cell carcinoma is significantly higher than that of other cell types (Mann-Whitney test, p<0.001). The serum level and sensitivity of CYFRA 21-1 were well correlated with staging and tumor size in squamous cell carcinoma. The CYFRA 21-1 values were measured for monitoring progression of disease in 20 patients with squamous cell carcinoma. There is significant difference in paired observation of CYFRA 21-1 level in patients with progressive disease (Wilcoxon signed-rank test, p<0.05), but no difference was observed in patients with stabilized disease (p>0.1).. For patients with NSCLC, especially in squamous cell carcinoma, CYFRA 21-1 is not only a sensitive and specific tumor marker, but also may be a useful adjunctive marker for disease monitoring.

Topics: Adenocarcinoma; Antibodies, Monoclonal; Antigens, Neoplasm; Biomarkers, Tumor; Carcinoembryonic Antigen; Carcinoma, Non-Small-Cell Lung; Carcinoma, Small Cell; Carcinoma, Squamous Cell; Disease Progression; Enzyme-Linked Immunosorbent Assay; Epithelium; Female; Humans; Keratins; Lung Diseases; Lung Diseases, Obstructive; Lung Neoplasms; Male; Neoplasm Staging; Pneumonia; Sensitivity and Specificity; Serine Proteinase Inhibitors; Serpins; Sex Factors; Smoking; Tuberculosis, Pulmonary

In the present study, epithelial cells in the bone marrow of 42 patients with pancreatic carcinoma were identified immunocytochemically with monoclonal antibodies (MAbs) CK2, KL1 and A45-B/B3 directed to epithelial cytokeratins (CK), using the alkaline phosphatase anti-alkaline phosphatase method. The specificity of the MAbs was demonstrated by negative staining of marrow from 25 non-carcinoma age-matched control patients. Analysis of bone marrow aspirates from cancer patients revealed CK-positive cells in 14 (58.3%) of 24 cancer patients treated with curative intent and 10 (55.6%) of 18 patients with extended disease. After a median follow-up of 15.6 months (range 3-31 months), 5 (35.7%) out of 14 patients who underwent complete surgical resection but had tumour cells in bone marrow presented with distant metastasis and 6 (42.9%) with local relapse as compared to none of 10 corresponding patients without such cells (P < 0.05). The described technique may help to identify patients with pancreatic cancer and potential high risk of early metastatic relapse. The results promise to be of important assistance in determining prognosis and consequences in therapy of early stage pancreatic cancer.

Topics: Adenocarcinoma; Antibodies, Monoclonal; Bone Marrow Neoplasms; Follow-Up Studies; Humans; Immunoenzyme Techniques; Keratins; Neoplasm Proteins; Neoplasm Recurrence, Local; Pancreatic Neoplasms; Prospective Studies

Genuine adenocarcinomas of the ureter are rare tumors and have to be distinguished from other gland-forming malignancies arising from the transitional epithelium, due to the poor clinical outcome. The histopathological features of a tumor combined with intestinal metaplasia of the adjacent urothelium are described. The tumor has to be distinguished from transitional cell cancer with glandular metaplasia, muco-urothelial cancer, microcystic transitional cell cancer and transitional cell cancer with mucoid cytoplasmatic inclusions. Immunohistochemical analysis of the cancer shows positivity for carcinoembryonic antigen and a staining pattern characteristic for adenocarcinomas. The expression of keratin types 7 and 13, which is typically found in transitional cell carcinomas, is lost.

Topics: Adenocarcinoma; Aged; Carcinoembryonic Antigen; Carcinoma, Transitional Cell; Diagnosis, Differential; Humans; Immunoenzyme Techniques; Keratins; Male; Metaplasia; Mucin-1; Neoplasm Proteins; Ureteral Neoplasms

Twenty-four salivary gland tumours (six pleomorphic adenomas, two myoepitheliomas, five basal cell adenomas, six adenoid cystic carcinomas and five polymorphous low grade adenocarcinomas) were investigated by an immunocytochemical technique using monoclonal antibodies against cytokeratins (CKs) 7, 8, 10, 13, 14, 18 and 19. The luminal cells of ductal structures of the tumours reacted with all the CKs studied except for CK 13 and CK 10 and sometimes CK 14, showing an immunoprofile comparable to that of the intercalated segment of a normal salivary gland. The outer cells of the ducts rarely stained with CK 14, confirming that full differentiation of the myoepithelial cells is seldom achieved in tumours. Considerations were made regarding the intriguing expression of CK 14, the heterogeneous expression of CKs in the modified myoepithelial cells and the immunoprofile of the polymorphous low-grade adenocarcinoma.

Topics: Adenocarcinoma; Adenoma; Adenoma, Pleomorphic; Antibodies, Monoclonal; Biomarkers, Tumor; Humans; Keratins; Myoepithelioma; Neoplasm Proteins; Salivary Gland Neoplasms

The histologic distinction between adenocarcinoma primary to the ovary and metastatic to the ovary can be difficult. In an effort to facilitate this distinction, we have evaluated the use of immunohistochemical techniques with antibodies to cytokeratins 7 and 20, along with antibodies to carcinoembryonic antigen. We studied 24 primary ovarian adenocarcinomas, 11 colonic adenocarcinomas metastatic to the ovary, and 10 primary adenocarcinomas of the colon. Four ovarian adenocarcinomas metastatic to the colon were also studied. All but one of the primary and metastatic colonic carcinomas were negative for cytokeratin 7, whereas all the primary and metastatic ovarian carcinomas were positive for cytokeratin 7. The tumors metastatic to the ovary were all positive for cytokeratin 20 and carcinoembryonic antigen. Among the primary ovarian carcinomas, none of six serous tumors, three of seven endometrioid tumors, and three of 11 mucinous tumors were positive for cytokeratin 20. Ten of the primary ovarian tumors were negative for carcinoembryonic antigen using both monoclonal and polyclonal antibodies. One of the ovarian tumors was negative for carcinoembryonic antigen with the monoclonal antibody but positive using the polyclonal antibody. Cytokeratin 7 is the most helpful marker in the distinction between primary ovarian carcinoma and colonic carcinoma metastatic to the ovary.

Topics: Adenocarcinoma; Antibodies, Monoclonal; Biomarkers, Tumor; Carcinoembryonic Antigen; Colonic Neoplasms; Female; Humans; Immunohistochemistry; Intermediate Filament Proteins; Keratin-20; Keratins; Ovarian Neoplasms

Keratin 19 is found primarily in simple epithelia. In mammary epithelia, keratin 19 was localized to a subset of luminal cells, suggesting that keratin 19-negative cells may be the proliferative compartment of the secretory cell lineage. The structural and functional similarities of prostate and breast led us to examine keratin 19 expression in the prostate. Immunohistochemical studies revealed that keratin 19 expression was heterogeneous and frequently occurred in basal as well as in luminal cells of normal, dysplastic, and benign hyperplastic tissues. Keratin 19 was observed in cancer, but usually in a minority of cells. This was in dramatic contrast to invasive breast cancers, which are reportedly uniformly positive for keratin 19. Prostatic epithelial cells cultured from tissues of all histologies expressed keratin 19. In summary, keratin 19 does not obviously correlate with any epithelial cell lineage or phenotype in the prostate.

Topics: Adenocarcinoma; Adult; Antibodies, Monoclonal; Atrophy; Cells, Cultured; Culture Techniques; Humans; Immunoblotting; Immunohistochemistry; Keratins; Male; Prostate; Prostatic Hyperplasia; Prostatic Neoplasms

Minimal residual disease in patients with operable pancreas carcinoma is frequently missed by current non-invasive tumor staging.. We applied an immunocytochemical cytokeratin assay that allows the identification of individual pancreas carcinoma cells disseminated to bone marrow.. Prior to therapy bone marrow was aspirated from the upper iliac crest of 42 patients with pancreas carcinoma and a control group of 30 non-carcinoma patients. Tumor cells in cytologic bone marrow preparations were detected with monoclonal antibodies (mAbs) CK2, KL1 and A45-B/B3 to epithelial cytokeratins (CK), using the APAAP-method.. CK-positive cells were found in 14 (58.3%) of 24 cancer patients treated in curative intent and 10 (55.6%) of 18 patients with extended disease. After a mean follow up of 12.7 (3-32) months, 6 (42.8%) out of 14 patients who underwent complete surgical resection presented with tumor relapse and 5 (35.7%) with distant metastases as compared to none of 10 corresponding patients without such cells (p < 0.04). Moreover, patients with epithelial tumor cells in bone marrow showed also a significantly shorter overall survival than those without tumor cells (p < 0.03).. Immunocytochemical screening for epithelial tumor cells in bone marrow might contribute to an improved staging and is of prognostic relevance for pancreas carcinoma patients.

Topics: Adenocarcinoma; Biomarkers, Tumor; Biopsy, Needle; Bone Marrow; Bone Marrow Neoplasms; Follow-Up Studies; Humans; Immunoenzyme Techniques; Keratins; Pancreas; Pancreatectomy; Pancreatic Neoplasms; Survival Rate

A subline of human pancreatic cells (PanC1) that expresses low levels of cytokeratins 8 and 18 but not MUC1 mucin was transfected with both 3.5-kb and 3.9-kb full-length MUC1 cDNA. The MUC1-positive clone expressing the larger mucin was shown to express increased levels of cytokeratins 8 and 18 compared with the parental line or vector controls. Growth of these MUC1-transfected cells in type I collagen gels produced marked gel contraction that could be significantly reduced by the synthetic peptide SRGDTG or by growth in serum and fibronectin-depleted media. Cellular binding to type I collagen was found to be reduced by two- to four-fold in cells expressing the MUC1 mucin, for which the greatest inhibition was observed in cells expressing the larger form. No difference in cellular binding to fibronectin was observed. From these data we conclude that the human MUC1 mucin modifies the differentiated state of human pancreatic cells by altering cytokeratin expression and reducing adhesion to type I collagen but paradoxically enhancing the cellular contractile phenotype, effects that appear to be mediated by integrin expression and/or function.

Topics: Adenocarcinoma; Blotting, Western; Cell Adhesion; Collagen; Extracellular Matrix; Fibronectins; Humans; Immunohistochemistry; Keratins; Mucin-1; Neoplasm Proteins; Pancreatic Neoplasms; Transfection; Tumor Cells, Cultured

Topics: Adenocarcinoma; Cardia; Duodenal Neoplasms; Duodenoscopy; Gastroscopy; Humans; Keratins; Male; Middle Aged; Mucins; Pyloric Antrum; Stomach Neoplasms

The differential expression of keratins in myoepithelial and epithelial cells of the breast makes immunohistochemical distinction of lesions an attractive possibility. High molecular weight keratin, 34BE12, is a monoclonal antibody that recognizes keratins 1, 5, 10, and 14. Because myoepithelial cells predominantly express keratins 5 and 14 and epithelial cells predominantly express keratins 8 and 18, it is natural to assume that 34BE12 may be a good marker of myoepithelial cells but not epithelial cells. However, recent studies of the breast have reported conflicting results. To determine the potential role of 34BE12 in the breast, we studied by immunohistochemistry 19 tubular carcinomas, 14 radial scars, two microglandular adenoses, and 9 sclerosing adenoses, using monoclonal antibodies to high molecular weight keratin, smooth muscle actin, type IV collagen, and antiserum to S100 protein. Actin was negative in all 19 (100%) tubular carcinomas, but it delineated the myoepithelial cells in 22 of 23 (95.6%) benign lesions of sclerosing adenosis and radial scars; it was also negative in microglandular adenosis. In comparison, epithelial cytoplasmic 34BE12 reactivity was seen in 3 of 19 (15.8%) tubular carcinomas, whereas myoepithelial cells failed to react in 4 of 23 (17.3%) benign conditions. Antiserum to S100 protein had a similar disadvantage of labeling both epithelial and myoepithelial cells with reactivity in 5 of 19 (26.3%) tubular carcinomas. In microglandular adenosis, the epithelial cells were strongly S100 protein positive and focally 34BE12 positive, but no staining was observed for actin. Type IV collagen staining outlined distinct basement membranes in microglandular adenosis and other benign conditions but not in tubular carcinomas. However, staining for type IV collagen requires enzymatic pretreatment and is difficult to perform, especially in sclerotic breast tissue. In conclusion, actin appears to be the most consistent and specific marker for distinguishing tubular carcinomas from other benign conditions, and type IV collagen has a contributory role, whereas 34BE12 is less valuable than in prostatic biopsies.

Topics: Actins; Adenocarcinoma; Adenofibroma; Antibodies, Monoclonal; Biomarkers, Tumor; Breast Diseases; Breast Neoplasms; Cell Division; Collagen; Diagnosis, Differential; Humans; Immunohistochemistry; Keratins; S100 Proteins

Epithelial cells in the bone marrow of 42 patients with pancreatic carcinoma were identified immunocytochemically with monoclonal antibodies directed to epithelial cytokeratins. The occurrence of tumor relapse in patients who underwent complete surgical resection was significantly associated with cytokeratin-positivity in bone marrow. The presence of these cells in indicative of an increased disseminative capability of the primary tumor and defines a new category of patients for neoadjuvant therapy.

Topics: Adenocarcinoma; Bone Marrow; Epithelium; Humans; Immunohistochemistry; Keratins; Neoplasm Recurrence, Local; Pancreatic Neoplasms; Prognosis; Prospective Studies

In order to improve the diagnosis of lung carcinoma, in which a complicated histologic pattern is present, the immunohistochemistry of 119 adenocarcinomas, 65 squamous cell carcinomas, 12 small cell carcinomas, 18 large cell carcinomas, and 15 metastatic adenocarcinoma in the lung were evaluated using a monoclonal antibody, KM195, against lung carcinoma, and compared with the immunohistochemical results using anti-human cytokeratin (CAM 5.2) and other monoclonal antibodies. Formalin-fixed, paraffin-embedded tissues were stained using the labeled streptavidin-biotin method. Extracts from fresh tissue homogenate, after fractionation by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, were transferred by Western blotting and stained with KM195. The anti-lung adenocarcinoma, murine, monoclonal antibody KM195 (IgG), was positive in 107 of 119 adenocarcinomas (90%), in 15 of 18 large cell carcinoma (83%), in three of 65 squamous cell carcinomas (5%), 13 of 15 (87%) metastatic adenocarcinoma in the lung, and was negative in 12 small cell carcinomas (P < 0.001). KM195-bound protein of primary and metastatic adenocarcinoma in the lung cases concentrated at about 40 kDa. In contrast, CAM 5.2 was positive in 52 of 67 (78%) adenocarcinomas, 10 of 62 (16%) squamous cell carcinomas, and was negative in six small cell carcinomas. These results suggest that the immunohistochemistry for KM195 may be a more useful marker over CAM 5.2 for the diagnosis of pulmonary adenocarcinoma.

Topics: Adenocarcinoma; Antibodies, Monoclonal; Bacterial Proteins; Biomarkers, Tumor; Biotin; Blotting, Western; Carcinoembryonic Antigen; Humans; Immunohistochemistry; Keratins; Lung; Lung Neoplasms; Oligosaccharides; Paraffin Embedding; Reference Values; Sialyl Lewis X Antigen; Tissue Fixation

We performed immunohistochemical studies on 90 surgically resected liver tumors, including 30 tumors each from hepatocellular carcinoma (HCC), cholangiocarcinoma (CC), and metastatic colorectal adenocarcinoma (MCA), using monoclonal antibodies against cytokeratin (CK) 7, CK 19, and CK 20 to examine the differences in the CK expressions in primary and metastatic carcinomas of the liver. We also investigated the usefulness of such expression in the differential diagnosis in addition to existing markers such as alpha-fetoprotein, carcinoembryonic antigen, and carbohydrate antigen 19-9. For CK 7, all except for one (97%) of the CCs were diffusely positive, whereas only two (7%) HCCs and one (3%) MCAs were diffusely positive. For CK 19, 23 (77%) CCs and 19 (64%) MCAs were diffusely positive, whereas no HCCs were positive. For CK 20, 22 (74%) MCAs were diffusely positive, whereas no HCC and three (10%) CCs were diffusely positive. The findings concerning the expression of immunohistochemical CK are therefore considered to be useful in addition to the diagnostic criteria when making a differential diagnosis of primary and metastatic carcinomas of the liver.

Topics: Adenocarcinoma; Bile Duct Neoplasms; Bile Ducts, Intrahepatic; Biomarkers, Tumor; Carcinoma, Hepatocellular; Cholangiocarcinoma; Colorectal Neoplasms; Diagnosis, Differential; Humans; Immunoenzyme Techniques; Intermediate Filament Proteins; Keratin-20; Keratins; Liver Neoplasms

Serum CYFRA21-1 levels were studied in 127 cases of colorectal cancer. The positive rates for serum CYFRA21-1 were 34.6% in primary colorectal cancer. There was a significant correlation between the positive rates of serum CYFRA21-1 and liver metastases, peritoneal dissemination, lymph node metastases, or clinical stage. The survival rate for patients in the CYFRA21-1 positive group was lower than those with CYFRA21-1 negative group. Among patients who underwent curative operation, patients is the CYFRA21-1 positive group gave a recurrence rate of 26.6%, against 9.4% in the CYFRA21-1 negative group. There was no correlation between serum CYFRA21-1 levels and serum CEA levels. These findings suggest that Serum CYFRA21-1 levels may be a useful indicator in estimating the prognosis for colorectal cancer.

Topics: Adenocarcinoma; Antibodies, Monoclonal; Biomarkers, Tumor; Colonic Neoplasms; Humans; Keratins; Liver Neoplasms; Lymphatic Metastasis; Neoplasm Invasiveness; Prognosis; Rectal Neoplasms; Survival Rate

To clarify the pattern of cytokeratin and vimentin expression in mixed adenocarcinoma and squamous cell carcinoma of the uterine cervix, twenty-three cases of formalin-fixed paraffin-embedded specimen were examined immunohistochemically using a panel of four different monoclonal anti-cytokeratin antibodies and anti-vimentin antibody. Fifty-seven cases of benign or malignant tissue were selected for controls. The results were summarized as follows. 1) In four cases of co-existing adenocarcinoma and squamous cell carcinoma, their immunostaining patterns were compatible with original histological cell type. 2) In four cases of adenoacanthoma, high molecular weight-cytokeratin (HCK) was positive in each acanthomatous component and only a small part of one adenocarcinomatous component. 3) In twelve cases of cervical adenosquamous carcinoma, HCK were positive in four adenocarcinomatous components. Out of eight cases with non-stained adenocarcinomatous components, six cases showed negativity for HCK even in the squamous cell carcinomatous component. 4) Though vimentin was negative in all cases of mixed type of cervical carcinoma, some cases of mixed type endometrial carcinoma were stained positively for vimentin. It was indicated from our study that adenosquamous carcinoma of the cervix could originate either in reserve cells or columunar epithelium and that vimentin positive cases could originate in the endometorial gland.

Topics: Adenocarcinoma; Antibodies, Monoclonal; Carcinoma, Squamous Cell; Female; Humans; Immunohistochemistry; Intermediate Filament Proteins; Keratins; Paraffin Embedding; Uterine Cervical Neoplasms; Vimentin

Serum soluble cytokeratin 19 fragment (CYFRA) levels were measured in 251 patients with lung cancer and 139 patients with benign lung diseases to determine the clinical usefulness of CYFRA level determination in the diagnosis and monitoring of lung cancer. Serum levels of CYFRA were measured by a 2-step sandwich ELISA method. When the cut-off value was defined as 3.5 ng/ml, which was associated with a specificity of 95% for benign lung diseases, CYFRA had a high sensitivity (53%) in all patients with lung cancer. Both the serum level of CYFRA and its sensitivity increased significantly with the increase in clinical stage. A comparison of areas under receiver operating characteristic curves showed that CYFRA had the most power of discrimination in the diagnosis of lung cancer among markers including carcinoembryonic antigen, squamous cell carcinoma antigen, carbohydrate antigen 19-9, and neuron-specific enolase. A good correlation was found between serial changes in serum CYFRA levels during therapy and clinical responses for 18 patients who underwent chemotherapy and/or radiotherapy. Our findings suggest that CYFRA may be a marker of choice for screening and monitoring of lung cancer, particularly squamous cell carcinoma.

Topics: Adenocarcinoma; Aged; Biomarkers, Tumor; Carcinoma; Carcinoma, Large Cell; Carcinoma, Non-Small-Cell Lung; Carcinoma, Squamous Cell; Enzyme-Linked Immunosorbent Assay; Female; Humans; Keratins; Lung Neoplasms; Male; Neoplasm Staging; Prognosis; Retrospective Studies; Sensitivity and Specificity; Survival Rate

The differentiation of ovarian metastases from colonic carcinoma and primary ovarian carcinoma can be difficult. To assess the utility of cytokeratin 7 and cytokeratin 20 immunostains in this setting, we studied routinely processed, formalin-fixed tissue from 165 ovarian tumors, including 45 serous carcinomas, 40 mucinous carcinomas, 64 endometrioid carcinomas, and 16 metastatic colonic adenocarcinomas with an avidin-biotin immunohistochemical technique. A cytokeratin 7+/cytokeratin 20- immunophenotype was seen in 86% of the endometrioid carcinomas, 27% of the mucinous carcinomas, 40% of the serous carcinomas, and none of the metastatic colorectal carcinomas. Conversely, a cytokeratin 7-/cytokeratin 20+ immunophenotype was seen in 94% of the metastatic colonic tumors, 5% of the mucinous carcinomas, and none of the endometrioid or serous tumors. We concluded that cytokeratin immunostains can be helpful in distinguishing metastatic colonic adenocarcinoma from primary ovarian carcinomas, particularly endometrioid carcinomas. Rare ovarian mucinous carcinomas may show the same immunophenotype as metastatic colonic carcinomas.

Topics: Adenocarcinoma; Biomarkers, Tumor; Carcinoma, Endometrioid; Colonic Neoplasms; Diagnosis, Differential; Female; Humans; Immunoenzyme Techniques; Keratins; Ovarian Neoplasms

We report here the development of bacterial chain reaction (BCR), a system using micro organisms as nanodevices to amplify and visualize signals from molecular bioprobes such as antibodies, binding proteins, lectins, and oligonucleotides. Unlike conventional enzyme-linked amplification systems in which the amount of enzyme is a constant parameter, in the BCR an enzyme (penicillinase) is used to trigger a proliferative chain reaction producing an exponential increase in enzyme. The detection limits and specificity of BCR were determined using a model system designed to detect and enumerate MCF-7 (a human breast adenocarcinoma cell line) cells disseminated at extremely low frequency (e.g., one tumor cell per million normal cells) among monocluclear cells (MNCs) of human peripheral blood. Results of testing 83 specimens of peripheral blood from presumably healthy donors showed 97.6% specificity. The system was capable of detecting tumor cells at a frequency of 2 x 10(-7).

Topics: Adenocarcinoma; Breast Neoplasms; Female; Humans; Immunohistochemistry; Keratins; Penicillinase; Reproducibility of Results; Sarcina; Sensitivity and Specificity

Intraluminal contents in benign and malignant prostate glands from 10 prostatectomies were studied by light and electron microscopy as well as X-ray microanalysis. Ultrastructural immunolocalization of keratin and analysis of the pattern of lectin binding for wheat germ agglutinin (WGA), peanut agglutinin (PNA) and soy bean agglutinin (SBA) were performed. By electron microscopy corpora amylacea were composed of bundles of fibrils and occasional interspersed electron-dense areas. Crystalloids on the other hand were relatively electron-dense formations without any identifiable substructure. Complete or partial enclosement of the crystalloids by the fibrillary or electron-dense material that forms the corpora amylacea was often seen. Histochemistry localized keratin and glycoproteins in all types of intraluminal contents. However, the proportion of these components varied. Keratin and WGA binding were identified primarily in the amorphous secretions and in corpora amylacea, but were only minimally represented in crystalloids. PNA and SBA were found predominantly in crystalloids, with only minimal amounts identified in corpora amylacea. By X-ray microanalysis sulfur was identified primarily in crystalloids and surrounding amorphous secretion, but lesser quantities of sulfur were also found in corpora amylacea. In summary, the morphological and histochemical findings indicate that the intraluminal contents in benign and malignant glands form a continuous spectrum and are largely composed of material derived from the components of lining cells.

Topics: Adenocarcinoma; Crystallization; Cytoplasmic Granules; Humans; Immunohistochemistry; Inclusion Bodies; Keratins; Lectins; Male; Prostate; Prostatic Diseases; Prostatic Neoplasms; Sulfur; X-Rays

Recently, the expression of vimentin has been reported in some carcinomas. This study was designed to clarify the significance of vimentin expression in solid type poorly differentiated adenocarcinomas of the stomach. Immunohistochemically, 239 poorly differentiated adenocarcinomas with solid components of the stomach were stained for vimentin. Vimentin-positive cases were also stained by CAM 5.2 using serial mirror sections. We found 15(6.3%) vimentin-positive cases. Twelve of them demonstrated varying amounts of rhabdoid-like cells. Eight cases diffusely co-expressed vimentin and cytokeratin simultaneously. In addition, four co-expressing cases showed positive staining with Keratin-903 which recognizes the high molecular-weight cytokeratin. Most of the co-expressing cases showed a diffuse proliferation of polygonal tumour cells with focal cell-to-cell contact. The prognosis of the co-expressing cases was poor in comparison with that of the 89 vimentin-negative tumours (P < 0.05).

Topics: Adenocarcinoma; Adult; Aged; Biomarkers; Female; Humans; Immunohistochemistry; Keratins; Male; Middle Aged; Prognosis; Stomach Neoplasms; Survival Analysis; Vimentin

In order to understand the characteristics of proliferative and malignant prostate lesions and to improve the differential diagnosis, immunohistochemical methods using high molecular weight cytokeratin monoclonal antibody 34BE12 to stain the basal cells and to differentiate prostate cancer from hyperplasia in 82 prostate biopsies and specimens, which included 21 adenocarcinoma, 30 intraepithelial neoplasia, 5 atypical adenomatous hyperplasia, 8 basal cell hyperplasia, 11 atrophy of prostate, 4 postatrophic hyperplasia and 3 cribriform hyperplasia. It was demonstrated that the basal cell layer was lost in all prostate adenocarcinomas, but existed in most of the proliferative lesions except for atypical adenomatous hyperplasia and grade 3 intra-epithelial neoplasia in which the basal layer was disrupted in some cases. The study showed that the 34BE12 antibody was useful in the differential diagnosis of prostate adenocarcinoma.

Topics: Adenocarcinoma; Diagnosis, Differential; Humans; Immunohistochemistry; Keratins; Male; Molecular Weight; Prostatic Hyperplasia; Prostatic Intraepithelial Neoplasia; Prostatic Neoplasms

Monoclonal antibodies against cytokeratin (AE1/AE3) were applied as a prob, using APAAP immunohistochemistry technique to detect 635 lymph nodes from 45 breast cancer patients with negative lymph nodes. Micrometastases were identified in 14 lymph nodes of 9 cases (20%). A significant difference was found between cytokeratin staining positive group and cytokeratin staining negative group in disease-free and over-all Kaplan-Meier survival curves. The detection of micrometastases had more clinical value for T1 and T2 patients. One of 2 T1 cytokeratin positive cases relapsed while only 1 of 19 T1 negative cases relapsed within 5 years, three of 5 T2 cytokeratin positive cases relapsed while 1 of 17 negative cases did. The presence of micrometastases had the same value in predicting local recurrence and distant metastases.

Topics: Adenocarcinoma; Adult; Aged; Axilla; Breast Neoplasms; Carcinoma, Ductal, Breast; Female; Follow-Up Studies; Humans; Keratins; Lymph Nodes; Lymphatic Metastasis; Middle Aged; Prognosis

Patterns of cell proliferation in the prostate were compared between benign epithelium and dysplasia. Proliferating cell nuclear antigen (PCNA) immunostaining was used to quantitate proliferation, and basal cells were tallied separately from secretory cells with the aid of keratin immunostaining. Using a novel technique, absolute cell densities (cells/mm) were determined and used to calculate growth fractions. In benign epithelium, 83% of PCNA+ cells were basal cells, while only 7% of PCNA+ cells in dysplasia were basal cells and there was a clear separation between groups. This dramatic shift of the proliferative compartment to the secretory cells in dysplasia was accompanied only by a moderate increase in overall secretory cell density and moderate reduction in basal cell density, but these ranges overlapped those of benign epithelium. The median PCNA+ secretory cell "growth fraction" was 0.12% in benign epithelium and 1.06% in dysplasia. The findings presented give further support to the concept that dysplasia represents an evolutionary stage in the malignant transformation of prostatic epithelium. The patterns of change in PCNA immunostaining may reflect certain aspects of the biologic nature of malignant transformation.

Topics: Adenocarcinoma; Cell Count; Cell Division; Epithelial Cells; Epithelium; Humans; Immunohistochemistry; Keratins; Male; Precancerous Conditions; Proliferating Cell Nuclear Antigen; Prostate; Prostatic Neoplasms

A hormone-dependent, clonal carcinoma cell line, designated RM22-F5, was derived from a malignant mammary mixed tumor spontaneously arising in an outbred old female Wistar rat. These cells expressed keratin and desmosomal protein and formed epithelial monolayers in a growth factor and hormone-supplemented medium (LHC-8) containing 10% fetal bovine serum (E-type cells). Cells subcultured for 6 to 8 passages in RPMI 1640 medium containing 10% fetal bovine serum without supplements appeared to be fibroblastic and expressed vimentin (F-type cells). The shift to a fibroblast-like morphology was associated with a more malignant phenotype which included rapid, hormone-independent growth and invasive sarcoma-like character in nude mice. F-type cells were no longer able to express their original epithelial phenotype in LHC-8 medium. Cytogenetic analysis revealed that both E- and F-type cells had essentially the same karyotype. Analysis of PCR-amplified DNA further demonstrated a point mutation of the H-ras-1 gene at codon 12 and loss of the normal H-ras-1 allele in both cell types. Genetic tagging of E-type cells with the neomycin-resistance gene resulted in the generation of F-type cells with neomycin resistance in RPMI 1640 medium, suggesting that F-type cells are a malignant variant of E-type cells arising during in vitro culture. Somatic cell fusion between E- and F-type cells revealed that with most hybrid clones tested, the fibroblast-like phenotype was greatly suppressed. These results suggest that an irreversible phenotypic transition, representative of tumor progression from hormone-dependent adenocarcinoma to more malignant hormone-independent spindle carcinoma cells, is a recessive event and may involve loss of a suppressor function.

Topics: Adenocarcinoma; Animals; Base Sequence; Carcinoma; Cell Division; Cell Fusion; Cell Transformation, Neoplastic; Culture Media; Desmosomes; Female; Flow Cytometry; Genes, ras; Keratins; Mammary Neoplasms, Animal; Mice; Mice, Nude; Molecular Sequence Data; Neomycin; Neoplasm Invasiveness; Neoplasms, Hormone-Dependent; Phenotype; Rats; Rats, Wistar; Transfection; Tumor Cells, Cultured; Vimentin

Circulating cancer cells in the blood play a central role in the metastatic process. Their number can be very small and techniques for their detection need to be both sensitive and specific. Polymerase chain reaction (PCR) has been successfully used to detect small numbers of tumour cells in haematological cancer in which abnormalities in DNA are sufficiently consistent to make this possible. For most solid tumours this not yet feasible. However, we have found that reverse transcriptase (RT)-PRC for tissue-specific gene expression is a useful technique for identifying small numbers of circulating cells in melanoma and neuroblastoma patients. In this report we describe detection of colon carcinoma cells by RT-PCR using CK 20 mRNA as a marker. Unlike other cytokeratin genes examined (CK 8 and CK 19), CK 20 was not transcribed in normal haematopoietic cells. This suggests a role for RT-PCR in the detection of colon carcinoma metastasis in blood and bone marrow, using CK 20 as the target gene. Future analysis of clinical material will determine the clinical significance of this technique.

Topics: Adenocarcinoma; Base Sequence; Biomarkers, Tumor; Bone Marrow; Breast Neoplasms; Carcinoma, Transitional Cell; Colonic Neoplasms; Epithelium; Humans; Keratins; Molecular Sequence Data; Neoplasm Metastasis; Neoplasm Proteins; Neoplastic Cells, Circulating; Polymerase Chain Reaction; RNA, Messenger; RNA, Neoplasm; Sensitivity and Specificity; Tumor Cells, Cultured; Urinary Bladder Neoplasms

Basal cell-specific anti-cytokeratin antibody (34 beta E12) decorates the basal cells of benign prostatic epithelium by standard immunohistochemical techniques, whereas adenocarcinoma of the prostate lacks immunoreactivity with this antibody. We reviewed our experience with this antibody to determine its utility in the diagnosis of adenocarcinoma of the prostate as well as its pattern of usage at a tertiary medical center. In all, 7,242 prostate specimens from 5,262 men were seen at Johns Hopkins Hospital between 1/89 and 4/93. Immunostaining for basal cell-specific cytokeratin (34 beta E12) was originally used for diagnostic purposes in 289 questionable area from 228 cases; 45% of these cases were seen in consultation. The distribution of cases using 34 beta E12 was 52% needle biopsies, 32% transurethral prostatic resections (TURPs). 13% radical prostatectomies, and 3% open enucleations. These procedures constituted 2.8% of all needle biopsies, 7.2% of all TURPs, 1.7% of all radical prostatectomies, and 3.5% of all enucleations seen during this time period. For this study the hematoxylin and eosin stain was reviewed without knowledge of the original diagnosis, a diagnosis was favored, the 34 beta E12 stain was examined, and a final diagnosis was determined. The 34 beta E12 stain established (14%), confirmed (58%), or changed (2%) our favored diagnoses, while 18% remained or became equivocal. The 34 beta E12 stain was of no use in 8% of the cases, yet we felt we were still able to render a final diagnosis even without the help of the stain. The differential diagnoses in the questionable foci using 34 beta E12 were cancer versus focus of atypical glands (44%), adenosis (39%), prostatic intraepithelial neoplasia (PIN) (8%), basal cell hyperplasia (5%), and atrophy (4%). However, 34 beta E12 was used in only 15-20% of all cases of adenosis and basal cell hyperplasia and in < 2% of PIN and atrophy cases seen during this time. Reasons for equivocal results were loss of suspicious glands on cut downs used for staining (49%), too few glands to rely on negative staining (23%), technical problems (15%), limited number of positive staining glands in a small focus (7%), and cautery artifact (6%). Although equivocal cases tended to have fewer negative stained glands than cases diagnosed with cancer, there was no minimum number of negative stained glands required to establish a diagnosis of cancer. From these data we conclude that 34 beta E12 staining is a useful tool

Topics: Adenocarcinoma; Antibodies; Diagnosis, Differential; Humans; Immunohistochemistry; Keratins; Male; Prostatic Neoplasms

Topics: Adenocarcinoma; Animals; Carcinoembryonic Antigen; Cecal Neoplasms; Female; Hylobates; Immunohistochemistry; Keratins; Membrane Glycoproteins; Monkey Diseases; Mucin-1; Mucins; Muramidase

We report on six patients with tumours of visceral organs (three patients with endometrial adenocarcinoma with squamous cell differentiation, one patient with atypical hyperplasia of endometrium, and two patients with adenocarcinoma of the colon with squamous cell differentiation), where unquestionable differentiation into shadow cells was observed. In all six cases the shadow cells were found mostly in the morules of immature squamous cells. The shadow cells were morphologically identical, on the light microscopical and ultrastructural level, to similar cells found in pilomatricomas. They were often accompanied by granulomatous giant cell reaction and calcification.

Topics: Adenocarcinoma; Adult; Carcinoma, Squamous Cell; Cell Differentiation; Colonic Neoplasms; Endometrial Neoplasms; Endometrium; Female; Humans; Hyperplasia; Keratins; Male; Microscopy, Electron; Middle Aged; Uterine Neoplasms; Uterus

We wanted to investigate the diagnostic and prognostic significance of serum CYFRA 21-1, especially in predicting the risk of recurrence in patients with operable squamous cell lung cancer. Serum levels of CYFRA 21-1 were measured using an immunoradiometric assay (CIS bio) in 76 patients with squamous cell lung cancer (64 operable and 12 with unresectable tumours), 22 with other non-small-cell type (12 with adenocarcinoma and 10 with large-cell type) and 45 with nonmalignant lung diseases. Elevated preoperative CYFRA 21-1 levels were identified in 63% of patients with squamous cell type (SqCC), 33% with adenocarcinoma, and 30% with large-cell carcinoma type. The diagnostic specificity of the assay was 96%. Positive CYFRA 21-1 levels were observed in 33% of stage I, 52% of stage II, 76% of stage IIIa and 83% of stage IIIb patients with SqCC type. Statistically significant differences were obtained between stages I and II and between II and IIIa, but not between stages IIIa and IIIb. Recurrence-free survival probability for patients with elevated serum CYFRA 21-1 levels before surgery was 63% (24/38) versus 92% (24/26) for patients with normal serum CYFRA 21-1 levels. However, the difference was not statistically significant when adjusted for the TNM stage (primary tumour, regional lymph node involvement, occurrence of distant metastasis). In 9 of the 10 patients with increased trend for CYFRA 21-1 during follow-up, elevated serum CYFRA 21-1 levels preceded (7) or coincided (2) with the clinical detection of tumour recurrence, providing a predictive value of an increased trend of 90%.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adenocarcinoma; Biomarkers, Tumor; Carcinoma, Non-Small-Cell Lung; Carcinoma, Squamous Cell; Humans; Immunoradiometric Assay; Keratins; Lung Neoplasms; Multivariate Analysis; Neoplasm Recurrence, Local; Prognosis; Proportional Hazards Models; Risk Factors; Sensitivity and Specificity; Survival Analysis

Eccrine (sweat gland) carcinoma is a rare form of skin cancer that may be locally destructive. It is known to recur after resection and can metastasize to regional or distant lymph nodes. There have been two reported cases in association with patients immunocompromised as the result of organ transplantation (I. Penn: Prog Allergy. 37: 259, 1986). We report here the first case of sweat gland carcinoma in a patient infected with the human immunodeficiency virus.

Topics: Acquired Immunodeficiency Syndrome; Adenocarcinoma; Carcinoembryonic Antigen; Humans; Immunohistochemistry; Keratins; Male; Middle Aged; Skin Neoplasms

Cytokeratins are epithelial markers whose expression is not lost during malignant transformation. Cyfra 21-1 is a cytokeratin-19 fragment that is soluble in serum and may be a useful circulating tumor marker.. The aims of this study were (1) to confirm sensitivity and specificity of Cyfra 21-1 in detecting non-small cell lung cancer (NSCLC) and especially the squamous cell subtype, (2) to assess the potential relationship between Cyfra 21-1 and disease stage of the disease in NSCLC, and (3) to evaluate prognostic effect of Cyfra 21-1 in NSCLC.. An immunoradiometric assay of serum Cyfra 21-1 was performed in 161 patients with lung cancers and 71 others with benign lung diseases. The ability of Cyfra 21-1 to detect different histologic subtypes of lung cancer vs benign lung diseases was assessed through receiver operating characteristic (ROC) curves and comparisons with other tumor markers such as carcinoembryonic antigen, neuron-specific enolase, and squamous cell carcinoma antigen. Comparisons of Cyfra 21-1 levels according to histologic subtype and disease stage were done using Kruskal-Wallis test. Independent prognostic value of Cyfra 21-1 was studied with a multivariate analysis of survival (Cox's model).. Using a threshold of 3.3 ng/mL for Cyfra 21-1, sensitivity and specificity were, respectively, 0.59 and 0.94 in NSCLC, 0.68 and 0.94 in the subgroup of the squamous cell carcinoma, and 0.19 and 0.94 in small cell lung cancer. Cyfra 21-1 levels were significantly higher in advanced NSCLC than in early-stage disease. All 29 patients with serum concentrations > 32 ng/mL had stage IIIB-IV and only one of 14 patients with stage I-II disease had Cyfra 21-1 level > 18 ng/mL. In the multivariate analysis of survival, Cyfra 21-1 was an independent prognostic factor along with performance status and disease stage in NSCLC.. Cyfra 21-1 is a sensitive and specific tumor marker of NSCLC, especially of squamous cell subtype. It also reflects the extent of the disease and has an independent prognostic role along with performance status and disease stage in NSCLC.. A high level of Cyfra 21-1 in apparently early-stage NSCLC should be an indication for more extensive workup before thoracotomy. The independent prognostic role of Cyfra 21-1 level may be useful in stratifying populations with advanced NSCLC or early-stage resected NSCLC as elevated Cyfra 21-1 levels might identify those patients at high risk for treatment failure.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Biomarkers, Tumor; Carcinoma, Non-Small-Cell Lung; Carcinoma, Squamous Cell; Female; Humans; Immunoradiometric Assay; Keratins; Lung Diseases; Lung Neoplasms; Male; Middle Aged; Predictive Value of Tests; Prospective Studies; ROC Curve; Sensitivity and Specificity

Radiation therapy is becoming a treatment of choice for many patients with prostatic carcinoma. Distinguishing radiation change in prostate glands from carcinoma may be difficult. In this study we objectively assessed, by morphometric methods, the nuclear characteristics of benign and malignant prostates with a history of radiation treatment (125I implant with or without prior external beam radiation). This is part of our continuing efforts to achieve difficult differential diagnoses by analyzing perimeter, diameter and nuclear profile area of cells or interest and applying methods of statistical classification. Biopsies were performed 18-36 months following implant therapy. Eleven cases with residual prostate tumor constituted the malignant group. These were compared to 20 benign cases (benign glands in the 11 carcinoma cases plus 9 other cases with no residual carcinoma). Immunohistochemical staining with keratin 903 was performed on all cases. Differences in the nuclear parameters were most evident in the average nuclear profile areas (32.5 microns 2 for the malignant groups vs. 39.6 for the benign) and in the mean maximal cord length (diameter) (7.4 microns for the malignant group vs. 9.0 for the benign). Classification, however, is based on the size distribution plots of nuclear profile areas, which, in the malignant cases, had a sharper peak at lower value, while the benign cases had higher value and a broader peak with a trailing off into the larger values. This study emphasized the marked nuclear alterations that occur in irradiated prostates.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adenocarcinoma; Atrophy; Biopsy, Needle; Brachytherapy; Cell Nucleus; Diagnosis, Differential; Follow-Up Studies; Humans; Image Processing, Computer-Assisted; Iodine Radioisotopes; Keratins; Male; Prostate; Prostatic Neoplasms

Pulmonary blastoma is a rare malignant neoplasm that histologically resembles airway structures and mesenchymal supporting tissues seen in the early phases of fetal lung development. The tumor either is biphasic with immature epithelial and stromal components or consists solely of an epithelial component. The preferred terminology for the latter is pulmonary endodermal tumor resembling fetal lung. Pulmonary blastoma is usually peripheral in location, and rarely does this tumor present intrabronchially. We report a case of pulmonary endodermal tumor resembling fetal lung presenting as a polypoid intrabronchial mass.

Topics: Adenocarcinoma; Adult; Animals; Carcinoembryonic Antigen; Diagnosis, Differential; Female; Humans; Immunohistochemistry; Keratins; Lung; Lung Neoplasms; Membrane Glycoproteins; Mucin-1; Mucins; Pulmonary Blastoma

The most common carcinomas metastatic to the ovary that mimic ovarian primaries are colonic adenocarcinomas and endometrial carcinomas. Conventional histochemical staining procedures, even in combination with additional immunohistochemical assays, are of limited value in distinguishing between these metastases and primary ovarian carcinomas. In this study we investigated whether the application of monoclonal antibodies against keratins 7, 8, and 20 could help in differentiating between these categories. The reactivity patterns of 40 carcinomas metastatic to the ovary were compared with those of their primary carcinomas on the one hand and with various primary ovarian carcinomas and mesotheliomas on the other. Colon cancer metastatic to the ovary was keratin 7 negative and keratin 20 positive in 94% of the cases; in contrast, all primary ovarian carcinomas were keratin 7 positive and keratin 20 negative, with the exception of two cases of mucinous cystadenocarcinoma. Ovarian metastases of gastric cancer usually contained keratins 7 and 20. Metastases of endometrial cancer to the ovary and primary ovarian carcinomas usually showed similar keratin expression. We propose that keratin 7 and 20 antibodies may be of help to distinguish between primary ovarian carcinomas and carcinoma metastases in the ovary.

Topics: Adenocarcinoma; Antibodies, Monoclonal; Biomarkers, Tumor; Female; Humans; Intermediate Filament Proteins; Keratin-20; Keratins; Mesothelioma; Ovarian Neoplasms

8-Cl-cAMP, a site-selective analogue of cAMP, decreased mdr-1 expression in multidrug-resistant human breast cancer cells. A sixfold reduction of mdr-1 mRNA expression by 8-Cl-cAMP began within 8 h of treatment and was associated with a decrease in the synthesis of P-glycoprotein and with an increase in vinblastine accumulation. A reduction in mdr-1 expression after 8-Cl-cAMP treatment was also observed in multidrug-resistant human ovarian cancer cell lines. 8-Cl-cAMP is known to change the ratio between the two regulatory subunits, RI and RII, of protein kinase A (PKA). We observed that RI alpha decreased within 24 h of 8-Cl-cAMP treatment, that RII beta increased after as few as 3 h of treatment, and that PKA catalytic activity remained unchanged during 48 h of 8-Cl-cAMP treatment. The results are consistent with the hypothesis that mdr-1 expression is regulated in part by changes in PKA isoenzyme levels. Although 8-Cl-cAMP has been used to differentiate cells in other model systems, the only differentiating effect that could be detected after 8-Cl-cAMP treatment in the MCF-7TH cells was an increase in cytokeratin expression. Evidence that the reduction of mdr-1 mRNA occurred at the level of gene transcription was obtained by measuring chloramphenicol acetyltransferase (CAT) mRNA in MCF-7TH cells transfected with an mdr-1 promoter-CAT construct prior to 8-Cl-cAMP treatment. Thus, 8-Cl-cAMP is able to downregulate mdr-1 expression and suggests a new approach to reversal of drug resistance in human breast cancer.

Topics: 8-Bromo Cyclic Adenosine Monophosphate; Adenocarcinoma; ATP Binding Cassette Transporter, Subfamily B, Member 1; Base Sequence; Breast Neoplasms; Cell Differentiation; Cyclic AMP; Cyclic AMP-Dependent Protein Kinase RIalpha Subunit; Cyclic AMP-Dependent Protein Kinase RIIbeta Subunit; Cyclic AMP-Dependent Protein Kinases; Drug Resistance, Multiple; Female; Gene Expression Regulation, Neoplastic; Genes, Reporter; Humans; Isoenzymes; Keratins; Molecular Sequence Data; Neoplasm Proteins; Promoter Regions, Genetic; Recombinant Fusion Proteins; RNA, Messenger; RNA, Neoplasm; Tumor Cells, Cultured; Vinblastine

One of the possible drawbacks to autologous bone marrow (BM) and peripheral blood progenitor cell (PBPC) transplantation in breast cancer patients is the potential for tumor cell contamination in the transplanted product. To assess the presence of breast cancer cells, we have developed a flow-cytometric method using cytokeratin-FITC and CD45-phycoerythrin (PE) to detect very low levels of cytokeratin-positive (CK+) tumor cells in mononuclear cell (MNC) preparations. In a model system using PBMNC and the breast cancer cell line CAMA, the sensitivity of detection of this flow-cytometric method was one tumor cell in 200,000 MNC. This method was used to evaluate BM, PB, and apheresis products (AP) from 44 patients with metastatic breast cancer. When possible, stained cytologic examination was performed on smears of the unprocessed specimens and on flow cytometry-sorted cells. Results indicated that CK+ tumor cells could be detected by flow cytometry in all three specimen types. When present, however, the tumor content (per MNC) tended to be higher in BM than in PB or AP. Samples from a given patient taken serially over the course of chemotherapy revealed variable results, suggesting that the presence of tumor contamination may be sporadic and requires evaluation of each stem cell product. Of 75 samples tested with both flow cytometry and cytology, the results were concordant in 54 cases (72%). In the remaining samples, flow cytometry only was positive in 15 cases (20%), and cytology only was positive in six cases (8%). This flow-cytometric technique is useful in the evaluation of transplant products for CK+ tumor cell contamination.

Topics: Adenocarcinoma; Adult; Biomarkers, Tumor; Blood Component Removal; Bone Marrow; Breast Neoplasms; Cell Separation; Flow Cytometry; Humans; Keratins; Middle Aged

Carcinoma of the papillary ducts of Bellini is a rare form of renal cancer. Patients are usually asymptomatic middle-aged men who frequently have metastatic disease at the time of diagnosis. The diagnosis is based on histological examination of the nephrectomy specimen with a precise immunohistochemical examination. Radical nephrectomy is the first-line treatment and adjuvant chemotherapy, recommended by certain authors, does not appear to improve the usually poor prognosis of these tumours.

Topics: Adenocarcinoma; Aged; Aged, 80 and over; Humans; Keratins; Kidney Neoplasms; Kidney Tubules, Collecting; Male; Membrane Glycoproteins; Mucin-1; Mucins; Neoplasm Invasiveness; Neoplasm Proteins; Vimentin

Immunohistochemical detection of bone marrow micrometastases has been reported as a prognostic marker in colorectal cancer. The aims of this study were to evaluate the potential advantage of flow cytometry as an objective method of identifying and quantifying micrometastatic deposits within bone marrow and to determine the prevalence and quantity of micrometastases in patients undergoing surgery for gastrointestinal cancers.. Flow cytometry was first validated by a controlled "spike" experiment in which varying numbers of neoplastic epithelial cells were added to bone marrow, and cytometry was performed in a blinded fashion. Three neoplastic cell lines (colonic and esophageal) with varying degrees of expression of cytokeratin-18 were used. Epithelial cells were detected by dual staining with fluorescence-labeled, monoclonal anti-cytokeratin, and propidium iodide.. Cytometry reproducibly detected the presence of > or = 10 neoplastic cells per 10(5) marrow cells. Micrometastases were found in 20%-30% of patients undergoing potentially curative resection of colorectal and gastroesophageal adenocarcinomas. There was a trend toward increasing positivity for marrow deposits with advanced Dukes' staging of colorectal cancer.. Flow cytometric assessment of bone marrow is a reliable, objective, and quantitative method of detecting micrometastatic deposits found in a substantial subset of patients undergoing surgery for gastrointestinal adenocarcinomas.

Topics: Adenocarcinoma; Antibodies, Monoclonal; Bone Marrow Neoplasms; Carcinoma, Squamous Cell; Colorectal Neoplasms; Esophageal Neoplasms; Flow Cytometry; Gastrointestinal Neoplasms; Humans; Keratins; Prognosis; Prospective Studies; Stomach Neoplasms

DNA is the primary target of cis-diamminedichloroplatinum (cisplatin), but the drug also interacts with the cellular cytoskeleton composed of microtubules and intermediate filaments. It was found that the cisplatin-resistant 2008/C13* cell line contained markedly lower levels (6-fold) of cytokeratin 18, when compared to the cisplatin-sensitive 2008 cell line. Northern blot analysis revealed a markedly decreased level of cytokeratin 18 mRNA in the resistant cell line. Southern blot analysis of the DNA extracted from the two cell lines and then digested with HpaII and its methylation-sensitive isoschizomer, MspI, revealed no detectable differences in the methylation status of the cytokeratin gene. Neither 5-azacytidine (5 microM) nor retinoic acid (1 microM) treatment enhanced the expression of cytokeratin 18 in the resistant cell line. However, transfection of full-length cytokeratin 18 cDNA into the cisplatin-resistant 2008/C13* cells resulted in clones with increased levels of cytokeratin 18, which was accompanied in the majority of clones by a marked increase in their sensitivity to cisplatin. These results demonstrate that modulating the expression of an intermediate filament protein results in sensitization of a drug-resistant human ovarian cell line to cisplatin.

Topics: Adenocarcinoma; Antineoplastic Agents; Azacitidine; Cisplatin; DNA Damage; Drug Resistance; Female; Humans; Keratins; Ovarian Neoplasms; Tumor Cells, Cultured

High resolution two-dimensional polyacrylamide gel electrophoresis (2-D PAGE) is a powerful research tool for the analytical separation of cellular proteins. The qualitative and quantitative pattern of polypeptides synthesized by a cell represents its phenotype and thus defines characteristics such as the morphology and the biological behavior of the cell. By analyzing and comparing the protein patterns of different cells it is possible to recognize the cell type and also to identify the most typical features of these cells. In applied pathology it is often difficult to identify the tissue of origin and the stage or grade of a neoplasia by cellular morphology analyzed by classical or immunostaining procedures. The protein pattern itself is the most characteristic feature of a cell and should therefore contribute to the identification of the cell type. For this reason we separated protein fractions originating from different lung tumor cell lines using 2-D PAGE and we compared the resulting patterns on a multivariate statistical level using correspondence analysis (CA) and ascendant hierarchical clustering (AHC). The results indicate that (i) protein patterns are highly typical for cells and that (ii) the comparison of the protein patterns of a set of interesting cell types allows the identification of potentially new marker proteins. 2-D PAGE is thus a unique and powerful tool for molecular cytology or histopathology, unveiling the protein expression level of tissues or cells.

Topics: Adenocarcinoma; Cytoskeletal Proteins; Electrophoresis, Gel, Two-Dimensional; Humans; Immunoblotting; Keratins; Lung Neoplasms; Membrane Proteins; Mesothelioma; Multivariate Analysis; Neoplasm Proteins; Tumor Cells, Cultured; Vimentin

Keratin 19 is an intermediate filament protein produced by cells of simple epithelia and basal cells of stratified epithelia of different organs. These cell types are associated with important human cancers. We have used the keratin 19 promoter to target the expression of the polyomavirus (Py) large T-antigen, an immortalizing oncogene known to bind to the tumor suppressor retinoblastoma gene product, to epithelial cells. Individuals of the transgenic mouse line K19PyLT-6 developed one or two nodules in one of their lungs. By histology, the nodules were papillary tumors that consisted of nonciliated epithelial cells of the terminal bronchioles. In addition, infiltrates emanating from the nodules were consistent with the development of pulmonary adenocarcinomas. In situ hybridization techniques demonstrated large T-antigen expression in the tumors. Primary cultures were established from a lung tumor dissected from a K19PyLT-6 transgenic mouse. These large T-antigen-expressing cell lines produced the keratin proteins reminiscent of the epithelial origin of the lung tumor. However, further molecular studies indicated that these cell lines did not express Clara cells or pneumocytes markers. s.c. injection of the cell lines into nontransgenic syngeneic mice produced tumors in 2 weeks that resembled malignant pulmonary adenocarcinomas. These animals, which display tumor progression in situ, and the cell lines derived thereof provide a useful system for the study of lung tumorigenesis.

Topics: Adenocarcinoma; Animals; Antigens, Polyomavirus Transforming; Bronchi; Cell Line; Culture Techniques; Humans; Immunohistochemistry; In Situ Hybridization; Keratins; Lung Neoplasms; Mice; Mice, Inbred Strains; Mice, Transgenic; Papilloma; Phenotype; Promoter Regions, Genetic; Restriction Mapping; RNA, Viral; Tumor Cells, Cultured

In the current study a comparative analysis of keratin typing and DNA content was carried out in human lung tumors from transthoracic fine needle aspiration biopsies (TFNAB) (18 patients) or from surgically resected tumor tissues (14 patients). According to the cytologic and histologic features, 2 of the 32 tumors were diagnosed as benign tumors, 11 as squamous cell carcinomas, 12 as adenocarcinomas, and 7 as undifferentiated large cell carcinomas. Two cases in the adenocarcinoma and one in the undifferentiated large cell carcinoma groups were pulmonary metastasis or second primary tumors. Malignant cells of tumors which reacted positively with KK8.60 anticytokeratin polypeptides No. 10 and 11 (and hence contain keratinizing cells) displayed diploid DNA content in a flow cytometric assay regardless of their cytologic or histologic appearance. In contrast, all tumors which lacked such positive cells (most of which were defined as adenocarcinomas and undifferentiated tumors) were hyperdiploid. The close correlation between high DNA content and both malignancy and the absence of advanced squamous differentiation (keratinization) suggests that such combined analysis may provide new tools for the cytologic diagnosis and prognosis of lung cancers.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Biomarkers, Tumor; Biopsy, Needle; Carcinoma, Non-Small-Cell Lung; Carcinoma, Squamous Cell; Cell Cycle; Diploidy; DNA, Neoplasm; Female; Flow Cytometry; G1 Phase; Humans; Keratins; Lung Neoplasms; Male; Middle Aged; Neoplasm Staging; Resting Phase, Cell Cycle

To determine whether human papillomavirus (HPV) 18 has a role in the development of adenocarcinoma from human endo- or ectocervical cells.. Secondary cultures of human endo- and ectocervical cells were assayed for immortalization by HPV 18 DNA using lipofection. The effects of immortalization on the patterns of cytokeratin expression were determined by indirect immunofluorescence using monoclonal antibodies. The differentiation phenotype of the immortalized cells was investigated by a modified in vivo implantation system.. Both endo- and ectocervical cells were immortalized by HPV 18. The immortalized cells contained integrated HPV 18 DNA and expressed E6-E7 RNA. The immortalized endocervical cells had a cytokeratin phenotype characteristic of adenocarcinoma, whereas the immortalized ectocervical cells retained a distinct cytokeratin expression pattern of normal parental cells. In an in vivo implantation system, endocervical cells formed a lesion resembling severe dysplasia or carcinoma in situ, whereas ectocervical cells developed into a lesion resembling mild dysplasia. Both cell lines were nontumorigenic in nude mice.. Both endo- and ectocervical cells are targets for immortalization by HPV 18. Based on cytokeratin expression patterns, immortalized endocervical cells, but not ectocervical cells, may be useful as a model for premalignant lesions that progress into adenocarcinoma.

Topics: Adenocarcinoma; Animals; Blotting, Northern; Blotting, Southern; Cell Line, Transformed; Cell Transformation, Viral; Cervix Uteri; DNA, Viral; Female; Fluorescent Antibody Technique; Gene Expression; Humans; Keratins; Mice; Mice, Nude; Papillomaviridae; Phenotype; Tumor Cells, Cultured; Uterine Cervical Neoplasms

The prostatic epithelium is composed of three distinct cell populations: secretory luminal, basal, and endocrine-paracrine cells. It is currently unknown whether these basic epithelial cell types are related in a hierarchical pathway of differentiation or are independent and separate entities. In the present study we used double-label techniques for cell-specific markers to search for multidirectional differentiation in normal, hyperplastic, and neoplastic prostate tissue. In normal and hyperplastic conditions subsets of basal cells revealed synchronous expression of basal cell-specific cytokeratins and the prostate-specific antigen, indicating intermediate differentiation between basal and secretory luminal cell types. Furthermore, endocrine-paracrine cells of the closed type focally showed simultaneous expression of chromogranin A and basal cell-specific cytokeratins. These findings highlight the phenotypic plasticity of the basal cell layer in the human prostate. In prostatic adenocarcinoma co-expression of exocrine (prostate-specific antigen) and endocrine (chromogranin A) markers was detected frequently in subsets of malignant cells. Conversely, this amphicrine phenotype was rarely found in hyperplastic glands. The occurrence of multidirectional differentiation within the prostatic endocrine cell system may indicate that endocrine-paracine cells derive from pluripotent stem cells of endodermal origin. Furthermore, the phenotypic plasticity of basal cells suggests that this epithelial compartment houses stem cell populations that give rise to all epithelial cell lineages encountered in the normal, hyperplastic, and neoplastic human prostate.

Topics: Adenocarcinoma; Biomarkers; Biomarkers, Tumor; Cell Differentiation; Chromogranin A; Chromogranins; Humans; Hyperplasia; Keratins; Male; Prostate; Prostate-Specific Antigen; Prostatic Neoplasms; Reference Values

The filament forming ability and post-translational modifications of the human intermediate filaments, keratin polypeptides 8 and 18 (K8/18), were studied in recombinant baculovirus-infected insect (Spodoptera frugiperda, Sf9) cells. No change in cell morphology was noted after high levels of K8/18 were expressed in Sf9 cells coinfected with recombinant virus-containing human K8 and K18. Immunofluorescence staining showed that K8/18 expressed in Sf9 cells formed somewhat what disorganized and rope-like filaments, in contrast with K8 or K18 expression alone, which did not result in filament formation. K8/18 expressed in Sf9 cells were glycosylated (O-linked N-acetylglucosamine) and phosphorylated, and each modification occurred on different molecules of K8 and K18, as previously found in human HT29 cells. The glycosylation and phosphorylation of K18 in human and insect cells were very similar as determined by tryptic peptide mapping and localization to the head and proximal rod domains. In contrast, differences were noted in the relative intensity of the tryptic phospho- and glycopeptides of K8 expressed in human and insect cells and in the ratio of K8 to K18 phosphorylation in human and insect cells. Our results show that although quantitative differences exist, the post-translational modification of K8/18 expressed in insect cells is quite similar to its mammalian counterpart, especially for K18. Baculovirus expressed K8/18 should prove useful for mapping phosphorylation and glycosylation sites and for studying factors involved in organized filament assembly in mammalian cells.

Topics: Adenocarcinoma; Amino Acid Sequence; Animals; Cell Line; Colonic Neoplasms; Female; Fluorescent Antibody Technique; Gene Expression Regulation; Genes, Insect; Glycosylation; Humans; Keratins; Molecular Sequence Data; Moths; Ovary; Peptide Mapping; Phosphorylation; Protein Processing, Post-Translational; Tumor Cells, Cultured

Epidemiological studies have implied that Chinese salted fish is a human nasopharyngeal carcinogen. In the present study, 162 Sprague-Dawley rats were randomly assigned to one of four experimental groups. Rats in groups 1 (n = 41) and 3 (n = 40) were exposed to salted fish from birth through the breast feeding period by giving the maternal rats a diet containing 10% and 5% salted fish, respectively, later feeding the rats with pellets containing 10% and 5% of salted fish respectively. In group 2, the rats (n = 41) were given pellets containing 10% of salted fish from 6 weeks of age. Rats in group 4 (n = 40), serving as controls, were only given ordinary pellets. Three rats had nasopharyngeal tumours, 2 from group 1 had a poorly differentiated carcinoma and a squamous cell carcinoma. One rat from group 2 had a squamous cell carcinoma. Four rats had nasal tumours, one fibrosarcoma and one adenocarcinoma were found in rats from group 1. One rhabdomyosarcoma was found in group 2, and one soft tissue sarcoma was found in a rat in group 3. No nasal or nasopharyngeal tumours appeared in the control group. The difference in the occurrence of malignant nasal and nasopharyngeal tumours among the four experimental groups was statistically significant (one tailed p for trend = 0.041). The frequency of tumours appearing in other organs such as the breast, kidney, lung, liver and brain was not significantly different between the salted fish treated groups and the control group.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adenocarcinoma; Animals; Animals, Newborn; Body Weight; Carcinoma; Carcinoma, Squamous Cell; Desmin; Diet; Female; Fibrosarcoma; Fishes; Food Preservation; Keratins; Male; Nasopharyngeal Neoplasms; Nose Neoplasms; Pregnancy; Rats; Rats, Sprague-Dawley; Rhabdomyosarcoma; Sarcoma, Experimental; Survival Rate; Vimentin

Histologic review of 48 radical prostatectomy specimens containing both prostatic adenocarcinoma (PC) and high-grade prostatic intraepithelial neoplasia (PIN) resulted in 23 cases containing neoplastic cribriform gland (CGs) at the periphery or within PC fields. The histologic characteristics of CG PIN mimic those of CG PC in that a discernible basal cell layer defines CG PIN, while CG PC lacks a basal layer. To detect the presence of basal cells in CGs, step sections were immunostained with monoclonal antibody 34 beta E12 to high-molecular-weight cytokeratins (HMCK) found in basal cells, but not in PC cells. Optimal staining of formalin-fixed sections required pepsin predigestion followed by 14-hour monoclonal antibody incubation at 4 degrees C. Of 436 CG foci identified, 239 (55%) were outlined by a circumferential HMCK-positive layer (identifying PIN); 182 (42%) totally lacked this layer (identifying PC), with appropriate internal controls; and 15 (3%) stained indeterminately. In an attempt to distinguish CG PIN from PC by routine histologic examination alone, CGs with open, round spaces were classified as classic (156 foci); nonclassic CGs (265 foci) featured irregular oblong to slitlike spaces. Cribriform gland PIN defined by HMCK outlining was more often nonclassic (193 CG foci) in histologic pattern, and CG PC was usually "classic" (110 CG foci) (chi 2 = 75; P < .001). We conclude that (1) more than half (55%) of the CGs in the PC tumors studied contain a basal cell layer fulfilling the definition of PIN; (2) focal and isolated HMCK positivity is found amid PC, and thus the overall pattern of staining together with morphological features is critical to correctly exclude carcinoma; (3) grading of PC on the basis of the presence of CGs may lead to erroneous results if PIN foci are misinterpreted as PC; and (4) since CG PIN is usually found in intimate anatomic association with PC, HMCK staining to detect basal cells in isolated CGs encountered in biopsy specimens may be a useful diagnostic discriminant.

Topics: Adenocarcinoma; Carcinoma in Situ; Humans; Immunohistochemistry; Keratins; Male; Prostatic Neoplasms

An important role in differentiation and proliferation has been demonstrated for the 20 cytokeratin (CK) polypeptides. The serum of 24 patients with biopsy-proven non-small cell lung cancer (NSCLC) and a similar number of controls was examined for evidence of CK8 and CK18. Using enzyme-linked immunosorbent assay (ELISA), all the control sera were negative, but 9 of the 24 patients were positive (mean 2.62 ng/ml; range 1.4-5.8; P = 0.0036). Western blotting confirmed the results of the ELISA in all cases, and indicated full size CK polypeptides. Advanced stage disease patients were more likely to be seropositive (P = 0.00024). Biopsy specimens showed CK8 expression in all 24 cases by immunochemistry and CK18 in 22 cases. This is the first study to demonstrate that a subgroup of NSCLC patients have intact CK8 and CK18 peptides in their serum, and their detection may correlate with advanced disease.

Topics: Adenocarcinoma; Aged; Aged, 80 and over; Blotting, Western; Carcinoma, Non-Small-Cell Lung; Cell Death; Enzyme-Linked Immunosorbent Assay; Female; Humans; Immunoenzyme Techniques; Keratins; Lung Neoplasms; Male; Middle Aged; Neoplasm Proteins; Tumor Cells, Cultured

Topics: Adenocarcinoma; Adult; Cell Nucleus; Diagnosis, Differential; Humans; Hyalin; Keratins; Male; Middle Aged; Neoplasm Invasiveness; Palatal Neoplasms; S100 Proteins

The levels of the new tumour marker CYFRA 21-1 were assessed in 115 patients with non-small cell lung cancer (NSCLC) and in 45 patients with non-malignant lung disease. Increased levels of CYFRA 21-1 were observed in 47.8%, mostly in patients with squamous cell carcinoma (SCC; 69.1%). Serum CYFRA 21-1 levels were correlated with the stage of SCC type. Positive CYFRA 21-1 levels in patients with SCC were present in 40% of stage I, 61.1% of stage II, and 85.2% of stage III. In addition, SCC patients who presented mediastinal lymph nodes (N2) demonstrated higher serum CYFRA 21-1 levels, compared with patients without mediastinal lymph nodes metastases (N0 or N1). With regard to tumour size, significant difference was observed between T1, T2 and T3. The study also showed that the percentage of patients who survived 18 months with normal preoperative level of CYFRA 21-1 was higher compared with those patients with elevated preoperative levels of this marker, but the differences were not statistically significant.

Topics: Adenocarcinoma; Antigens, Neoplasm; Biomarkers, Tumor; Carcinoembryonic Antigen; Carcinoma, Large Cell; Carcinoma, Non-Small-Cell Lung; Carcinoma, Squamous Cell; Evaluation Studies as Topic; Female; Humans; Keratins; Lung Diseases; Lung Neoplasms; Lymphatic Metastasis; Male; Neoplasm Staging; Peptide Fragments; Serpins

The diagnostic value of the water-soluble cytokeratin 19 fragment CYFRA 21-1 in lung cancer was assessed in comparison with carcinoembryonic antigen, squamous cell carcinoma antigen, and neuron-specific enolase. The cut-off value, defined as 95% specificity versus a group of 526 patients suffering from benign chest diseases, was set at 3.3 micrograms/l for cytokeratin 19 fragment CYFRA 21-1 (carcinoembryonic antigen: 7.8 micrograms/l, squamous cell carcinoma antigen: 1.9 micrograms/l, neuron-specific enolase: 13.7 micrograms/l). Elevated pretreatment cytokeratin 19 fragment CYFRA 21-1 concentrations were recorded: in 112 of 244 (46%) patients with all histological types of lung cancer (carcinoembryonic antigen: 32%, squamous cell carcinoma antigen: 25%, neuron-specific enolase: 28%), in 89 of 177 (50%) patients with non-small cell lung cancer (carcinoembryonic antigen: 33%, squamous cell carcinoma antigen: 24%, neuron-specific enolase: 12%), in 47 of 81 (58%) patients with squamous cell carcinoma (carcinoembryonic antigen: 23%, squamous cell carcinoma antigen: 32%, neuron-specific enolase: 14%), in 27 of 63 (42%) patients with adenocarcinoma (carcinoembryonic antigen: 44%, squamous cell carcinoma antigen: 14%, neuron-specific enolase: 9%), in 15 of 33 (45%) patients with other non-small cell lung cancer (carcinoembryonic antigen: 36%, squamous cell carcinoma antigen: 24%, neuron-specific enolase: 14%), and in 20 of 55 (36%) patients with small cell lung cancer (carcinoembryonic antigen: 32%, neuron-specific enolase: 77%). Three of 12 patients with undefined histological type showed cytokeratin 19 fragment CYFRA 21-1 elevations. The best performance in terms of sensitivity and diagnostic accuracy was attained with the cytokeratin 19 fragment CYFRA 21-1 test in squamous cell carcinoma. In small cell lung cancer neuron-specific enolase was confirmed to be superior to the other markers. Cytokeratin 19 fragment CYFRA 21-1 concentrations increased with the extent of the malignant disease in non-small cell lung cancer. The positivity rate of cytokeratin 19 fragment CYFRA 21-1 in tumour stage TNM I was only 23% (carcinoembryonic antigen: 23%, squamous cell carcinoma antigen: 14%), i.e. the markers under study cannot be used for the diagnosis of early stage disease. Cytokeratin 19 fragment CYFRA 21-1 differentiated significantly between squamous cell carcinoma and the other histological types (p < 0.01). In addition, cytokeratin 19 fragment CYFRA 21-1 distinguishe

Topics: Adenocarcinoma; Antigens, Neoplasm; Biomarkers, Tumor; Carcinoembryonic Antigen; Carcinoma, Non-Small-Cell Lung; Carcinoma, Squamous Cell; Female; Humans; International Cooperation; Keratins; Lung Neoplasms; Male; Peptide Fragments; Phosphopyruvate Hydratase; Sensitivity and Specificity; Serpins

We have performed immunocytochemical, immunoelectron microscopy, Western blot, and culture techniques using monoclonal antibodies against cytokeratin, vimentin, and desmin on 17 benign and 20 malignant effusions of pleural and ascitic origin. Triple coexpression of these three antigens was observed in benign reactive mesothelial cells as well as in one case of mesothelioma. All metastatic adenocarcinoma cells were consistently negative to desmin and positive to cytokeratin and vimentin. Present results were helpful to distinguish reactive and malignant mesothelioma from metastatic carcinoma cells in effusions.

Topics: Adenocarcinoma; Ascitic Fluid; Blotting, Western; Cells, Cultured; Desmin; Diagnosis, Differential; Epithelium; Female; Follow-Up Studies; Humans; Immunoenzyme Techniques; Keratins; Mesothelioma; Models, Biological; Pleural Effusion; Vimentin

The intermediate filament (IF) proteins present in the normal and pathological exocrine human pancreas were studied by immunolocalization using antibodies to cytokeratins (CKs) and vimentin. Acinar cells of normal pancreas showed a presence of simple CKs 8 and 18. Duct epithelium consistently expressed CKs 7, 8, 18 and 19 whereas centroacinar cells were rather low in CK 7. A subpopulation of CK 4 cells was detected in inter-intralobular ducts. In addition, some ducts contained individual cells or groups of cells that were positive for the stratification-related CKs (CKs 4, 5, 13, 15, 16). All pancreatic ductal adenocarcinomas regularly expressed CKs 7, 8, 18, 19 and were also positive for the 34 beta E12 antibody. Cytokeratin 4 was detected in a minor population of tumor cells. Pancreatic carcinoma also contained minor amounts of stratification-related CKs in variable combinations. Mucinous cystoadenocarcinoma showed the presence of CKs 7, 8, 18, 19 and was also positive for 34 beta E12, whereas the serous microcystic tumor presented CKs 8, 18, 19 and a variable amount of CKs 4 and 7. The duct-ductular alterations of the exocrine pancreas contained a different combination and distribution of CK isoforms similar to normal pancreatic ductal system. Mucinous hypertrophy and pyloric gland metaplasia reacted with antibodies to CKs 7, 8, 18 and 19. Vimentin was focally present both in normal and neoplastic tissue. Our results indicate that pancreatic ducts are characterized by an intrinsic "biliary-pancreatic duct type" immunoprofile (CKs 7, 8, 18 and 19), in contrast to acinar cells expressing exclusively CKs 8 and 18. We also detected a subpopulation of ducts regularly expressing CK 4. Surprisingly, several stratification-related CKs were detected both in normal and neoplastic exocrine pancreas. Moreover, the differentiation phenotypes of pancreatic tumors were reminiscent of normal cellular compartments.

Topics: Adenocarcinoma; Antibodies, Monoclonal; Biomarkers, Tumor; Humans; Intermediate Filament Proteins; Keratins; Pancreas; Pancreatic Neoplasms; Pancreatitis

We investigated the expression of keratin subtypes 7, 8, 10, 13, 14, 17, 18 and 19 in the normal cervix, in cervical intraepithelial neoplasia (CIN) lesions and in cervical carcinomas, using a selected panel of monoclonal keratin antibodies, reactive with routinely processed, formalin fixed paraffin embedded tissue fragments. The reaction patterns derived for each keratin antibody were compared with known expression patterns of the various epithelia, previously examined in frozen tissues. Although the reactivity of the antibodies was generally acceptable, considerable modifications to the manufacturers' staining instructions were often necessary. For some antibodies, which were previously thought to be reactive with fresh frozen tissue only, we developed staining protocols rendering them reactive with routinely processed material. As with previous findings in frozen sections we observed increasing expression of keratins 7, 8, 17, 18 and 19 with increasing grade of CIN. In cervical carcinomas the differences in keratin detectability between the main categories were more pronounced than in frozen sections, probably due to fixation and processing. For routine pathology, keratin phenotyping of cervical lesions may be of value in classification. The fact that keratin 7 was detected for the first time in reserve cells, and that this keratin was also found to be expressed in a considerable number of CIN lesions and cervical carcinomas supports the suggestion that reserve cells are a common progenitor cell for these lesions.

Topics: Adenocarcinoma; Antibodies, Monoclonal; Carcinoma, Adenosquamous; Carcinoma, Neuroendocrine; Carcinoma, Squamous Cell; Epithelial Cells; Epithelium; Female; Histological Techniques; Humans; Immunoenzyme Techniques; Keratins; Uterine Cervical Dysplasia; Uterine Cervical Neoplasms

Serum samples from 137 lung cancer patients were examined by RIA to evaluate the clinical efficacy of the new tumor marker, CYFRA 21-1, which could identify the soluble fragment of cytokeratin 19. The cut-off value was determined to be 2.2 ng/ml according to the receiver operating characteristic curve. The sensitivity, specificity and accuracy of the RIA for CYFRA 21-1 were 57.7, 91.9 and 64.9%, respectively. The serum concentration of CYFRA 21-1 and the sensitivity of the assay increased as the disease progressed. Histologically, the sensitivity was highest for squamous cell carcinomas (SQ) (76.5%) in comparison with adenocarcinomas (47.8%) and small cell lung cancers (42.1%) (P < 0.01, P < 0.05, respectively). The sensitivities for SQ were 60.0, 83.3, 80.0 and 100% at stages I, II, III and IV, respectively. When compared with CEA (45.3%) and squamous cell carcinoma related antigen (SCC) (22.6%) in all lung carcinomas, CYFRA 21-1 showed the highest sensitivity (57.7%), (P < 0.05, P < 0.01, respectively). In SQ, the sensitivity of the CYFRA 21-1 RIA was significantly higher than that of the assay for SCC (47.1%) (P < 0.05). In patients with adenocarcinomas, the sensitivity of the CYFRA 21-1 assay was almost the same as that for CEA (49.3%). In a combination of CYFRA 21-1 and CEA for non-small cell lung cancers (NSCLC), the sensitivity and accuracy increased to 75.4 and 78.1%, respectively, although the specificity decreased to 86.5%. It is concluded that CYFRA 21-1 could replace SCC, a less satisfactory tumor marker, for SQ of the lung. The potentiality of the combination of CYFRA 21-1 and CEA for NSCLC should be estimated using larger samples in the near future.

Topics: Adenocarcinoma; Biomarkers, Tumor; Carcinoma, Small Cell; Carcinoma, Squamous Cell; Female; Humans; Keratins; Lung Neoplasms; Male; Middle Aged; Radioimmunoassay; Sensitivity and Specificity

To obtain a better understanding of the cellular and hormonal mechanisms responsible for the malignant bone resorption associated with metastatic carcinoma, we sought to identify whether tumor cells or tumor infiltrating macrophages were capable of lacunar bone resorption.. Tumor cells and tumor-infiltrating macrophages (TIMS), (nonspecific esterase and F4/80 positive: cytokeratin and tartrate-resistant acid phosphatase and calcitonin response negative), were isolated from carcinomas that developed after subcutaneous implantation of human breast, colon, and cervical carcinoma cell lines into MFI athymic nude mice. These cells were cultured alone or with stromal cells on bone slices and evidence of lacunar resorption sought by scanning electron microscopy.. After 7 to 14 days in co-culture with UMR106 osteoblast-like cells in the presence of 1,25-dihydroxy vitamin D3, only cells of the TIM population differentiated into osteoclast-like cells (nonspecific esterase-negative: tartrate-resistant acid phosphatase-positive) capable of extensive lacunar bone resorption.. Cells within the TIM population but not tumor cells are capable of differentiation into osteoclast-like cells which can resorb bone extensively. Both 1,25 dihydroxyvitamin D3 and bone stromal cells are necessary for this to occur. TIM differentiation into cells capable of lacunar resorption could account for a component of the extensive osteolysis associated with carcinomatous skeletal metastases.

Topics: Adenocarcinoma; Animals; Bone Resorption; Breast Neoplasms; Calcitonin; Calcitriol; Carcinoma, Squamous Cell; Cell Differentiation; Cells, Cultured; Colonic Neoplasms; Female; Humans; Immunohistochemistry; Keratins; Macrophages; Mice; Mice, Nude; Microscopy, Electron, Scanning; Neoplasm Transplantation; Osteoblasts; Osteoclasts; Time Factors; Tumor Cells, Cultured; Uterine Cervical Neoplasms

The expression of epidermal growth factor receptor (EGFr) and transforming growth factor alpha (TGF-alpha) was compared with the presence of "squamous differentiation" (SD) visualized in various histotypes of endometrial carcinoma by using a panel of monoclonal antibodies. The results of the current study demonstrate that EGFr and TGF-alpha are present in routinely processed endometrial carcinoma. The highest positive EGFr and TGF-alpha expression was seen in the group of adenocarcinomas with SD. The more intense EGFr and TGF-alpha immunoreactivity was observed in "squamous" foci both in adenoacanthomas (AA) and in adenosquamous carcinomas (AS). These EGFr- and TGF-alpha-positive squamous areas prevalently displayed a "stratification-related" cytokeratin (CK) immunoprofile characterized by the expression of CKs 1, 4, 5, 10, 13, 14, and 16. No correlation was found between EGFr- and TGF-alpha-positive status and depth of myometrial invasion or surgical stage. These results clearly demonstrate that EGFr and TGF-alpha expression is related remarkably to endometrial carcinoma with "squamous" areas both morphologically and immunophenotypically. This specific association leads us to suggest that EGFr and TGF-alpha expression in endometrial carcinoma may be prevalently involved in the equilibrium of cell differentiation of the "squamous" foci commonly observed in this group of neoplasias.

Topics: Adenocarcinoma; Aged; Biomarkers, Tumor; Carcinoma, Adenosquamous; Cell Differentiation; Endometrial Neoplasms; ErbB Receptors; Female; Humans; Immunohistochemistry; Keratins; Metaplasia; Middle Aged; Transforming Growth Factor alpha

Adenocarcinomas of uncertain origin are a frequent problem for surgical pathologists. To determine the utility of immunostaining for cytokeratin 7 and cytokeratin 20 in the separation of pulmonary adenocarcinomas from colonic adenocarcinomas, we studied routinely processed, formalin-fixed tissue from 151 of these tumors using commercially available monoclonal antibodies and an avidin-biotin immunohistochemical technique. Used alone, neither cytokeratin 7 immunostaining or cytokeratin 20 immunostaining reliably separated these tumors. However, the immunophenotype of cytokeratin 7 positive/cytokeratin 20 negative was seen in 86% of the pulmonary adenocarcinomas, and in 0% of the colonic adenocarcinomas. Conversely, the cytokeratin 7-negative/cytokeratin 20-positive immunophenotype was seen in 77% of the colonic carcinomas, and in 0% of the pulmonary tumors. In conclusion, cytokeratin 7/cytokeratin 20 immunostaining patterns may be helpful in separating pulmonary adenocarcinomas from colonic adenocarcinomas.

Topics: Adenocarcinoma; Colonic Neoplasms; Diagnosis, Differential; Humans; Immunohistochemistry; Intermediate Filament Proteins; Keratin-20; Keratins; Lung Neoplasms

Thirty-seven feline and 38 human spontaneous mammary gland carcinomas were studied immunohistochemically. Commercially available antibodies directed against high and low molecular weight keratins (RCK-102 and NCL-5D3), vimentin, desmin, glial fibrillary acidic protein (GFAP), neurofilament (NF) proteins and muscle actin (HHF35) were used in the avidin biotin peroxidase complex (ABC) technique on formalin-fixed paraffin wax-embedded tumour tissue samples. Healthy feline and human mammary gland tissue adjacent to the neoplasms was also examined. The distribution pattern of intermediate filament proteins and muscle actin was comparable in healthy mammary gland tissue of the two species: both RCK-102 and NCL-5D3 antibodies reacted with luminal epithelial cells of ducts and acini, but basal/myoepithelial cells were stained by RCK-102 exclusively. In addition, basal/myoepithelial cells expressed vimentin and muscle actin in both species, and GFAP was found in some feline basal/myoepithelial cells. No immunoreactivity to desmin and NF proteins was observed. Feline mammary gland carcinoma cells reacted with RCK-102 (89%), NCL-5D3 (62%), vimentin (76%) and GFAP (30%) antibodies, while human mammary gland carcinoma cells reacted with RCK-102 (95%), NCL-5D3 (100%) and vimentin (13%) antibodies. HHF35 immunoreactivity was observed in stromal cells only. These results indicate that mammary gland carcinomas of both species share a heterogeneous immunophenotype with respect to intermediate filament proteins, which adds to the list of known similarities between mammary gland carcinomas of both species.

Topics: Actins; Adenocarcinoma; Animals; Breast; Breast Neoplasms; Carcinoma; Cat Diseases; Cats; Female; Humans; Immunohistochemistry; Intermediate Filament Proteins; Keratins; Mammary Glands, Animal; Mammary Neoplasms, Animal

We examined the expression of carcinoembryonic antigen (CEA) and cytokeratin (CK) as well as the sialo- and sulphomucin content of 40 hyperplastic polyps (HPs), 6 mixed hyperplastic-adenomatous polyps, 30 adenomas and 40 adenocarcinomas of the colorectum. HPs showed a positive CEA expression in 95% of cases and a decreased sialo- and sulphomucin content compared with normal mucosa. Similar changes were observed in adenomas with low-grade dysplasia. The increase in CEA expression from HPs and adenomas to carcinomas was accompanied by a reduction of sialo- and sulphomucins with about three fourths of carcinomas being sialo- and sulphomucin negative. Oncofetal antigen expression concomitant with mucin changes observed in HPs may indicate impaired cellular maturation at a functional level before dysplastic changes become visible. CEA and CK positive macrophages were found in carcinomas predominantly at sites of tumor disruption and necrosis as well as within veins and lymphatic vessels. Our findings suggest that macrophages may play a role in CEA and CK release into the circulation and thus may be determinants of tumor marker serum levels.

Topics: Adenocarcinoma; Adenocarcinoma, Mucinous; Adenomatous Polyps; Biomarkers, Tumor; Carcinoembryonic Antigen; Cell Transformation, Neoplastic; Colon; Colonic Polyps; Colorectal Neoplasms; Humans; Hyperplasia; Keratins; Macrophages; Mucins; Necrosis; Neoplastic Cells, Circulating; Precancerous Conditions; Rectum

Proliferative rates of 73 node-negative adenocarcinomas of breast with 5-year or greater follow-up were studied using cytokeratin staining in two-parameter DNA flow cytometry of archival specimens. Quality control data of accuracy of the measurements were determined and all analyses were compared with single-parameter results of the same specimens, using demarcated tumor areas, quadruple analyses, and computerized nonspecific staining subtraction. Mitotic rates of the same samples correlated highly significantly with the S-phase fractions and proliferative index (S + G2 + M phases), especially for the cytokeratin data. The predictive value of mitotic rates was found significant, but that of the DNA flow-cytometry-obtained indices was not, probably because of low numbers of deaths in this study. The cytokeratin method identified heteroploid tumors containing a diploid cell population not identifiable by single-parameter analysis. In conclusion, cytokeratin staining can be reliably applied to DNA flow cytometry of archival specimens giving accurate ploidy, S-phase fractions, and proliferative index data limited almost exclusively to neoplastic cell populations. This will permit large-scale retrospective studies aimed at establishing the usefulness of DNA flow cytometry for clinical decisions on therapy of surgically removed node-negative adenocarcinomas of breast.

Topics: Adenocarcinoma; Analysis of Variance; Breast Neoplasms; Cell Division; DNA, Neoplasm; Flow Cytometry; Humans; Keratins; Retrospective Studies; Survival Analysis

Endocrine cells (EC) were found in 19 out of 42 cases of the pancreas carcinoma (42.5%). Among them, 4 cases had a positive rate of EC more than 50%. The positive rate of EC in the well differentiated carcinomas (5/20) was lower than that of the poorly-differentiated ones (12/19) or mucinous carcinoma (2/2), and the positive rate in histologic grade I cases (5/18) was significantly lower than that of the grade III cases (7/8). The number of mast cells infiltrating in the matrix in EC positive cases was significantly higher than that of the negative ones. The positive rate of EC in the cases with metastasis (8/14) was higher than that of the non-metastasis cases (7/21). Immunocytochemical staining showed that GN (8), SS(4), HCG(5), CK(12), EMA(13) and CEA(9) were positive in 19 EC positive cases.

Topics: Adenocarcinoma; Adenocarcinoma, Mucinous; Adult; Aged; Female; Gastrins; Humans; Keratins; Male; Middle Aged; Neurosecretory Systems; Pancreatic Neoplasms

DNA flow cytometry measurements were performed using cytokeratin as a second parameter to identify epithelial cells selectively in fresh and in archival paraffin samples of normal and adenocarcinoma tissues from breast and colon. Fresh specimens consisted of 22 adenocarcinomas of breast, 20 adenocarcinomas of colon, 16 control breast samples, and 13 control colon samples. Paraffin block specimens consisted of 22 adenocarcinomas of breast (the same as fresh samples), 20 adenocarcinomas of colon (the same as fresh samples), 37 control breast samples and 34 control colon samples. The average proportion of cytokeratin-positive cells per group ranged from 31 to 55% for fresh samples and from 14 to 34% for paraffin samples. For aneuploid cells populations of adenocarcinomas, which consist only of epithelial cells, the average percentage of cytokeratin-positive cells ranged from 60 to 72%. The technique gave satisfactory measurements of ploidy and of cell cycle data in both types of samples. Cell cycle measurements were less accurate than ploidy measurements in both types of samples, and multiple sampling will be required for adequate accuracy. The average S-phase fraction of cytokeratin-positive cells ranged from 6 to 15% for fresh specimens and from 11 to 20% for paraffin samples. Similar data were obtained for the proliferative index (G1 + S + G2 + M phases). The coefficients of variation were smaller for proliferative index than for S-phase fraction data, indicating greater accuracy. Paraffin data give higher cycling cell measurements than corresponding fresh data, so separate standardization of measurements may be required for fresh and for paraffin data.

Topics: Adenocarcinoma; Breast Neoplasms; Colonic Neoplasms; DNA, Neoplasm; Epithelium; Flow Cytometry; Humans; Keratins; Paraffin Embedding; Staining and Labeling

Ten malignant canine mammary gland tumours and five metastases from three of these tumours were studied immunohistochemically with monoclonal antibodies (MoAbs) directed against different human keratin types (K), alpha-smooth muscle actin, vimentin, and desmin. In all tumours the neoplastic epithelium was rather homogeneously labelled with the keratin MoAbs RCK 102 (K 5 and 8) and CAM 5.2 (K 8). The adenocarcinomas (n = 5), the solid carcinomas (n = 2), and the carcinosarcoma (n = 1) showed heterogeneous labelling with the MoAbs specific for luminal cell antigens in the normal canine mammary gland, i.e., K 18, K 7 and K 19 MoAbs. These cells were also immunoreactive with K 4 and K 10 MoAbs. The spindle cell carcinomas (n = 2), however, did not react with these MoAbs. All tumours except one adenocarcinoma were characterized by the absence of immunoreactive labelling with the alpha-smooth muscle actin MoAb. In the solid carcinomas this was associated with the absence of labelling with one or both basal cell specific keratin MoAbs, i.e., 8.7 (K 14 and 17) and RCK 107 (K 14), respectively. In contrast, the other malignant tumours showed marked labelling of neoplastic epithelium with these MoAbs. Another remarkable finding was the labelling of a limited to moderate number of neoplastic epithelial cells with the vimentin MoAb. The presence of such labelling patterns in canine mammary gland tumours may be indicative of malignancy. Metastatic tumour tissues had a labelling pattern largely similar to that of the primary tumour, although also loss of reactivity for some keratin MoAbs was seen.

Topics: Actins; Adenocarcinoma; Animals; Antibodies, Monoclonal; Carcinoma; Carcinosarcoma; Desmin; Dog Diseases; Dogs; Immunoenzyme Techniques; Intermediate Filament Proteins; Keratins; Mammary Neoplasms, Animal; Vimentin

The histological and ultrastructural features, as well as the immunoreactivity of one case of uncommon primary papillary and psammomatous adenocarcinoma of the umbilicus are studied in the present work. The observations have been undertaken in a nine-year follow-up, and have included the primitive tumour, two local recidives, and inguinal lymphatic metastasis on two occasions. Papillary structures, numerous psammoma bodies, as well as weak and focal positive reactions to CEA and cytokeratin were present in all the tumours. Since these features and their ultrastructural characteristics were identical to primary papillary serous neoplasias of the peritoneum and ovarium, the hypothesis of an origin in coelomic remnants is considered.

Topics: Adenocarcinoma; Adenocarcinoma, Papillary; Calcinosis; Carcinoembryonic Antigen; Female; Humans; Keratins; Microscopy, Electron; Middle Aged; Organelles; Umbilicus

The present study was performed to evaluate the diagnostic reliability of antibodies to breast carcinoma-specific antigen and antibodies to cytokeratin catalogue in a metastatic hepatic lesion. Immunohistochemical examinations using antibodies to gross cystic disease fluid protein-15 (GCDFP-15), BCA-225 (a glycoprotein secreted by T47D breast carcinoma cell line) and BRST-5 (a glycoprotein identified in SK-BR-7 breast carcinoma cell line), anti-cytokeratin monoclonal antibodies of MA904, AE3, CAM5.2, PKK1 and cytokeratin 19, and polyclonal anti-keratin antibodies were done. These were on 15 cases of primary breast carcinoma, eight cases of metastatic breast carcinoma in the liver, five cases of cholangiocarcinoma, eight cases of hepatocellular carcinoma and 11 cases of metastatic adenocarcinoma of another primary tumor in the liver. Results showed that GCDFP-15 antigen was most reliable: it was 100% positive in both primary and metastatic breast carcinomas unrelated to histological subtypes, and 100% negative in primary or other metastatic carcinomas in the liver. BCA-225 antigen was detected in high amounts in breast carcinomas (100%, 23/23), but it was positive in cholangiocarcinomas (80%, 4/5) and another metastatic carcinoma in the liver (64%, 7/11). BRST-5 was specifically positive in breast carcinomas but the positivity was low (13%, 3/23). Cytokeratin 19 and keratin were useful to discriminate hepatocellular carcinomas (0%, 0/8) from breast carcinomas (87%, 20/23; 96%, 22/23), but they were also positive in cholangiocarcinomas (100%, 5/5) and other metastatic carcinomas in the liver (91%, 10/11).(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Apolipoproteins; Apolipoproteins D; Breast Neoplasms; Carcinoma; Carcinoma, Hepatocellular; Carrier Proteins; Cholangiocarcinoma; Female; Glycoproteins; Humans; Immunohistochemistry; Keratins; Liver Neoplasms; Male; Membrane Transport Proteins; Middle Aged

A human monoclonal antibody, BM2, was produced by a hybridoma line generated by fusion of lymph node cells from a patient with squamous cell carcinoma (SCC) of the tongue with human B-lymphoblastoid cell line HO-323. BM2, an IgM class antibody, was reactive with all of the SCC cell lines tested. Frozen sections of normal and malignant tumor specimens were investigated to examine the reactivity of BM2 towards them. All 35 oral SCC specimens reacted with BM2. Normal stratified squamous epithelium showed positive staining in basal cells, but no staining was seen in other layers of the stratified epithelium, simple epithelium, and tissues of nonepithelial origin. Ductal basal cells of normal salivary gland also showed positive staining. Western blotting and immunoprecipitation analysis revealed that BM2 recognized 52 kDa membrane-associated protein. BM2 may therefore be a useful tool for biological and clinical studies of SCC.

Topics: Adenocarcinoma; Antibodies, Monoclonal; Antigens, Neoplasm; Carcinoma, Squamous Cell; Epithelial Cells; Epithelium; Fluorescent Antibody Technique; Formaldehyde; Humans; Hybridomas; Immunoglobulin Isotypes; Immunoglobulin M; Immunohistochemistry; Keratins; Membrane Proteins; Mitosis; Mouth Mucosa; Neuraminidase; Periodic Acid; Pronase; Submandibular Gland; Tumor Cells, Cultured

Thymus consists of some distinct epithelial cells that contain different sets of cytokeratins (CK). Epithelium-derived tumors maintain the expression of some of the CK of the specific nontransformed cells. Therefore, it seems reasonable to hypothesize that thymic epithelial tumors may differentiate toward distinct subsets of intrathymic epithelial cells in terms of CK expression.. Eighty-one thymomas and 14 thymic carcinomas were studied immunohistologically using monoclonal antibodies specific for a single CK or a CK pair.. Thymic epithelial neoplasms could not be distinguished from each other on the basis of the profile of CK expression because the degree of overlap was extensive. However, polygonal cell thymomas differentiate toward a CK13-positive cortical subset that is rare in normal thymus. Spindle cell thymomas differentiate toward a CK13-positive medullary subset. Mixed cell thymomas are comprised of a CK13-positive medullary subset and a CK13-negative medullary subset, both of which are typical in normal thymus. CK18 was expressed to a greater extent on the epithelium of thymic carcinomas than on that of thymomas. Polygonal cell thymomas more frequently were invasive than spindle and mixed cell thymomas.. There is a possibility that the epithelium of polygonal cell thymomas is immature because it is a phenotypically unusual subset in normal thymus. A thymic carcinoma arising in a thymoma has been reported, although the relationship between the thymoma and the thymic carcinoma was not clear. Nevertheless, given the similar cellular differentiation of thymoma and thymic carcinoma, CK18-positive epithelium in thymomas may be transformed into thymic carcinoma cells in certain conditions.

Topics: Adenocarcinoma; Carcinoma; Carcinoma, Small Cell; Carcinoma, Squamous Cell; Child; Child, Preschool; Humans; Infant; Keratins; Thymoma; Thymus Gland; Thymus Neoplasms

Short-term chronic exposures of rats to furan were recently found by us to preferentially induce a unique liver lobe pattern of development of small intestinal metaplasia and subsequent cholangiofibrosis, being essentially localized to the caudate and right liver lobes (L. W. Elmore, and A. E. Sirica, Cancer Res., 51: 5752-5759, 1991). We now demonstrate the preferential development of primary hepatic adenocarcinomas exhibiting small intestine mucosal cell differentiation, which have arisen at 70 to 90% incidences from the right/caudate liver lobes of Fischer 344 adult male rats by 16 months after their receiving furan by gavage at a daily dose of 30 mg/kg of body weight, five times a week, for 9, 12, and 13 weeks, respectively. In contrast, the incidences of primary hepatocellular carcinomas that developed in the furan-treated rats ranged from 0 to 20%, with the two hepatocellular carcinomas observed to be originating from the median/left liver lobes. Twenty-six of 27 hepatic adenocarcinomas analyzed exhibited glands containing on average 30.2% goblet cells, 2.1% Paneth cells, and 0.5% serotonin-positive neuroendocrine cells. Phenotypically, the glandular epithelial cells of the furan-induced intestinal-type adenocarcinomas were immunohistochemically positive for cytokeratin 19, but exhibited a heterogeneous pattern of immunohistochemical staining for gamma-glutamyl transpeptidase and showed no detectable immunostaining for transforming growth factor alpha. In addition, many of the glandular structures within these primary hepatic adenocarcinomas showed evidence of basement membrane disruption, as demonstrated by both electron microscopy and immunohistochemical staining for basement membrane laminin. While these intestinal-type adenocarcinomas appeared to have spread intrahepatically, none showed evidence of extrahepatic metastases. However, six of eight randomly selected adenocarcinomas grew progressively and retained their intestinal pattern of differentiation following serial transplantation into the fat pads of young adult Fischer 344 recipient rats. In this study, we also observed one primary hepatic cholangiocarcinoma that was characterized by a more native biliary rather than intestinal-type of differentiation. Interestingly, this was the only primary liver cancer observed by us to exhibit extrahepatic metastasis. In conclusion, our current findings clearly indicate that the small intestinal metaplasia and subsequent cholangiofibrosis developing e

Topics: Adenocarcinoma; Animals; Cell Differentiation; Furans; Histocytochemistry; Intestines; Keratins; Liver Neoplasms; Male; Microscopy, Electron; Rats; Rats, Inbred F344; Transforming Growth Factor alpha

Basal cell adenocarcinoma is a recently defined category of salivary gland neoplasms. As the terminology implies, this group of tumors has many histopathologic features that are similar to the more well-known basal cell adenomas. To better characterize these tumors, 23 basal cell adenocarcinomas were reviewed and compared with 11 basal cell adenomas with the use of light microscopic and immunohistochemical methods. Evaluation of cytokeratin, S-100 protein, glial fibrillary acidic protein, carcinoembryonic antigen, epithelial membrane antigen, smooth muscle actin, vimentin, B72.3, Ber-EP4, and milk fat globulin immunoreactivity was performed. Parallel to the morphologic similarity, the immunoprofiles of the basal cell adenocarcinoma and basal cell adenoma were quite similar. Both tumors showed reactivity patterns indicative of ductal epithelial and myoepithelial differentiation. In addition, reactivity to some polymorphic epithelial mucins was observed, which suggested glandular differentiation. The identification of antigens found normally in myoepithelial and epithelial cells supports the concept that these tumors are derived from pluripotential salivary gland epithelial cells. The comparable immunohistochemical profiles imply evolvement from similar cell lines and lead us to conclude that distinction between the two is not possible on the basis of these findings.

Topics: Actins; Adenocarcinoma; Adenoma; Antigens, Neoplasm; Carcinoembryonic Antigen; Glial Fibrillary Acidic Protein; Humans; Immunoenzyme Techniques; Keratins; Membrane Glycoproteins; Mucin-1; Parotid Neoplasms; S100 Proteins; Submandibular Gland Neoplasms; Vimentin

Cytokeratin expression in rat lung tumors was studied using polypeptide-specific monoclonal antibodies (MAbs) to human cytokeratins 4, 5, 7, 8, 10, 13, 14, 18 and 19. Experiments were performed on tumor fragments derived from 5 experimental rat squamous-cell lung tumors and one adenocarcinoma, as well as on cell lines obtained from the same tumors. The aims of this study were to investigate the differentiation profile of the rat tumor tissue and established tumor cell lines based on light and electron microscopical features and on cytokeratin phenotype, to characterize the tumor type and degree of differentiation of the lung tumors maintained during passaging in experimental animals, and to compare the cytokeratin expression pattern in transplanted tumors with that of the cultures derived from these tumors. Our results indicate that, in general, the antibodies used cross-react with rat cytokeratins and that these MAbs can be used to phenotype rat lung carcinomas. Both the tumor fragments and the cultured cells revealed a similar pattern of cytokeratin expression. In addition, the degree of differentiation was maintained upon prolonged culturing in vitro. MAbs to cytokeratin sub-types can therefore be used to distinguish the main sub-types of rat lung tumors and can give an indication about the degree of differentiation.

Topics: Adenocarcinoma; Animals; Blotting, Western; Bronchial Neoplasms; Carcinoma, Squamous Cell; Cell Differentiation; Fluorescent Antibody Technique; Immunoenzyme Techniques; Keratins; Microscopy, Electron; Rats; Tumor Cells, Cultured

Expression of keratins 1, 6, 15, 16, and 20 was examined in normal cervical epithelia, squamous metaplasia, various grades of cervical intraepithelial neoplasia, and both squamous cell carcinomas and adenocarcinomas of the cervix with monospecific antibodies. Ectocervical epithelium contains all of these keratins except keratin 20. They show a heterogeneous distribution, with a basally restricted detection of keratin 15. Endocervical columnar cells were found to contain significant amounts of keratin 16, whereas the subcolumnar reserve cells expressed considerable amounts of keratin 15 and 16, and frequently keratin 6. These reserve cell keratins were also found in immature and mature squamous metaplastic epithelium. In the cervical intraepithelial neoplastic lesions they were generally found with increasing intensity as the severity of the lesion progressed. In the keratinizing variety of squamous cell carcinoma of the cervix, these three keratins seem to constitute an important part of the intermediate filament cytoskeleton, whereas in nonkeratinizing squamous cell carcinoma, they occur to a much lesser extent. Surprisingly, these keratins were also occasionally found in adenocarcinomas. From these data we conclude that the keratin phenotype of reserve cells and endocervical columnar cells is more complex than previously suggested. In particular, the keratins occurring in reserve cells are also present in most of the premalignant and in a considerable number of the malignant lesions of the cervix. The differentiation features of the various carcinoma types are, however, reflected in their specific keratin filament composition.

Topics: Adenocarcinoma; Carcinoma; Carcinoma, Squamous Cell; Cervix Uteri; Epithelium; Female; Humans; Immunohistochemistry; Keratins; Metaplasia; Reference Values; Uterine Cervical Neoplasms

The endometrial carcinoma cell lines EC-MZ-1, 2, 3, 5, 9, and 11 were established between 1986 and 1990. Four cell cultures were started from endometrial tissue, one from ascites, and one from a lymph node metastasis. Lines have to date been subcultured up to 180 times and the doubling time varies between 26 hr and 3 weeks. Immunocytochemically the coexpression of cytokeratin (predominantly simple-epithelial cytokeratin polypeptides) and vimentin intermediate filaments was detectable in all cell lines, but three lines (EC-MZ-5, 9, 11) expressed vimentin only at low level. By transmission electron microscopy the tumor cells exhibited features of epithelial differentiation. After subcutaneous transplantation into nude mice three lines (EC-MZ-1, 2, 5) produced slow-growing tumors. The histological classification of these tumors ranged from moderately differentiated adenocarcinoma to undifferentiated carcinoma and closely corresponded to the original tumor. Even after long-term in vitro culture, without any addition of estrogens to the culture medium, the moderately differentiated receptor-positive cell line (EC-MZ-2) retained its morphological differentiation. The cells were propagated without estrogens in the culture medium. The estrogen and progesterone receptor levels of cultured cells were determined. Three lines (EC-MZ-1, 2, 3) were positive for the progesterone receptor in low passage number only, the other cell lines were negative for both receptors. The transplantable lines were investigated for hormonal receptor expression in ovariectomized nude mice. In the moderately differentiated cell line (EC-MZ-2) we observed an enhanced expression of the estrogen receptor under optimal stimulation of the nude mouse with estradiol benzoate. There was no effect on the expression of the progesterone receptor.

Topics: Adenocarcinoma; Adenocarcinoma, Papillary; Adult; Aged; Aged, 80 and over; Animals; Carcinoma, Squamous Cell; Endometrial Neoplasms; Endometriosis; Female; Humans; Immunohistochemistry; Keratins; Lymphatic Metastasis; Mice; Mice, Nude; Microscopy, Electron; Microscopy, Electron, Scanning; Middle Aged; Neoplasm Invasiveness; Neoplasm Transplantation; Receptors, Estrogen; Receptors, Progesterone; Tumor Cells, Cultured; Vimentin

A polypoid caecal adenocarcinoma in a 72-year-old female was found microscopically to be composed mainly of rhabdoid cells. Deposits in the liver and lymph nodes had a similar histological appearance to the primary tumour. The rhabdoid cells were typified by abundant eosinophilic cytoplasm, eccentric nuclei and prominent nucleoli. The differential diagnosis included rhabdomyosarcoma, metaplastic carcinoma (carcinoma with sarcomatoid dedifferentiation), carcinosarcoma and extra-renal rhabdoid tumour. The rhabdoid cells showed strong immunoreactivity with cytokeratin, epithelial membrane antigen and vimentin. Ultrastructurally, cytoplasmic whorls of intermediate filaments were noted. Multiple sections, immunohistochemistry and ultrastructural examination all revealed an adenocarcinomatous component which blended with the rhabdoid areas. In one area a rhabdoid cell was present within a malignant gland. This case illustrates that the rhabdoid appearance of many tumours can be misleading and is merely a non-specific morpho-phenotypic pattern seen in extra-renal sites. In the extra-renal setting, careful search for evidence of differentiation should be undertaken.

Topics: Adenocarcinoma; Aged; Cecal Neoplasms; Cytoplasm; Female; Humans; Immunohistochemistry; Keratins; Membrane Glycoproteins; Microscopy, Electron; Mucin-1; Phenotype; Vimentin

Early dissemination of malignant cells is the main cause for metastatic relapse in patients with solid tumours. By use of monoclonal antibodies (mAbs) specific for cytokeratins, disseminated individual epithelial tumour cells can now be identified in mesenchymal organs such as bone marrow. Further to characterize such cells in patients with prostate cancer, an immunocytochemical procedure was developed for simultaneous labelling of cytokeratin component no. 18 (CK18) and prostate specific antigen (PSA). In a first step, cells were incubated with mAb ER-PR8 against PSA and secondary gold-conjugated goat anti-mouse antibodies. In a second step, biotinylated mAb CK2 to CK18 was applied as primary antibody and subsequently incubated with complexes of streptavidin-conjugated alkaline phosphatase, which were developed with the Newfuchsin substrate. The binding of gold-labelled antibodies was visualized by silver enhancement. The sensitivity and specificity of the technique was demonstrated on cryostat sections of hyperplastic prostatic tissue, and cytological preparations of LNCaP prostatic tumour cells. Double staining was restricted to cells derived from the secretory epithelium of the prostate. Cross-reactivity between both detection systems was excluded by several controls, including the use of unrelated antibodies of the same isotype and the staining of CK18+/PSA- HT29 colon carcinoma cells. CK18+ cells co-expressing PSA were found in bone marrow aspirates from 5 out of 13 patients with carcinomas of the prostate, a finding that is consistent with the relative fraction of double-positive LNCaP cells. The specificity of CK18 for epithelial tumour cells in bone marrow was supported by negative staining of 12 control aspirates from patients with benign prostatic hypertrophy.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adenocarcinoma; Alkaline Phosphatase; Antibodies, Monoclonal; Antibody Specificity; Bone Marrow; Cross Reactions; Humans; Immunoglobulin G; Immunohistochemistry; Keratins; Male; Prostate; Prostate-Specific Antigen; Prostatic Neoplasms; Staining and Labeling

Human basal epithelium (myoepithelium)-specific (312C8-1) and luminal epithelium-specific (13H5) cytokeratin antibodies were applied to frozen sections of normal canine mammary tissues (seven), benign adenomas and hyperplasias (five), mixed tumors (12), and adenocarcinomas (18) to determine if epithelial subsets could be discriminated by the use of an avidin biotin peroxidase complex immunohistochemical procedure. The 312C8-1 and 13H5 antibodies were consistently reactive with basal and luminal epithelium, respectively, in the normal mammary gland (7/7) and in benign adenomas and hyperplasias (5/5). Mixed mammary tumors had similar basal and luminal epithelial reactivity and also had proliferating spindle-shaped stromal cells that were reactive with 312C8-1 (10/12) and 13H5 (4/12). The adenocarcinomas were subclassified into basal, luminal, and basal/luminal on the basis of 312C8-1 reactivity (4/18), 13H5 reactivity (2/18), and dual reactivity with mutually exclusive anatomic distribution (11/18), respectively. Those tumors with dual immunoreactivity were indicative of noninvasive carcinomas. Dogs with neoplasms that were reactive with 312C8-1 and nonreactive with 13H5 had local recurrence or distant metastasis within 2 weeks to 6 months after diagnosis. Other antibodies used for comparison were pan cytokeratin AE1/AE3, actin HHF35, and vimentin. 312C8-1 and 13H5 antibodies are specific for canine mammary basal and luminal epithelium, respectively, and by employing these antibodies, the origin and differentiation of canine mammary neoplasms can be determined more accurately than on the basis of hematoxylin and eosin-stained tissue alone.

Topics: Actins; Adenocarcinoma; Adenoma; Animals; Dog Diseases; Dogs; Female; Hyperplasia; Immunohistochemistry; Keratins; Mammary Glands, Animal; Mammary Neoplasms, Animal; Vimentin

Distinguishing primary hepatocellular carcinoma (HCC) from metastatic carcinomas to the liver is often difficult, if not impossible, particularly in needle biopsy and fine-needle aspiration specimens. In an attempt to identify a specific immunohistochemical profile that would distinguish HCC from metastatic carcinomas, we studied 56 HCCs, 8 cholangiocarcinomas, and 24 metastatic adenocarcinomas with monoclonal antibodies to alpha-fetoprotein (AFP), keratin (AE1, AE3, and CAM5.2), Leu-M1, human milk fat globule (HMFG-2), tumor-associated glycoprotein-72(B72.3), epithelial specific membrane antigen (Ber-EP4), and BCA-225 (CU-18). Both monoclonal and polyclonal (mCEA and pCEA) antibodies to carcinoembryonic antigen also were used. Metastatic adenocarcinomas were often positive for CU-18(71%), Leu-M1 (75%), B72.3 (50%), HMFG-2 (67%), Ber-EP4(83%) and mCEA(71%). Using these antibodies, the frequency of positivity for HCC was 9%, 16%, 11%, 20%, 36%, and 11%, respectively. CU-18 was the only monoclonal antibody in which there was a significant difference in positive rates between HCC and metastatic adenocarcinomas. Most HCCs (71%) revealed a bile canalicular staining pattern with pCEA. Because this staining pattern was absent in metastatic carcinomas, pCEA appears to be useful in confirming a diagnosis of HCC. AE1, AE3 and CAM5.2 antibodies were not useful in distinguishing HCC from metastatic carcinomas. Each cholangiocarcinoma shared a staining profile similar to that of metastatic carcinomas.

Topics: Adenocarcinoma; Adenoma, Bile Duct; alpha-Fetoproteins; Antibodies, Monoclonal; Antigens, Differentiation, Myelomonocytic; Carcinoembryonic Antigen; Carcinoma, Hepatocellular; Diagnosis, Differential; Humans; Immunohistochemistry; Keratins; Liver Neoplasms; Membrane Glycoproteins; Mucin-1; Retrospective Studies

This study compares the frequency of prominent nucleoli in low-grade adenocarcinoma with that of its frequent mimicker, adenosis. One hundred thirteen transurethral resection specimens of stage A purely low-grade adenocarcinoma (only Gleason score 1 or 2) were evaluated. Eighteen cases of adenosis were evaluated for comparison. Prominent nucleoli were defined as those with a greatest dimension more than 1.6 microns as measured with an ocular micrometer. The frequency of prominent nucleoli in each focus was estimated as (1) none, (2) rare (< 5% of epithelial cells), (3) occasional (5% to 50% of epithelial cells), and (4) frequent (> 50% of epithelial cells). Twenty percent of cases of adenocarcinoma had, at most, rare prominent nucleoli. Eight percent of adenocarcinoma cases had no prominent nucleoli. Twenty-eight percent of cases of adenosis had at least one focus of occasional or frequent prominent nucleoli. We conclude that a small but significant subset of low-grade prostatic adenocarcinomas lack prominent nucleoli and, likewise, a significant proportion of cases of adenosis have prominent nucleoli. Like many other histologic features of these lesions, we feel there is a spectrum of frequency of prominent nucleoli, with overlap between the two. The significance of nucleoli should be taken in context with other cytologic and architectural features characteristic of prostatic adenocarcinoma and adenosis. In difficult cases basal cell-specific immunohistochemical stains may be helpful.

Topics: Adenocarcinoma; Cell Nucleolus; Humans; Keratins; Male; Prostatic Hyperplasia; Prostatic Neoplasms

This report describes an immunohistopathologic analysis characterizing the incidence, pattern of distribution, and hormonal content of neuroendocrine (NE) cells in human benign prostate and prostatic adenocarcinoma.. Formaldehyde-fixed, paraffin-embedded material from 15 benign prostates, 31 primary prostatic adenocarcinomas, 16 metastatic lesions, 21 primary tumors treated with short-course diethylstilbestrol (DES), and 10 specimens from hormone-refractory patients were examined. NE cells were identified using silver histochemistry and a panel of immunohistochemical NE markers (chromogranin-A, serotonin, neuron-specific enolase), and specific peptide hormone antibodies.. NE cells were identified in all benign prostates. NE cells were identified in 77% of primary untreated adenocarcinomas with no significant differences with respect to pathologic stage. NE cells were found isolated and dispersed in the tumor, composing the minority of malignant cells. Double-labeling and serial section immunohistochemistry demonstrated the coexpression of prostate-specific antigen (PSA) in NE cells. In addition to serotonin, some tumors expressed multiple hormone immunoreactivities. NE cells were identified in 56% of metastatic deposits, with a similar pattern of distribution. In DES-treated cases, NE cells were found consistently in the adjacent benign epithelium, whereas 52% of tumors contained NE cells. Hormone-refractory tumors contained NE cells in 60% of cases.. This analysis demonstrates that a significant proportion of primary and metastatic prostatic adenocarcinomas contain a subpopulation of NE cells, the expression of which does not appear to be suppressed with androgen ablation and does not correlate with pathologic stage. Furthermore, NE cells coexpress PSA, suggesting a common precursor cell of origin. The elaboration of biogenic amines and neuropeptides suggests that NE cells dispersed in prostatic carcinoma may play a paracrine growth-regulatory role.

Topics: Adenocarcinoma; Aged; Aged, 80 and over; Basement Membrane; Calcitonin; Carcinoma; Cell Differentiation; Chromogranin A; Chromogranins; Cytoplasm; Diethylstilbestrol; Gastrin-Releasing Peptide; Gastrins; Humans; Keratins; Lymphatic Metastasis; Male; Middle Aged; Neoplasm Staging; Neurosecretory Systems; Peptides; Prostate; Prostate-Specific Antigen; Prostatic Neoplasms; Seminal Vesicles; Serotonin; Staining and Labeling; Thyrotropin

Cryosections of normal colon (NC), tubular and villous adenomas (TA, VA), and variably differentiated colon adenocarcinomas (CA) were immunostained with monoclonal antibodies to alpha 1-6 and alpha v, and beta 1-4 integrin subunits; select samples were stained for cytokeratin (Ck) 20 and villin. In NC, alpha 2 staining was strongest in crypt cells; alpha 1,3 and alpha v, and beta 1,3 and beta 4, and Ck 20 and villin predominated in superficial enterocytes. In TA and VA, monolayered glands showed integrin, Ck 20 and villin patterns that differed slightly from both crypt and superficial enterocytes. Complex glands in VA showed decreased integrin staining and basal polarization; Ck 20 and villin were strong only in luminal cells. CA showed overall weaker integrin staining than adenomas. Regardless of invasion depth, well formed malignant glands mimicked TA; pleomorphic glands mimicked VA with focal basal integrin polarization and solid clusters displayed scanty integrins, uneven Ck 20, and villin in occasional cells. Diverse integrins in crypt compared with superficial enterocytes reflect changing adhesive requirements as cells migrate and terminally differentiate. Decreasing expression and altered distribution of integrins, Ck 20 and villin noted in TA, VA, and in CA of increasing grade indicate that certain adhesive and cytoskeletal features more closely relate to glandular architecture than to depth of invasion.

Topics: Adenocarcinoma; Adenoma; Antibodies, Monoclonal; Carcinoma; Carrier Proteins; Cell Differentiation; Colon; Colonic Neoplasms; Epithelium; Fluorescent Antibody Technique; Humans; Immunoenzyme Techniques; Integrins; Keratins; Microfilament Proteins; Tissue Distribution

A case of adenoendocrine cell carcinoma of the gallbladder with adenomucous cells and neuroendocrine cells is reported. A histochemical and immunohistochemical study revealed that the primary tumor in the gallbladder was composed of mucus-secreting and/or argyrophil cells. Furthermore, the tumor showed a positive reaction to carcinoembryonic antigen (CEA) in all tumor cells, to chromogranin A and cytokeratin in many tumor cells, to endocrine granule constituent (EGC) in some tumor cells, and to serotonin and somatostatin in a few tumor cells. In addition, a few mucous cells showed argyrophilia and EGC-positivity in their cytoplasms. This case suggests that the adenoendocrine cell tumor is derived from endodermal stem cells as a result of bidirectional (exocrine and endocrine) differentiation.

Topics: Adenocarcinoma; Aged; Carcinoembryonic Antigen; Female; Gallbladder Neoplasms; Humans; Immunohistochemistry; Keratins; Neurosecretory Systems

We studied 71 patients with solid-type gastric adenocarcinoma selected from 5,437 surgically resected specimens during the period from 1975 to 1988; six had vimentin-positive adenocarcinomas, and five of these were advanced. One was at an early stage. All six tumors showed the same histologic features and had either a diffuse or alveolar arrangement, with tumor cells having either poor or no cohesiveness. Many tumor cells were round to polygonal, with eosinophilic or clear cytoplasm and large, eccentric vesicular nuclei, as seen in malignant rhabdoid tumors of the kidney. In all cases, the cytoplasm showed coexpression of vimentin and cytokeratin as revealed by double immunostaining. Four of the five cases with advanced carcinoma died of the disease 1 to 6 months after surgery. The cases with vimentin-positive tumors had significantly poorer prognoses than those with vimentin-negative tumors. We also studied adenocarcinomas of various histologic types randomly selected from our file (160 intestinal type and 69 diffuse type of Lauren) but failed to detect any vimentin positive ones. These results indicate that vimentin is expressed in some of the solid-type adenocarcinomas, which have a poor prognosis, and indicating that rhabdoid-like cells may be found in a variety of adenocarcinomas of the stomach.

Topics: Adenocarcinoma; Aged; Carcinoembryonic Antigen; Cell Nucleus; Female; Humans; Immunohistochemistry; Keratins; Male; Membrane Glycoproteins; Middle Aged; Mucin-1; Prognosis; Stomach Neoplasms; Vimentin

Topics: Adenocarcinoma; Aged; Aged, 80 and over; Female; Humans; Keratins; Male; Sebaceous Gland Neoplasms

The development of monoclonal antibodies (MAbs) to cytokeratins, which are integral components of the epithelial cytoskeleton, has made possible immunocytochemical detection of epithelial tumor cells. Importantly, this technique allows the detection of epithelial tumor cells that have metastasized from primary adenocarcinomas to secondary sites such as the bone marrow.. The aim of the study was not only to detect micrometastatic cells in bone marrow, but also to assess the expression of nuclear proliferation markers (Ki-67 and p120) and the erbB2 oncogene (also known as ERBB2) in these cells and, thus, hopefully improve prognostic precision.. Bone marrow aspirates were obtained from both sides of the upper iliac crest of 532 patients having definitive diagnoses of either breast or gastrointestinal cancer. The presence of micrometastatic epithelial tumor cells in bone marrow was assayed using the MAb cytokeratin 2 (CK2) to cytokeratin component 18 (CK18), in combination with the alkaline phosphatase-anti-alkaline phosphatase immunostaining technique. After primary screening of all marrow samples with MAb CK2, representative subgroups of CK18+ samples were selected for co-labeling with MAbs either to ErbB (n = 16), ErbB2 (n = 121), Ki-67 (n = 33), or p120 (n = 36) protein. An alternative labeling protocol based on the combination of immunogold and immunoenzymatic techniques was utilized to confirm the results derived from immunoenzymatic double staining.. In total, single CK18-positive tumor cells were detected in 180 (33.8%) of 532 bone marrow aspirates, with few differences among patients with breast or gastrointestinal cancer in TNM stage M0 (i.e., no distant metastasis). In patients with overt metastasis (stage M1), however, the incidence of metastatic cells in marrow increased to 73.7% in breast cancer, 52.5% in gastric cancer, and 39.0% in colon cancer. Whereas expression of Ki-67 or p120 on micrometastatic cells was observed only in 11 (15.9%) of 69 cancer patients analyzed, ErbB2+/CK18+ cells were found in 48 (67.6%) of 71 breast cancer patients and 14 (28.0%) of 50 patients with gastrointestinal cancer (P = .0001). The incidence of ErbB2+/CK18+ cells was positively correlated with the clinical stage of tumor progression.. The high incidence of ErbB2 expression on micrometastatic breast cancer cells in the bone marrow suggests that these cells might have been positively selected during early stages of metastasis. The majority of these cells appear to be in a dormant state of cell growth.. Although support from clinical follow-up is still needed, this study demonstrates that, beyond the mere presence of micrometastatic cells in bone marrow, useful prognostic information can be obtained by analysis of additional cell growth markers.

Topics: Adenocarcinoma; Antigens, Neoplasm; Biomarkers, Tumor; Bone Marrow; Cell Division; Gene Expression; Humans; Immunohistochemistry; Keratins; Ki-67 Antigen; Neoplasm Proteins; Nuclear Proteins; Protein-Tyrosine Kinases; Proto-Oncogene Proteins; Receptor, ErbB-2; tRNA Methyltransferases

Inositol hexaphosphate (InsP6 or phytic acid) has been shown to have antineoplastic action in in vivo models of colon carcinogenesis. We therefore investigated its effect on proliferation and differentiation of the human colon cancer cell line HT-29 in vitro. Proliferation was evaluated by neutral red incorporation assay, and differentiation was assessed by expression of the markers, cytokeratin, carcinoembryonic antigen (CEA) and beta-D-galactose-[1-->3]-N-acetyl-galactosamine (Gal-GalNAc). InsP6 in the culture media (0.66-10 mM) inhibited cell proliferation in a dose-dependent manner (P < 0.001), while inositol or inositol hexasulfate used as controls or media without InsP6 did not show any suppressive effect. The expression of the tumor marker, Gal-GalNac, was augmented (100.7% increase) by low dose (0.66 mM) of InsP6 but was subsequently suppressed with higher concentrations of InsP6. The expression of cytokeratin and CEA were both augmented by either InsP6 or inositol at all concentrations tested, although the degree of augmentation was milder with inositol than with InsP6. The combination of InsP6 and inositol (both 0.66 mm) resulted in augmentation (P < 0.001) of cytokeratin expression, while that of CEA remained unchanged. The inhibitory effect of InsP6 on cell proliferation was not altered by combination with additional inositol at any concentrations tested. Our results show that InsP6 inhibits cell proliferation and concomitantly increases differentiation and is therefore a candidate chemopreventive and chemotherapeutic agent for human large intestinal cancer.

Topics: Adenocarcinoma; Carcinoembryonic Antigen; Cell Differentiation; Cell Division; Colonic Neoplasms; Dose-Response Relationship, Drug; Drug Screening Assays, Antitumor; Edetic Acid; Galactosamine; Humans; Keratins; Phytic Acid; Tumor Cells, Cultured

We studied the solubility of keratin polypeptides 8 and 18 (K8/18), which are the predominant intermediate filaments in the human colonic epithelial cell line HT29. We find that asynchronously growing cells (G0/G1 stage of the cell cycle) have a substantial pool of soluble keratin that constitutes approx. 5% of total cellular keratin. This soluble keratin pool was observed after immunoprecipitation of K8/18 from the cytosolic fraction of cells disrupted using three detergent-free methods. Several other cell lines showed a similar significant soluble cytosolic K8/18 pool. Arrest of HT29 cells in G2/M stage of the cell cycle was associated with a concurrent increase in keratin solubility. Comparison of K8/18 obtained from the soluble cytosolic fraction and the insoluble high-speed pellet fraction showed similar levels of phosphorylation and glycosylation and similar tryptic radiolabeled phospho- and glycopeptide patterns. Soluble K8/18 can form characteristic 10 nm filaments in vitro as determined by electron microscopy. Cross-linking of soluble K8/18 followed by immunoprecipitation resulted in dimeric and tetrameric forms, based on migration in SDS-polyacrylamide gels. In addition, cross-linked and native soluble K8/18 showed similar migration on nondenaturing gels and similar sedimentation after sucrose density gradient centrifugation. Our results indicate that simple epithelial keratins are appreciably more soluble than previously recognized. The soluble keratin form is assembly competent and appears to be primarily tetrameric. Although K8/18 solubility was found to increase during mitotic arrest, glycosylation and phosphorylation did not play an obvious role in generating the soluble fraction, suggesting an alternate mechanism for keratin solubility.

Topics: Adenocarcinoma; Animals; Cell Line; Colonic Neoplasms; Epithelium; Glycosylation; HeLa Cells; Humans; Intermediate Filaments; Interphase; Keratins; Kidney; Macropodidae; Metaphase; Neoplasm Proteins; Phosphorylation; Protein Processing, Post-Translational; Solubility; Tumor Cells, Cultured

Keratins are a subgroup of cytoskeletal intermediate filament proteins found in most epithelial cells. Some reports have suggested that keratins may be found on the cell surface as well as their well-accepted cytoskeletal location. A major part of the evidence in the interpretation of cell surface expression of keratins is cell surface radioiodination. Here we show that lactoperoxidase-catalyzed iodination of colonic and breast tissue culture cells results in radiolabeling of the keratins when cells are manipulated. No labeling of keratins is detected when cells are labeled directly on the tissue culture dish. A similar result was obtained when intact cells were biotinylated using water-soluble sulfo-NHS-biotin. Partitioning of the keratins to a soluble and an insoluble pool after "cell surface" 125I-labeling showed that both pools became iodinated. Indirect immunofluorescence showed that binding of a panel of anti-keratin antibodies to intact epithelial cells occurs only on the cells that are more adherent, which are the cells that require longer manipulation to remove from the tissue culture dish. Taken together, our results indicate that the reported expression of cell surface keratins in some cells likely reflects intracellular keratins. In addition, the method of epithelial cell handling can dramatically alter the leakiness of cell surface iodination techniques.

Topics: Adenocarcinoma; Antibodies, Monoclonal; Biotin; Breast Neoplasms; Cell Membrane; Cell Membrane Permeability; Colonic Neoplasms; Cytoskeleton; Fluorescent Antibody Technique; Humans; Intermediate Filaments; Iodine Radioisotopes; Keratins; Methods; Precipitin Tests; Specimen Handling; Tumor Cells, Cultured

The distribution pattern of cytokeratin (CK) subtypes, an intermediate filament of cytoskeleton, was examined in adenomas and carcinomas of the colon and rectum. For the detection of the cytokeratin subtypes, monoclonal antibodies to the 54 Kd keratin polypeptide (CK No. 7 according to Moll's classification), 52.5 Kd (CK No. 8), 45 Kd (CK No. 18), and 40 Kd (CK No. 19) were used for immunohistochemical observation. Although No. 7 was positive in normal mucosa and adenoma with mild to moderate atypia, it could not be recognized in carcinoma. On the other hand the expression of No. 18 was confirmed in carcinoma, adenoma, and normal mucosa, and there were some differences in its distribution pattern in those with or without glandular formation and in areas showing infiltration of tumor cells. No. 18 expression was on the luminal side of normal colonic mucosa, adenoma, and well-differentiated adenocarcinoma; in the infiltrating area its reactivity was localized diffusely in the cytoplasm of tumor cells showing moderately or poorly differentiated adenocarcinoma cells. As to No. 8 and No. 19, they were recognized in normal mucosa, adenoma, and carcinoma. These results suggested the intimate relationship between expression of CK subtypes, cellular differentiation, and structural differentiation of colorectal carcinoma.

Topics: Adenocarcinoma; Adenoma; Colon; Colonic Neoplasms; Humans; Immunoenzyme Techniques; Intestinal Mucosa; Keratins; Rectal Neoplasms; Rectum

Seven cases of sweat-gland carcinomas showing eccrine ductal differentiation (ductal carcinomas) are presented. The tumors had a variable histological appearance, but were basically characterized by the following histological elements: (a) tubular structures, sometimes cystic or having a "tadpole" appearance; (b) solid islands of squamous, basaloid, or clear cells; (c) periodic acid-Schiff-positive endoluminal and/or intracellular material; and (d) infiltrating growth. Immunocytochemically, tumor cells were positive for keratin and negative for actin. Endoluminal material contained carcinoembryonic antigen in five of seven cases. Although it is not yet clear whether carcinomas exhibiting eccrine ductal differentiation may represent a specific histotype or a group encompassing several distinct clinicopathological entities, the histological analysis of the cases suggested that the wide spectrum of their histological appearances may be due to variable grades of differentiation.

Topics: Adenocarcinoma; Aged; Aged, 80 and over; Carcinoembryonic Antigen; Eccrine Glands; Facial Neoplasms; Female; Humans; Keratins; Lip Neoplasms; Male; Middle Aged; Scalp; Skin Neoplasms; Sweat Gland Neoplasms; Thoracic Neoplasms

The expression of differentiation associated high PM Keratin polypeptides of the oral mucosa lesions were studied by immunohistochemical and immunoblotting techniques applied to adjacent sections of each biopsy specimen. The material studied included specimens of leukoplakia, verrucous carcinoma, squamous cell carcinoma, adenocarcinoma and keratoacanthoma. Little or no expression of 65-67 Kd keratins was evident in squamous cell carcinoma and adenocarcinoma. Hyperkeratotic (both benign and dysplastic) lesions such as verrucous carcinoma, leukoplakia, and keratoacanthoma, showed great variations in the intensity of 65-67 bands and a very irregular immunohistochemical staining pattern. Increased amounts of horny substance was usually accompanied by absence of, or decreased expression of 65-67 Kd keratins, thus indicating a change in the polypeptide composition of the horny layer in pathological conditions of the oral epithelium.

Topics: Adenocarcinoma; Antigens, Differentiation; Carcinoma, Squamous Cell; Carcinoma, Verrucous; Cell Differentiation; Electrophoresis, Polyacrylamide Gel; Humans; Immunoblotting; Immunoenzyme Techniques; Immunohistochemistry; Keratins; Keratoacanthoma; Leukoplakia, Oral; Mouth Mucosa; Mouth Neoplasms

Basal cell hyperplasia classically has been described as having bland cytologic features. During the past 2 years, we have seen 12 cases (11 in consultation) with atypical features that were confused with adenocarcinoma of the prostate. Eleven of these 12 cases contained prominent nucleoli mimicking carcinoma; in the 12th case, nuclei were enlarged, hyperchromatic, and moderately pleomorphic. Immunohistochemistry with antibodies against high-molecular-weight cytokeratin (34 beta E12) was performed in nine of the cases, verifying their basal cell nature. Additional findings in these cases were necrotic intraluminal secretions (two cases), immature squamous metaplasia (two cases), peculiar hyaline cytoplasmic globules (two cases), adenosis (one case), markedly atypical nuclei of uncertain nature occurring elsewhere in the specimen (one case), and intraluminal blue mucin (two cases). We analyzed nine cases of typical basal cell hyperplasia, all of which showed classic features of basal cell hyperplasia with benign cytology. Both atypical and classical basal cell hyperplasia were frequently infiltrated by lymphocytes such that the cytologic changes could not be attributable to inflammation. Atypical basal cell hyperplasia must be differentiated from ordinary adenocarcinoma of the prostate, prostatic intraepithelial neoplasia, and basaloid carcinoma (adenoid cystic carcinoma) of the prostate.

Topics: Adenocarcinoma; Aged; Aged, 80 and over; Carcinoma, Adenoid Cystic; Diagnosis, Differential; Follow-Up Studies; Humans; Immunohistochemistry; Keratins; Male; Prostate; Prostatic Hyperplasia; Prostatic Neoplasms; Time Factors

Numerous reports have claimed that because acidic mucin is absent in benign prostatic glands and is present in some prostatic adenocarcinomas, this stain may be an adjunctive aid in the diagnosis of adenocarcinoma of the prostate. However, adenosis that mimics low-grade adenocarcinoma has not been evaluated to date. We studied 28 foci of adenosis for the presence of high iron diamine-alcian blue (HID-AB). Fifteen foci of adenosis (54%) showed strong staining for HID-AB; staining was diffuse in 11 cases and focal in four cases. An additional two cases (7%) showed equivocal staining. The remaining 11 cases (39%) lacked positivity. All cases of adenosis were verified with immunohistochemistry for keratin 903, a basal cell-specific antibody. This study demonstrates the limited use of acid mucin staining in the diagnosis of adenocarcinoma. The finding of HID-AB positivity in occasional isolated benign small prostatic glands within hyperplastic nodules suggests that acid mucin secretion may be a reflection of gland size or proliferation rather than evidence that adenosis is related to adenocarcinoma of the prostate.

Topics: Adenocarcinoma; Biomarkers, Tumor; Diagnosis, Differential; Histocytochemistry; Humans; Immunohistochemistry; Keratins; Male; Mucins; Prostate; Prostatic Diseases; Prostatic Neoplasms

Miltefosine (hexadecylphosphocholine, HPC, CAS 58066-85-6) was investigated in transplanted primary methylnitrosourea-induced PYH mammary carcinoma of F344 rats. The therapy was performed in the 5th and 10th passage. At first HPC (113 mg/kg body weight) significantly reduced the median tumor volume, but a loss of activity was observed in the 10th passage. To explain the loss of sensitivity and to obtain information on the mechanism of action histology, cytoskeleton and hormone receptor content were investigated. The most important change was observed in the histopathology of the tumor. The initial tubular papillary adenocarcinoma was transformed into a malignant adenoacanthoma with epithelial structure. Vimentin as an endothelial marker of the cytoskeleton was equally expressed in all passages. Cytokeratin was weakly expressed in the earlier passages and intensively present in the late passages. The histopathological change from tubular adenocarcinoma to malignant adenoacanthoma might be caused by an overgrowth of the primary epithelial tumor cells or by a real transformation in the morphological characteristics of the tumor, which may occur during repeated transplantation.

Topics: Adenocarcinoma; Animals; Antineoplastic Agents; Biomarkers, Tumor; Body Weight; Female; Keratins; Mammary Neoplasms, Experimental; Neoplasm Transplantation; Phosphorylcholine; Rats; Rats, Inbred F344; Vimentin

Characteristics of keratins of five carcinomas of sweat gland origin were immunohistochemically investigated with several antikeratin monoclonal antibodies with differing specificities. Specimens were obtained from two cases of mucinous carcinoma of the skin, two cases of classic type of eccrine adenocarcinoma, and a case of eccrine porocarcinoma. The tumor cells of mucinous carcinoma expressed only simple epithelial keratins. In a case of eccrine adenocarcinoma, simple epithelial keratin 19 was diffusely expressed. The expression of the other simple epithelial keratins was confined to the luminal cells, whereas the remaining tumor cells further expressed stratified epithelial keratins. Eccrine porocarcinoma and a second case of eccrine adenocarcinoma did not express simple epithelial keratins, although stratified epithelial keratins were diffusely expressed. These data suggest that carcinomas of sweat glands express various combinations of simple and stratified epithelial keratins. Development of additional data along these lines may help to further define their classification.

Topics: Adenocarcinoma; Adenocarcinoma, Mucinous; Aged; Aged, 80 and over; Antibodies, Monoclonal; Female; Humans; Immunohistochemistry; Keratins; Male; Middle Aged; Sweat Gland Neoplasms

A 55-year-old female with meningeal signs was suspected to have carcinomatosis meningitis based on cytospin cytology study of cerebrospinal fluid (CSF) with Wright stain. There was no primary site of any malignancy which could be identified as the source of metastasis. Immunochemical staining for cytokeratin and carcinoembryonic antigen on suspicious large immature cells in the CSF gave positive results and confirmed the malignant nature of her disease. Intrathecal chemotherapy with methotrexate and whole brain irradiation then eradicated the symptoms rapidly. Immunocytochemistry was considered to be a very powerful diagnostic tool in management of this patient.

Topics: Adenocarcinoma; Carcinoembryonic Antigen; Female; Humans; Immunohistochemistry; Keratins; Meningeal Neoplasms; Middle Aged; Neoplasms, Unknown Primary

Hormonal manipulation of prostate cancer is an effective therapy for metastatic disease. Unfortunately, following an initial response tumors reestablish themselves as hormone independent variants and progress. This study was designed to assess the interrelationship of cytokeratin P (Cyto P), vimentin, epidermal growth factor receptor (rEGF) and tissue testosterone following androgen deprivation therapy. Animals bearing the hormone dependent Dunning R3327 G subline prostatic adenocarcinoma were surgically castrated and progressing tumors from both hormone intact and castrated groups were quantitatively assayed for immunohistologic reactivity against the described markers. The results demonstrate a significant (p < 0.05) decrease in cytokeratin (Cyto P), rEGF and testosterone levels following castration. When the expression of both rEGF and Cyto P are related to the tissue testosterone content, it is observed that the ratio between rEGF and testosterone remains essentially unchanged (0.65 +/- 0.21 to 0.65 +/- 0.41), suggesting that in the Dunning R3327 G subline, rEGF expression is coordinately under androgen control. At least some cytokeratin expression also appears to be particularly sensitive to androgen levels, since the ratio between Cyto P and testosterone decreased from 0.92 +/- 0.39 to 0.35 +/- 0.41 following castration. In contrast, following castration, the expression of vimentin was unaffected.

Topics: Adenocarcinoma; Animals; ErbB Receptors; Intermediate Filament Proteins; Keratins; Male; Neoplasm Transplantation; Neoplasms, Hormone-Dependent; Orchiectomy; Prostatic Neoplasms; Rats; Testosterone; Vimentin

Double-label immunofluorescence was used to monitor basement-membrane composition and integrity in 22 human colon polyps, 36 adenocarcinomas and 2 metastases. Cryostat sections were stained with polyclonal anti-laminin anti-serum combined with monoclonal antibodies (MAbs) to all major basement-membrane components (laminin, entactin/nidogen, collagen type IV and large heparan sulfate proteoglycan), as well as to keratin 8. In all adenocarcinomas, including mucinous, basement membranes were altered more at the invasive front than in the parenchyma. The degree of this alteration was inversely correlated with the level of tumor differentiation. An uncoordinated loss of basement membrane components (dissociation of markers), previously described by us in rat colon adenocarcinomas, was also found in human tumors. In the great majority of adenocarcinomas a pronounced stromal reaction was seen. It was manifested by the presence of fibrillar deposits of basement-membrane components, mainly of collagen type IV and/or heparan sulfate proteoglycan. This reaction was never observed in polyps and may be derived from myofibroblasts reported to accumulate in colon cancer stroma. The combined use of antibodies to basement-membrane components and to a specific keratin may constitute an adequate immunohistochemical test for the presence of invasion, and may be useful in the histologic analysis of polyps, especially in dubious cases.

Topics: Adenocarcinoma; Antibodies, Monoclonal; Basement Membrane; Blotting, Western; Collagen; Colon; Extracellular Matrix Proteins; Fluorescent Antibody Technique; Heparan Sulfate Proteoglycans; Heparitin Sulfate; Humans; Intestinal Neoplasms; Intestinal Polyps; Keratins; Laminin; Lymphatic Metastasis; Membrane Glycoproteins; Proteoglycans

An immunohistochemical study of squamous metaplasia (n = 10), dysplasia (n = 18), squamous cell carcinoma (n = 48) and 3 cases of adenosquamous carcinoma of the uterine cervix with anti-56KD keratin and 68KD keratin antibodies was performed. In the cases of squamous metaplasia, there were two types of staining of which one type had 56KD positive and 68KD negative and another type had both positive. In the cases of dysplasia, there were two types of staining the same as in squamous metaplasia. But in the cases of carcinoma in situ (CIS) (n = 25), there were three types of staining of which the first type had both 56KD and 68KD negative (n = 7), the second type had 56KD positive and 68KD negative (n = 15), and the third type had both 56KD and 68KD positive (n = 3). In invasive carcinoma (n = 23), there were two types of staining the same as in dysplasia of which one type had 56KD positive and 68KD negative (n = 17) and another type had both positive (n = 6). The keratin negative cases in CIS showed morphologically atypical reserve cell hyperplasia composed of atypical small cells with round nuclei and had a small lesion compared with other types. This result suggested that keratin negative CIS was an early form of CIS which was keratin positive. The results indicating that all dysplasia had 56KD keratin positive and CIS had not always 56KD keratin positive suggested that dysplasia was not always a precursor lesion of CIS.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adenocarcinoma; Antibodies, Monoclonal; Carcinoma in Situ; Carcinoma, Squamous Cell; Cell Transformation, Neoplastic; Cervix Uteri; Female; Humans; Hyperplasia; Immunoenzyme Techniques; Keratins; Metaplasia; Molecular Weight; Neoplasms, Multiple Primary; Uterine Cervical Neoplasms

Six patients with adenosquamous carcinoma (ASqC) of the pancreas were studied clinicopathologically and immunohistochemically. In five of six ASqC tumors, both malignant squamous and glandular elements were reactive with CA 19-9, ST 439, and keratin antibodies. In contrast, a portion of the glandular element in the remaining one ASqC was reactive with CA 19-9 and ST 439 antibodies, but that of the squamous cell carcinoma (SqCC) was not reactive. However, SqCC of this tumor was intensely reactive with keratin antibody. These immunohistochemical results suggest that the histogenesis in one ASqC tumor was different from that of the other 5 ASqCs, and that this tumor may be a collision tumor rather than transformation to SqCC from adenocarcinoma, which is a very rare pattern of histogenesis in ASqC. The patients with ASqC of the pancreas showed shorter survivals following operations because of systemic metastasis including liver metastasis.

Topics: Adenocarcinoma; Aged; Aged, 80 and over; Antigens, Tumor-Associated, Carbohydrate; Carcinoma, Squamous Cell; Female; Humans; Immunohistochemistry; Keratins; Liver Neoplasms; Male; Middle Aged; Neoplasm Invasiveness; Neoplasm Staging; Pancreatic Neoplasms; Survival Rate

Cytokeratin-type intermediate filaments are a polygenic family of insoluble proteins that vary according to cell of origin and have been proposed as potentially useful markers of differentiation in epithelial malignancies. Because gastrointestinal malignancies resemble each other in their expression of many soluble antigens, we compared the cytokeratins of seven colonic, three gastric, six pancreatic, and one duodenal carcinoma cell lines, and one colon villous adenoma cell line. Cytokeratins were characterized by one- and two-dimensional gel electrophoresis, immunoblotting, and immunocytochemistry. These cell lines expressed combinations of cytokeratins 7, 8, 18, and 19, which are typical of the "simple" epithelial pattern found in normal ductal and glandular tissues of the gastrointestinal tract. However, pancreatic carcinoma cell lines expressed additional cytokeratins that are normally found in stratified squamous epithelium and epidermoid (squamous cell) carcinomas. These additional cytokeratins consisted of cytokeratin 16 in all six cell lines and cytokeratins 4, 13, and 16 in one cell line. These results suggest that cytokeratin patterns represent stable markers that may aid in distinguishing gastrointestinal malignancies.

Topics: Adenocarcinoma; Animals; Cell Line; Colonic Neoplasms; Diagnosis, Differential; Humans; Keratins; Mice; Pancreatic Neoplasms; Stomach Neoplasms; Tumor Cells, Cultured

Fifty-six lymph nodes excised from 11 patients with pancreatic adenocarcinoma were studied for evidence of metastasis by standard light microscopy and immunohistochemistry using an anticytokeratin monoclonal antibody. Eight of 56 nodes contained metastatic carcinoma as demonstrated by conventional techniques. By immunohistochemistry, positive-staining cells were easily identified. In 10 of 56 nodes, the positive staining was accompanied by cytologic atypia, changes consistent with malignancy. In seven additional nodes, positive-staining cells were present, but cytologic atypia was lacking. The use of immunohistochemistry facilitated recognition of malignant cells and raised questions that single-cell metastasis may be present. Positive staining for cytokeratin should prompt a close examination of cells to determine if morphologic features of malignancy are present.

Topics: Adenocarcinoma; Antibodies, Monoclonal; Humans; Immunohistochemistry; Keratins; Lymph Nodes; Lymphatic Metastasis; Pancreatic Neoplasms

The expression patterns of basement membrane components and keratin intermediate filament proteins were studied in normal human bronchial epithelium and 56 lung carcinomas using monoclonal antibodies to laminin, type VII collagen and the individual keratins 14, 16, 17 and 18. In normal lung, laminin and type VII collagen were present between the epithelium and the lamina propria of bronchi and bronchioles. Keratin 14 was expressed in the basal cells, keratin 17 in the basal and some suprabasal cells and keratin 18 in the columnar cells of the bronchi and bronchioles. Keratin 16 was not present in normal bronchial epithelium. Laminin was found in all subtypes of lung carcinoma, but type VII collagen was present only in squamous cell carcinomas, where it showed a reduction in expression with decreasing differentiation. Type VII collagen was not identified in adenocarcinomas, small cell carcinomas or carcinoids. Antibodies to basal cell keratins 14 and 17 also displayed positivity only in squamous cell carcinomas, although no correlation with the degree of differentiation could be observed. Keratin 16 appeared to be a marker of the squamous phenotype, rather than of hyperproliferation. The keratin 18 marker for columnar epithelial cells showed a reaction pattern opposite to that of the basal cell keratins, being extensively present in adenocarcinomas, small cell carcinomas and carcinoids, with less expression in squamous cell carcinomas. This study shows a correlation between the presence of type VII collagen and the basal cell keratins 14 and 17, and a negative correlation between these components and keratin 18. These findings are likely to be useful in identifying lung cancer subtypes.

Topics: Adenocarcinoma; Antibodies, Monoclonal; Carcinoid Tumor; Carcinoma, Small Cell; Carcinoma, Squamous Cell; Collagen; Humans; Immunoenzyme Techniques; Keratins; Laminin; Lung Neoplasms

Antibodies to cytokeratins (CKs) have found extensive application in the differential diagnosis of epithelial tumors. The chain-specific anti-CK reagents appear to be of practical value for further subtyping of carcinomas. The authors have produced a novel anti-CK 18 monoclonal antibody (ACK-156) using a modified immunization procedure that included sequential injections of human epidermal keratin, cyclophosphamide, and enriched cytoskeletal extracts from a human lung carcinoma cell line. This protocol effectively amplified clones with reactivity toward CK epitopes not present in epidermal keratin. Monospecificity of the antibody was confirmed by immunoblot analysis using both total cell lysates and cytoskeletal extracts as antigens. Immunoperoxidase staining of adenocarcinomas from a variety of sites, including lung, was strongly positive. Squamous cell carcinomas of lung were also strongly stained whereas squamous cell carcinomas of head and neck origin were stained focally or not at all. In contrast, several commercially available anti-CK 18 monoclonal antibodies did not distinguish squamous cell carcinomas of lung from those of head and neck origin. Immunoblot analysis of tumor lysates corroborated the tissue staining results and revealed that the commercially available antibodies that were tested recognize at least one other low molecular weight peptide in addition to the CK 18 peptide recognized by ACK-156.

Topics: Adenocarcinoma; Antibodies, Monoclonal; Carcinoma, Squamous Cell; Cytoskeleton; Electrophoresis, Polyacrylamide Gel; Epitopes; Humans; Hybridomas; Immunoblotting; Immunologic Techniques; Keratins; Lung Neoplasms; Peptide Mapping; Staining and Labeling

The immunocytochemical detection of amylase, carboxypeptidase A, alpha 1-antitrypsin, carcinoembryonic antigen (CEA) and keratin in normal canine pancreatic tissue and in carcinomas of the exocrine pancreas of the dog is described. In the normal pancreas, the acinar cells contain amylase, carboxypeptidase and alpha 1-antitrypsin. The pancreatic ducts react with the antikeratin antibody. Twelve out of 14 pancreatic exocrine carcinomas showed immunoreaction with antiamylase antibody, and 10 with anticarboxypeptidase antibody. Five neoplasms reacted with anti-CEA antibody and three with the anti-alpha 1-antitrypsin antibody. It was not possible to find any systematic difference in the immunocytochemical profiles of acinar, tubular and undifferentiated carcinomas. These results indicate that immunocytochemical marking of amylase and carboxypeptidase is of value in the diagnosis of pancreatic neoplasms in the dog, especially if metastasis is the only material available for study and the tumour does not show any diagnostic feature on routine light microscope preparations.

Topics: Adenocarcinoma; alpha 1-Antitrypsin; Amylases; Animals; Biomarkers, Tumor; Carboxypeptidases; Carboxypeptidases A; Carcinoembryonic Antigen; Carcinoma; Dog Diseases; Dogs; Immunohistochemistry; Keratins; Pancreatic Neoplasms

In the present study we investigated the cytokeratin (CK) polypeptide expression in gastric and colonic adenocarcinomas. A battery of monoclonal anti-cytokeratin-specific antibodies and anti-vimentin were used. While the majority of cases displayed simple epithelial characteristics, in three of 17 cases of gastric adenocarcinomas and in one of 20 cases of colonic adenocarcinomas, CK polypeptides 13 (54 kd) and 16 (48 kd) were occasionally detected. These CK polypeptides, characteristic of squamous nonkeratinizing epithelia, were found in cases in which no evidence of squamous differentiation could be demonstrated by histologic examination. We believe that the presence of these unique CK polypeptides points to the squamous differentiation potential of the tumor cells.

Topics: Adenocarcinoma; Antibodies, Monoclonal; Colonic Neoplasms; Fluorescent Antibody Technique; Humans; Keratins; Peptides; Stomach Neoplasms

Expression of keratins (cytokeratins, CK) in healthy feline epithelia and 2 established feline mammary carcinoma cell lines was examined immunohistochemically and by use of immunoblotting analysis. A panel of specific anti-CK monoclonal antibodies (MAb) identifying epitopes unique to individual keratins or shared by 2 (or 3) CK polypeptides was used. Besides already available anti-human CK MAb, this panel of MAb consisted of 9 newly generated anti-human CK MAb and 1 newly generated anti-feline CK MAb. Immunohistochemical analysis on normal epithelia revealed that most of the anti-human CK MAb and the anti-feline CK MAb reacted with both feline and human epithelia, with a comparable tissue distribution pattern. However, slight differences in CK tissue distribution pattern between human beings and cats were detected by one MAb. Immunoblotting analysis revealed that all anti-human CK MAb that were immunohistochemically reactive with feline tissues detected analogous CK in cats, indicating the presence of a number of common epitopes on human and feline CK. Two continuous cell lines derived from 2 distinct feline mammary adenocarcinomas, K248C and K266, were analyzed with respect to their CK phenotype. Although no difference in CK expression between the 2 cell lines was detected in vitro, a difference in CK phenotype was detected on subcutaneous transplantation of the 2 cell lines into nude mice. Although the K248C-induced adenocarcinomas maintained the same CK phenotype as observed in vitro, the CK pattern of the K266 heterotransplants, growing as adenosquamous carcinomas, changed with squamous differentiation. Our findings confirm the high degree of homology between mammalian CK, and on the basis of those findings, we suggest that CK proteins provide a set of markers valuable for the characterization of normal and neoplastic feline tissues and for studies of squamous metaplasia.

Topics: Adenocarcinoma; Animals; Antibodies, Monoclonal; Antibody Specificity; Carcinoma, Squamous Cell; Cats; Epithelium; Fluorescent Antibody Technique; Immunoblotting; Immunohistochemistry; Keratins; Mammary Neoplasms, Animal; Tissue Distribution; Tumor Cells, Cultured

A patient with skin metastases several years after surgical treatment of carcinoma of the cervix and the rectum is presented. Comparative histology and immunohistochemical analysis with anti-cytokeratin antibodies implicated the carcinoma of the cervix as the source of the skin infiltrates. Based on this patient's case record, the use of anti-cytokeratin antibodies for identification and subtyping of epithelial or carcinoma cells is discussed with special reference to cytokeratin 7.

Topics: Adenocarcinoma; Aged; Aged, 80 and over; Biomarkers, Tumor; Combined Modality Therapy; Female; Humans; Immunoenzyme Techniques; Keratins; Neoplasm Staging; Neoplasms, Second Primary; Rectal Neoplasms; Skin; Skin Neoplasms; Uterine Cervical Neoplasms

Topics: Adenocarcinoma; Aged; Esophageal Neoplasms; Etretinate; Hair Diseases; Humans; Keratins; Male; Paraneoplastic Syndromes

Using a panel of 21 monoclonal and 2 polyclonal keratin antibodies, capable of detecting separately 11 subtypes of their epithelial intermediate filament proteins at the single cell level, we investigated keratin expression in 16 squamous cell carcinomas, 9 adenocarcinomas, and 3 adenosquamous carcinomas of the human uterine cervix. The keratin phenotype of the keratinizing squamous cell carcinoma was found to be most complex comprising keratins 4, 5, 6, 8, 13, 14, 16, 17, 18, 19, and usually keratin 10. The nonkeratinizing variety of the squamous cell carcinoma expressed keratins 6, 14, 17, and 19 in all cases, usually 4, 5, 7, 8, and 18, and sometimes keratins 10, 13, and 16. Adenocarcinomas displayed a less complex keratin expression pattern comprising keratins 7, 8, 17, 18, and 19, while keratin 14 was often present and keratins 4, 5, 10 and 13 were sporadically found in individual cells in a few cases. These keratin phenotypes may be useful in differential diagnostic considerations when distinguishing between keratinizing and nonkeratinizing carcinomas (using keratin 10, 13, and 16 antibodies), and also in the distinction between nonkeratinizing carcinomas and poorly differentiated adenocarcinomas, which do not express keratins 5 and 6. Keratin 17 may also be useful in distinguishing carcinomas of the cervix from those of the colon and also from mesotheliomas. Furthermore the presence of keratin 17 in a CIN I, II, or III lesion may indicate progressive potential while its absence could be indicative of a regressive behavior. Because most carcinomas express keratins 8, 14, 17, 18, and 19, we propose that this expression pattern reflects the origin of cervical cancer from a common progenitor cell, i.e., the endocervical reserve cell that has been shown to express keratins 5, 8, 14, 17, 18, and 19.

Topics: Adenocarcinoma; Adult; Aged; Carcinoma; Carcinoma, Squamous Cell; Endometriosis; Female; Humans; Immunoenzyme Techniques; Keratins; Middle Aged; Staining and Labeling; Uterine Cervical Neoplasms

Much of the information recorded at the time of surgery for malignant disease has been used, alone or in combination, to indicate the outlook for that patient, including probability of metastasis. However, direct evidence of tumour seeding in distant organs at that time is not available. An immunocytochemical assay for the epithelial cytokeratin protein (CK18) may fill this gap since it is a feature of epithelial cells but would not normally be in bone marrow. We looked for disseminated tumour cells preoperatively in bone marrow from 88 patients with radically resected colorectal carcinomas. Smears for 28 (32%) patients were positive for cells of epithelial origin, which were absent from aspirates taken from 102 controls with non-malignant disease. The prognostic value was assessed in a follow-up study with a median observation time of 35 (12-58) months. Patients who had bone marrow tumour cells in the aspirate showed a significantly shorter disease-free survival than those without tumour cells (p = 0.0084). In a Cox regression model multivariate analysis demonstrated that the finding of tumour cells in bone marrow is an independent, significant (p = 0.0035) determinant of relapse. Although the skeleton is not a preferred site of overt metastasis in colorectal cancer the demonstration of tumour cells in bone marrow has to be taken as evidence of the general disseminative capability of an individual tumour.

Topics: Adenocarcinoma; Bone Marrow; Colorectal Neoplasms; Female; Follow-Up Studies; Humans; Keratins; Male; Middle Aged; Prognosis

A human monoclonal antibody (MAb), MS2B6, produced from splenocytes isolated from a patient with advanced papillary serous cystadenocarcinoma of the ovary, defines a unique human tumor-associated antigen. This antigen, EA2B6 (epithelial antigen 2B6), is expressed in a tissue-restricted manner on cultured and fresh human adenocarcinomas and some normal glandular epithelial tissues. EA2B6 is a 38-48 kD protein antigen that co-fractionates with the nuclear matrix-intermediate filament scaffold of simple glandular epithelial tissues. EA2B6 is a molecule with restricted solubility, and in vitro antigen-antibody binding is dependent on the antigen being presented on a solid support. To determine if EA2B6 is a cytokeratin, competition studies were undertaken with several cytokeratin-specific murine monoclonal antibodies. None of these antibodies inhibited the binding of human MAb MS2B6 to partially purified EA2B6. Less than 1% of HT29 colon adenocarcinoma cells and fresh ovarian adenocarcinoma ascites cells express EA2B6 on their surface. The majority of EA2B6 is intracellular. Because of the restricted tissue distribution of this antigen and stability of the antibody, we believe MS2B6 is a good candidate for MAb-mediated diagnosis and therapy of human adenocarcinomas.

Topics: Adenocarcinoma; Antibodies, Monoclonal; Antibodies, Neoplasm; Antibody Affinity; Antigens, Neoplasm; Binding, Competitive; Carbohydrates; Epithelium; Humans; Keratins

A panel of seven monoclonal antibodies including anti-vimentin, anti-keratin markers AE1/AE3 and EAB902, human milk fat globule (HMFG-2), B72.3, anti-carcinoembryonic antigen (CEA), and anti-Leu-M1 were used for an immunoperoxidase staining assay to determine their value in the differentiation of pleural mesothelioma from lung adenocarcinoma. Anti-vimentin positively identified 86% of the mesotheliomas and none of the adenocarcinomas. AE1/AE3, EAB902, and B72.3 reacted with a high percentage of both mesothelioma and adenocarcinoma specimens. With HMFG-2, both membrane and cytoplasmic staining was observed in 92% of the adenocarcinomas and in 14% of the mesotheliomas, whereas 26% of the mesotheliomas only exhibited membrane staining. Eighty percent of the adenocarcinomas and 8% of the mesothelioma tissues stained with anti-Leu-M1. Anti-CEA did not react with any of the 50 mesotheliomas tested but did react with 95% of the lung adenocarcinomas tested. From this study, it was concluded that anti-CEA and anti-Leu-M1 were the most effective of the seven tumor markers evaluated; and that 100% of the pleural mesothelioma tissues could be correctly differentiated from lung adenocarcinomas using a panel consisting of anti-vimentin, HMFG-2, anti-CEA and anti-Leu-M1 monoclonal antibodies.

Topics: Adenocarcinoma; Antibodies, Monoclonal; Antigens, Differentiation, Myelomonocytic; Antigens, Neoplasm; Carcinoembryonic Antigen; Diagnosis, Differential; Glycoproteins; Humans; Immunoenzyme Techniques; Immunohistochemistry; Keratins; Lung Neoplasms; Membrane Glycoproteins; Mesothelioma; Mucin-1; Pleural Neoplasms; Vimentin

Ten renal cell carcinomas in children under 15 years were investigated. The average age was 122.5 months and the girls predominated in our cases (7 girls, 3 boys). By using the classification of Thoenes et al., Pathol Res Pract 181: 125-143, 1986 a predominance of clear cell-eosinophilic tumor cell type and of the tubulopapillary growth pattern was found. Immunohistochemistry revealed a heterogeneity of cytokeratin expression. By using the monoclonal antibodies Cam 5.2 and KL 1, cytokeratins were found in 7 cases each. The other 4 cytokeratin antibodies used were less sensitive. The expression of cytokeratin 13 in 3 cases suggested a more complex histogenesis than assumed. Vimentin was found in 3 tumors, but an association to a higher grade (G) of malignancy was not found in these cases. One tumor expressed the Tamm-Horsfall-protein, which is predominantly found in the distal tubule of the normal kidney. In summary the results of immunohistochemistry characterized the great heterogeneity of these tumors. Follow-up information was available in 9 cases. All patients with G I- and G II-tumors were free of disease after an average time of 39.6 months (mean 27 months). Two of the 3 cases with G III-tumors died after 9 and 15 months, despite additional chemo- or radiotherapy. Therefore tumors of grade I and II of the Thoenes classification seem to have a good prognosis.

Topics: Adenocarcinoma; Adolescent; Antibodies; Carcinoma, Renal Cell; Child; Child, Preschool; Eosine Yellowish-(YS); Female; Follow-Up Studies; Humans; Immunohistochemistry; Keratins; Kidney Neoplasms; Lectins; Male; Prognosis; Staining and Labeling; Wilms Tumor

Primary tumours from 40 patients with epithelial ovarian cancer, treated at St Thomas's Hospital over a 10-year period, were studied for the immunocytochemical expression of the following tumour markers in formalin-fixed paraffin embedded material: carcinoembryonic antigen (CEA), epithelial membrane antigen (EMA), cytokeratin (CAM 5.2), and DD9. An indirect immunoperoxidase staining technique was used. All of the tumours were positive for EMA and CAM 5.2, and 30% of them were positive for both CEA and DD9. The absence of CEA and DD9 may be of value in differentiating between metastatic abdominal adenocarcinomas of ovarian origin and those of gastrointestinal origin, but no indication of prognosis was obtained using these epithelial markers. The strong and widespread staining of all the tumours for EMA suggests that this may be a useful marker for detecting metastatic or recurrent disease by immunoscintigraphy.

Topics: Adenocarcinoma; Adenocarcinoma, Mucinous; Adult; Aged; Antigens, Neoplasm; Biomarkers, Tumor; Carcinoembryonic Antigen; Carcinoma; Cystadenocarcinoma; Endometriosis; Female; Humans; Immunoenzyme Techniques; Keratins; Membrane Glycoproteins; Middle Aged; Mucin-1; Ovarian Neoplasms

Two cases of monophasic spindle cell carcinomas and one case of adenosquamous carcinoma with the spindle cell component located in the lower respiratory tract are presented. In the biphasic tumor, areas of transition from carcinoma to sarcomatous spindle cells were clearly found. The two monophasic tumors and the spindle cell component of the biphasic tumor were histologically characterized by sheets of spindle cells. However, by electron microscopic and immunohistochemical study, several features of squamous epithelial differentiation were found in the spindle cell areas of all cases. Keratin and vimentin were, in various degrees, coexpressed in all the cases. Therefore, it is supposed that the spindle cell component displays a spectrum of phenotypes originating from squamous cell carcinoma, and monophasic spindle cell carcinoma is considered as a kind of the extreme phenotype of squamous cell carcinoma pretending mesenchymal differentiation.

Topics: Adenocarcinoma; Adult; Carcinoma; Carcinoma, Squamous Cell; Female; Humans; Immunoenzyme Techniques; Keratins; Lung Neoplasms; Male; Middle Aged; Vimentin

Cytogenetic analysis of two pulmonary chondroid hamartomas and nine breast adenofibromas revealed clonal chromosome aberrations in both hamartomas and in four breast tumors. To determine lineage of the cells with chromosome aberrations, a combined immunohistochemical/cytogenetic approach was developed that enabled simultaneous ascertainment of cytogenetic aberrations and immunohistochemical features in individual cells. Immunohistochemical/cytogenetic evaluation of one hamartoma and two adenofibromas demonstrated that neoplastic proliferation, in each case, was confined to the mesenchymal (stromal) component, whereas epithelial cells appeared to be reactive. Cytogenetically abnormal short-term cultures of the remaining hamartoma and another of the breast adenofibromas were composed entirely of mesenchymal elements, indicating mesenchymal clonality in those tumors as well. Our findings support redesignation of pulmonary chondroid hamartomas as 'pulmonary chondromas' and suggest that carcinomas developing within fibroadenomas arise from reactive epithelial proliferation. Combined immunohistochemical/cytogenetic analysis might be useful in the development of novel therapeutic approaches that selectively target neoplastic populations within solid tumors.

Topics: Adenocarcinoma; Breast Neoplasms; Cell Transformation, Neoplastic; Chromosome Aberrations; Hamartoma; Humans; Immunohistochemistry; Karyotyping; Keratins; Lung Neoplasms; Mesoderm; Trisomy; Tumor Cells, Cultured; Vimentin

We report a modification of the avidin-biotin-peroxidase complex (ABC) technique for the light and electron microscopic detection of antigens in tissue sections. An immunological approach was used instead of the DAB reaction to reveal ABC bound to antigen-antibody complexes. Affinity-purified polyclonal antibodies against horseradish peroxidase were complexed to particles of colloidal gold and applied for reaction with the horseradish peroxidase molecules of the ABC. For light microscopic immunolabeling, the signal produced by the anti-horseradish peroxidase antibody-gold complex required silver intensification. The ABC immunogold reaction as compared with the standard ABC technique, in particular with silver intensification of the DAB reaction product, provided superior resolution in paraffin sections. Furthermore, section pre-treatment to block endogenous peroxidase activity could be omitted and no potentially hazardous substrate was used. The ABC immunogold reaction was successfully applied for electron microscopic immunolabeling on Lowicryl K4M thin sections. We propose that the ABC immunogold reaction is a useful alternative to the standard ABC technique and can be equally well applied to light and electron microscopy.

Topics: Adenocarcinoma; Carcinoembryonic Antigen; Colon; Colonic Neoplasms; Horseradish Peroxidase; Humans; Immunoenzyme Techniques; Immunohistochemistry; Keratins

Microglandular adenosis (MA) of the breast is a benign, disorganized proliferation of glands lined by a single layer of cells. As such, differential diagnosis between MA and tubular carcinoma may be challenging in selected cases. A panel of antibodies was applied to 10 cases of MA and 10 of tubular carcinoma to investigate the potential benefit of immunohistochemistry in the separation of these lesions and the possible role of myoepithelial cells in MA. The luminal cells in nine cases of MA were surrounded by a cuff of muscle-specific actin-reactive cells, which also coexpressed cytokeratin and vimentin. The immunophenotype of these cells is characteristic of myoepithelial differentiation, which was heretofore thought to be lacking in MA. This finding demonstrates that myoepithelial cells are indeed present in MA subjacent to luminal epithelial cells; moreover, it distinghuishes MA from tubular carcinoma, all examples of which were actin negative in this analysis. In addition, circumferential type IV collagen deposition was observed around constituent glands of MA in nine cases but was lacking in all tubular carcinomas. Other markers included in this evaluation (S100 protein, gross cystic disease fluid protein 15, carcinoembryonic antigen, estrogen receptor protein) were of no differential diagnostic value.

Topics: Actins; Adenocarcinoma; Adult; Aged; Biomarkers, Tumor; Collagen; Female; Fibrocystic Breast Disease; Humans; Immunoenzyme Techniques; Immunophenotyping; Keratins; Middle Aged; S100 Proteins; Vimentin

Twenty-seven uterine cervical biopsies with histological diagnoses ranging from normal through dysplasia to invasive carcinoma were analysed for cytokeratin pattern in two-dimensional gel electrophoresis. No direct correlation between histological diagnosis and cytokeratin pattern was observed.

Topics: Adenocarcinoma; Antibodies, Monoclonal; Biopsy; Carcinoma in Situ; Carcinoma, Squamous Cell; Cervix Uteri; Female; Fluorescent Antibody Technique; Humans; Intermediate Filaments; Keratins; Uterine Cervical Dysplasia; Uterine Cervical Neoplasms

Sixteen polymorphous low-grade adenocarcinomas were reviewed and compared with 17 adenoid cystic carcinomas and with 21 other histologically similar minor salivary gland neoplasms. The polymorphous low-grade adenocarcinomas were for the most part distinctive in their microscopic appearance. Typically they exhibited infiltrative growth by small uniform cells in single-layered ducts. A syncytium of tumor cells was also characteristic, although solid and cribriform patterns were seen, making definitive diagnosis difficult with some tumors. Immunohistochemical staining for S-100 protein, glial fibrillary acidic protein, actin, vimentin, and keratins resulted in relatively distinctive antigenic profiles for the tumors studied. Of significance was strong S-100 protein and weak actin staining of polymorphous low-grade adenocarcinomas, moderate actin staining of adenoid cystic carcinomas, moderate glial fibrillary acidic protein staining of monomorphic adenomas and pleomorphic adenomas, and nonreactivity of monomorphic adenomas for vimentin. It is believed that the immunoprofiles could be useful in the microscopic diagnosis of salivary gland tumors. The identification of antigens found normally in myoepithelial and epithelial cells supports the concept that these tumors are derived from pluripotential reserve cells.

Topics: Actins; Adenocarcinoma; Adult; Aged; Aged, 80 and over; Carcinoma, Adenoid Cystic; Female; Glial Fibrillary Acidic Protein; Humans; Immunoenzyme Techniques; Immunohistochemistry; Keratins; Male; Middle Aged; Molecular Weight; S100 Proteins; Salivary Gland Neoplasms; Salivary Glands, Minor; Vimentin

A prostatic lesion, histologically identical to sclerosing adenosis of the breast, was found in five (1.9%) of 263 patients who underwent transurethral resection, open prostatic adenectomy, radical prostatectomy, or total cystoprostatectomy. This uncommon lesion was a localized proliferation of crowded small glands, small solid nests, and individual cells embedded in a cellular stroma, mimicking a small acinar prostatic adenocarcinoma. The proliferating glands were lined by a single layer of secretory cells surrounded by an eosinophilic membranous structure. Basal cells were disclosed in individual glands or as small nests and even individual cells with immunostainability for basal cell-specific cytokeratin (EAB903), S-100 protein, and muscle-specific actin (HHF35). These findings indicate the benign nature of the lesion with myoepithelial differentiation of the basal cells. In contrast, all 25 small acinar adenocarcinomas examined as controls lacked positive stains for the above three antibodies, verifying the usefulness of these antibodies to distinguish between this benign lesion from adenocarcinoma.

Topics: Acid Phosphatase; Actins; Adenocarcinoma; Aged; Aged, 80 and over; Antigens, Neoplasm; Diagnosis, Differential; Humans; Immunohistochemistry; Keratins; Male; Prostate-Specific Antigen; Prostatic Diseases; Prostatic Neoplasms; S100 Proteins; Sclerosis

We have previously described the neoplastic transformation of immortalized human bronchial epithelial cells (BEAS-2B) by the combination of the c-raf-1 and c-myc protooncogenes and the concomitant induction of neuron-specific enolase mRNA expression (A. Pfeifer et al., Proc. Natl. Acad. Sci. USA, 86: 10075-10079, 1989). In this paper we describe the morphological, biochemical, and immunohistochemical characteristics of the primary c-raf-1/c-myc tumors, xenografts of these tumors, and tumors that originated from cell lines of the primary neoplasm. The tumors were morphologically characterized by the appearance of desmosomes and tonofilaments, microvilli, and dense core granules representing markers of squamous, glandular, and neuroendocrine differentiation, respectively. A total of 11 of 13 tumors were positive by immunohistochemical techniques for neuron-specific enolase, serotonin (nine of 13), and calcitonin (six of 13). Keratins were expressed in 11 of 13 tumors, and while specific keratins (K5, K7, K16/K17) decreased, there was an increase of vimentin in the tumor cells. Gastrin-releasing peptide immunoreactivity was detectable in a small number of tumors (five of 13). BEAS-2B cells transfected with the c-raf-1 and c-myc protooncogenes and cell lines established from the primary tumors expressed major histocompatibility Class II antigen which has been found on small cell lung carcinoma cells. The tumors induced by the c-raf-1 and c-myc protooncogenes resemble the multidifferentiated phenotype of small cell lung cancer frequently detected in vivo and present a defined model to study the relation between molecular markers, phenotypical appearance, and response to chemotherapeutic agents and radiation.

Topics: Adenocarcinoma; Animals; Antigens, Neoplasm; Bronchi; Carcinoma, Squamous Cell; Cell Line; Cell Transformation, Neoplastic; Epithelium; Genes, myc; Histocompatibility Antigens Class II; Humans; Immunohistochemistry; Keratins; Lung Neoplasms; Mice; Neoplasm Transplantation; Phosphopyruvate Hydratase; Proto-Oncogene Proteins; Proto-Oncogene Proteins c-raf; Proto-Oncogenes; Transplantation, Heterologous

Atypical mesothelial hyperplasia encountered in pleural fluid or in a pleural biopsy specimen raises the suspicion that one may be dealing with a diffuse malignant mesothelioma of the pleura. We studied eight cases with cytologic or histologic changes of mesothelial atypia thought to be suspicious for diffuse malignant mesothelioma. In each case, the hyperplasia was associated with a bronchogenic carcinoma in the lung subjacent to the mesothelial hyperplasia. Bronchogenic carcinoma should be added to the list of causes of atypical mesothelial hyperplasia. This combination of reactive and malignant processes should be appreciated, since pleural carcinomatosis and diffuse malignant mesothelioma must be separated for clinical and epidemiologic reasons.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Antigens, Neoplasm; Carcinoma, Bronchogenic; Carcinoma, Squamous Cell; Female; Humans; Hyperplasia; Keratins; Lung; Lung Neoplasms; Male; Middle Aged; Pleura; Pleural Effusion, Malignant

A 45-year-old Japanese male with a history of macroscopic hematuria for more than 6 months presented multiple metastatic lesions in the lungs. Cystoscopic examination demonstrated a large tumor mass protruding from the dome of the urinary bladder. Ultrasonography and CT highlighted a solid and cystic urachal tumor continuous from the vesical dome to the navel. Serum levels of alpha-fetoprotein (AFP) and carcinoembryonic antigen (CEA) were elevated to 17,100 ng/ml and 17.7 ng/ml, respectively. He underwent palliative curettage of the vesical dome tumor twice, followed by chemotherapy with little effect. One year after admission, he died of progressive metastases to the lungs, left pleura, liver and brain. Final serum levels of AFP and CEA were 86,200 ng/ml and 60.9 ng/ml, respectively. The tumor was histologically classified as adenocarcinoma with a medullary growth pattern. Both papillotubular and solid (hepatoid) components were observed. The cancer cells were rich in glycogen and were immunoreactive diffusely for AFP and focally for CEA. CA15-3, CA19-9, epithelial membrane antigen and cytokeratin were also positive. In addition, argyrophilic cancer cells with immunoreactivities of neuron-specific enolase, chromagranin A and peptide YY were demonstrated. To our knowledge, this is the first reported case of AFP-producing adenocarcinoma of urachal origin.

Topics: Adenocarcinoma; alpha-Fetoproteins; Antigens, Tumor-Associated, Carbohydrate; Carcinoembryonic Antigen; Humans; Immunohistochemistry; Keratins; Male; Membrane Glycoproteins; Middle Aged; Mucin-1; Urinary Bladder; Urologic Neoplasms

A case of primary clear cell carcinoma of the pelvic and abdominal peritoneum which occurred in a 67-year-old woman and with histological characteristics of Mullerian derivation is presented. To our knowledge, this is the first report of such a case. Although clear cell carcinomas have been previously described in peritoneal or retroperitoneal locations, these have been mass lesions thought to arise from endometriosis. All other cases of diffuse primary peritoneal adenocarcinomas have been of the serous type.

Topics: Adenocarcinoma; Aged; Female; Humans; Immunohistochemistry; Keratins; Peritoneal Neoplasms

This paper presents an immunocytochemical study performed on cytocentrifuged deposits from 109 peritoneal and pleural effusions including 20 transudates, 43 malignant metastatic effusions and 46 effusions containing atypical cells, unidentifiable as reactive mesothelial or malignant epithelial cells on the classical morphological criteria. A panel of four monoclonal antibodies (MAb) was used, including KL1 directed to cytokeratins (KER), V9 to vimentin (VIM), NEO 723 to carcinoembryonic antigen (CEA) and E29 to epithelial membrane antigen (EMA). In most transudates the reactive mesothelial cells coexpressed VIM and KER with a ring-like pattern for the latter proteins. In contrast, they were unreactive to anti-CEA and weakly and inconsistently reactive to anti-EMA. In malignant effusions, most carcinoma cells coexpressed EMA, CEA and KER with a predominant diffuse cytoplasmic pattern for the latter. Only a few malignant epithelial cells from five metastatic adenocarcinomas weakly expressed VIM. When used on the 46 effusions with unidentifiable cells, the panel of MAb allowed reactive mesothelial cells and malignant epithelial cells to be distinguished from each other in 39 of 46 cases (85%).

Topics: Adenocarcinoma; Antibodies, Monoclonal; Ascitic Fluid; Carcinoembryonic Antigen; Carcinoma; Cytodiagnosis; Epithelium; Exudates and Transudates; Humans; Immunohistochemistry; Immunophenotyping; Keratins; Lung Neoplasms; Membrane Glycoproteins; Mucin-1; Pleural Effusion, Malignant; Vimentin

Of 17 cases of small cell carcinoma of the stomach, three were early and 14 were advanced. Grossly, the tumors were mostly polypoid at the early stage, and as they advanced, deep ulcerations developed. Histologically, only one tumor was "oat cell type," and the other 16 were "intermediate cell type." With regard to tumor components, five were "pure" tumor, and 12 were "composite" admixing glandular and/or squamous differentiation. Argyrophil cells were seen in eight tumors. Immunohistochemically positive cells for chromogranin, neuron-specific enolase, and keratin were seen in 12, 10, and 7 tumors, respectively. Carcinoembryonic antigen was negative in the small cell component of most tumors as opposed to strong positivity in the glandular component. Electron-dense core granules were evident in seven of nine tumors examined. These findings suggest that histologic variety is quite characteristic of the small cell carcinomas of the stomach, and this type of carcinoma takes an aggressive clinical course like its counterparts in other organs.

Topics: Adenocarcinoma; Aged; Aged, 80 and over; Carcinoembryonic Antigen; Carcinoma, Small Cell; Chromogranins; Female; Humans; Immunoenzyme Techniques; Keratins; Male; Middle Aged; Phosphopyruvate Hydratase; Stomach Neoplasms; Survival Analysis

Endometrial carcinomas may originate from endometrial glandular epithelium and show endometrial differentiation, or from various types of metaplasias developing in the endometrium from pluripotent Müllerian epithelium. They then show endocervical or serous papillary differentiation. Because of their differences in spread, speed of growth and survival rates, it is important to subclassify these endometrial carcinomas. Immunohistochemically, adenocarcinoma with endometrial differentiation including adenoacanthomas and adenosquamous carcinomas can be recognized by their coexpression of cytokeratin 8 and vimentin, and by their negative reaction for CEA. Distinction from adenocarcinomas with mucinous differentiation, including mucoepidermoid adenocarcinomas, is possible by their negative reaction for vimentin and by their positive reaction for CEA. On the other hand, carcinomas with mucinous differentiation primarily located in the endometrium can not be distinguished from those primarily located in the endocervix by immunohistochemistry; that distinction must be made topographically. The same holds true for clear cell carcinomas of both locations. Over the past decade, mucinous adenocarcinomas and clear cell carcinomas originating from the endometrium have increased, whereas adenocarcinomas with endometrial differentiation have become less frequent. This shift is closely related to the altered postmenopausal hormone substitution with the addition of the synthetic gestagens. These apparently stimulate proliferation of endocervical epithelium not only in the endocervix, but also that arising in endocervical metaplasias of the endometrium.

Topics: Adenocarcinoma; Carcinoembryonic Antigen; Carcinoma; Diagnosis, Differential; Female; Humans; Immunohistochemistry; Keratins; Uterine Neoplasms; Vimentin

Four cases of adenosquamous carcinoma from the oral and pharyngeal cavities were analyzed by light microscopy and immunohistochemistry. Lymph node metastases were present in three cases. One patient died 2 years after treatment. All four carcinomas presented a mixture of squamous and glandular mucus-secreting neoplastic elements. Immunostaining for high-molecular-weight cytokeratins (KL1) was constantly positive in both squamous and glandular tumor cells. Antibodies against low-molecular-weight cytokeratins (K19) and carcinoembryonic antigen were positive only in the glandular component. The histological aspect and the immunohistochemical phenotype of these tumors is similar to the ordinary squamous cell carcinoma and adenocarcinoma, respectively.

Topics: Adenocarcinoma; Carcinoembryonic Antigen; Carcinoma, Squamous Cell; Humans; Immunoenzyme Techniques; Immunohistochemistry; Keratins; Male; Middle Aged; Mouth Neoplasms; Pharyngeal Neoplasms

The immunohistochemical localization of five antibodies against carcinoembryonic antigen (CEA), CA19-9, keratin, alpha-tubulin and secretory component (SC) was investigated in 14 lesions of adenocarcinoma (AC), 22 of adenoma with high-grade atypia (AH), 50 of adenoma with low-grade atypia (AL), and 15 of non-neoplastic mucosa (NNM) of the large intestine. The positive patterns for each staining were divided into three categories (patterns 1, 2, and 3). All neoplastic lesions (AC, AH and AL) were positive for CEA, while 85.7% of AC, 36.4% of AH and 6.0% of AL showed strongly positive staining (pattern 3). 78.6% of AC and 54.5% of AH were positive for CA19-9 in comparison to 20.0% of AL. For keratin, more than 95% of the neoplastic lesions were positive, while 78.6% of AC, 27.3% of AH and 22.0% of AL showed strongly positive staining (pattern 3). For alpha-tubulin, more than 85% of neoplastic lesions were positive, while 50.0% of AC, 36.3% of AH and 26.0% of AL showed strongly positive staining (pattern 3). For SC, in contrast, 42.9% of AC, 27.3% of AH and 8.0% of AL were negative, but 93.3% of NNM were positive. It was concluded that the positive staining rate, especially the rate of pattern 3 for each antibody correlated with the degree of atypia of the colorectal neoplastic lesions (AC, AH and AL).

Topics: Adenocarcinoma; Adenoma; Antibodies, Anti-Idiotypic; Antibodies, Neoplasm; Antigens, Tumor-Associated, Carbohydrate; Carcinoembryonic Antigen; Colorectal Neoplasms; Cytoskeleton; Humans; Keratins; Secretory Component; Staining and Labeling; Tubulin

One case of aggressive intramandibular epithelial tumor is presented. This tumor demonstrated an unusual pattern with areas of follicular ameloblastoma together with undifferentiated trabeculae or lobules composed of basophilic cells and of clear glycogenic-rich cells. The odontogenic nature of this tumour and its analogies with common ameloblastoma were demonstrated by electron microscopy, immunohistoenzymology and immunohistochemistry. The signification of such a neoplasm is discussed.

Topics: Adenocarcinoma; Aged; Humans; Immunohistochemistry; Keratins; Male; Mandibular Neoplasms; Odontogenic Tumors; Phosphoric Monoester Hydrolases

Cytokeratin shedding into urine was measured using a double-antibody sandwich enzyme-linked immunosorbent assay (ELISA) in 282 individuals. Samples included urine from normal controls, patients with urogenital conditions and bladder cancer patients. A monoclonal antibody prepared against cytokeratins extracted from a hyperkeratotic low grade squamous cell carcinoma (UNME/K1) was used in the assay. The results indicated reasonable levels of sensitivity (83%), specificity (67%) and overall accuracy (70%) in the detection of bladder cancer. The levels of sensitivity in detecting squamous and transitional cell carcinoma patients were 87 and 73% respectively. The low level of specificity was due to a high frequency of false positive results (55%) within the urogenital controls; this suggests that further immunochemical and immunohistopathological analyses of associated urothelial cytokeratins are required.

Topics: Adenocarcinoma; Antibodies, Monoclonal; Biomarkers, Tumor; Carcinoma, Squamous Cell; Carcinoma, Transitional Cell; Enzyme-Linked Immunosorbent Assay; Female; Humans; Keratins; Male; Schistosomiasis haematobia; Sensitivity and Specificity; Urinary Bladder Neoplasms

The present study was performed to identify tumor cells in lymph nodes from colorectal adenocarcinomas considered free of disease by the classic hematoxylin-eosin stain, based on the detection of the carcinoembryonic antigen (CEA) and cytokeratins in neoplastic epithelial cells. For this purpose, 603 lymph nodes from 46 lesions were stained by the peroxidase-antiperoxidase technique. Tumor cells were detected in 22 nodes from 12 patients, mainly in the subcapsular sinuses, permitting a restaging of these patients into two groups: those now considered to have metastatic disease and those free of metastases. However, the 5-year follow-up showed no statistical differences in survival between the two groups.

Topics: Adenocarcinoma; Carcinoembryonic Antigen; Colorectal Neoplasms; Follow-Up Studies; Humans; Immunoenzyme Techniques; Keratins; Lymphatic Metastasis; Macrophages; Neoplasm Staging

A comparative study with 21 recently raised monoclonal antibodies (3 of which are reported here for the first time) to human keratin polypeptides was performed on a wide range of paraffin-embedded tissues and tumors, aimed at the examination of effects of four different fixatives and protease pretreatment on the immunohistochemical detection of keratins. Our data demonstrated that: (a) formaldehyde-based fixatives modified by acidification and/or addition of methanol gave results superior to those achieved by routinely used formol saline; (b) relatively rare antibodies (4 out of 21) could be identified which gave reliable immunostaining patterns even on routine formalin-fixed material; (c) a proteolytic digestion step preceding the immunostaining was beneficial for the performance of the majority of antibodies in our panel. Additional options which could potentially lead to further improvement of keratin immunohistochemistry in paraffin embedded specimens are also suggested. This work provides the necessary basis for wider application of the anti-keratin antibodies of the C-series in both routine oncopathology and research-oriented retrospective studies.

Topics: Adenocarcinoma; Animals; Antibodies, Monoclonal; Electrophoresis, Polyacrylamide Gel; Endopeptidases; Frozen Sections; Humans; Immunoblotting; Immunoenzyme Techniques; Keratins; Neoplasm Proteins; Paraffin Embedding; Tissue Fixation; Tumor Cells, Cultured

We report a case of extramammary Paget's disease in ovarian mature cystic teratoma. The patient was a 70-year-old Japanese woman who complained of lower abdominal pain. Examination showed elevation of carcinoembryonic antigen and CA 19-9. Ultrasonography and computer tomography revealed a cystic tumor of the left ovary. The gross appearance of the resected ovary was typical for mature cystic teratoma. Microscopic observation revealed a lesion of Paget's disease within the squamous epithelium. The tumor cells had intracytoplasmic mucin and positive immunoreactivity for carcinoembryonic antigen, epithelial membrane antigen, and cytokeratin; but they were negative for S-100 protein and vimentin. On multiple and serial sections, underlying adenocarcinomas were not found either in the ovary or other primary sites. From these pathological findings, we concluded that the disease was an intraepithelial adenocarcinoma, possibly derived from multipotential cells in squamous epithelium of ovarian mature cystic teratoma. This is the first reported case, to our knowledge, of extramammary Paget's disease arising in mature cystic teratoma of the ovary.

Topics: Adenocarcinoma; Aged; Antigens, Tumor-Associated, Carbohydrate; Carcinoembryonic Antigen; Dermoid Cyst; Female; Humans; Immunohistochemistry; Keratins; Membrane Glycoproteins; Mucin-1; Ovarian Neoplasms; Paget Disease, Extramammary; S100 Proteins; Vimentin

Several studies have suggested that HMB-45 is a specific marker for melanoma, presumably due to its ability to detect a glycoprotein that is present in premelanosomes. The present study was conducted to evaluate whether HMB-45 is an absolutely specific antigenic determinant for melanoma and the role that testing with this antibody has in the differential diagnostic workup of amelanotic melanoma vs adenocarcinoma. Formaldehyde solution-fixed, paraffin-embedded tissue samples from 52 adenocarcinomas (primary or metastatic) and five melanomas (two primary and three metastatic) were immunostained with the use of a commercially available monoclonal antibody (MoAb), ie, HMB-45 (Enzo), a polyclonal antibody to S100 protein, a wide-spectrum keratin polyclonal antibody, and a keratin MoAb, ie, AE1/AE3. Approximately 10% (ie, 9.6%) of the adenocarcinomas (five cases) expressed HMB-45 with varied intensity and distribution. Positive primary tumors (n = 3) included one each from the breast, colon, and kidney; positive metastatic tumors (n = 2) included one each from the breast and endometrium. Fifty-two percent of the adenocarcinomas were positive for S100 protein. One renal carcinoma was negative for both keratins when tested with the AE1/AE3 MoAb and polyclonal antibody (Dako). This was the only adenocarcinoma that was negative when the keratin polyclonal antibody (Dako) was used. All but one additional adenocarcinoma demonstrated keratin expression when the AE1/AE3 MoAb was used for testing. This study showed that HMB-45 is not absolutely specific for melanoma. HMB-45 may react with some adenocarcinomas, at least when tested with the commercially available MoAb (Enzo). This fact, in conjunction with aberrant keratin expression by some melanomas and S100 protein expression by adenocarcinomas and other neoplasms other than melanomas, should be considered when antibody panels are evaluated in the workup of poorly differentiated tumors. However, HMB-45 appears to be the most specific marker that is available at the present time for supporting a diagnosis of melanoma.

Topics: Adenocarcinoma; Antibodies, Monoclonal; Antigens, Neoplasm; Biomarkers, Tumor; Humans; Immunoenzyme Techniques; Keratins; Melanoma; S100 Proteins; Staining and Labeling

We used immunohistochemical procedures to study the cellular expression and distribution of cytokeratins (CKs) in rat 13762NF mammary adenocarcinoma cells growing at mammary fat pad sites and at spontaneous lymph node and lung sites. In order to establish CK distribution in normal rat mammary epithelia, immature, resting, and lactating rat mammary glands were probed with a panel of monospecific antibodies that recognize individual CKs. Basal/myepithelial cells were distinguished by expression of CKs 5 and 14 and coexpression of vimentin from luminal cells, which expressed CKs 8, 18, and 19. Antibody to CK 7 recognized luminal epithelium of immature and resting, but not lactating, mammary glands. Myoepithelial cells of lactating mammary gland were weakly recognized by antibodies to CKs 7 and 19. Tumors formed by cell lines and clones derived from parental 13762NF tumor (MTPa, MTC, MTA, and MTF7) were not recognized by any of the anti-CK antibodies. Only vimentin was expressed in these tumors and their metastases. In tumors and metastases generated from cell lines and clones derived from lymph node (MTLY) and lung metastases (MTLn2 and MTLn3) of the 13762NF tumor we observed heterogeneous CK phenotypes. Expression of CKs 5 and 18 was greatly reduced or lacking, while CK 14 was coexpressed with CKs 7, 8, and 19 with or without vimentin. Tumors from the highly metastatic clone MTLn3 had a dominant cellular phenotype, expressing CKs 7, 8, 14, and 19 and vimentin, a pattern that did not match normal mammary epithelia, whether luminal, basal/myoepithelial, or the dual-phenotype stem cell, in which CKs 5, 8, 14, and 18 were coexpressed. MTLn3 lymph node and lung metastases expressed the same cellular phenotype as the s.c. growing MTLn3 tumor. The results appear to contradict the belief that malignant mammary tumors may be distinguished from benign tumors or hyperplastic growths by the lack of basal/myoepithelial markers.

Topics: Adenocarcinoma; Animals; Animals, Newborn; Antibodies, Monoclonal; Biomarkers, Tumor; Cell Line; Female; Fluorescent Antibody Technique; Gene Expression; Keratins; Lung Neoplasms; Lymphatic Metastasis; Mammary Glands, Animal; Mammary Neoplasms, Experimental; Neoplasm Metastasis; Phenotype; Rats; Vimentin

Cutaneous squamous carcinoma with true glandular differentiation has only rarely been documented. Ten patients with such tumors are presented. There were six men and four women, aged 48 to 87 years. The tumors were located on the central face (eight), scalp (one), and hand (one) and consisted of minimally elevated, indurated, keratotic plaques, up to 6 cm in size. Microscopically, the neoplasms exhibited multifocal origin from the epidermis; deep, dispersed, infiltrative growth; perineural invasion; and stromal desmoplasia. Squamous differentiation was most marked superficially. Glandular differentiation was more obvious in deeper areas. Lumens typically developed within squamous nests and were often lined by cells with cytoplasmic vacuoles, some of which contained mucin. The neoplastic cells had obvious cytologic atypia and easily identified mitotic figures. Immunohistochemically, nine neoplasms studied contained carcinoembryonic antigen in glandular foci. Each patient had one or more surgical resections, and six also received radiation and/or chemotherapy. Five patients died with uncontrolled local recurrence, and two are alive with extensive disease and clinical evidence of regional lymph node involvement. Two individuals with small, superficial neoplasms that could be completely removed are disease free. One patient died of unrelated causes shortly after diagnosis. Cutaneous adenosquamous carcinoma is more aggressive than the usual carcinoma of the skin. It must be distinguished from the cytologically bland, microcystic adnexal (sclerosing sweat duct) carcinoma which is capable of recurring but rarely, if ever, proves fatal. The question of whether adenosquamous carcinoma is an epidermally derived squamous tumor with divergent differentiation or should be viewed as a newly recognized adnexal carcinoma remains to be resolved.

Topics: Adenocarcinoma; Aged; Aged, 80 and over; Antibodies, Monoclonal; Carcinoembryonic Antigen; Carcinoma, Squamous Cell; Cell Transformation, Neoplastic; Female; Humans; Immunohistochemistry; Keratins; Male; Middle Aged; Mucins; S100 Proteins; Skin Neoplasms

Histologic diversity is intrinsic to salivary gland tumors, but it is a particular feature of polymorphous low-grade adenocarcinoma as denoted by the terminology. Application of immunohistochemistry and electron microscopy to three examples allowed the study of some aspects of tumor cell differentiation in this minor salivary gland lesion. In one case where the tumor cells were cytologically of one type, immunohistochemistry clearly identified both luminal and nonluminal tumor cells, but the latter showed no evidence of myoepithelial cell differentiation. A second case revealed differentiation only of luminal-type tumor cells, while a third example was largely differentiated as myoepithelial cells but again immunohistochemistry confirmed focal formation of duct-like structures by luminal epithelium. These cases show a considerable range of tumor cell heterogeneity as well as variations in their organization. This variation in differentiation characteristics underlies the histology of polymorphous low-grade adenocarcinomas, and likely occurs in other salivary gland tumors. To establish specific and reliable diagnostic criteria for such tumors requires awareness of this neoplastic process. The limited malignant potential and excellent survival of patients with polymorphous low-grade adenocarcinoma is apparently little affected by patterns of differentiation in this particular neoplasm.

Topics: Actins; Adenocarcinoma; Aged; Aged, 80 and over; Cell Differentiation; Cell Transformation, Neoplastic; Female; Humans; Immunohistochemistry; Intermediate Filaments; Keratins; Male; Microscopy, Electron; Neoplasm Invasiveness; S100 Proteins; Salivary Gland Neoplasms; Salivary Glands, Minor; Vimentin

A number of chemical agents have been found to influence the proliferation, morphology, enzymatic activity, and antigen expression of neoplastic cells toward a more differentiated phenotype. We studied the effects of differentiating agents retinoic acid, sodium butyrate, and dibutyryl cyclic AMP on the expression of the tumor-associated antigen CA 125 and several biochemical markers of differentiation in cultured OVCA 433 ovarian cancer cells. Treatment of OVCA 433 cells with these agents for 96 hr reduced cellular proliferation and altered cellular morphology. Quantitation of cell surface CA 125 using flow cytometry revealed that CA 125 expression was reduced by 35-50%. The amount of CA 125 antigen shed into the culture media was reduced to a similar degree. In addition, differentiation inducers markedly enhanced cellular alkaline phosphatase activity and induced the expression of a 65-67-kDa cytokeratin. These findings provide support for the induction of a more differentiated phenotype by these agents.

Topics: Adenocarcinoma; Alkaline Phosphatase; Antigens, Tumor-Associated, Carbohydrate; Bucladesine; Butyrates; Butyric Acid; Cell Differentiation; Dose-Response Relationship, Drug; Female; Humans; Keratins; Osmolar Concentration; Ovarian Neoplasms; Time Factors; Tretinoin; Tumor Cells, Cultured

Extravascular coagulation and fibrinolysis are intimately involved in and modulate cancer cell growth, invasion and metastasis. Samples from resection specimens of patients with primary lung cancer (adenocarcinomas) were tested with monoclonal (MAb) and polyclonal (PAb) antibodies against various factors of the coagulation or fibrinolysis systems, or against antigens of inflammatory or proliferating cells. MAb Ki-67 specific to nuclear antigens of proliferating cells showed a distinct but variable staining of cell nuclei throughout the tumor tissue. Nests of tumor tissue stained with cytokeratin-specific antibodies (PKK1), whereas other parts were negative. Fibrin(ogen) and fibronectin were found throughout the tumor tissue stroma and in the alveolar lining, and the most densely stained areas were at the transition zone between normal and tumor tissue. Fibrinolytic system components like tissue plasminogen activators (t-PA), and urokinase (u-PA), and their inhibitors PAI-1 and PAI-2 were all studied. All specimens were negative for t-PA (except endothelial linings), whereas urokinase-specific antibodies stained loosely packed tumor cells and macrophages within the tumor stromal tissue and alveolar septa. Both PAI-1 and PAI-2 were most prominently expressed within interstitial and alveolar macrophages. A weaker staining of tumor tissue cells was demonstrated. Inflammatory cells like macrophages and T lymphocytes were located in aggregates or diffusely spread within tumor stromal tissue. The inflammatory reaction was most intense at the border between normal lung and tumor tissue.

Topics: Adenocarcinoma; Antibodies; Antibodies, Monoclonal; Biomarkers; Blood Coagulation; Fibrin; Fibrinogen; Fibrinolysis; Fibronectins; Humans; Immunohistochemistry; Inflammation; Keratins; Ki-67 Antigen; Lung Neoplasms; Macrophages; Nuclear Proteins; Plasminogen Inactivators; T-Lymphocytes; Tissue Plasminogen Activator; Urokinase-Type Plasminogen Activator

By indirect immunofluorescence microscopy and electron microscopy, we studied the behavior of intermediate filaments during mitosis in three human epithelial cell lines, derived from normal epidermis (PcaSE-1, from a cancer patient), stratified epithelium (CNE, from nasopharyngeal carcinoma) and simple epithelium (SPC-A-1 from lung adenocarcinoma) respectively. CNE cells and SPC-A-1 cells express two different intermediate filament systems; keratin filaments and vimentin filaments, but PcaSE-1 cells only express keratin filaments. The keratin filament system in PcaSE-1 cells remained intact and encircled the developing mitotic spindle as the cells entered mitosis. In contrast, in CNE cells and SPC-A-1 cells, keratin filaments appeared to disassemble into amorphous cytoplasmic bodies during mitosis. However, their vimentin filaments remained morphologically intact throughout mitosis. We propose; (1) The disassembly of keratin filaments in mitotic epithelial cells is more or less associated with the degree of their cell malignancy rather than with the abundance of keratin filaments in interphase. (2) Intermediate filaments may be involved in the positioning and/or centering of the spindle during mitosis. (3) The possible function of vimentin filament system in CNE cells is positioning and orientation of chromosomes.

Topics: Adenocarcinoma; Cell Line; Epithelial Cells; Epithelium; Humans; Intermediate Filaments; Keratins; Lung Neoplasms; Mitosis; Nasopharyngeal Neoplasms; Tumor Cells, Cultured; Vimentin

Topics: Adenocarcinoma; Aged; Duodenal Neoplasms; Female; Humans; Immunohistochemistry; Keratins; Neoplasms, Multiple Primary; Pancreatic Neoplasms; Paraganglioma

Ninety-eight consecutive patients with primary operable breast cancer and an initial diagnosis of no regional lymph node metastases as assessed by conventional light microscopy were studied. Immunohistological staining of routine lymph node sections was assessed using two monoclonal antibodies: CAM 5.2 (Becton Dickinson) with specificity for low molecular weight cytokeratin, and NCRC-11 (CRC Laboratories, Nottingham) with specificity for epithelial mucin antigen. Positive staining for occult metastases was seen in nine patients with CAM 5.2 and in eight of these nine with NCRC-11. At a follow-up out to 14 years, there was no difference in overall survival, in recurrence-free survival, or in frequency of or time to presentation of local or regional recurrences between occult metastasis-positive and occult metastasis-negative patients. This study concludes that while immunohistological staining of routine lymph node sections increases the diagnostic yield of metastases, it is not to be recommended as this increase is of no useful clinical value.

Topics: Adenocarcinoma; Adenocarcinoma, Mucinous; Antibodies, Monoclonal; Antigens, Neoplasm; Breast Neoplasms; Carcinoma; Carcinoma, Intraductal, Noninfiltrating; Female; Humans; Immunohistochemistry; Keratins; Lymph Nodes; Lymphatic Metastasis; Middle Aged; Prognosis

Topics: Adenocarcinoma; Antigens, Neoplasm; Female; Humans; Keratins; Membrane Glycoproteins; Middle Aged; Mucin-1; Parotid Neoplasms; Vimentin

Various grades of adenomatous hyperplasia represent precancerous states leading to the most common type of adenocarcinoma with endometrial differentiation. Grades 1 and 2 are characterized by architectural abnormalities only (complex hyperplasia). They rarely progress to carcinoma. Grade 3 in addition is characterized by cytological atypicalities (atypical hyperplasia) and shows a much higher progression rate into invasive carcinoma. Endometrial carcinomas may originate from endometrial glandular epithelium and show endometrial differentiation, or from various types of metaplasias developing in the endometrium from pluripotent Müllerian epithelium. They then show endocervical or serous papillary differentiation. Because of their differences in spread, speed of growth and survival rates, it is important to subclassify these endometrial carcinomas. Immunohistochemically, adenocarcinomas with endometrial differentiation including adenoacanthomas and adenosquamous carcinomas can be recognized by their coexpression of cytokeratin 8 and vimentin, and by their negative reaction for CEA. Distinction from adenocarcinomas with mucinous differentiation, including muceopidermoid adenocarcinomas, is possible by their negative reaction for vimentin and by their positive reaction for CEA. On the other hand, carcinomas with mucinous differentiation primarily located in the endometrium can not be distinguished from those primarily located in the endocervix by immunohistochemistry; that distinction must be made topographically. The same holds true for clear cell carcinomas of both locations. Over the past decade, mucinous adenocarcinomas and clear cell carcinomas originating from the endometrium have increased, whereas adenocarcinomas with endometrial differentiation have become less frequent. This shift is closely related to the altered postmenopausal hormone substitution with the addition of the synthetic gestagens. These apparently stimulate proliferation of endocervical epithelium not only in the endocervix, but also that arising in endocervical metaplasias of the endometrium.

Topics: Adenocarcinoma; Carcinoembryonic Antigen; Carcinoma, Squamous Cell; Diagnosis, Differential; Endometrial Neoplasms; Female; Humans; Immunohistochemistry; Keratins; Precancerous Conditions; Vimentin

Formalin is hazardous for the environment and for the laboratory personnel and deleterious to cytoskeleton proteins. The pathology and anatomy laboratory can be formalin-free when Kryofix is used as a substitute fixative. In four years experience with Kryofix, we learned that immunostaining on paraffin sections is reproducible and of excellent quality. The current study concerns the comparison of interfilament staining on paraffin sections made from formalin or from Kryofix-treated tumors. For both keratin and vimentin there were false-negative findings in the formalin-fixed tumors. Of these two, vimentin was het most susceptible to formalin fixation. Three of the ten adenocarcinomas were positive for both keratin and vimentin, indicating that this double staining pattern is not uncommon. Postfixation of Kryofix-treated tissue with formalin results in false-negative immunostaining.

Topics: Adenocarcinoma; Antibodies, Monoclonal; Ethanol; False Negative Reactions; Female; Fixatives; Formaldehyde; Humans; Immunohistochemistry; Intermediate Filament Proteins; Keratins; Ovarian Neoplasms; Paraffin; Polyethylene Glycols; Vimentin

A new cell line was established from a liver metastasis of a human pancreatic adenocarcinoma. The cell line, MDAPanc-3, which arose from a moderately differentiated adenocarcinoma, produces carbonic anhydrase II mRNA, but no detectable levels of insulin or alpha amylase mRNA. The stem line chromosome number was determined to be 43, with six marker chromosomes. Growth of MDAPanc-3 is stimulated by cholecystokinin (CCK) fragment 26-33. The cell line will be useful in further studies on the mechanism(s) by which CCK stimulates growth of certain human pancreatic adenocarcinomas and normal human pancreatic exocrine tissue.

Topics: Adenocarcinoma; alpha-Amylases; Blotting, Northern; Cell Division; Humans; Insulin; Karyotyping; Keratins; Male; Middle Aged; Molecular Weight; Pancreatic Neoplasms; Protein Biosynthesis; RNA, Neoplasm; Sincalide; Tumor Cells, Cultured

A case of glassy cell carcinoma of the endometrium in a 62-year-old woman is reported. Microscopically, a cytoplasm of ground-glass appearance was observed with a distinct cell wall and large nuclei containing prominent nucleoli. These histologic characteristics are consistent with those of glassy cell carcinoma of the cervix. Treatment consisted of total abdominal hysterectomy and bilateral salpingo-oophorectomy with pelvic lymph node dissection followed by external irradiation to the whole pelvis. The patient was alive without evidence of disease at 5 1/2 years.

Topics: Adenocarcinoma; Carcinoma, Squamous Cell; Female; Humans; Keratins; Middle Aged; Uterine Neoplasms

The histopathological diagnosis of minimal deviation adenocarcinoma (adenoma malignum) of the endocervix may be difficult. Two cases of minimal deviation adenocarcinoma (MDA) were examined using mucin histochemistry and immunocytochemistry with antibodies to epithelial membrane antigens (HMFG1, Ep1), low-molecular-weight cytokeratins (CAM 5.2), carcinoembryonic antigen (CEA), and alpha-amylase. The results were compared with those for normal endocervical glands. Reactivity for CEA in MDA was focal and would be unreliable for biopsy diagnosis. Both cases of MDA contained abundant neutral mucins and sialomucins, whereas sulfomucins were rarely detected; this pattern contrasted with that of normal endocervix. Neoplastic glandular epithelial cells in MDA consistently showed both luminal and cytoplasmic reactivity with Ep1 and HMFG1, whereas normal cervix showed luminal labeling only. Thus, mucin histochemistry and immunohistochemical detection of epithelial membrane antigens may distinguish between extremely well differentiated neoplastic glands in MDA and normal endocervical glands, and hence may aid diagnosis in biopsy specimens.

Topics: Adenocarcinoma; Adult; Amylases; Carcinoembryonic Antigen; Cervix Uteri; Female; Humans; Immunohistochemistry; Keratins; Membrane Glycoproteins; Mucin-1; Mucins; Uterine Cervical Neoplasms

Thymic carcinoma (TCA) is a thymic epithelial neoplasm with obvious cytologic atypia. We studied 13 cases of TCA by light microscopy, immunohistochemistry, and electron microscopy and correlated the findings with clinical features. The patients' mean age was 54.2 years (range 30-74); the male/female ratio was 7/6. Twelve of the 13 patients presented with signs and symptoms caused by compression of mediastinal organs; the other patient was asymptomatic. Paraneoplastic syndromes were never seen. At thoracotomy, 11 tumors invaded or adhered to surrounding structures; the other two were encapsulated. The histologic types include squamous carcinoma including the lymphoepithelioma-like subtype (seven cases), small cell carcinoma (four cases), clear cell carcinoma (one case), and adenosquamous carcinoma (one case). Positive immunoperoxidase studies were as follows: keratin (13 cases), epithelial membrane antigen (EMA) (13 cases), leukocyte common antigen (none), carcinoembryonic antigen (CEA) (five cases), B72.3 (seven cases), Leu 7 (two cases), human placental alkaline phosphatase (none), vimentin (none), and chromogranin (one case). This profile is similar to those of normal thymus and thymoma except for the absence of CEA, B72.3, EMA in normal thymus, and the absence of CEA and B72.3 in thymoma. Electron-microscopic studies performed on eight cases showed glandular and squamous differentiation in one adenosquamous carcinoma, squamous differentiation in five squamous carcinomas, and neuroendocrine differentiation in one small-cell carcinoma. Nine patients died (three due to postoperative complications and six due to recurrences or metastasis at 3-36 months). Four patients (all with squamous carcinoma) were alive without disease at 2-60 months. The clinical and pathologic features were comparable with those of approximately 62 other cases of TCA previously reported. There are a number of well-defined histologic types of TCA that allow the pathologist to make a differential diagnosis of TCA from tumors extending or metastatic to thymus or other primary mediastinal tumors. Although neither asymptomatic presentation nor encapsulation improves the poor prognosis of TCA, the squamous carcinoma subtype is associated with a better outcome than the other subtypes. Based on the electronmicroscopic and immunohistochemical findings, the presence of normal thymic tissue at the periphery of several tumors, and the observation that several TCA arose from preexisting thymomas

Topics: Adenocarcinoma; Adult; Aged; Alkaline Phosphatase; Carcinoembryonic Antigen; Carcinoma, Small Cell; Carcinoma, Squamous Cell; Female; Humans; Immunohistochemistry; Isoenzymes; Keratins; Male; Membrane Glycoproteins; Middle Aged; Mucin-1; Thymus Neoplasms

The present study aimed to examine possible changes in keratin expression during neoplastic transformation of the uterine mucosa and possible differences in keratin expression between endocervical and endometrial adenocarcinomas. Routinely processed specimens with normal morphology or neoplastic changes were stained immunohistochemically using 5 commercial antibodies to keratin-filaments of molecular weight 39-58 kD: CAM 5.2, RCK 102, MCA 144, PKE and PRE. We generally found a change in keratin expression during the neoplastic transformation, consisting of pronounced heterogeneity compared with normal epithelia. In distinguishing koilocytic atypia from CIN, RCK 102 (52.5, 58 Kd) may prove helpful as it stains neoplastic cells strongly and shows no reaction in koilocytic. Staining with the antibody CAM 5.2 (reactive with 39, 43, 50 kD filaments) may aid in distinguishing between cervical and endometrial adenocarcinomas. The former is stained uniformly; the latter shows a more variable staining.

Topics: Adenocarcinoma; Cervix Uteri; Female; Humans; Immunohistochemistry; Keratins; Metaplasia; Mucous Membrane; Neoplasm Invasiveness; Pregnancy; Staining and Labeling; Uterine Cervical Neoplasms; Uterine Neoplasms; Uterus

Optically clear cytoplasm in tumor cells in the absence of mucin is most often associated with renal cell carcinoma. However it is important to recognize the rare occurrence of "clear-cell" variants among tumors arising in other sites. This report describes a clear-cell carcinoma arising in the transitional zone of the anal canal.

Topics: Adenocarcinoma; Anus Neoplasms; Carcinoembryonic Antigen; Carcinoma, Transitional Cell; Humans; Immunohistochemistry; Keratins; Male; Membrane Glycoproteins; Microscopy, Electron; Middle Aged; Mucin-1

Myoepithelial cell tumors of the mammary gland have been observed in several mammalian species and are composed of a single cell type (myoepithelium) or, more often, present as a biphasic process including neoplastic ductal epithelial cells. In dogs, these are common tumors, but in humans they are rare neoplasms of the breast, and little is yet known of their pathogenesis, particularly with respect to myoepithelial origin. The present report describes bicellular mammary gland tumors arising from the duct epithelium that were induced in (C57BL/6NCr X DBA/2NCr)F1 (B6D2F1) mice by four weekly oral applications of 1 mg 7,12-dimethylbenz[a]anthracene (DMBA) starting at 8 weeks of age. Mammary tumors developed 7 to 8 months later in 14 of 57 mice, and most showed great morphologic resemblance to human adenomyoepitheliomas and myoepithelial carcinomas. Ultrastructurally, the induced tumors were composed of cuboidal epithelium with a microvillous border originating from the lining duct epithelium and plump oval or highly elongated cells that were identified as myoepithelial in origin. These spindle cells contained abundant microfilaments in parallel orientation, some with focal densities and intermediate filaments that frequently formed loose bundles or compact tonofibrils. The myoepithelial cells possessed well-developed desmosomes and plasma membrane caveolae and were regularly bordered by single or reduplicated basement membranes. By immunohistochemistry, strong immunoreactivity was observed for actin in the myoepithelial tumor component only, whereas cytokeratin was variably present in both duct epithelium and myoepithelium. Neoplastic myoepithelial cells stained purple with phosphotungstic acid hematoxylin (PTAH) and brilliant red with Masson's trichrome. It is suggested that DMBA-induced mouse mammary gland adenomyoepitheliomas and myoepithelial carcinomas may serve as very useful animal models to study myoepithelial tumorigenesis.

Topics: 9,10-Dimethyl-1,2-benzanthracene; Actins; Adenocarcinoma; Animals; Female; Immunohistochemistry; Keratins; Mammary Neoplasms, Experimental; Mice; Microscopy, Electron; Myoepithelioma

Monoclonal antibodies (MAbs) to specific keratin subtypes were prepared and characterized by immunoblotting and immunohistochemical assays on human cell cultures and normal and malignant human tissues. Chain-specific MAbs to keratin 7 (RCK 105, OV-TL 12/30) and keratin 18 (RGE 53, RCK 106, CK18-2), as well as broadly cross-reacting keratin MAbs (RCK 102, OV-TL 12/5) could be shown to react with different types of human epithelial tissues and were therefore tested for their usefulness in the differential diagnosis of carcinomas. The two broad-spectrum antibodies stained virtually all of the more than 350 carcinomas tested, especially when combined, and distinguished them from most nonepithelial tumors. The keratin 18 MAbs distinguished adenocarcinomas (which are keratin 18 positive) from most squamous cell carcinomas (which are generally keratin 18 negative). The MAbs to keratin 7 could be shown to recognize specific subtypes of adenocarcinoma and could, for example, distinguish between ovarian carcinomas (keratin 7 positive) and carcinomas of the gastrointestinal tract (keratin 7 negative), or between transitional cell carcinomas (keratin 7 positive) and prostate cancer (keratin 7 negative). In general, malignancies showed the expected keratin reactivity pattern as concluded from the keratin pattern of its cell of origin or its type of differentiation. The use of an extended series of malignancies did, however, also illustrate that exceptions to this rule exist. For example, certain antibodies to keratin 18 stained tumor areas in squamous cell carcinomas of the lung. Also a certain percentage of tumors, which generally showed no keratin 7 expression, were positive with RCK 105 or OV-TL 12/30. On the other hand, a certain percentage of tumors, which were generally positive for keratin 7, did not show a staining reaction with these MAbs. Furthermore subtle differences between reactivity patterns of different MAbs recognizing the same keratin protein were observed, both in the normal and malignant human tissues, indicating that specific keratin epitopes may be masked in certain tissues and that unmasking of such epitopes can occur with malignant progression. This phenomenon may be of some use in a further subtyping of carcinomas, especially those of the gastrointestinal tract. Despite these exceptional staining patterns, the keratin MAbs described above have proved to be useful tools in the characterization of epithelial tumors in routine histopathology and

Topics: Adenocarcinoma; Adult; Aged; Antibodies, Monoclonal; Carcinoma, Squamous Cell; Diagnosis, Differential; Female; Gastrointestinal Neoplasms; Histocytochemistry; Humans; Immunoblotting; Keratins; Lung Neoplasms; Male; Middle Aged; Ovarian Neoplasms; Prostatic Neoplasms

The distinction between sclerosing adenosis, radial scars, noninvasive carcinomas occurring in sclerosing adenosis, and invasive carcinoma can be difficult. The identification of a myoepithelial (ME) cell layer is helpful in establishing a diagnosis of complex benign breast proliferation as well as intraepithelial neoplasia in sclerosing adenosis. We reviewed pathologic material from patients with tubular carcinoma (23) and complex breast proliferations (28), including sclerosing adenosis (12), radial scars (9), sclerosing adenosis with intraepithelial neoplasia (5), and sclerosing adenosis with atypical apocrine metaplasia (2). Immunoperoxidase stains on formalin-fixed, paraffin-embedded tissue using a muscle actin-specific antibody of clone HHF35 and high molecular weight cytokeratin of clone 34 beta E12 (HMW keratin) were performed to identify myoepithelial cells. Muscle actin was uniformly reliable in staining ME cells, as well as other actin-containing cells such as myofibroblasts and vascular smooth muscle. HMW keratin was less reliable, being poorly sensitive and less specific than muscle actin for labeling of ME cells. ME cells were readily identified at the periphery of ductules in all complex benign breast lesions. The presence of ME cells distinguished intraepithelial neoplasia involving sclerosing adenosis from invasive carcinomas. Well differentiated invasive carcinoma forming tubular structures lacked a ME cell layer.

Topics: Actins; Adenocarcinoma; Breast; Breast Diseases; Breast Neoplasms; Carcinoma; Carcinoma, Intraductal, Noninfiltrating; Diagnosis, Differential; Female; Humans; Immunohistochemistry; Keratins; Molecular Weight; Muscles; Reference Values

Four monoclonal antibodies reactive with the rod portion of human cytokeratin No. 8 were evaluated using experimental tumour radio-immunolocalization. Nude mice carrying human HeLa cell tumours were injected with 125I-labelled F(ab')2 fragments or intact IgG antibodies. Positive immunolocalization was observed with all the specific antibodies, the intact antibodies being superior to their analogous F(ab')2 fragments. High localization efficiency was observed despite the fact that the targets are intracellular filaments. The presence of necrotic areas in the tumours may favour the high uptake in the tumours. By computerized gamma-scintigraphic evaluation of the antibody distribution in the animals, several kinetic parameters of the antibody behaviour in vivo could be determined. The biological half-lives in the tumours were determined to be greater than 600 h for some of the antibodies compared to a half-life of 40-80 h in non-tumour tissues. Optimal imaging was obtained as late as 10-14 days after administration of the antibody. Up to 10% of the injected antibody could be identified in the tumours, indicating a potential value in radio-immunolocalization and radio-immunotherapy using anticytokeratin antibodies.

Topics: Adenocarcinoma; Animals; Antibodies, Monoclonal; HeLa Cells; Humans; Immunoglobulin Fab Fragments; Immunoglobulin Fragments; Iodine Radioisotopes; Keratins; Mice; Neoplasm Transplantation; Neoplasms, Experimental; Radioimmunoassay; Radionuclide Imaging; Transplantation, Heterologous

Seventeen gastric carcinomas (intestinal n = 12; diffuse n = 1; mixed type n = 4) and one Barrett's carcinoma were prospectively studied by immunohistochemistry for the expression of different keratin polypeptides and of the brush border markers villin, sucrase isomaltase and aminopeptidase N. All carcinomas expressed the keratin polypeptides 8, 18, and 19 and were stained by the broad specific keratin antibody KL1, irrespective of histologic type. Keratin 7, however, was expressed in only one carcinoma in most tumor cells and in two further carcinomas in some tumor cells. Thus, specific differentiation of the various histologic types of gastric carcinoma does not seem to be aided by the use of keratin antibodies. Villin was positive in 80% of the tumors and sucrase isomaltase and aminopeptidase N were positive in 67% respectively with no obvious histologic difference. The frequent positivity of the brush border markers, usually typical for intestinal epithelium, reflects the high degree of intestinal differentiation of gastric carcinomas, but again does not seem to be associated with a particular histologic type.

Topics: Adenocarcinoma; Adult; Aged; Aminopeptidases; Biomarkers, Tumor; Carrier Proteins; CD13 Antigens; Diagnosis, Differential; Female; Fluorescent Antibody Technique; Gastrectomy; Humans; Intestinal Mucosa; Keratins; Male; Microfilament Proteins; Middle Aged; Peptides; Stomach Neoplasms; Sucrase-Isomaltase Complex

Three patients are described who presented with a large colonic adenoma in which a solid, undifferentiated carcinomatous component was found on microscopic examination. Despite small size (1.0 and 1.5 cm) and submucosal location in two cases, the tumours had metastasized to regional lymph nodes and the liver and death ensued at 4, 11 and 18 weeks after surgery. Immunocytochemistry was positive for carcino-embryonic antigen, low molecular weight cytokeratins and neuron specific enolase in all three cases and scanty dense core granules of neurosecretory type were found in one of two examined by electron microscopy. These 'neuroendocrine' carcinomas are compared with 'pure' adenomas and 'ordinary' poorly differentiated adenocarcinomas of the colon from which they differ, mainly by lack of glandular differentiation and mucus secretion, although two adenocarcinomas also showed patchy reactivity for neuron specific enolase. The term 'neuroendocrine' may be disputed but is now well established to describe a tumour that runs a uniquely aggressive course and for which radical surgery alone cannot provide a cure.

Topics: Adenocarcinoma; Adenoma; Aged; Aged, 80 and over; Carcinoma, Small Cell; Cell Differentiation; Colonic Neoplasms; Female; Humans; Immunohistochemistry; Keratins; Male; Middle Aged; Phosphopyruvate Hydratase

We report the clinicopathologic, immunohistochemical, and ultrastructural features of three small-cell neuroendocrine carcinomas of the ampullary region of the duodenum. All patients were men; their ages were 51, 62, and 66 years. The therapy consisted of pancreatoduodenectomy. All patients died of the disease; median survival was 10 months from the diagnosis. The histological appearance was identical to pulmonary and extrapulmonary small-cell carcinoma. The neuroendocrine differentiation was demonstrated ultrastructurally by the presence of dense-core granules, and by the positive immunoreaction for neuron-specific enolase and Leu-7 in each case. One case expressed a focal positivity for chromogranin A (PHE-5) and argyrophilic granules. The same case showed the presence of neurofilaments on frozen material. Neurofilament proteins could not be demonstrated in any case in paraffin sections. Neoplastic cells exhibited cytoplasmic immunostaining for cytokeratins (CAM 5.2) in all cases. In one case, a large number of neoplastic cells (60-70%) exhibited nuclear Ki-67 positivity. We postulate that the disease's histogenesis was from epithelial stem cell expressing both epithelial and neuroendocrine characteristics. The clinical behavior of small-cell neuroendocrine carcinomas of the ampullary region appears to be extremely aggressive, with early metastases and fatal outcome.

Topics: Adenocarcinoma; Aged; Antigens, Differentiation; Antigens, Surface; Carcinoma, Small Cell; CD57 Antigens; Chromogranin A; Chromogranins; Common Bile Duct Neoplasms; Humans; Immunohistochemistry; Keratins; Ki-67 Antigen; Male; Microscopy, Electron; Middle Aged; Phosphopyruvate Hydratase

Normal epithelia and carcinomas of the human uterine cervix were studied by monoclonal antibodies chain specific for cytokeratins 4, 8, 10, 13, 14, 18, and 19. Most cells in 13 examined squamous carcinomas revealed a cytokeratin phenotype detected in ectocervical basal cells and endocervical subcolumnar reserve cells: 8+, 14+, 18+, 19+, 4-, 10-, 13-. We propose that these two cell types are closely related or identical and that squamous carcinoma of the cervix originates in this cell type. In more differentiated tumor cells cytokeratins 4, 10, and 13, which are present in suprabasal layers of the normal ectocervical epithelium, were coexpressed with basal cell cytokeratins. Thus, contrary to previous beliefs, all cytokeratins detected in carcinomas were also present in normal epithelium of uterine cervix. The cytokeratin profile of cervical adenocarcinomas corresponded to that of columnar endocervical cells (8+, 18+, 19+), although two of the three adenocarcinomas also expressed cytokeratin 4, which in the normal endocervix was detected in scattered single columnar cells only. The new monoclonal antibody DE-K14, specific for cytokeratin 14, proved a specific marker of subcolumnar reserve cells in the endocervix. It was also the only one that reacted with all cervical squamous carcinomas but with none of the cervical adenocarcinomas and, as such, has a potential value for pathological differential diagnosis of cervical tumors.

Topics: Adenocarcinoma; Antibodies, Monoclonal; Carcinoma, Squamous Cell; Cervix Uteri; Electrophoresis, Gel, Two-Dimensional; Epithelial Cells; Epithelium; Female; Fluorescent Antibody Technique; Humans; Immunoblotting; Keratins; Reference Values; Uterine Cervical Neoplasms

Paraffin wax embedded, formalin fixed sections of 22 adenocarcinomas of the exocrine pancreas were stained with four mouse monoclonal antibodies: DD9-E7, an antibody raised against a human pancreatic tumour xenograft; carcino-embryonic antigen (CEA); epithelial membrane antigen (EMA); and cytokeratin (CAM 5.2). An indirect immunoperoxidase technique without enzyme pre-digestion and an affinity-purified sheep anti-mouse peroxidase conjugate were used. All of the tumours were positive for DD9-E7, EMA, and CAM 5.2. Twenty out of 22 were focally positive for CEA and the staining was often weak. As all of these adenocarcinomas were DD9-E7 positive, absence of staining for DD9-E7 in a tumour makes the diagnosis of adenocarcinoma of the exocrine pancreas very unlikely, and this is of value in distinction from endocrine carcinomas with a marked acinar pattern. The weak CEA staining distinguished pancreatic carcinomas from colorectal tumours. Because the distribution of staining for EMA and CAM 5.2 was no different from that previously seen in adenocarcinomas from other sites, these markers are likely to be of limited value in the differential diagnosis of abdominal adenocarcinomas of uncertain origin.

Topics: Adenocarcinoma; Antibodies, Monoclonal; Antigens, Neoplasm; Biomarkers, Tumor; Carcinoembryonic Antigen; Humans; Immunoenzyme Techniques; Keratins; Membrane Glycoproteins; Mucin-1; Pancreatic Neoplasms

Four colon adenocarcinoma cell lines, CC-M2, CC-M3, CC-M4, and CC-M2NM, have been established from surgical specimens of 18 unselected patients without the use of "feeder" cells and additional growth factors (e.g., insulin, hydrocortisone, etc.) in the culture medium. The methods of primary cultivation of tissue explants are described. Studies of determination of morphology, growth curve, plating efficiency, chromosomal analysis, CEA and beta-HCG synthesis, and tumorigenicity, were done to characterize the cell lines. Significant variations have been found in one of the four cell lines, both in vitro and in vivo studies. There are distinct phenotypes in the established cell lines which may be useful in studying the cell differentiation and progression of colorectal cancer.

Topics: Adenocarcinoma; Aged; Aged, 80 and over; Animals; Carcinoembryonic Antigen; Chorionic Gonadotropin; Chorionic Gonadotropin, beta Subunit, Human; Chromosome Aberrations; Chromosome Disorders; Colorectal Neoplasms; Female; Humans; Karyotyping; Keratins; Male; Mice; Mice, Inbred BALB C; Middle Aged; Neoplasm Transplantation; Peptide Fragments; Tumor Cells, Cultured

There are a number of benign, small-acinar lesions in the prostate gland that may be difficult to differentiate from small-acinar adenocarcinoma. An important diagnostic criterion in this differentiation is the loss of the basal layer in small-acinar adenocarcinoma and its preservation in benign conditions. A monoclonal antibody to high-molecular-weight cytokeratins (34 beta E12) has been shown to stain these basal cells preferentially. To assess the usefulness of this antibody in distinguishing benign from malignant small-acinar lesions, we examined 21 cases of small-acinar adenocarcinoma and 47 examples of benign lesions, which included atypical adenomatous hyperplasia, atrophy, post-sclerotic hyperplasia, basal cell hyperplasia, and fibroepithelial nodule. Positive staining with 34 beta E12 was seen in 13/13 cases of atypical adenomatous hyperplasia, although in some cases the staining was weak and focal. Positivity with 34 beta E12 was also demonstrated in all other benign lesions studied. All 21 cases of small-acinar adenocarcinoma showed no reactivity with 34 beta E12. The results suggest that 34 beta E12 is of value in distinguishing between well-differentiated, small-acinar prostatic adenocarcinoma and its mimics. However, care is needed in interpretation of staining in formalin-fixed material due to the variable reactivity, particularly in cases of atypical adenomatous hyperplasia.

Topics: Adenocarcinoma; Adenoma; Antibodies, Monoclonal; Atrophy; Diagnosis, Differential; Evaluation Studies as Topic; Humans; Hyperplasia; Immunoenzyme Techniques; Keratins; Male; Molecular Weight; Prostate; Prostatic Diseases; Prostatic Neoplasms; Staining and Labeling

The case of a woman who died from cerebral metastasis of adenocarcinoma of the uterine corpus, clinical stage IA at the time of first referral, is described. Three months after preoperative endocavitary radiotherapy followed by radical surgery followed by postoperative radiotherapy, the 59-year-old patient developed neurological symptoms. A cerebral tumor was diagnosed and subsequently excised. Histology showed metastasis of an adenocarcinoma. The patient died 3 weeks after cranial surgery. Meticulous postmortem examination failed to reveal any other tumor besides the endometrial neoplasm. Comparative immunohistochemical examination of the primary tumor and the cerebral process supported the assertion that the brain metastasis derived from the adenocarcinoma of the endometrium. Literature reports on cerebral metastasis of endometrial carcinoma are discussed.

Topics: Adenocarcinoma; Antigens, Tumor-Associated, Carbohydrate; Brain Neoplasms; Carcinoembryonic Antigen; Female; Humans; Immunohistochemistry; Keratins; Middle Aged; Uterine Neoplasms

Twenty-two cases of keratin granulomas of the peritoneum associated with endometrioid adenocarcinoma with squamous differentiation of the endometrium, the ovary, or both, and with an atypical polypoid adenomyoma of the endometrium were reviewed. Follow-up data were available in 18 cases. Twelve patients were well and disease free 13 months to 15.2 years postoperatively; one patient died of unrelated disease 21 years postoperatively; three patients were tumor free with a short duration of follow-up; one patient, who had a stage Ic ovarian tumor, died of pulmonary embolism during the treatment of recurrent tumor 1 year after operation; and a final patient, who had been followed for 3 months after operation for stage IV disease, was alive with residual tumor. At least six patients with stage I carcinomas were treated with postoperative irradiation because the granulomas had raised a suspicion of advanced disease. Follow-up data on the patients in this series suggest that peritoneal keratin granulomas have no prognostic significance and should be distinguished from viable tumor implants on microscopic examination.

Topics: Adenocarcinoma; Adult; Aged; Endometriosis; Female; Follow-Up Studies; Granuloma; Humans; Keratins; Middle Aged; Neoplasms, Multiple Primary; Ovarian Neoplasms; Peritoneal Diseases; Uterine Neoplasms

The neoplastic cells present in a sialadenoma pappiliferum were found by immunoperoxidase method and immunofluorescent staining technique to co-express 3 different types of intermediate-sized filaments (IFs) defined by monoclonal antibodies to cytokeratin, vimentin and desmin. When other salivary gland tumors such as 18 pleomorphic adenomas, 15 adenolymphomas, 2 oxyphilic adenomas, 7 mucoepidermoid tumors, 5 acinic cell tumors, 8 adenoid cystic carcinomas and 6 adenocarcinomas were examined immunohistochemically for the expression of IFs, no tumors with all 3 types of IFs observed in sialadenoma papilliferum were found.

Topics: Adenocarcinoma; Adenolymphoma; Adenoma, Pleomorphic; Carcinoma; Carcinoma, Adenoid Cystic; Desmin; Fluorescent Antibody Technique; Humans; Immunoenzyme Techniques; Intermediate Filaments; Keratins; Papilloma; Salivary Gland Neoplasms; Vimentin

An immunohistochemical study of reactive pleural lesions, adenocarcinomas and mesotheliomas using carcinoembryonic antigen (CEA), cytokeratin and vimentin was carried out. All the specimens were obtained at surgery except for 11 mesotheliomas found at necropsy. Vimentin was positive in 23 of 27 mesotheliomas and negative in all the adenocarcinomas and 4 of 17 reactive mesothelial lesions. Conversely, CEA was positive in all the adenocarcinomas but negative in all mesotheliomas. Immunoreactivity for vimentin was seen in only 3 of 11 post-mortem mesotheliomas. Vimentin is a useful adjunct to the tissue diagnosis of mesothelioma especially when CEA is negative and cytokeratin positive. Its use appears largely confirmed to well fixed surgically derived tissues.

Topics: Adenocarcinoma; Carcinoembryonic Antigen; Humans; Immunoenzyme Techniques; Keratins; Mesothelioma; Pleura; Pleural Neoplasms; Vimentin

Two cases of carcinoma of the minor salivary glands are presented in which most cells had clear cytoplasm. Both patients had clinical histories in excess of 10 years and, in the one case with adequate follow-up, no recurrence had occurred after a further 11 years. Both tumours were locally invasive. The clear cells contained small amounts of glycogen, but no intracytoplasmic mucin. Immunohistochemical and ultrastructural studies showed epithelial features, with no evidence of myoepithelial differentiation. These tumours were very similar to the small number of previously reported cases, which were all considered to be low-grade carcinomas. Amongst the differential diagnoses, the most important is metastatic clear cell carcinoma of the kidney and this can only be confidently excluded clinically or by the use of imaging techniques. In summary, we consider intraoral clear cell carcinoma to be a distinct tumour of low malignant potential.

Topics: Adenocarcinoma; Aged; Female; Humans; Immunohistochemistry; Keratins; Male; Microscopy, Electron; Salivary Gland Neoplasms

Topics: Adenocarcinoma; Colonic Neoplasms; Humans; Immunohistochemistry; Keratins; Lymph Nodes; Plasma Cells; Plasmacytoma

A case of malignant mixed müllerian tumor of the ovary in a 57-year-old woman is reported along with the results of an immunohistochemical study. The tumor, measuring 16 x 10 x 9 cm, was composed predominantly of adenocarcinoma with a smaller amount of anaplastic carcinoma as an epithelial component and chondrosarcoma, liposarcoma, fibrosarcoma and rhabdomyoblasts as mesenchymal elements. Immunohistochemistry using paraffin sections demonstrated cytokeratin (CK) and epithelial membrane antigen (EMA), generally regarded as epithelial markers, not only in the epithelial component but also in chondrosarcoma cells. Vimentin and desmin, generally regarded as mesenchymal markers, were exhibited partly in carcinoma cells as well as in mesenchymal elements. Positive staining for S-100 protein was obtained not only in chondrosarcoma and liposarcoma cells, but also partly in adenocarcinoma cells. This intricate immunohistochemical picture reflected the histologic findings. It is noteworthy that both carcinoma cells and chondrosarcoma cells demonstrated simultaneous expression of CK, EMA, vimentin, desmin and S-100 protein. This somewhat unusual antigen expression by tumor cells may indicate a change in the nature of tumor cells due to microenvironmental factors.

Topics: Adenocarcinoma; alpha-Fetoproteins; Chondrosarcoma; Chorionic Gonadotropin; Desmin; Female; Fibrosarcoma; Humans; Immunohistochemistry; Keratins; Liposarcoma; Membrane Glycoproteins; Middle Aged; Mucin-1; Myoglobin; Neoplasms, Germ Cell and Embryonal; Ovarian Neoplasms; Rhabdomyoma; S100 Proteins; Vimentin

Recent studies suggest that the proliferation and expression of HLA-DR molecules in endometrial epithelium may be regulated by systemic steroids and local cytokines. To test the interacting influences of cytokines and steroids on the expression of HLA-DR and proliferation of epithelial cells, an endometrial cell model is required that is sensitive to both signals. In this study, we characterize cells of carcinoma cell lines of endometrial lineage for their responsiveness to cytokines and steroids. Independently developed for its response to steroid hormones from a well-differentiated adenocarcinoma of human endometrium, EnCa101AE cell line is further cloned for the expression of progesterone receptor. Immunohistochemical localization using monoclonal antibodies demonstrates that both EnCa101AE cell line and cloned ECC1 cells are purely epithelial, as evidenced by the expression of cytokeratin and epithelial membrane antigen, express estrogen receptors, and concomitantly exhibit IFN-gamma receptor. Experiments using radioiodinated IL-1 reveal that these cell lines also possess high affinity receptors for IL-1. As indicated by the induction of HLA-DR molecules, and alterations in morphologic characteristics, these cell lines are sensitive to both IFN-gamma and IL-1 action. The class II molecules (HLA-DR, HLA-DP, and HLA-DQ) are differentially induced by IFN-gamma treatment in carcinoma cell lines, with HLA-DR being the prevailing induced molecule. IFN-gamma inhibits and estradiol-17 beta promotes growth of ECC1 cells in a dose- and time-dependent manner. These findings indicate that the interacting effect(s) of the cytokines and steroid hormones on endometrial epithelium may be studied in these unique steroid- and cytokine-sensitive epithelial cell lines.

Topics: Adenocarcinoma; Cell Division; Cytokines; Estradiol; Female; HLA-DP Antigens; HLA-DQ Antigens; HLA-DR Antigens; Humans; Immunohistochemistry; Interferon-gamma; Interleukin-1; Keratins; Membrane Glycoproteins; Mucin-1; Receptors, Estrogen; Receptors, Immunologic; Receptors, Interleukin-1; Receptors, Progesterone; Steroids; Tumor Cells, Cultured; Uterine Neoplasms

The expression of cytokeratins (CKs) was investigated in cell lines and clones established from the rat 13762NF mammary adenocarcinoma tumor and its spontaneous lymph node and lung metastases. Two-dimensional polyacrylamide gel electrophoresis of intermediate filament-enriched protein fractions from cultured cells revealed that clones established from spontaneous metastases contained three CKs (Mr approximately 54,000, approximately 52,000, and approximately 40,000) characteristic of simple epithelia and two CKs (Mr approximately 51,000 and approximately 47,000) characteristic of stratified epithelia. CK expression varied qualitatively and quantitatively between the different metastasis-derived cell clones. In contrast, cell clones established from the original mammary fat pad tumor expressed low or undetectable levels of CKs. Western blot analyses with a panel of anti-CK antibodies with defined specificities confirmed the observations. One-dimensional polyacrylamide gel electrophoresis of whole-cell lysates and intermediate filament-enriched extracts were transferred and probed with the panel of antibodies. The relative expression of individual CKs varied according to the cell line or clone examined and environmental conditions (low versus high passage and in vitro versus in vivo growth), whereas the amount of total CKs expressed relative to total cell protein varied according to cell line or clone and growth conditions.

Topics: Adenocarcinoma; Animals; Female; Keratins; Mammary Neoplasms, Experimental; Molecular Weight; Neoplasm Metastasis; Rats; Tumor Cells, Cultured; Vimentin

Keratin and carcinoembryonic antigen immunoperoxidase staining were applied to lung cancer cells in paraffin sections of cell blocks from sputa and bronchial washings. The results correlate well with cytologic diagnosis. The large cell carcinomas are nonreactive with both antibodies.

Topics: Adenocarcinoma; Bronchi; Bronchoalveolar Lavage Fluid; Carcinoembryonic Antigen; Carcinoma, Small Cell; Carcinoma, Squamous Cell; Histological Techniques; Humans; Immunoenzyme Techniques; Keratins; Lung Neoplasms; Paraffin; Sputum

Postirradiation prostatic biopsy is believed by many to be the best measure of radiation effectiveness in prostatic cancer. Therapeutic irradiation may induce prostatic glandular atypia, which in its severe form can be confused with persistent adenocarcinoma on prostatic biopsies. In the current study, 37 postirradiation prostate biopsy specimens were evaluated by immunohistochemistry using a specific monoclonal anticytokeratin antibody (KA1) that reacts with the basal cells of normal or hyperplastic glands, but is nonreactive with the lumenal cells or with prostatic carcinoma cells. Persistent carcinoma was observed in 19 cases in which antibody staining was absent. The noncarcinomatous glands retained reactivity, but this reactivity appeared in a new and previously undescribed pattern. The irradiated lesion was characterized by cellular pleomorphisism, with enlargement of nuclei and loss of polarity. The immunoreactivity was seen in the enlarged basal cells and was seen to focally extend to involve the lumenal cell layer. In five of 37 cases, glands were seen that were so atypical on the routinely stained sections that a distinction from cancer could not be made. These same glands in the adjacent section reacted with KA1 in each case allowing us to conclude that the changes were benign. We conclude that the interpretation of postirradiation prostatic biopsy specimens may be aided by immunohistochemistry with this anticytokeratin antibody.

Topics: Adenocarcinoma; Antibodies, Monoclonal; Biopsy; Humans; Immunohistochemistry; Keratins; Male; Prostate; Prostatic Neoplasms

We present two cases of small-bowel adenocarcinoma and dysplasia in patients with longstanding Crohn's disease. In one case, the dysplasia and cancer were exclusively located in the terminal ileum, whereas in the other case, several cancers were found from the ileum toward the transverse colon. In both cases, we found a clinically unsuspected Dukes C1 mucinous adenocarcinoma together with large foci of polypoid villous dysplasia or with multifocal high-grade dysplasia and intramucosal carcinoma. Immunohistochemical staining for carcinoembryonic antigen (CEA) revealed a different staining pattern in various diseased areas. The intensity of CEA staining paralleled the histologic degrees of dysplasia and neoplasia. Cytokeratin expression was disturbed in inflamed mucosa, and it was more pronounced in high-grade dysplasia and invasive carcinoma. We conclude that the presence of dysplasia in an intestinal biopsy of a patient with Crohn's disease should arouse the pathologist's suspicion of carcinoma and force him or her to take multiple sections from strictures and polypoid lesions, especially since the clinical symptoms of a carcinoma may be obscured by the symptoms of inflammatory bowel disease. Immunohistochemical staining with CEA and cytokeratin are useful in the objectivation of dysplasia.

Topics: Adenocarcinoma; Adult; Carcinoembryonic Antigen; Colitis; Colonic Neoplasms; Crohn Disease; Female; Humans; Ileal Neoplasms; Ileitis; Intestinal Mucosa; Keratins; Male; Middle Aged; Neoplasm Invasiveness

We used a battery of antigens to determine whether immunohistochemistry can (a) contribute to resolving the histogenesis of the stromal component of the capillary hemangioblastoma, and (b) answer cases of difficult pathologic differential diagnosis with metastatic clear cell carcinoma. The stromal cells of the capillary hemangioblastoma are antigenically polymorphous and may express immunoreactive erythropoietin, renin, keratin, Leu M1, Leu 7, actin, neuron-specific enolase, S100 protein, and glial fibrillary acidic protein. However, the use of epithelial membrane antigen allows certain histopathologic distinction between capillary hemangioblastoma and metastatic clear cell carcinoma.

Topics: Adenocarcinoma; Aged; Antigens, Differentiation; Antigens, Neoplasm; Carcinoma, Renal Cell; Cerebellar Neoplasms; Diagnosis, Differential; Erythropoietin; Hemangiosarcoma; Humans; Immunoenzyme Techniques; Keratins; Kidney Neoplasms; Male; Membrane Glycoproteins; Mucin-1; Renin

Specimens of neoplastic tissues from 19 dogs and 4 cats were examined immunohistochemically for intermediate filament expression, using commercially available antibodies. Staining was observed in a wide range of tumor tissues and in normal internal controls by use of antibodies to vimentin, desmin, glial fibrillary acidic protein, and low and high molecular weight cytokeratins. Intermediate filament expression was found to be consistent with light and/or electron microscopic findings, and hence believed to be an accurate indicator of tumor histogenesis in cats and dogs. Three fixatives were evaluated for their relative abilities to preserve antigenicity. Absolute alcohol was superior to B5 fixative and both were superior to formalin. Some tissues that clearly displayed intermediate filament antigens with alcohol and B5 fixative failed to stain when fixed in formalin.

Topics: Adenocarcinoma; Animals; Astrocytoma; Cat Diseases; Cats; Cytoskeleton; Desmin; Dog Diseases; Dogs; Immunohistochemistry; Intermediate Filament Proteins; Intermediate Filaments; Keratins; Leiomyosarcoma; Melanoma; Neoplasms; Neurilemmoma

We report the light and electron microscopic findings of an unusual, locally aggressive cutaneous clear cell carcinoma involving extensively the left cheek and upper lip of a 61-year-old woman. The patient remained free of recurrence 5 years after wide local excision. Microscopically, the tumor was a poorly circumscribed and deeply invasive clear cell neoplasm characterized by large lobules and convoluted trabeculae of polygonal and columnar cells with palisading of the peripheral cells rimmed by thick basement membranes, and horn microcysts with tricholemmal keratinization. The tumor infiltrated the muscle and the salivary glands. Only slight cytologic atypia and a few mitotic figures were present. No definite ductal differentiation was found. Immunoperoxidase staining for carcinoembryonic and epithelial membrane antigens was negative. Ultrastructurally, the tumor cells were joined by desmosomes, and surrounded by thick basal lamina. The cytoplasm contained large pools of glycogen. Peculiar whorls of tonofilaments and aggregates of needle-shaped and club-shaped structures were observed in a small keratinizing focus. The tumor showed features resembling the outer root sheath of the hair follicle microscopically. Furthermore, the lack of duct-like structures and immunoreactivity of carcinoembryonic antigen tend to favor tricholemmal over sweat gland differentiation in this tumor which possibly represents a rare example of tricholemmal carcinoma.

Topics: Adenocarcinoma; Basement Membrane; Cell Differentiation; Diagnosis, Differential; Facial Neoplasms; Female; Glycogen; Humans; Keratins; Microscopy, Electron; Middle Aged

Topics: Adenocarcinoma; Douglas' Pouch; Female; Granuloma; Humans; Keratins; Middle Aged; Peritoneal Diseases; Uterine Neoplasms

The identification of basal cells is often helpful in excluding a diagnosis of prostate carcinoma. However, it can be difficult to distinguish basal cells from underlying fibroblasts or an artifactual two-cell layer in neoplastic glands. To determine the usefulness of anti-keratin antibody 903 for identifying basal cells in glandular patterns sometimes confused with carcinoma, we examined frozen sections from radical prostatectomy specimens and formalin-fixed needle biopsy, radical prostatectomy, and transurethral resection specimens. Atrophic glands, basal cell hyperplasia, intraductal severe dysplasia and various grades of carcinoma were examined. Also evaluated were cases of atypical adenosis, defined as clusters of small glands that mimic low-grade carcinoma yet focally appear to have a basal cell layer and merge with more recognizable benign glands. Almost all normal glands showed some staining, although it was often discontinuous with formalin fixation. Intraductal dysplasia stained in a manner similar to normal glands. Ninety-two percent of atrophic glands and 88% of glands in basal cell hyperplasia stained. Sixty-one percent of the glands in atypical adenosis stained intensely but discontinuously. All grades of adenocarcinoma lacked any immunoreactivity. These results indicate that keratin 903 is useful in the diagnosis of prostatic carcinoma because positive staining identifies a questionable focus as benign whereas negative staining helps to substantiate the diagnosis of carcinoma.

Topics: Adenocarcinoma; Antibodies, Monoclonal; Humans; Keratins; Male; Prostatic Neoplasms

An improved immunohistochemical determination of the cytokeratin profiles of epithelia and their neoplasms is possible using monoclonal antibodies that will either identify all 19 cytokeratins (AE1/3) or delineate specific subsets (35 beta H11, 34 beta E12, 34 beta B4 and Cam 5.2). Ovarian common "epithelial" tumors (CET) contain cytokeratin filaments. To determine the nature and differences in the cytokeratin profiles of ovarian CET, eight benign Brenner tumors, four serous cystadenofibromas, 28 mucinous tumors, 27 serous tumors and six endometrioid, five clear cell and five undifferentiated carcinomas, as well as nine normal ovaries were immunostained with the above five antibodies. AE1/3 staining was predominant, while Cam 5.2 and 35 beta H11 displayed the most frequent staining thereafter. Statistically significant staining differences were found between a number of tumor groups using the antibodies 35 beta H11, 34 beta E12 and Cam 5.2. In this study, all ovarian CET, except the benign Brenner tumors, displayed a predominantly low molecular weight cytokeratin profile. The same profile in the normal surface epithelium lends credence to the belief that these tumors are derived from this epithelium. A significant staining difference between some of the tumor types using some of the antibodies suggests a possible ancillary, diagnostic role of cytokeratin profiling in situations where exact tumor typing is difficult.

Topics: Adenocarcinoma; Adenocarcinoma, Mucinous; Adenofibroma; Adenoma; Antibodies, Monoclonal; Brenner Tumor; Carcinoma; Endometriosis; Female; Humans; Immunohistochemistry; Keratins; Ovarian Neoplasms

By co-culturing regional lymph node B-cells and HAT-sensitive mutant cells obtained from RPMI-1788 cells, no less than 20,000 Epstein-Barr (EB)-transformed colonies were obtained from 32 patients with gastric cancer. From B-cell cultures generating antibodies reactive with gastric cancer tissues as well as cultured gastric cancer cells, two EB-transformed cell clones termed C418-59 and C1218-39 were isolated. Both of them produced human IgM-class antibodies, termed Mab418-59 and Mab1218-39, respectively. Both antibodies reacted with an antigen with a molecular weight of 45 kd existing in gastric cancer MKN-45, MKN-1, and Kato-III cells, and also with all of 4 adenocarcinomas of the stomach in paraffin sections. The antigen recognized by both antibodies was identified as a kind of cytoskeletal protein, cytokeratin 18. In this study, it was confirmed that B-cell clones generating autoantibodies against cytokeratin 18 were present in some patients with gastric cancer.

Topics: Adenocarcinoma; Antibodies, Monoclonal; Antigens; Antigens, Neoplasm; Autoantibodies; B-Lymphocytes; Blotting, Western; Cell Transformation, Viral; Electrophoresis, Polyacrylamide Gel; Herpesvirus 4, Human; Humans; Immunoenzyme Techniques; Immunoglobulin M; Keratins; Lymph Nodes; Molecular Weight; Stomach Neoplasms; Tumor Cells, Cultured

The presence of axillary metastases in carcinoma of the breast is of major prognostic significance. The avidin-biotin complex immunohistochemical method was used to determine if a monoclonal antibody cocktail (AE1/AE3) to cytokeratins was as specific and sensitive in detecting metastases as routine light microscopic examination of hematoxylineosin (HE)-stained sections. This study was unique in that identical sections were examined by both standard HE and immunohistochemical methods. Ninety hyperplastic axillary lymph nodes, removed from 14 female patients for a variety of diagnostic reasons, demonstrated no epithelial cells by either technique. Six of 42 nodes removed from five patients with breast cancer and known axillary metastases demonstrated tumor cells when examined with HE, whereas 13 of these nodes demonstrated cytokeratin-positive metastases. The immunohistochemical detection of cytokeratin-positive axillary metastases is both specific and sensitive.

Topics: Adenocarcinoma; Antibodies, Monoclonal; Axilla; Breast Neoplasms; Female; Humans; Immunohistochemistry; Keratins; Lymph Nodes; Lymphatic Metastasis

Using four human tumor cell lines, MCF-7 and T47-D from breast tumors, MOLT-4 and K-562 from leukemia, flow cytometric DNA analysis of pure and mixed cell population was performed using monoclonal antibodies to cytokeratin to distinguish cytokeratin-containing carcinoma cells from leukemia cells which do not contain cytokeratins. Surprisingly, on pure or mixed K-562 cells, we found positive labeling with KL1, CK8, and CK18 antibodies (results confirmed by immunocytology). This preliminary study has allowed a DNA analysis on epithelial cells of human breast tumors.

Topics: Adenocarcinoma; Antibodies, Monoclonal; Breast Neoplasms; Cell Line; DNA, Neoplasm; Flow Cytometry; Humans; Keratins; Leukemia; Tumor Cells, Cultured

Small-cell and poorly differentiated carcinomas of the cervix were studied immunohistochemically for several neuroendocrine and epithelial markers. Neuroendocrine markers were frequently expressed in small-cell carcinomas with argyrophilia; of the seven such tumors, four were immunoreactive with anti-chromogranin, seven with antineuroendocrine, five with anti-Leu 7, and seven with anti-neuron-specific enolase. Only neuron-specific enolase, however, was expressed in two of the three small-cell carcinomas without argyrophilia. On the other hand, one of the epithelial markers, epithelial membrane antigen, was strongly positive in all three small-cell carcinomas without argyrophilia and all seven poorly differentiated carcinomas, while it was expressed only weakly and focally in all small-cell carcinomas with argyrophilia except in one case. In conclusion, it is suggested that the immunohistochemical demonstration of several neuroendocrine markers may be helpful in diagnosing neuroendocrine carcinoma of the cervix as a supplement to conventional light microscopy, silver staining, and electron microscopy.

Topics: Adenocarcinoma; Antigens, Neoplasm; Carcinoma; Carcinoma, Small Cell; Carcinoma, Squamous Cell; Chromogranins; Female; Humans; Immunohistochemistry; Keratins; Membrane Glycoproteins; Mucin-1; Phosphopyruvate Hydratase; Uterine Cervical Neoplasms

The authors have previously studied the presence and distribution of a 24-kilodalton (KD) estrogen-regulated protein in the human normal cervix (Am J Obstet Gynecol 1986; 155:1090-1096). This protein has recently been identified as a heat-shock protein, and in order to continue its study the authors have now examined its expression in preneoplastic to neoplastic cervical samples. The study involved 53 patients, the presence of 24-KD protein together with keratin and carcinoembryonic antigen (CEA) was investigated by immunohistochemical analysis. Cytosol samples from 15 patients with squamous cervical carcinomas were also studied by the Western blot technique, and the presence of estrogen receptors was analyzed biochemically. The 24-KD protein was observed in cervical intraepithelial neoplasias (CIN), but it was not useful to identify the different degrees of CIN examined. The 24-KD protein, keratin, and CEA were predominantly expressed in well and moderately differentiated squamous carcinomas in the more differentiated areas, and the protein was also found in cervical adenocarcinomas. The presence of 24-KD protein did not correlate with that of estrogen receptors in squamous cervical carcinomas. The Western blot and the immunohistochemical studies revealed that the antibody to 24-KD protein does not cross-react with epitopes of CEA and keratins.

Topics: Adenocarcinoma; Blotting, Western; Carcinoembryonic Antigen; Carcinoma, Squamous Cell; Cervix Uteri; Female; Heat-Shock Proteins; Humans; Immunohistochemistry; Keratins; Molecular Weight; Precancerous Conditions; Receptors, Estrogen; Uterine Cervical Neoplasms

We studied one case of atypical polypoid adenomyoma of the uerus immunohistochemically using antisera against keratins, vinentin, S-100 protein, desmin and actin. The stromal cells were reactive with anti-actin and antidesmin antibodies suggesting a muscular phenotype and confirming previous ultrastructural data. Immunohistochemical investigations have proved to be useful in differential diagnosis of APA with invasive adenocarcinoma, adenosarcoma and adenofibroma of the endometrium.

Topics: Actins; Adenocarcinoma; Adenofibroma; Desmin; Diagnosis, Differential; Endometriosis; Female; Humans; Immunohistochemistry; Keratins; Middle Aged; S100 Proteins; Uterine Neoplasms; Vimentin

Using immunoperoxidase staining of monoclonal antibody 312C8-1 against 51,000 dalton human keratin polypeptide, immunolocalization was observed in frozen sections of normal tissue and mammary tumours of adult female mice and rats. In normal tissue, the epitope was recognized in myoepithelial cells of the mammary, sweat and salivary glands, and in basal and suprabasal cells of the epidermis. However, the antibody did not react with luminal epithelial cells of the above glands or with mesenchymal cells. In spontaneous mammary tumours of mice, marker-positive tumour cells were distributed only in the outer layer of adenocarcinoma Type A, while they were scattered in some foci of adenocarcinoma Type B, and encircled the epithelial foci of pregnancy dependent tumours (plaque). All layers of epidermoid structures in adenoacanthoma revealed positivity. In rat mammary tumours induced by local dusting with 7, 12-dimethylbenz(a)anthracene (DMBA) powder, the staining pattern of benign tumours was comparable to that of the normal mammary gland. But, in addition to basally situated cells, marker-positive tumour cells were found scattered in the foci of adenocarcinoma, and were not restricted to basal cells in squamous cell carcinoma. The marker was not found in sarcomatous tissue. This antibody can therefore also be applied to rodents, and the staining pattern can be used to identify the epithelial subclass specific marker in normal tissue and in mammary tumours.

Topics: Adenocarcinoma; Adenoma; Animals; Antibodies, Monoclonal; Biomarkers, Tumor; Carcinoma, Squamous Cell; Epithelial Cells; Epithelium; Female; Immunohistochemistry; Keratins; Mammary Glands, Animal; Mammary Neoplasms, Experimental; Mice; Mice, Inbred BALB C; Mice, Inbred C3H; Mice, Inbred Strains; Rats; Rats, Inbred Strains

Ovarian endometrioid carcinomas resembling sex cord-stromal tumors (ECSCSs) may simulate Sertoli cell tumors, Sertoli-Leydig cell tumors (SLCTs), and adult granulosa cell tumors (AGCTs), both clinically and pathologically. Differing clinical features and histologic findings are almost always successful in distinguishing these tumor types, although in some cases the differential diagnosis is difficult. Immunohistochemical staining of 17 ECSCSs, 14 Sertoli cell tumors or SLCTs, and 15 AGCTs was performed with the use of antibodies against cytokeratins (AE1/AE3, 902, and CAM 5.2), epithelial tumor-associated antigens (EMA, OM-1, B72.3, and carcinoembryonic antigen B1.1), vimentin, S-100, neuron-specific enolase, and lysozyme to determine the immunohistochemical profile of each tumor type and to define further the nature of the sex cord-like components in ECSCSs. All 17 ECSCSs, none of the 15 AGCTs, and one of 14 Sertoli cell tumors or SLCTs stained with EMA. Staining for OM-1 was almost as helpful diagnostically, with positive results for 15 of 17 ECSCSs, 0/15 AGCTs, and 1/14 Sertoli cell or SLCTs. Antikeratins were immunoreactive with all the ECSCSs as well as some of the AGCTs and Sertoli cell tumors or SLCTs. The B72.3 and B1.1 were immunoreactive with some ECSCSs and Sertoli cell tumors, but were nonreactive with AGCTs. Neuron-specific enolase was demonstrated in 11 of 17 ECSCSs, two of 14 Sertoli cell tumors or SLCTs, and 0 of 15 AGCTs. Vimentin, S-100, and lysozyme were least helpful in the differential diagnosis. These studies suggest that an immunohistochemical approach may be useful in the differentiation of ECSCSs and sex cord-stromal tumors. Furthermore, it supports the conclusion that the sex cord-like cells in ECSCSs are not Sertoli or granulosa cells, but cells of surface epithelial type growing in architectural patterns similar to those of sex cord-stromal tumors.

Topics: Adenocarcinoma; Antigens, Tumor-Associated, Carbohydrate; Diagnosis, Differential; Endometriosis; Female; Granulosa Cell Tumor; Humans; Immunohistochemistry; Keratins; Leydig Cell Tumor; Lysosomes; Male; Ovarian Neoplasms; Phosphopyruvate Hydratase; S100 Proteins; Sertoli Cell Tumor; Testicular Neoplasms; Vimentin

Two unique cases of pulmonary carcinomas showing squamous and glandular differentiation and the production of excessive amounts of extracellular waxy eosinophilic material resembling amyloid are reported. Immunohistochemical studies showed strong staining of the neoplastic cells with antibodies directed at cytokeratin, epithelial membrane antigen, and carcinoembryonic antigen. Of particular interest was the simultaneous strong staining for S-100 protein and vimentin. The histology, ultrastructure, and immunohistochemical findings suggest focal myoepithelial differentiation in these mixed carcinomas and indicate an analogy to salivary gland neoplasms, particularly adenoid cystic carcinoma and dermal analog tumors.

Topics: Adenocarcinoma; Aged; Antigens, Neoplasm; Carcinoembryonic Antigen; Carcinoma, Squamous Cell; Extracellular Matrix; Female; Humans; Hyalin; Keratins; Lung Neoplasms; Male; Membrane Glycoproteins; Middle Aged; Mucin-1; S100 Proteins; Vimentin

The most important discriminant in staging carcinoma of the breast is the presence of positive axillary lymph nodes. In this study, we determined if 45 female breast cancer patients originally classified as lymph node-negative by standard light microscopy (SLM) could be more accurately classified by immunohistochemical (IH) examination of their lymph nodes with an anticytokeratin monoclonal antibody cocktail. Identical sections of lymph nodes were sequentially examined by SLM and IH. Eight nodes (1%) in a total of five patients (11%) were positive by SLM. In comparison, 12 nodes (1.5%) in a total of nine patients (20%) were positive by IH. Five nodes were positive by IH and negative by SLM. There was no correlation between IH-detected metastases and tumor size or patient age. The survival curve for patients with IH-detected metastases was significantly worse than that of patients without IH-detected metastases. IH detection methods may be an important adjunct in staging breast cancer patients.

Topics: Adenocarcinoma; Adult; Antibodies, Monoclonal; Axilla; Biomarkers, Tumor; Breast Neoplasms; Female; Humans; Immunoenzyme Techniques; Keratins; Lymph Nodes; Lymphatic Metastasis; Middle Aged; Prognosis

Keratin expression with the use of chain-specific monoclonal antikeratin antibodies was investigated in normal thyroid tissue (n = 4), colloid nodules (n = 19), follicular thyroid adenomas (n = 18), follicular carcinomas (n = 10), and papillary carcinomas (n = 12). Frozen sections were stained with monoclonal antibodies M20 (keratin 8), M9 (keratin 18), and LP2K (keratin 19) with the use of the indirect immunoperoxidase technique. The immunohistochemical findings showed that the expression of keratins 8 and 18 was equally extensive in all normal, benign, and malignant lesions tested. In contrast, different staining patterns were observed with the use of monoclonal antibody to keratin 19. Follicular carcinomas were only focally stained with this antibody or were not reactive at all. Keratin 19, however, was present in all the tumor cells of papillary tissues and in a moderate amount of cells of nonneoplastic thyroid lesions and follicular adenomas. In papillary carcinoma, an identical homogeneous expression of keratin 19 was observed in both papillary and follicular structures, which suggests a common cellular origin. These results show that immunohistochemical staining with the use of monoclonal antibody against keratin 19 is useful to distinguish papillary thyroid carcinomas from follicular adenomas and follicular thyroid carcinomas.

Topics: Adenocarcinoma; Adenoma; Antibodies, Monoclonal; Carcinoma, Papillary; Diagnosis, Differential; Histocytochemistry; Humans; Immunoenzyme Techniques; Keratins; Thyroid Neoplasms

Most prostatic adenocarcinomas reveal a hypoechoic peripheral zone lesion on transrectal ultrasonography. Numerous benign processes can have similar transrectal ultrasound findings. We report 8 cases of transrectal ultrasound-guided prostatic biopsies of peripheral zone hypoechoic lesions that demonstrated prostatic intraepithelial neoplasia, a presumed premalignant lesion. Immunohistochemistry using an antibody directed against cytokeratins 5 and 14 was performed to exclude carcinoma. Of the men 2 had invasive carcinoma on repeat biopsy and 1 had carcinoma diagnosed on subsequent transurethral resection. Patients with prostatic intraepithelial neoplasia on biopsy of hypoechoic peripheral zone lesions merit careful monitoring.

Topics: Adenocarcinoma; Antibodies, Monoclonal; Biopsy; Diagnosis, Differential; Humans; Immunohistochemistry; Keratins; Male; Prostate; Prostatic Hyperplasia; Prostatic Neoplasms; Ultrasonography

Synthesis of individual keratins (Nos. 8 and 19) was shown to continue in the simple epithelium of tumor cells by application of monoclonal antibodies in 20 cases of different patterns of human colonic malignancies. No correlation between the synthesis and degree of cataplasia of said cells was found. The increase in manifestations of cellular and structural anaplasia in tumor was matched by the enhanced intensity of cells' staining with antibodies. Application of said procedure in oncomorphological practice helps reliably evaluate the real extent of tumor spreading and detects invasion which other microscopic methods fail to do.

Topics: Adenocarcinoma; Antibodies, Monoclonal; Humans; Intestinal Mucosa; Intestinal Neoplasms; Intestine, Large; Keratins

The purpose of this study is to demonstrate the localization and distribution of keratin-positive cells (KPC) in the various pathological types of prostatic cancer, and to investigate the correlation between the basal cell and KPC. The localization of keratin was immunohistochemically investigated in 20 benign prostatic hyperplasia (BPH) and 33 human prostatic adenocarcinomas by the indirect immunoperoxidase technique, using anti human keratin rabbit serum on frozen sections. In BPH, strongly positive staining for keratin was detected in the cytoplasm of basal cells. Glandular epithelial cells were positive. In the cancer sections, no KPC was observed in all 6 cases of the large acinar type, all 10 cases of the small acinar type and all 12 cases of the column and cord type. On the other hand, KPC remained around the cancer cell populations in all 10 cases of the cribriform type. In the fused gland type, KPC was localized in 3 of 9 cases and in the medullary type 3 of 7 cases. If KPC was regarded as the marker of the basal cell as shown in BPH, it would be speculated that the absence of KPC occurred in some type of prostatic cancer showed the disappearance of basal cell. That is, KPC could not be detected in large acinar, small acinar and column and cord type, while KPC remained completely or partially in the cribriform, fused gland and medullary type. These histochemical alteration would suggest the different degree of malignancy in the various histological type of prostatic cancer.

Topics: Adenocarcinoma; Humans; Immunoenzyme Techniques; Keratins; Male; Prostatic Hyperplasia; Prostatic Neoplasms

A case of C cell carcinoma of the thyroid with an unusual follicular growth pattern of the cancerous C cells is described. The primary tumor consisted of a mixture of medullary and follicular features while the metastatic foci in the lymph nodes and liver displayed only a medullary arrangement. Histochemical study disclosed numerous argyrophilic cells in both the follicular and medullary parts. These cells were immunohistochemically positive for calcitonin, calcitonin gene-related peptide (CGRP) and other peptides as well as carcinoembryonic antigen (CEA), but negative for thyroglobulin. Radioimmunoassay done on the tissue extract revealed a high content of calcitonin. Electron microscopy showed small intracytoplasmic secretory granules and, in the follicular lining cells, formation of microvilli. A minor component consisting of glandular structures has been reported in medullary carcinoma of the thyroid, suggesting a potentiality for glandular differentiation of the C cells. In equivocal cases, immunohistochemical examination for calcitonin and thyroglobulin is essential for accurate diagnosis of thyroid carcinoma.

Topics: Adenocarcinoma; Aged; Calcitonin; Calcitonin Gene-Related Peptide; Carcinoembryonic Antigen; Carcinoma; Female; Humans; Immunohistochemistry; Keratins; Microscopy, Electron; Phosphopyruvate Hydratase; Radioimmunoassay; Serotonin; Somatostatin; Thyroglobulin; Thyroid Neoplasms

Warthin's tumor (adenolymphoma) is a monomorphous adenoma of the salivary glands well characterized histologically. Its clinical evolution is almost invariably benign, the malignant change being extremely unusual. We present the case of a 67 year-old man with a right retromandibular tumor which has evolved over a two year period, with peripheral involvement of V, VI and VII cranial nerves on the same side, and direct invasion of intracranial structures. The biopsy revealed a classic adenolymphoma which shows foci of well differentiated adenocarcinoma. Transitional areas between benign and malignant epithelium were evident. In addition, histological findings support the hypothesis of the origin of adenolymphoma from epithelial ducts trapped in the regional lymphatic tissue.

Topics: Adenocarcinoma; Adenolymphoma; Aged; Carcinoembryonic Antigen; Humans; Immunoenzyme Techniques; Keratins; Male; Salivary Gland Neoplasms; Thyroglobulin

According to the World Health Organization histological classification of bronchial tumors, clear and giant cell carcinomas are two subtypes of large cell carcinoma. As clear and giant cells can also be observed in other types of bronchial carcinoma, we investigated the frequency of the finding of these cells in different histological types. The tumor size and degree of differentiation, the amount of necrosis and keratinization, and the presence of giant and clear cells were analyzed. Statistical analysis by X2 test showed (for all classified histological types of bronchial carcinomas, except small cell carcinoma) that: 1) larger tumors had a great quantity of giant cells (P less than 0.05; P less than 0.01), 2) large tumors had more clear cells (P less than 0.05; P less than 0.01) and 3) tumors with a greater amount of necrosis had a larger number of giant and clear cells (P less than 0.05; P less than 0.01). Findings of an identical cytological characteristic can cause some difficulty in determination of bronchial cancer.

Topics: Adenocarcinoma; Carcinoma, Bronchogenic; Carcinoma, Small Cell; Carcinoma, Squamous Cell; Female; Humans; Keratins; Lung Neoplasms; Male; Middle Aged; Necrosis; World Health Organization

In previous biochemical analyses, keratin 5 (Mr 58,000) has been detected in most mesotheliomas with epithelial component but not in pulmonary adenocarcinomas (Blobel et al., Am J Pathol 121: 235-247, 1985). In the present study, we have characterized a monoclonal antibody, AE14, as being selectively specific for keratin 5 (apart from the reactivity with certain hair proteins) as shown by immunoblotting of gel-electrophoretically separated proteins from various tissues. Immunohistochemical screening of a variety of normal human tissues, using immunoperoxidase microscopy on cryostat sections, revealed the binding of this antibody to the basal, immature cells of stratified squamous epithelia, to basal cells of pseudostratified epithelia, to some myoepithelial cells, thymic reticulum cells, certain pancreatic duct cells, as well as a variable subpopulation of mesothelial cells of the pleura and the peritoneum. In 12/13 epithelial and biphasic mesotheliomas of the pleura, heterogeneous but extended staining with antibody AE14 was seen whereas 21 pulmonary adenocarcinomas were negative or, in six of these cases, showed staining of only a few cells. Among carcinomas from other sites, colonic adenocarcinomas and renal cell carcinomas were negative whereas limited staining was found in some pancreatic adenocarcinomas. It is suggested that antibody AE14 may be useful, as a defined polypeptide-specific reagent, in the histologic distinction between mesotheliomas and most adenocarcinomas. Furthermore, the expression patterns of keratin 5 as detected by antibody AE14 in various normal and malignant epithelial tissues are discussed, particularly their relation to processes of squamous metaplasia and their indication of phenotypic tumor heterogeneity.

Topics: Adenocarcinoma; Antibodies, Monoclonal; Diagnosis, Differential; Epithelium; Female; Hair; Humans; Immunoblotting; Immunoenzyme Techniques; Immunohistochemistry; Keratins; Male; Mesothelioma

42 renal cell carcinomas and 1 oncocytoma were investigated by means of immunofluorescence (including double immunofluorescence) using a panel of mono- and polyclonal antibodies to vimentin and cytokeratins. In all tumors except chromophobe cell renal carcinoma (CCRC) and oncocytoma generally a coexpression of vimentin and cytokeratins could be demonstrated; however, the intermediate filament expression was often very heterogeneous with regard to the distribution of vimentin and cytokeratins in general, depending on the mono- and polyclonality of the antibodies and on the areas of a tumor investigated. In CCRC and oncocytoma all tumor cells contained cytokeratin filaments. In addition, as revealed by double immunofluorescence, in only occasional tumor cells we could demonstrate vimentin.

Topics: Adenocarcinoma; Antibodies, Monoclonal; Carcinoma, Renal Cell; Fluorescent Antibody Technique; Humans; Intermediate Filaments; Keratins; Kidney Neoplasms; Vimentin

A composite tumor of the gastric antrum composed of areas of adenocarcinoma and poorly differentiated carcinoid is described, with histochemical and immunohistochemical documentation of endocrine and nonendocrine differentiation. The neoplasm maintained a composite architecture both within the site of origin and in lymph node metastases. The adenocarcinoma displayed a predominantly tubular architecture with focal sheets of clear cells. The poorly differentiated carcinoid was argyrophilic, chromogranin immunoreactive, and focally serotonin immunoreactive, and contained keratin intermediate filaments in a distinctive distribution suggestive of endocrine differentiation. Among the tumors of the carcinoma-carcinoid spectrum, the composite tumor is less common than either carcinomas with interspersed endocrine cells or carcinoids with interspersed nonendocrine cells.

Topics: Adenocarcinoma; Carcinoid Tumor; Chromogranins; Humans; Immunohistochemistry; Intermediate Filaments; Keratins; Male; Middle Aged; Stomach Neoplasms

S-100 protein has been used as a marker of various lesions, including peripheral nerve sheath, cartilaginous and salivary gland tumors, chordomas, histiocytosis X, and melanomas, among others. The list of neoplasms that can express S-100 protein continues to expand. It has been suggested that staining for S-100 protein may be of aid in the differential diagnosis of amelanotic melanoma versus poorly differentiated tumors. Three hundred fifty primary and metastatic adenocarcinomas from various sites were immunostained for S-100 protein with the use of a commercially available polyclonal antibody. Forty-two percent of the adenocarcinomas tested expressed S-100 protein to varying degrees. The relative incidence of S-100-positive tumors varied with the primary sites, some expressing S-100 protein more often than others. A primary neoplasm able to express S-100 protein was usually associated with metastatic foci also expressing this marker. However, occasionally, a primary S-100-positive tumor was associated with metastasis that lacked expression of S-100. This study emphasizes the importance of testing for a panel of tumor markers in the evaluation of poorly differentiated tumors and cautions on possible difficulties that may arise in the interpretation of immunocytochemistry results.

Topics: Adenocarcinoma; Humans; Keratins; Melanoma; S100 Proteins

In order to differentiate between malignant pleural mesothelioma and adenocarcinoma of the lung, the glycoconjugate profiles of 6 reactive mesothelial lesions, 23 mesotheliomas (17 epithelial, 1 desmoplastic, 2 biphasic, and 3 fibrous types), and 28 well-differentiated pulmonary adenocarcinomas were evaluated with the use of 8 lectins in addition to anti-carcinoembryonic, anti-keratin and anti-epithelial membrane antigen. Formalin-fixed, paraffin-embedded tissues were stained with the avidin-biotin peroxidase complex method. Reactions of wheat germ (WGA) and peanut (PNA) agglutinin with neuraminidase treatment lectins were positive in 5 of 6 (83%) and 3 of 6 (50%) cases, respectively, in reactive mesothelial lesions. Thirteen of 23 (57%) malignant mesotheliomas of the pleura showed a positive reaction for WGA and PNA with neuraminidase treatment; other lectins were low-positive, below 9%. In contrast, pulmonary adenocarcinomas showed positive reactions in 27 of 28 cases (96%) for PNA, 26 of 28 (93%) for Ricinus communis (RCA-I), 25 of 28 (89%) for WGA, and 22 of 28 (79%) for succinylated WGA (SucWGA). The findings suggest that malignant pleural mesothelioma and pulmonary adenocarcinoma have consistent and distinct glycoconjugate profiles, and that stains for RCA-I and SucWGA may be useful for differential diagnosis.

Topics: Adenocarcinoma; Carcinoembryonic Antigen; Diagnosis, Differential; Histocytochemistry; Humans; Keratins; Lectins; Lung Neoplasms; Membrane Glycoproteins; Mesothelioma; Mucin-1; Pleural Neoplasms

Forty nasopharyngeal carcinomas (NPC) were studied by immunohistochemistry using an antibody to involucrin and the following three keratin antibodies: (1) an antibody to low molecular weight keratin reactive with nonsquamous epithelium, (2) a high molecular weight keratin antibody reactive with suprabasal squamous epithelium, and (3) a keratin antibody reactive with full thickness stratified epithelium. In its pattern of reactivity, the last antibody overlaps the low and high molecular weight keratin antibodies and is used as a broad spectrum keratin antibody. By World Health Organization (WHO) classification, the cases in this article included eight keratinizing squamous cell carcinomas, eight nonkeratinizing carcinomas, 20 undifferentiated carcinomas, and four adenocarcinomas. The antibody to broad spectrum keratin had an overall sensitivity of 87.5% and was positive in all eight keratinizing squamous cell carcinomas, seven nonkeratinizing carcinomas (87.5%), 18 undifferentiated carcinomas (90%), and two adenocarcinomas (50%). Low molecular weight keratin antibody stained one additional NPC, which was negative when broad spectrum keratin antibody was used. Involucrin and high molecular weight keratin antibodies demonstrated near parallel staining in all histologic classes; there was marked localization to areas of squamous differentiation. While involucrin is a marker for foci of greater squamous differentiation, broad spectrum keratin antibody may aid in the diagnosis of all histologic subtypes of NPC.

Topics: Adenocarcinoma; Adolescent; Adult; Aged; Antibody Specificity; Carcinoma; Carcinoma, Squamous Cell; Female; Humans; Immunoenzyme Techniques; Keratins; Male; Middle Aged; Nasopharyngeal Neoplasms; Protein Precursors

Eighty five ovarian epithelial and non-epithelial tumours were studied by peroxidase histochemical staining for their reactivity with six monoclonal human milk fat globule (HMFG) antibodies, peanut agglutinin (PNA) lectin, and a monoclonal cytokeratin antibody. HMFG IIIC12 and cytokeratin antibodies distinguished epithelial from non-epithelial tumours. The staining patterns of mucinous and serous tumours were essentially different from each other; poorly differentiated anaplastic carcinomas showed similar antigenic content to that of the serous cystadenocarcinomas. Furthermore, staining with PNA lectin and HMFG antibodies was useful in distinguishing clear cell carcinomas from other malignant epithelial tumours of the ovary.

Topics: Adenocarcinoma; Antibodies, Monoclonal; Cystadenocarcinoma; Epitopes; Female; Granulosa Cell Tumor; Humans; Immunoenzyme Techniques; Keratins; Lectins; Membrane Glycoproteins; Mucin-1; Ovarian Neoplasms; Peanut Agglutinin

In order to improve the accuracy of diagnosis and subtyping of pulmonary adenocarcinomas, immunohistochemical studies were carried out on 105 adenocarcinomas of the lung procured from both surgery and autopsy. Avidin-biotin-peroxidase complex methods were used for identifying keratin, vimentin, carcinoembryonic antigen (CEA), and secretory component (SC) on deparaffinized tissue sections. Keratin was positive in 29% of well differentiated adenocarcinoma, significantly lower than in moderately or poorly differentiated adenocarcinoma. Likely, vimentin was positive in 27% of well differentiated adenocarcinoma, significantly lower than in moderately or poorly differentiated adenocarcinoma. SC was positive in 66% of well differentiated adenocarcinoma, significantly higher than in moderately or poorly differentiated adenocarcinoma. In the subtyping of well differentiated adenocarcinomas, keratin showed higher positive results in the bronchial surface epithelial, goblet cell, and bronchial gland types than in the Clara cell or type II alveolar epithelial cell type. These findings suggest that immunoperoxidase stains for keratin, vimentin, and SC may be useful for determining the degree of differentiation of adenocarcinomas of the lung as well as for subtyping of well differentiated pulmonary adenocarcinomas.

Topics: Adenocarcinoma; Antibodies, Monoclonal; Biomarkers, Tumor; Carcinoembryonic Antigen; Humans; Immunoenzyme Techniques; Immunohistochemistry; Keratins; Lung Neoplasms; Secretory Component; Vimentin

The expression and distribution of cytokeratins and vimentin in fifteen malignant salivary neoplasms were examined by immunocytochemical techniques using, five monoclonal antibodies (mAbs) against different epitopes of Cytokeratins (CKs) (mAbs PKK1, PKK2, and PKK3, identifying CKs 8, 18 and 19, CKs 7, 17 and 19, and CK 18, respectively) and Vimentin (mAbs V9 and V24). Antibody PKK1 gave strong reactions in all neoplasms showing the similarity of these tumours to other digestive system adenocarcinomas. Three general staining patterns of the neoplasms were recognized with respect to the reactivity of mAbs PKK2, PKK3, and V9. Mucoepidermoid cancer, salivary duct carcinoma and a clear cell carcinoma had a higher relative content of CKs 7, 17 and 19 than of CK 18. Adenoid cystic carcinoma showed the same CK pattern but in the periphery of the tumour cords vimentin was readily detected. In two acinic cell carcinomas, the relative content of CK 18 was higher than that of CKs 7, 17 and 19. Furthermore vimentin was expressed in the tumour cells. However, one mucoepidermoid carcinoma showed vimentin expression and two acinic cell carcinomas were vimentin negative and more reactive for PKK2 than PKK3. Pecularities in CK expression were seen: squamous areas of mucoepidermoid carcinomas were stained by mAb PKK3 although CK 18 is not present in normal squamous epithelia or in squamous cell carcinomas of tongue and skin. In conclusion, the different salivary neoplasms can be distinguished on basis of IFP content. Such a differentiation fits with current theories of histogenesis, i.e. vimentin is seen in tumours presumed to arise from intercalated duct reserve cells, whilst the vimentin negative neoplasms would be expected to arise in excretory duct reserve cells.

Topics: Adenocarcinoma; Adolescent; Aged; Antibodies, Monoclonal; Carcinoma; Carcinoma, Adenoid Cystic; Female; Humans; Keratins; Male; Middle Aged; Salivary Gland Neoplasms; Vimentin

A human cell line has been established from a renal adenocarcinoma rib metastasis of a 58-y-old male. This cell line has been maintained in continuous culture for 20 mo. through more than 50 passages. It displays simultaneous expression of the intermediate filaments cytokeratin and vimentin. Flow cytometric analysis of DNA content reveals a major hyperdiploid population.

Topics: Adenocarcinoma; Cell Line; Flow Cytometry; Fluorescent Antibody Technique; Gene Expression Regulation; Humans; Keratins; Kidney Neoplasms; Male; Middle Aged; Vimentin

The efficacy of utilizing immunocytochemical staining of prostatic basal cells in separating benign from malignant prostatic epithelium was tested by staining fine-needle aspiration smears of prostatic lesions with the monoclonal antibody EAB-903. This antibody has been shown to stain keratin subtypes present in the prostate only in basal cells. The study utilized 12 benign, nine malignant, and four suspicious-for-carcinoma cases. Ten of 12 benign cases showed an intermingled pattern of staining, which was not found in the malignant cases. Our findings indicate that this distinctive pattern of staining may assist in distinguishing benign epithelium from well-differentiated prostatic adenocarcinoma.

Topics: Adenocarcinoma; Antibodies, Monoclonal; Biopsy, Needle; Epithelium; Histocytochemistry; Humans; Immunoenzyme Techniques; Keratins; Male; Prostatic Neoplasms

An immunocytochemical investigation has been performed on 83 common epithelial tumours of the ovary, to ascertain their capability of expressing vimentin in addition to cytokeratins. Our results demonstrate that vimentin coexpression is related to the tumour histotype and -to a lesser extent- to the degree of differentiation of malignant variants. Indeed, most serous tumours (80%), some endometrioid adenocarcinomas, and all the clear cell carcinomas investigated exhibited a variable number of neoplastic cells co-synthesizing the two distinct intermediate filament (IF) proteins, whereas only one of 29 mucinous tumours and none of the Brenner tumours displayed vimentin-immunoreactive cells. Moreover, in serous and endometrioid carcinomas, the expression of vimentin was related to the degree of tumour differentiation, being consistently identifiable in the better differentiated cases. The immunocytochemical findings of a parallel investigation on IF expression in the ovarian coelomic epithelium and in the müllerian-derived epithelia of the female genital tract allowed us to ascertain that ovarian epithelial tumours (with the possible exception of poorly differentiated carcinomas) maintain the pattern of IF expression typical of the normal epithelia. This investigation emphasizes the usefulness of IF typing as a tool for the more precise characterization of the origin and differentiation of human neoplasms.

Topics: Adenocarcinoma; Brenner Tumor; Carcinoma; Cystadenocarcinoma; Cystadenoma; Endometriosis; Epithelium; Female; Genitalia, Female; Humans; Immunohistochemistry; Keratins; Ovarian Neoplasms; Ovary; Vimentin

Immunoperoxidase stains were performed on normal and neoplastic tissue from prostate, colon, thyroid, lung, nerve, uterus, and placenta embedded in both plastic (glycolmethacrylate [GMA]) and paraffin. Positive results in plastic section were obtained for carcinoembryonic antigen (CEA), keratin, epithelial membrane antigen (EMA), thyroglobulins, S-100, prostate-specific antigen, human chorionic gonadotrophin (HCG), and beta-HCG. More delicate staining with more precise localization of antigens is noted. Superior (paraformaldehyde) fixation and cold processing followed by GMA polymerization (4 degrees C) allow for optimum antigen survival. After fixation, tissue processing involves a series of 0.1 mol/L phosphate buffer rinses with sucrose and ammonium chloride in a conventional dip-and-dunk processor placed in a 4 degrees C cold room. Acetone dehydrations are used before GMA infiltration, cold polymerization, and sectioning. Before immunoperoxidase staining, the plastic section is digested in .25% bovine trypsin for ten minutes. The immunoperoxidase methods described can be useful when small biopsies are routinely embedded in plastic to obtain improved histologic (hematoxylin-eosin) sections. There may also be research applications in quantifying antigen expression in benign, dysplastic, and neoplastic tissues by examining the stains under high power.

Topics: Adenocarcinoma; Antigens; Carcinoembryonic Antigen; Colonic Neoplasms; Humans; Immunoenzyme Techniques; Keratins; Male; Membrane Glycoproteins; Methacrylates; Mucin-1; Paraffin; Placenta; Prostatic Hyperplasia; Thyroglobulin; Thyroid Gland

Ten examples of giant cell carcinoma of the lung were examined by immunohistochemistry for expression of keratin and vimentin intermediate filaments and for epithelial membrane antigen (EMA). Six cases were also examined electron microscopically. Keratin expression and, to a lesser extent, EMA immunoreactivity were reduced in comparison with better differentiated forms of lung carcinoma. Vimentin expression was increased, often taking the form of strong paranuclear staining. This may correspond to dense paranuclear aggregates of intermediate filaments seen ultrastructurally. Desmosomes were absent or sparse in most tumours. We propose that giant cell carcinoma arises by a process of dedifferentiation. The resulting loss of epithelial features gives rise to neoplastic cells which have features in common with some forms of sarcoma.

Topics: Adenocarcinoma; Antigens; Carcinoma; Cell Differentiation; Cell Transformation, Neoplastic; Desmosomes; Humans; Keratins; Lung Neoplasms; Membrane Glycoproteins; Microscopy, Electron; Microvilli; Mucin-1; Vimentin

The association of certain human papillomavirus (HPV) types with the majority of human cervical carcinomas suggests a role for the virus in the development of this type of cancer. In this paper, we have examined the transforming properties of several HPV types where the early region genes of the virus are under the control of a strong heterologous promoter and show that major differences exist between the HPV types in their ability to transform primary rat kidney epithelial cells in conjunction with an activated ras oncogene. Those HPV types most commonly found in carcinomas--types 16, 18, 31 and 33--are capable of co-operating with ras to transform primary cells, but those types most commonly found in benign lesions--types 6 and 11--are not. We further demonstrate that the E7 gene of HPV16 by itself is sufficient to co-operate with activated ras to produce transformed cells which are tumorigenic in immunocompetent animals.

Topics: Adenocarcinoma; Animals; Cell Transformation, Viral; Cells, Cultured; DNA, Recombinant; DNA, Viral; Epithelium; Genes, Viral; Keratins; Kidney; Neoplasm Proteins; Oncogene Proteins, Viral; Oncogenes; Papillomaviridae; Rats

Human lymphocytes derived from a lymph node draining a primary breast adenocarcinoma were fused with the mouse myeloma P3X63Ag8.653 to generate human-mouse hybridomas secreting human monoclonal antibodies (MAbs) to tumor associated antigens (TAAs). One of the resulting human MAbs, YBB 190 (IgM) is described. Enzyme-linked immunosorbent assays (ELISA) employing membrane and cytosol fractions of human tissues demonstrated YBB 190 reactivity against cytosol but not membrane components of malignant and normal epithelial tissues. When tested by an indirect immunoperoxidase staining method against fresh frozen human tissue sections, YBB 190 reacted with malignant cells in 26 of 28 epithelial cancers and with normal epithelia in 11 different benign tissues. Preliminary western blot antigen characterization indicated that YBB 190 recognizes cytokeratin intermediate filaments, or a protein that is closely associated with cytokeratins. These data indicate that B cells with specificity for intermediate filaments are present in tumor draining lymph nodes. Our findings provide insights into the nature of potential autoimmune responses in cancer patients and suggest that improved tumor directed sensitization procedures may be required to more effectively utilize lymphocytes from tumor draining lymph nodes to generate therapeutically useful human MAbs to TAAs.

Topics: Adenocarcinoma; Antibodies, Monoclonal; Antigens, Neoplasm; Breast Neoplasms; Female; Humans; Immunoenzyme Techniques; Keratins; Lymph Nodes

Retinoic acid has marked effects on the growth, morphological features, and biological markers of a neoplastic human salivary intercalated duct cell clone in culture, whereas the cell clone was not affected by other retinoids such as retinol and retinal. A cell clone with ultrastructure and biological markers specific to the intercalated duct cells of human salivary glands was cultivated in the presence of retinoic acid. Major alterations, such as expression of tonofilaments, Mr 68,000 cytokeratin, and involucrin, were observed in those cells with a phenotype similar to that of keratinizing squamous cells. In addition, the coexpression of Mr 68,000 cytokeratin and carcinoembryonic antigen in these altered cells was found. Both the anchorage-independent and anchorage-dependent growths were markedly suppressed in the presence of retinoic acid. After the removal of retinoic acid from the culture, the treated cells returned rapidly to the phenotype of the untreated cells. These findings indicate that reversible differentiation into the keratinizing squamous cells of a neoplastic human salivary intercalated duct cell clone occurs in growth medium containing retinoic acid.

Topics: Adenocarcinoma; Biomarkers, Tumor; Carcinoembryonic Antigen; Cell Line; Fluorescent Antibody Technique; Humans; Immunoenzyme Techniques; Keratins; Microscopy, Electron; Molecular Weight; Salivary Gland Neoplasms; Tretinoin

Topics: Adenocarcinoma; Humans; Keratins; Lung Neoplasms

A panel of human lung carcinoma lines was studied with respect to hormone production and intermediate filament expression to distinguish between endodermal and neuroendocrine differentiation. An index of the degree of neuroendocrine differentiation of each line was derived from the presence or absence of hormone production, cytokeratins, neurofilaments and an embryonic endodermal cell marker, which allowed identification of three groups showing high, intermediate or low neuroendocrine expression. This grouping correlated well with the in vitro radiosensitivity of the lines, those expressing pure neuroendocrine features being significantly more radiosensitive than those with an endodermal phenotype, with the intermediate group having intermediate sensitivity. Use of such an index might predict those patients likely to benefit from the use of radiotherapy in their management.

Topics: Adenocarcinoma; Adrenocorticotropic Hormone; Calcitonin; Carcinoma, Small Cell; Carcinoma, Squamous Cell; Cell Line; Humans; Intermediate Filaments; Keratins; Lung Neoplasms; Radiation Tolerance; Vasopressins

An immuno-histological study of metastatic adenocarcinoma has revealed the following results. Metastatic adenocarcinomas of the lymph-node of pulmonary and colonic origin were positive for CEA and negative for lysozymes, and those from gastric, pancreatic, and gallbladder tumors were positive CEA and lysozymes, and those from gastric and pancreatic tumors were positive for the secretory component. The prostate specific antigen was exclusively positive for metastatic prostatic adenocarcinoma with a low frequency and prostate acid phosphatase had many false positive results. Thyroglobulin was found to be positive only to colloid. Lactalbumin showed no specificity to metastatic breast adenocarcinoma. For achieving the final diagnosis of a primary tumor, its location in lymph nodes, the clinical history and the results of other examinations must also be taken into consideration.

Topics: Adenocarcinoma; Biomarkers, Tumor; Carcinoembryonic Antigen; Colonic Neoplasms; Humans; Keratins; Lactalbumin; Lung Neoplasms; Lymphatic Metastasis; Muramidase; Neoplasms, Unknown Primary; Secretory Component

Prostatic samples from 30 hyperplastic prostates and 61 prostatic adenocarcinomas were examined for vimentin and cytokeratins. The co-expression of cytokeratins and vimentin was found in all benign prostatic epithelium and in 83% of adenocarcinomas. Benign prostatic epithelium showed vimentin intermediate filaments distinctively distributed in the basal regions and as paranuclear sheaves along the long axis of the cell. This pattern of vimentin staining was seen in adenocarcinomas with low Gleason scores, whereas high-grade tumours showed intense diffuse perinuclear staining.

Topics: Adenocarcinoma; Epithelium; Histocytochemistry; Humans; Keratins; Male; Prostatic Hyperplasia; Prostatic Neoplasms; Vimentin

Keratin patterns in benign prostatic hyperplasia and prostatic adenocarcinoma were evaluated using frozen and formalin-fixed tissue. Five different commercially available antibodies were used. In frozen tissue basal cells of benign acinic and ductal structures stained with PKE, and to a lesser degree with MCA 144, CAM 5.2 and RCK 102. Luminal cells stained with MCA 144, CAM 5.2, RCK 102 and to a lesser degree with PKE. In formalin-fixed tissue basal cells stained exclusively with Z622, predominantly with PKE and RCK 102, and to lesser degree with MCA 144 and CAM 5.2. Luminal cells stained with MCA 144 and CAM 5.2 and to some degree with PKE and RCK 102, while Z622 stained luminal cells of ductal epithelium weakly, but acinic cells not at all. Luminal phenotype dominated in prostatic adenocarcinomas which were stained with MCA 144 and CAM 5.2 irrespective of differentiation, and independently of whether frozen or formalin-fixed tissue was used. However, the different keratin phenotype of benign and malignant prostatic epithelium depends to some degree on the immunohistochemical procedures used. In diagnostic pathology Z622 may be able to separate intraluminal neoplastic lesions from invasive carcinoma, a problem particularly seen when cribriform growth pattern is found.

Topics: Adenocarcinoma; Antibodies, Monoclonal; Humans; Immunoenzyme Techniques; Keratins; Male; Prostate; Prostatic Hyperplasia; Prostatic Neoplasms

An antiserum to carcinoembryonic antigen (CEA) and a monoclonal antibody to cytokeratin 19 (CK 19) were studied for their suitability as diagnostic reagents for the differential diagnosis of primary and secondary malignant epithelial tumours of the liver, on paraffin sections. With the antiserum to CEA, positive bile canalicular structures were found in 60 per cent of the hepatocellular carcinomas. All the cholangiocarcinomas and 66.6 per cent of the metastatic carcinomas were positive for CEA, without displaying a canalicular staining pattern. All the hepatocellular carcinomas were negative for CK 19. All the cholangiocellular carcinomas and the metastatic carcinomas were positive for CK 19. This staining profile may prove helpful in difficult diagnostic cases.

Topics: Adenocarcinoma; Adenoma, Bile Duct; Carcinoembryonic Antigen; Carcinoma, Hepatocellular; Diagnosis, Differential; Humans; Keratins; Liver Neoplasms

Topics: Adenocarcinoma; Carcinoma; Carcinoma, Squamous Cell; Humans; Immunohistochemistry; Intermediate Filament Proteins; Keratins; Nasopharyngeal Neoplasms; Staining and Labeling; Vimentin

The clinicopathologic and immunohistochemical features of 16 pure adenocarcinomas primary in the urinary bladder were reviewed. Only 3 patients were found to have disease confined to the urinary bladder. Of 13 cases with follow-up only 3 are free of disease. Histologically, the tumors were classified as signet ring cell (3), colloid (3), colonic type (5), clear cell (1), and not otherwise specified (NOS, 4). Immunohistochemically, all tumors but one colloid carcinoma were immunoreactive for cytokeratin and epithelial membrane antigen, and most tumors were likewise immunoreactive for carcinoembryonic antigen. Eight cases were immunoreactive for Leu M1 antigen. Prostate specific antigen, S-100 protein, and placental alkaline phosphatase were uniformly negative. No correlation between immunohistochemical profile and histologic type or clinical outcome was found. The utility of immunohistochemistry and other pathologic findings is reviewed.

Topics: Adenocarcinoma; Adenocarcinoma, Mucinous; Adult; Aged; Carcinoembryonic Antigen; Female; Humans; Keratins; Male; Membrane Proteins; Middle Aged; Mucin-1; Urinary Bladder; Urinary Bladder Neoplasms

The immunohistochemical profile (i.e., carcinoembryonic antigen, keratin proteins, epithelial membrane antigen, human milk fat globule-derived antigen, and mucin) of paraffin-embedded cell blocks of 20 malignant effusions from patients with malignant mesothelioma was compared with that of 39 malignant effusions from patients with metastatic adenocarcinoma to determine whether these markers distinguished between these tumor types. Twenty-three adenocarcinomas (59 per cent) stained for mucin. Immunoreactivity for carcinoembryonic antigen (CEA) was observed in 28 adenocarcinomas (72 per cent). All were immunoreactive for keratin proteins, and 29 adenocarcinomas (74 per cent), including seven that were mucin and CEA negative and exhibited a "peripheral predominant" staining pattern for keratin proteins. By contrast, none of the mesotheliomas stained for mucin or for CEA, and, although all were immunoreactive for keratin proteins, none demonstrated a peripheral predominant pattern of staining. Epithelial membrane antigen and milk fat globule-derived antigen were identified in the majority of both mesotheliomas and adenocarcinomas. Neither staining intensity nor pattern of reactivity of these markers clearly distinguished the tumors. This study of cell blocks of serous effusions suggests that staining for mucin, immunoreactivity for carcinoembryonic antigen, and a peripheral predominant pattern of reactivity for keratin proteins represent highly characteristic markers of adenocarcinomas, which identify the majority of these tumors (38 of 39) and allow their distinction from malignant mesotheliomas.

Topics: Adenocarcinoma; Antigens; Carcinoembryonic Antigen; Female; Humans; Immunoenzyme Techniques; Keratins; Male; Membrane Proteins; Mesothelioma; Middle Aged; Mucin-1; Mucins; Pleural Effusion; Pleural Neoplasms

A panel of seven monoclonal antiepithelial antibodies of different specificities, including anticytokeratin, human milk fat globule membrane, C, and carcinoembryonic antigen (CEA) were used with the alkaline phosphatase-antialkaline phosphatase (APAAP) immunostaining technique to determine their value in the differentiation between benign and malignant mesothelial cells and lung carcinoma in histological preparations. The anticytokeratin antibody reacted strongly with all cases of reactive mesothelium, mesothelioma, and lung carcinoma. Antibodies to human milk fat globule membrane and the Ca antigen stained mesothelioma and carcinoma and 43% of cases of reactive mesothelium. Staining for carcinoembryonic antigen was not detected in reactive mesothelium or mesothelioma, but was present in most of the lung carcinomas. CEA seemed to be the single most useful marker in distinguishing carcinoma from mesothelioma in that a positive reaction for CEA would indicate carcinoma rather than mesothelioma.

Topics: Adenocarcinoma; Antibodies, Monoclonal; Antigens, Neoplasm; Antigens, Tumor-Associated, Carbohydrate; Carcinoembryonic Antigen; Carcinoma; Diagnosis, Differential; Epithelium; Humans; Immunoenzyme Techniques; Keratins; Lung Neoplasms; Membrane Proteins; Mesothelioma; Mucin-1

A case of Merkel cell carcinoma that developed on the right cheek of a 77-year-old woman is reported. The diagnosis was ultrastructurally made by demonstrating dense-core granules in the cytoplasm of the tumor cells. Immunohistochemically, the tumor cells were shown to possess simple epithelia-type keratin intermediate filaments, but no neurofilaments. This finding was in accordance with that obtained on normal Merkel cells. No bioactive peptides examined could be detected in the tumor cells. Typing of intermediate filaments in tumor cells may be one of the important markers, along with the ultrastructural findings, in diagnosing Merkel cell carcinoma.

Topics: Adenocarcinoma; Aged; Cheek; Cytoskeleton; Epithelium; Female; Fluorescent Antibody Technique; Histocytochemistry; Humans; Intermediate Filaments; Keratins; Skin Neoplasms

Sections of primary lung carcinomas, lung metastases, mesotheliomas, and lung metastases of some rare mesenchymal tumors were incubated with different cytokeratin (CK), vimentin, desmin, and tissue polypeptide antigen (TPA) antibodies and with antibodies reactive with different hormones (ACTH, PTH, alpha-HCG, Calcitonin CT), CEA, carcinoma-associated antigen (CA1), secretory component (SC), neuron-specific enolase (NSE), alpha-1-antitrypsin (alpha-1-AT), lysozyme (lyso), and S-100 protein (S 100). CK antibodies derived from a 49 kD (reactive with simple epithelia [SE]) and a 67 kD CK polypeptide fraction (reaction with complex epithelia [CE] were useful differentiation markers for the four major groups of lung carcinomas. In one half of small cell carcinomas a positive reaction with NSE antibodies was found. S 100 and SC were good markers for papillary and bronchioloalveolar adenocarcinomas, whereas CEA was less important because of its reactivity with different types of lung carcinomas. To discern clear cell carcinomas of lung and renal origin a positive reaction with vimentin antibodies (some renal but not lung types) and with CA1 (no renal but all lung types) seemed to be useful. All hormone antibodies were of no importance as markers for difficult differential diagnosis, because positive reactivities were found in cases from every major carcinoma group. In addition, a Ca2+-activated adenosine triphosphatase (ATPase) was found in mesotheliomas but not in papillary adenocarcinomas.

Topics: Adenocarcinoma; Carcinoembryonic Antigen; Carcinoma, Small Cell; Carcinoma, Squamous Cell; Cell Differentiation; Desmin; Diagnosis, Differential; Histocytochemistry; Hormones; Humans; Immunologic Techniques; Keratins; Kidney Neoplasms; Lung Neoplasms; Mesothelioma; Muramidase; Neoplasm Metastasis; Peptides; Phosphopyruvate Hydratase; Pleural Neoplasms; S100 Proteins; Secretory Component; Tissue Polypeptide Antigen; Vimentin

Five established cell lines of human endometrium, two of normal endometrium and three of proven tumorigenicity, have been compared in terms of morphology and chromosomal numbers. Each of the five cell lines was then analyzed using immunocytochemical techniques to show that the epithelial and stromal elements could be separately identified. Antibodies directed against cytokeratin and desmoplakins were used to identify epithelial elements and antibodies directed against fibronectin were used as a marker for stroma. These results were then confirmed using Western blot analysis. We conclude that cell lines of human endometrium in culture can be differentiated as being of epithelial or stromal origin. Cell lines derived from reportedly normal human endometrium exhibit a stromal phenotype with a normal karyotype, whereas cells of tumorigenic human endometrial cell lines exhibit an epithelial phenotype and abnormal karyologic characteristics.

Topics: Adenocarcinoma; Antibodies, Monoclonal; Carcinoma; Cell Line; Cytoskeleton; Desmosomes; Endometrium; Epithelium; Female; Fibroblasts; Fibronectins; Fluorescent Antibody Technique; Humans; Immunosorbent Techniques; Keratins

A case of adenosquamous carcinoma of the gallbladder showing extensive spindle transformation is presented. By light microscopy, areas showing interwoven fascicles of fusiform, poorly differentiated cells closely resembling a sarcoma were seen to merge imperceptibly with areas showing more obvious glandular and squamous cell features. Immunocytochemistry utilizing tissue-specific antibodies against intermediate filaments demonstrated the exclusive presence of prekeratin antibodies in both components of the tumour, thus establishing the epithelial nature of this neoplasm. The importance of immunological phenotyping in the differential diagnosis of epithelial tumours of the gallbladder showing pseudosarcomatous features is underscored.

Topics: Adenocarcinoma; Antibodies, Monoclonal; Carcinoma; Carcinoma, Squamous Cell; Female; Gallbladder Neoplasms; Humans; Keratins; Middle Aged

Topics: Adenocarcinoma; Breast Neoplasms; Carcinoma, Squamous Cell; Carcinoma, Transitional Cell; Cytoskeleton; Diagnosis, Differential; Epithelium; Female; Gastrointestinal Neoplasms; Humans; Intermediate Filament Proteins; Intermediate Filaments; Keratins; Lung Neoplasms; Neoplasms; Skin Neoplasms; Urinary Bladder Neoplasms; Uterine Cervical Neoplasms

Lung cancers were investigated for their heterogeneity as expressed by their immunoreactivity for cytokeratins and neurofilament proteins, as well as for the neuroendocrine differentiation antigen MOC-1. Using broadly cross-reacting antibodies, cytokeratins were detected in nearly all cases of lung carcinomas. Keratinization could be detected only in cases of moderately to well-differentiated squamous cell carcinoma (SQC) using a monoclonal antibody to cytokeratin 10, while a monoclonal antibody reactive with cytokeratin 18, and specific for glandular epithelia, reacted with adenocarcinomas, small cell lung carcinomas (SCLC), and lung carcinoids. In SQC this antibody could detect non-squamous cell differentiation, showing increasing numbers of positive cells with decrease of histologically detectable SQC differentiation. Cells positive for neurofilaments were demonstrated in some of the poorly differentiated SQCs and in some of the cases of SCLC, possibly representing the variant type of SCLC. Also in some of the lung carcinoids neurofilament proteins were present, colocalizing with cytokeratins. MOC-1 was present in all SCLC and lung carcinoids. This antibody could also detect neuroendocrine differentiation in all combined small cell carcinomas, in one poorly differentiated adenocarcinoma, and in about 30% of the poorly differentiated SQCs. Therefore, lung cancer heterogeneity can be detected using a panel of well-defined antibodies to intermediate filaments in combination with the MOC-1 antibody. The use of these antibodies in diagnosis can have prognostic significance and can lead to a more selective therapeutic approach.

Topics: Adenocarcinoma; Antibodies; Antigens, Neoplasm; Carcinoid Tumor; Carcinoma, Small Cell; Carcinoma, Squamous Cell; Cross Reactions; Cytoskeleton; Histocytochemistry; Humans; Immunoenzyme Techniques; Intermediate Filaments; Keratins; Lung Neoplasms

Monoclonal antibody based immunohistochemistry is a very powerful tool for the establishment of a pathological diagnosis of lung cancer. Applying a panel of intermediate filament antisera and an antibody recognizing neuroendocrine differentiation we have tested about 240 human lung tumors and 15 human lung tumor cell lines. Our results can be summarized as follows: a differential diagnosis between neuroendocrine and non-neuroendocrine lung tumors can be obtained by the application of the monoclonal antibody MOC-1 directed against neuroendocrine antigens. Immunohistochemistry can lead to a better recognition of lung tumor heterogeneity within the established histologies. Examples of this phenomenon are: the presence of neuroendocrine and/or neural components within non-neuroendocrine tumors. The presence of squamous cell or adenocarcinomatous differentiation in non-SCLC can be detected by chain specific anti-cytokeratin antibodies. The degree of differentiation towards the variant type within SCLC can be detected by the monoclonal antibody directed against neurofilaments. lung cancer cell lines can serve as an in vitro model for immunohistochemical studies on different lung cancer subtypes.

Topics: Adenocarcinoma; Antibodies, Monoclonal; Carcinoma, Small Cell; Carcinoma, Squamous Cell; Cell Differentiation; Cells, Cultured; Diagnosis, Differential; Humans; Intermediate Filaments; Keratins; Lung Neoplasms

Metastatic poorly differentiated carcinomas often represent diagnostic difficulties in surgical pathology. Therefore, the expression of cytokeratins of different molecular weights (54, 57, and 66 kd) were compared in paraffin sections of 37 primary carcinomas with their lymph node metastases by an avidin-biotin complex (ABC) method, using monoclonal antibodies. The epithelial tumors consisted of 16 squamous cell carcinomas (SCCs) and 17 adenocarcinomas with different degrees of differentiation (well, moderately, or poorly differentiated), a renal cell carcinoma, a hepatocellular carcinoma, a transitional cell carcinoma of the bladder, and a carcinoid tumor of the stomach. The primary and metastatic tumors showed the same cytokeratin profiles. All SCCs and their metastases were positive for 57-kd cytokeratin and negative for 54-kd cytokeratin. All adenocarcinomas and their metastases were positive for 54-kd cytokeratin and negative for 66-kd cytokeratin. The extent of reactions varied with the differentiation of the carcinomas, with well-differentiated tumors showing more diffuse staining. Cases of lymphoma, sarcoma, and melanoma were negative for the three types of cytokeratins. The results indicate that identification of different molecular weight cytokeratins may be used to distinguish poorly differentiated SCCs from poorly differentiated adenocarcinomas, even in metastatic tumors. In addition, demonstration of these cytokeratins is useful in substantiating presence and identity of small foci of metastases in lymph nodes.

Topics: Adenocarcinoma; Antibodies, Monoclonal; Carcinoma, Squamous Cell; Diagnosis, Differential; Histocytochemistry; Humans; Immunoenzyme Techniques; Keratins; Lymphatic Metastasis; Molecular Weight; Neoplasms; Staining and Labeling

Pleural mesotheliomas and peripheral pulmonary adenocarcinomas were evaluated by immunohistochemistry at two institutions (Yale University School of Medicine and the City of Hope National Medical Center). Twenty-three mesotheliomas, 11 with ultrastructural verification, and 24 pulmonary adenocarcinomas were studied. Antikeratin, anticarcinoembryonic antigen, anti-human milk fat globule related antigen, MC-1, B72.3, and Leu M-1 antibodies were employed. The immunohistochemistry of each case prepared at one institution was reviewed at the other. As groups, the two tumor types were distinguishable using this antibody panel. Essentially, mesotheliomas were keratin positive only. The adenocarcinomas were positive for CEA, MFG, B72.3, and Leu M-1. However, there were some ambiguities presented by the immunohistochemistry. The higher molecular weight keratins were found in most but not all mesotheliomas and in only a few adenocarcinomas. Lower molecular weight keratins were positive not only in all the mesotheliomas, but also in nearly all the adenocarcinomas, but also in a tumor determined by electron microscopy to be mesothelioma. Preabsorption of CEA decreased the sensitivity for adenocarcinoma, but did not change the positivity of the putative mesothelioma. B72.3 and Leu M-1 were specific for adenocarcinoma, but were found in only half of them. The MFG was apparently specific for adenocarcinoma, but the findings were difficult to interpret. At the level of individual cases, greater sensitivity of separation can be achieved by combining the results of two or more antibodies, but the lack of a detectable specific antigen in mesothelioma continues to make some cases difficult to evaluate by immunohistochemistry alone.

Topics: Adenocarcinoma; Antibodies, Monoclonal; Carcinoembryonic Antigen; Diagnosis, Differential; Humans; Immunoenzyme Techniques; Keratins; Lung Neoplasms; Mesothelioma; Microscopy, Electron; Pleural Neoplasms

We investigated the effects of recombinant human gamma interferon on the induction of HLA-DR expression by two human squamous cell carcinoma, three trichilemmoma, one eccrine carcinoma, two adenocarcinoma cell lines, and cultured human keratinocytes in vitro. None of eight epithelial cell lines or keratinocytes expressed HLA-DR without gamma interferon treatment. In contrast, pure gamma interferon (500 IU/ml, 72-h treatment) induced HLA-DR expression on 1/2 squamous cell carcinoma, 3/3 trichilemmoma, 2/2 adenocarcinoma cell lines, and 4/4 keratinocyte cell lines, as determined using a fluorescence-activated cell sorter. A maxillary squamous cell carcinoma line and an eccrine carcinoma cell line failed to express HLA-DR with gamma interferon treatment; however, the growth of cells was inhibited by gamma interferon treatment. By indirect immunoperoxidase techniques, tumor cells such as Bowen's disease and squamous cell carcinoma were found to express HLA-DR. Since HLA-DR expression has been shown to be important for various immune responses, these findings suggest that gamma interferon plays important roles in various immune-related skin diseases.

Topics: Adenocarcinoma; Carcinoma, Squamous Cell; Cell Division; Cell Line; Epidermis; Hair; Histocytochemistry; HLA-D Antigens; HLA-DR Antigens; Humans; Immunochemistry; Interferon-gamma; Keratins; Recombinant Proteins; Skin Neoplasms

Among the monoclonal antibodies capable of detecting epithelial lineage, some recognize keratin and others identify antigens of epithelial membranes. Of the latter, the most commonly used is directed against an antigen present in cell membranes derived from milk fat globules, epithelial membrane antigen (EMA). To determine their relative sensitivity and specificity and hence their diagnostic value, we compared four commercially available monoclonal antibodies to low-molecular-weight keratins--AE1, CAM 5.2, PKK1, and 35 beta H11--with the monoclonal antibody to EMA (anti-EMA). We studied 383 samples of human neoplasms of diverse histogenetic types and degrees of differentiation. Anti-EMA was found to be less sensitive than the monoclonal antibodies to keratin in several epithelial tumors, including tumors of the prostate (11 of 13 negative), gastrointestinal tract (13 of 34 negative), and thymus (seven of eight negative). Anti-EMA was also less sensitive in mesotheliomas (nine of 24 negative). Of the embryonal carcinomas, all stained with the monoclonal antibodies to keratin, whereas none stained with anti-EMA. False-positive staining with anti-EMA was seen in two of 14 T-cell lymphomas. We conclude that the monoclonal antibodies to low-molecular-weight keratins are more sensitive and specific for the identification of epithelial origin of neoplasms than is monoclonal anti-EMA. Anti-EMA should not be used as the sole marker of epithelial differentiation in tumor diagnosis.

Topics: Adenocarcinoma; Antibodies, Monoclonal; Colonic Neoplasms; False Positive Reactions; Histocytochemistry; Humans; Keratins; Lymphoma; Male; Membrane Proteins; Mucin-1; Neoplasms; Prostatic Neoplasms

The reaction patterns in 80 adenocarcinomas of the lung were examined with PAP-method using a monoclonal antibody against keratin and one against carcinoembryonic antigen (CEA) and a polyclonal antiserum against CEA. Almost all tumors showed a positive reaction to the antibodies which, however, varied quantitatively. Even though a reliable correlation of positive immunohistochemical reaction with the different light microscopical types was not possible according to WHO subtypes and degrees of differentiation, specific localization of the reaction within the tumor cells was seen with increasing differentiation. There was no correlation between the immunohistochemical reactions and 14 clinically measured plasma CEA levels. The plasma CEA level not only depends on CEA production by the tumor but also on other factors.

Topics: Adenocarcinoma; Antibodies, Monoclonal; Carcinoembryonic Antigen; Carcinoma, Small Cell; Carcinoma, Squamous Cell; Humans; Immunoenzyme Techniques; Keratins; Lung Neoplasms

Fifty cases (20 cases of benign hyperplasia, 30 cases of adenocarcinoma) of prostatic tissues were studied for expression of keratin. The basal cells were strongly and continuously positive in normal prostatic glands and in benign prostatic hyperplasia. The secretory cells and carcinoma cells were negative. The basal cells remained partially in intra-ductal carcinoma, revealing keratin positive cells in a spotty pattern. These findings may be useful in differential diagnosis between benign prostatic hyperplasia and carcinoma of the prostate.

Topics: Adenocarcinoma; Carcinoma, Intraductal, Noninfiltrating; Humans; Hyperplasia; Immunoenzyme Techniques; Keratins; Male; Prostate; Prostatic Neoplasms

Thirty-four cases of sarcomatoid carcinoma with minimal epithelial components (SC) and six cases of sarcomatous tumour without any epithelial component (ST) in various organs were studied by the immunoperoxidase technique for the expression of epithelial markers, cytokeratins and epithelial membrane antigen (EMA). Employing antibodies against both high and low molecular weight cytokeratins, sarcomatoid components in 30 examples of SC were stained positively. Epithelial membrane antigen was demonstrated in 19 out of 34 SC. The positive cells for epithelial markers within sarcomatoid components in some cases of SC, which were regarded as originating from squamous cell carcinoma, tended to be seen less frequently than in the tumours derived from adenocarcinoma or transitional cell carcinoma. In six cases of ST, stain for EMA was negative and stain for cytokeratins was positive in three examples. The immunohistochemical examination of epithelial markers in the tumours of these types may be of value in differentiating these tumours from true sarcomas.

Topics: Adenocarcinoma; Antigens; Carcinoma; Carcinoma, Squamous Cell; Epithelium; Histocytochemistry; Humans; Immunochemistry; Keratins; Membrane Proteins; Mucin-1; Sarcoma

In serous effusions the distinction between reactive mesothelial cells and malignant cells (especially adenocarcinoma cells and malignant mesothelial cells) is frequently a cause of diagnostic difficulty. The present paper describes the immunocytochemical staining of cells in 76 effusions from 71 patients with different malignancies. In 91% of the effusions obtained from patients with adenocarcinomas, the cells stained positive for anti-EMA, 94% for anti-CEA, 64% for anti-LeuM1-antigen and 75% for anti-keratins. In more than 90% of the cases the reactive mesothelial cells stained positive for anti-keratins, but not for anti-EMA, anti-CEA or anti-LeuM1-antigen. It is concluded that a panel of the antibodies against EMA, CEA, LeuM1-antigen and keratins is valuable in the distinction between adenocarcinoma cells, malignant mesothelial cells and reactive mesothelial cells in serous effusions.

Topics: Adenocarcinoma; Antibodies; Antigens, Differentiation, T-Lymphocyte; Antigens, Surface; Ascitic Fluid; Carcinoembryonic Antigen; Histocompatibility Antigens; Humans; Keratins; Leukocyte Common Antigens; Membrane Proteins; Mesothelioma; Mucin-1; Pleural Effusion

The histological diagnosis of malignant mesothelioma of the pleura, especially the distinction from peripheral adenocarcinoma of the lung, may be difficult. The immunohistochemical reports previously published on this subject show diverging results mainly because a variety of antibodies and staining techniques have been used by the different authors. To obtain comparable and reproducible results standard techniques and commercialized antibodies should be applied in routine pathology. In order to investigate the value of immunohistochemistry for the separation of the two entities formalin fixed and paraffin embedded blocks of 47 mesotheliomas and 22 adenocarcinomas were investigated with the PAP technique and commercially available antibodies to carcino-embryonic antigen (CEA), keratin, vimentin, epithelial membrane antigen (EMA), pregnancy specific antigen (SP1), S-100 protein and monoclonal antibody lu-5 (mAB lu-5). CEA positivity was found in all 22 adenocarcinomas examined, but only 2/47 (4%) of all mesotheliomas showed a positive result. SP1 was positive in 13/22 (59%) of the adenocarcinomas, whereas only 3/47 (6%) mesotheliomas were positive for this marker. No significant difference in the rate of positive cases in the adenocarcinoma and mesothelioma group could be found with the other above mentioned antigens. The results of our study indicate that especially CEA, but also SP1 are valuable markers in the diagnosis of malignant mesothelioma.

Topics: Adenocarcinoma; Antibodies, Monoclonal; Carcinoembryonic Antigen; Diagnosis, Differential; Histocytochemistry; Humans; Immunochemistry; Keratins; Lung Neoplasms; Membrane Proteins; Mesothelioma; Mucin-1; Pleural Diseases; Pregnancy-Specific beta 1-Glycoproteins; Vimentin

Dunning R3327-H rat prostate adenocarcinoma cells, when grown in syngeneic (Copenhagen) rats or nude mice, produce tumors with prominent hypercellular stroma. The authors have previously demonstrated the presence of anomalous steroid-sensitive cells in both the epithelium and stromal compartments of this model system. In order to better understand the histogenesis of these cells, the authors studied samples of the tumor which were radiolabeled overnight with tritiated dihydrotestosterone (3H-DHT). Frozen sections of the tissues were thaw-mounted onto autoradiographic emulsion-coated slides to permit silver grain identification in association with nuclei of androgen-sensitive cells. Surprisingly, numerous silver grains were found to be associated with nuclei of large cells within the stroma. Therefore, these cells were termed "epithelioid" pending confirmation of their origin. To further define these cells and their relationship to the surrounding matrix, autoradiograms have now been examined immunohistochemically with antibodies directed against the basement membrane glycoprotein, laminin, as well as antibodies specific for intermediate cytoskeletal filaments. Following identification of acinar basement membranes, epithelioid cells were identifiable both in the stroma and in the acinar epithelial cell layer. Histochemical staining with acid phosphatase, a marker for prostatic epithelium, was performed and shown to be present in acinar epithelial cells as well as in epithelioid cells. Additionally, fluorescence-activated cell sorting was employed to characterize the DNA content of cell types within the H tumor. Epithelioid cells were found to be in highest concentration in an aneuploid peak with a ploidy of approximately 6N. The autoradiographic, immunohistochemical, cytometric, and ultramicroscopic studies suggest that 1) epithelioid cells are epithelial derived stromal cells; 2) these epithelioid cells arise by pathologic division of aneuploid neoplastic precursor cells of approximately 3N ploidy, which are found within the prostatic epithelium; and 3) the resulting 6N cells degrade the basement membrane locally, invade the stroma, and populate it. Here, they can be distinguished from fibroblasts by their size, acid phosphatase activity, and hormone receptor content. Thus, the term "epithelioid" is inappropriate; and these cells should be regarded simply as large neoplastic epithelial (LNE) cells. The presence of this cell type suggests that this tumor s

Topics: Acid Phosphatase; Adenocarcinoma; Animals; Autoradiography; Cell Nucleus; Cell Separation; Cytoplasm; Dihydrotestosterone; Epithelium; Flow Cytometry; Histocytochemistry; Immunoenzyme Techniques; Keratins; Male; Mice; Mice, Nude; Prostatic Neoplasms; Rats; Tritium

Pancreatic carcinoma induced in the Syrian hamster by the carcinogen N-nitrosobis(2-oxopropyl)amine (BOP) is of interest because of the ductal/ductular morphology of the tumors, which resembles human pancreatic cancer. However, whether hamster tumors arise from pre-existing ductal epithelium or from acinar cells has not yet been determined. The present study shows that a monoclonal antiserum to cytokeratin (an epithelial marker), when applied to normal hamster pancreas sections, stained centroacinar, ductular and ductal epithelium but did not stain acinar cells. We therefore examined pancreatic tissue from hamsters with benign and malignant neoplasms induced by BOP. The antiserum strongly stained the cells of all BOP-induced lesions (cysts, pseudoductules, hyperplasia, dysplasia and carcinomas). No acinar cell staining was observed in BOP-treated pancreas. These findings support the hypothesis that BOP-induced neoplasms arise from ductal epithelium and not from acinar cells.

Topics: Adenocarcinoma; Animals; Antibodies, Monoclonal; Cricetinae; Immunohistochemistry; Keratins; Male; Mesocricetus; Nitrosamines; Pancreatic Neoplasms

Topics: Adenocarcinoma; Antibodies, Monoclonal; Humans; Immunoenzyme Techniques; Keratins

A middle-aged woman presented with a pelvic mass. Pathologic examination of the resected specimen revealed a primary adenosquamous carcinoma of the left fallopian tube. Special studies supported the concept of the neoplastic cells differentiating along two major pathways, squamous cell carcinoma and mucin-producing adenocarcinoma.

Topics: Adenocarcinoma; Adult; Carcinoma, Squamous Cell; Fallopian Tube Neoplasms; Fallopian Tubes; Female; Humans; Immunohistochemistry; Keratins; Microscopy, Electron; Mucins; Necrosis

Follicular, papillary, anaplastic and medullary cancers of the thyroid were investigated using immunohistochemical methods. The following antibodies were used: anti-S-100, antineuron-specific enolase (NSE), antikeratin, antithyroglobulin, anticalcitonin, anticarcinoembryonic antigen (CEA), antiepithelial membrane antigen (EMA); the following hormones were also tested in the medullary carcinoma: gastrin, ACTH and serotonin. Papillary and follicular carcinoma in particular reacted with anti-S-100 and anti-NSE; the anaplastic neoplasia reacted with anti-S-100 (25%), anti-NSE (12%), antikeratin (12%), antithyroglobulin (12%), anti-CEA (37%) and anti-EMA (37%). Medullary carcinoma reacted with anticalcitonin (100%), anti-CEA (96%), anti-NSE (79%), anti-EMA (4%) and anti-S-100 (17%). We were not able to correlate the virulence of the medullary carcinoma with the anticalcitonin and anti-CEA reactivity, while the hyperplastic C cells were immunoreactive both with calcitonin or with CEA.

Topics: Adenocarcinoma; Adolescent; Adult; Aged; Calcitonin; Carcinoembryonic Antigen; Carcinoma; Carcinoma, Papillary; Female; Humans; Immunohistochemistry; Keratins; Male; Middle Aged; Phosphopyruvate Hydratase; S100 Proteins; Thyroid Neoplasms

The expression of cytokeratins was investigated in rat 13762NF adenocarcinoma cell lines and clones growing in vitro and in vivo. The anti-cytokeratin monoclonal antibody PKK1 used in this study recognized one cytokeratin with a molecular weight of 54,000 in these cells. Immunofluorescence staining of cultured tumor cells with PKK1 detected cytokeratins in less than 1% of the tumor cells isolated from the locally growing parental tumors, but intense cytokeratin staining in the form of fibrils and networks was found in the cell cultures derived from spontaneous metastases. There were variable degrees of staining with the anti-cytokeratin antibody in cultured cells from metastases, indicating phenotypic diversity in the expression of cytokeratins. Staining with PKK1 of frozen sections from locally growing tumors obtained after injecting the cells into the mammary fat pads of syngeneic rats also demonstrated considerable heterogeneity in cytokeratin expression. The anti-cytokeratin reagent stained only a few, isolated cells in frozen sections of tumors established from parental tumor cells, while this reagent stained intensely cells in local tumors and their metastases established from tumor cells cultured from spontaneous lymph node or lung metastases.

Topics: Adenocarcinoma; Animals; Electrophoresis, Polyacrylamide Gel; Female; Fluorescent Antibody Technique; Keratins; Mammary Neoplasms, Experimental; Microscopy, Fluorescence; Rats; Tumor Cells, Cultured

Topics: Adenocarcinoma; Adult; Aged; Antibodies, Monoclonal; Carcinoembryonic Antigen; Female; Humans; Immunohistochemistry; Keratins; Middle Aged; Uterine Cervical Neoplasms; Uterine Neoplasms

Topics: Adenocarcinoma; Antibodies, Monoclonal; Diagnosis, Differential; Female; Humans; Keratins; Uterine Cervical Neoplasms; Uterine Neoplasms; Vimentin

A clonal neoplastic epithelial duct cell (HSGc) of human salivary gland origin has a fine structure similar to the intercalated duct cell and the capacity to express secretory component and lactoferrin. HSGc cells tend to form an occasional glandular arrangement in vitro and in vivo, and transplantation of cells into nude mice resulted in production of adenocarcinoma. By repeated single cell cloning, different types of clones could be isolated from HSGc. Cuboidal clones resemble the parent cell, but fail to form the glandular arrangement or express lactoferrin, suggesting a less differentiated type. Elongated clones have a fine structure similar to myoepithelial cells and carry myoepithelial markers such as S100 protein, actin, and myosin which are not detected in the HSGc and its cuboidal clones. These myoepithelial-like clones are able to express secretory component, lactoferrin, and lysozyme and to produce glycosaminoglycans, suggesting that they are a functionally active form of the neoplastic cell but different from the normal myoepithelial cell. Judging from their growth properties in vitro and in vivo, the myoepithelial-like clones are less malignant than HSGc or its cuboidal clones. Of four elongated clones, two did not produce tumors in athymic mice, while all of the cuboidal clones were tumorigenic. These findings suggest a possible conversion of the neoplastic duct cell to myoepithelial-like variants with low malignancy.

Topics: Actins; Adenocarcinoma; Antigens; Carcinoma; Cell Cycle; Cell Line; Cell Separation; Clone Cells; Epithelium; Fluorescent Antibody Technique; Humans; Keratins; Lactoferrin; Microscopy, Electron; Muramidase; Myosins; S100 Proteins; Salivary Gland Neoplasms; Secretory Component

The correct distinction between malignant mesothelioma of the pleura and adenocarcinoma of the lung has become increasingly complex, with a variety of histochemical, immunohistochemical, and ultrastructural studies to be performed on biopsy material. The reliability of immunohistochemical studies has been hampered by the use of polyclonal antisera to "carcinoembryonic antigen (CEA)" and keratin. Hybridoma technology now offers monoclonal antibodies (MAbs) in unlimited quantity and standardized quality to selective ranges of specific antigenic determinants. MAb B72.3, generated against a membrane-enriched fraction of human metastatic breast carcinoma, was used to distinguish malignant mesothelioma of the pleura from adenocarcinoma of the lung in tissue sections and was compared in terms of diagnostic utility with polyclonal anti-keratin and anti-CEA to make the same distinction. Reactivity with MAb B72.3 in at least 10% of tumor cells or more was noted in 19 of 22 adenocarcinomas of the lung (P greater than 0.0001), whereas none of the 20 cases of malignant mesothelioma demonstrated comparable reactivity. Furthermore, MAb B72.3 showed no reactivity with benign mesothelial proliferations. MAb B72.3 thus appears to be an appropriate diagnostic adjunct capable of discriminating between these malignancies.

Topics: Adenocarcinoma; Antibodies, Monoclonal; Antigens, Neoplasm; Carcinoembryonic Antigen; Diagnosis, Differential; Histocytochemistry; Humans; Immunoenzyme Techniques; Keratins; Lung Neoplasms; Mesothelioma; Pleural Neoplasms

Mammary tumorigenesis was surveyed in retired breeding females in four sublines of the C3H strain: in standard milk-transmitted early oncogenic mouse mammary tumor virus (MMTV)-infected C3H/He and C3H/Ki mice, and in standard milk-transmitted early oncogenic MMTV free C3Hf/He and C3Hf/Ki mice. All of 58 C3H/Ki mice and 98% (306 of 309) of the C3H/He mice developed palpable mammary tumors at average ages of 276 and 284 days, respectively. Thirty-one % (47 of 152) of the C3Hf/Ki mice and 77% (168 of 218) of the C3Hf/He mice developed palpable mammary tumors at average ages of 798 and 757 days, respectively. The mammary tumors removed from C3H/He and C3H/Ki mice were all adenocarcinomas of epithelial origin, and all contained MMTV. The mammary tumors removed from C3Hf/He and C3Hf/Ki mice were either adenocarcinomas or sarcomas. The carcinomas were of epithelial origin and all expressed the late oncogenic endogenous MMTV. The sarcomas were of histiocyte or fibrocyte origin and contained neither virus particles nor MMTV antigenic markers. It is concluded that exogenous standard milk-transmitted oncogenic MMTV oncogenesis in C3H mice is not modified by host genetic factors. In contrast, late oncogenic endogenous MMTV oncogenesis is influenced both by host genetic control of the expression of the late oncogenic MMTV provirus and by the location of the proviral genes in the germline DNA.

Topics: Adenocarcinoma; Animals; Disease Models, Animal; Female; Genes, Viral; Keratins; Mammary Neoplasms, Experimental; Mammary Tumor Virus, Mouse; Mice; Mice, Inbred C3H; Sarcoma; Vimentin

As there is little published information on the ultrastructure of poorly differentiated squamous carcinoma of the bronchus 18 examples of this tumour were studied. On light microscopy 10 of the tumours contained foci of keratinisation or intercellular bridges and therefore fulfilled the World Health Organisation's diagnostic criteria. In eight these features were absent, but the overall appearance was sufficiently squamoid to preclude their placement in any other category. On electron microscopy many cells showed the characteristic desmosomes and tonofilament of of squamous carcinoma, but there were also areas of adenodifferentiation. The ultrastructure of both light microscopic groups was identical. In conclusion, this type of tumour is dimorphic with characteristics of adenocarcinoma and squamous carcinoma on electron microscopy. Keratinisation and bridges are not essential diagnostic criteria: the overall pattern and cellular morphology are more important.

Topics: Adenocarcinoma; Bronchial Neoplasms; Carcinoma, Squamous Cell; Cell Membrane; Cytoplasmic Granules; Desmosomes; Humans; Intercellular Junctions; Keratins; Microscopy, Electron; Vacuoles

To evaluate the usefulness of an immunohistologic approach to the differential diagnosis of mesothelioma and pulmonary adenocarcinoma, the authors studied paraffin-embedded, fixed tissue sections from 50 primary adenocarcinomas of the lung and 28 mesotheliomas of the pleura by using a panel of monoclonal antikeratin, antihuman milk fat globule (HMFG-2), anti-Leu M1, and monoclonal anticarcinoembryonic antigen (CEA) antibody; we also used a conventional heterologous anti-CEA antiserum with and without prior absorption with spleen powder to remove antibodies to nonspecific cross-reacting antigen (NCA). Keratin was present in both mesotheliomas and adenocarcinomas and did not help in distinguishing between these two neoplasms. HMFG-2 was detected in 48 (96%), and Leu M1 was positive in 47 (94%) of the adenocarcinomas, but not in any of the mesotheliomas. By using conventional rabbit antiserum, the authors detected CEA in the majority of adenocarcinomas (96%), but also in two cases of mesothelioma. When the anti-CEA antiserum was absorbed with NCA, the number of positively reacting adenocarcinomas decreased considerably to 76%; however, after this treatment, none of the mesotheliomas gave positive reactions. The monoclonal anti-CEA antibody was reactive in 36 of the adenocarcinomas (72%), but in none of the mesotheliomas. Our results indicate that, in addition to HMFG-2 and CEA, the expression of Leu M1 antigen by most primary pulmonary adenocarcinoma (94%) and its absence in mesothelioma could be used as a valuable marker for primary adenocarcinoma of the lung that involves the pleura and permits its differentiation from mesothelioma.

Topics: Adenocarcinoma; Antibodies, Monoclonal; Antigens, Differentiation, T-Lymphocyte; Antigens, Surface; Carcinoembryonic Antigen; Diagnosis, Differential; Humans; Keratins; Lung Neoplasms; Membrane Proteins; Mesothelioma; Mucin-1; Phenotype; Pleural Neoplasms

The existence of different neuroendocrine markers was investigated by immunocytochemistry in a case of Merkel cells tumor. Neuroplastic cells contain NSE,NF,CK and chromogranin A i.r. On the basis of the results the neuroendocrine nature of this uncommon neoplasm of the skin is confirmed and it is suggested that chromogranin A could represent an additional marker for Merkel cells tumors.

Topics: Adenocarcinoma; Aged; Chromogranin A; Chromogranins; Humans; Immunoenzyme Techniques; Intermediate Filaments; Keratins; Lymphatic Metastasis; Male; Phosphopyruvate Hydratase; Skin Neoplasms; Staining and Labeling

The expression of vimentin in pulmonary carcinomas was studied in 285 cases of surgically resected lung cancer from our hospital files. Formalin fixed, paraffin-embedded sections were studied by immunoreactive staining techniques using two monoclonal antibodies against vimentin. Cases demonstrating vimentin positivity by the avidin-biotin-peroxidase method included 11 of 129 adenocarcinomas studied (8.5%), and 15 of 61 large cell carcinomas studied (24.6%). Vimentin expression was not seen in any of the 51 squamous cell carcinomas or 35 small cell carcinomas in our series. The positive cases of adenocarcinoma were in moderately and poorly differentiated cancers. Four of the eight giant cell carcinomas (50%) demonstrated vimentin expression. All cases that exhibited vimentin positivity were studied for cytokeratin expression. Coexpression of vimentin and cytokeratin was demonstrated not only within the same tumor but also within the same cells in some cases stained by double antibody technique, including both adenocarcinomas and large cell carcinomas. Similar immunoreactive methods were also applied to sections from human lung cancer transplants grown in the nude mouse. Of 28 tumors studied, four of 11 adenocarcinomas (36%) and all 4 large cell carcinomas demonstrated coexpression of vimentin and cytokeratin, while none of the five squamous cell carcinomas or eight small cell carcinomas expressed vimentin.

Topics: Adenocarcinoma; Animals; Antibodies, Monoclonal; Carcinoma, Small Cell; Carcinoma, Squamous Cell; Histocytochemistry; Humans; Keratins; Lung Neoplasms; Mice; Mice, Inbred BALB C; Mice, Nude; Transplantation, Heterologous; Vimentin

We examined the distribution of high- and low-molecular-weight cytokeratins, vimentin, and carcinoembryonic antigen (CEA) in normal endometrial glands and endocervical glands (20 cases each) and in endometrial and endocervical adenocarcinomas (29 cases and 15 cases respectively). Low- and high-molecular-weight cytokeratin staining was present in normal endometrial and endocervical epithelium and in carcinomas. Coexpression of vimentin and cytokeratin was universally present in normal proliferative endometrial glands, with marked decrease or absence of vimentin staining in secretory phase patterns. Vimentin staining had a perinuclear distribution within the cells, in contrast to the cytokeratins, which stained diffusely. Vimentin was found in only 65% of endometrial adenocarcinomas. Staining was typically focal as well as regional in portions of the tumors. Vimentin was never observed in normal or neoplastic endocervical epithelium. Ultrastructural studies corroborate the perinuclear vimentin immunostaining pattern we observed in endometrial adenocarcinomas. CEA staining results were similar to those previously reported. These data indicate that the presence of vimentin may readily distinguish endometrial from endocervical carcinoma and is diagnostically useful in the study of metastatic adenocarcinomas.

Topics: Adenocarcinoma; Carcinoembryonic Antigen; Cytoskeleton; Diagnosis, Differential; Female; Humans; Intermediate Filaments; Keratins; Microscopy, Electron; Retrospective Studies; Uterine Cervical Neoplasms; Uterine Neoplasms; Vimentin

We determined the reactivity of two monoclonal antibodies to cytokeratins that are typically expressed in certain stratified epithelia and several human squamous cell carcinomas using immunoblotting techniques and immunofluorescence microscopy. Antibody KS 8.12 reacted specifically with cytokeratin polypeptides nos. 13 and 16, and stained noncornified squamous epithelia in a rather uniform way. The examination of diverse human carcinomas showed all squamous cell carcinomas to be positively stained with this antibody, whereas all adenocarcinomas were negative. Another antibody, KK 8.60, reacted with polypeptides nos. 10 and 11, and uniformly stained the suprabasal layers of the epidermis. In several noncornified squamous epithelia (e.g., tongue, exocervix), in thymus reticulum epithelial cells, and in moderately and well differentiated squamous cell carcinomas this antibody exhibited a nonuniform labeling pattern that allowed the detection of individual cytokeratin-10/11-positive cells scattered throughout the tissue. It is concluded that antibodies KS 8.12 and KK 8.60 represent specific molecular probes for the definition of certain stages of squamous differentiation in normal development as well as in pathological processes such as squamous metaplasia and carcinogenesis. We propose the use of these antibodies in the differential diagnosis of carcinomas and their metastases.

Topics: Adenocarcinoma; Antibodies, Monoclonal; Antigen-Antibody Complex; Carcinoma, Squamous Cell; Epithelial Cells; Female; Fluorescent Antibody Technique; Humans; Keratins; Skin; Tissue Distribution

Four cases of neuroendocrine carcinomas (NECA) of the skin were studied by indirect immunofluorescence, using a monoclonal antikeratin antibody and a polyclonal antineurofilament antibody. Fifty to ninety percent and 80 to greater than 95% of the NECA cells stained with the antineurofilament antibody and the antikeratin antibody, respectively. Using double-labeling indirect immunofluorescence we could also demonstrate that, in 3 cases studied, some of the NECA cells, but not all, stained with both antikeratin and antineurofilament antibodies. These results, together with the recent knowledge of the intermediate filament protein type of normal Merkel cells (MC), tend to support the hypothesis that NECA cells do not originate from epithelial MC but from dermal neuroendocrine cells. A dual concept of intraepithelial MC and extraepithelial intradermal neuroendocrine cells, "from possible distinct origin," is proposed. Such a system has already been suggested for the neuroendocrine cells of the appendix and bronchial mucosae.

Topics: Adenocarcinoma; Aged; Female; Fluorescent Antibody Technique; Humans; Intermediate Filament Proteins; Keratins; Male; Middle Aged; Neoplasm Proteins; Neurofilament Proteins; Skin Neoplasms

Intermediate filaments are composed of 5 groups which follow the classic histogenetic division of tissue. The application of antibodies against the 5 groups for the analysis of salivary gland tumours reveals the presence of keratin in normal and neoplastic epithelial tissue. All carcinomas e.g. adenocarcinomas, acinic cell tumours, mucoepidermoid tumours and squamous cell carcinomas were positive for keratin. Vimentin was regularly found in the cells of the stroma. A special distribution pattern of intermediate filaments was found in pleomorphic adenomas and in adenoid cystic carcinomas. These tumours display the presence of two systems, keratin and vimentin filaments. The application of antibodies against intermediate filaments is useful for differential diagnosis of salivary gland tumours and for histogenetic analysis of special tumour groups.

Topics: Adenocarcinoma; Adenolymphoma; Adenoma, Pleomorphic; Antibodies; Carcinoma, Adenoid Cystic; Carcinoma, Squamous Cell; Cytoskeleton; Humans; Intermediate Filaments; Keratins; Salivary Gland Neoplasms; Vimentin

The localization of keratin was investigated in normal human prostate, benign prostatic hyperplasia (BPH), and prostatic adenocarcinoma using immunohistochemical technique on frozen tissue sections. The purpose of this study was to identify changes in the distribution patterns of keratin due to malignancy. In normal and benign tissue specimens, keratin was detected in the cytoplasm of basal cells and glandular epithelial cells. In the glandular epithelial cells keratin was found as a deposit of fine granules. In the basal cells, the positive staining for keratin had a uniform distribution in the scanty cytoplasm. In specimens of prostatic adenocarcinoma, the basal cells retained a strong positive reaction for keratin. The shapes and the distributions of basal cells were markedly different in malignant specimens. Basal cells formed a discontinuous layer and surrounded the population of neoplastic cells in tissue sections containing the cribriform patterns. The cells expressed characteristic protrusions into extracellular spaces between the cancer cells. Keratin-positive granules were demonstrated in the adenocarcinoma cells as well. These granules had slightly smaller sizes and were distributed randomly. The study demonstrates that the immunohistochemical localization of keratin provides a refinement for the characterization of cells in tissue sections of prostate.

Topics: Adenocarcinoma; Cytoplasm; Histocytochemistry; Humans; Immunoenzyme Techniques; Keratins; Male; Prostate; Prostatic Hyperplasia; Prostatic Neoplasms

Ten cases each of papillary, follicular, anaplastic and medullary carcinoma of the thyroid were stained for thyroglobulin, calcitonin, epithelial membrane antigen (EMA), carcinoembryonic antigen (CEA) and cytokeratin (CAM 5.2). Monoclonal or affinity purified polyclonal antibodies, and an indirect immunoperoxidase technique were used. All the papillary and follicular tumours, 5/10 anaplastic and 3/10 medullary carcinomas contained thyroglobulin. Only the 10 medullary carcinomas stained positively for calcitonin. Three out of 10 papillary, 1/10 follicular, 0/10 anaplastic and 10/10 medullary carcinomas were positive for CEA. Nine out of ten papillary, 7/10 follicular, 2/10 anaplastic and 3/10 medullary carcinomas were positive for EMA. Ten out of 10 papillary, 10/10 follicular, 5/10 anaplastic and 10/10 medullary carcinomas were positive for cytokeratin. The presence of calcitonin and CEA is of value in the diagnosis of medullary carcinoma, and enable its distinction from anaplastic thyroid carcinoma. Thyroglobulin is a useful marker in thyroid carcinomas.

Topics: Adenocarcinoma; Antibodies; Antibodies, Monoclonal; Antigens, Surface; Calcitonin; Carcinoembryonic Antigen; Carcinoma; Epithelial Cells; Humans; Immunoenzyme Techniques; Keratins; Thyroglobulin; Thyroid Neoplasms

The results of neuron-specific enolase (NSE) and keratin immunodetection in cytological specimens of sputum secured from 41 patients with lung cancer are presented. All 19 cases of small-cell carcinoma showed intense immunoreactivity for NSE. No such immunoreactivity was found in 21 of 22 cases of non-small-cell carcinoma. The single positive result was from a case of large-cell undifferentiated carcinoma. All 10 cases of squamous-cell carcinoma showed immunoreactivity for keratin. The 19 cases of small-cell carcinoma showed no such reactivity. Our findings indicate that immunostaining for NSE and keratin is a valuable aid when a definite diagnosis of small-cell carcinoma of the lung can not be made on the basis of conventional cytologic features.

Topics: Adenocarcinoma; Carcinoma, Small Cell; Carcinoma, Squamous Cell; Clinical Enzyme Tests; Diagnosis, Differential; Histocytochemistry; Humans; Immunoenzyme Techniques; Keratins; Lung Neoplasms; Phosphopyruvate Hydratase; Sputum

Fifteen neuroendocrine carcinomas of the skin (Merkel cell tumors) were stained within the constraints of tissue availability by the Grimelius method and immunohistochemically for keratin, neuron-specific enolase (NSE), carcinoembryonic antigen (CEA), S-100, common leukocyte antigen (CLA), met-enkephalin, bombesin, calcitonin, ACTH, gastrin, and somatostatin. Focal argyrophilia was present in 5 of 12 tumors. All tumors tested demonstrated immunoreactivity for NSE and 5 tumors were positive for keratin. One tumors appeared to demonstrate focal ACTH-like immunoreactivity, but otherwise no immunoreactivity for the above mentioned polypeptide hormones was noted in 11 completely studied tumors. One tumor contained histologically obvious areas of squamous differentiation in addition to areas of Merkel cell tumor. In various tumors, keratin immunoreactivity was present either in areas of histologically obvious squamous differentiation, in randomly scattered single cells not histologically identifiable as squamous, or in a paranuclear dot-like distribution. Immunoreactivity for CEA, S-100 and CLA was not present in any tumors. The lack of met-enkephalin and the presence of squamous differentiation in these tumors indicates multidirectional differentiation in a fashion not phenotypically typical of Merkel cells.

Topics: Adenocarcinoma; Adrenocorticotropic Hormone; Bombesin; Calcitonin; Carcinoembryonic Antigen; Enkephalin, Methionine; Gastrins; Histocompatibility Antigens; Humans; Immunoenzyme Techniques; Keratins; Leukocyte Common Antigens; Phosphopyruvate Hydratase; Skin Neoplasms; Somatostatin

The authors assessed whether distinct patterns for keratin could be demonstrated in 10 adenocarcinomas, 10 carcinoids, and 4 mesotheliomas by an immunoperoxidase reaction using 3 polyclonal and 3 monoclonal antibodies to keratin. When color development in diaminobenzidine (DAB) was allowed to proceed for less than 2 minutes, distinct patterns for keratin could be demonstrated using two polyclonal and two monoclonal antibodies; these were plasma membrane and/or web-like in the adenocarcinomas, punctate or crescentic in the carcinoids, and perinuclear in the mesotheliomas consisting of tumor cells with abundant cytoplasm. Immunoelectron microscopy using protein A colloidal gold confirmed these results. When color development in DAB was allowed to proceed for more than 2 minutes, only diffuse staining was seen. The distinct patterns of immunostaining for keratin obtained with the shorter color development were helpful in differentiating adenocarcinomas, carcinoids, and mesotheliomas.

Topics: Adenocarcinoma; Antibodies, Monoclonal; Carcinoid Tumor; Electrophoresis, Polyacrylamide Gel; Female; Humans; Immunoenzyme Techniques; Keratins; Mesothelioma

An immunohistological study of 15 chordomas, six chondrosarcomas, four liposarcomas and seven carcinomas on paraffin embedded samples using anti-cytokeratin, anti-epithelial membrane antigen (EMA), anti-S100 protein, anti-vimentin and anti-neurofilaments showed that chordomas has a characteristic immuno-staining, i.e. positive for cytokeratin, EMA, S100 protein and vimentin; and negative for neurofilaments. This immuno-staining allows a clear distinction of chordomas from other tumours.

Topics: Adenocarcinoma; Adenocarcinoma, Mucinous; Chondrosarcoma; Chordoma; Humans; Immunoenzyme Techniques; Keratins; Liposarcoma; Membrane Proteins; Mucin-1; S100 Proteins; Vimentin

Cells of the normal colonic mucosa express several types of cytokeratins, the characteristic intermediate filament proteins of epithelial cells. An immunohistochemical study was designed to examine the expression of two distinct groups of cytokeratins, recognized by monoclonal antibodies AE1 and AE3, in the colonic mucosa and to compare the findings with those obtained with a large number of polypoid lesions (adenomatous and hyperplastic) and carcinomas of the colon. AE1 and AE3 immunostaining was found in the surface epithelium and upper portions of the crypts of Lieberkühn (functional zone) of normal colonic mucosa, whereas the lower portions of the crypts (proliferative compartment) were unreactive with both AE1 and AE3. Polypoid lesions of the colonic mucosa can be placed into two categories based on their patterns of cytokeratin expression. Solitary tubular adenomas and hyperplastic polyps are composed of AE1 and AE3 nonexpressing cells with only few, patchy areas of AE1 and AE3 expressing cells present within glands and in the surface epithelium. In contrast, villous adenomas show strong AE1 and AE3 reactivity throughout the glands. Furthermore, tubular and villous adenomas, and even histologically normal mucosa in patients with familial polyposis, show AE1/AE3 expression throughout the glands and surface epithelium. Colonic carcinomas show a predominance of AE1/AE3 expressing cells. Thus, cytokeratins recognized by monoclonal antibodies AE1 and AE3 represent molecular markers of cellular maturation in the normal colonic mucosa, that are expressed in colonic carcinomas and, in addition, serve as markers that distinguish colonic mucosa and adenomas with a high risk for development of cancers from those with a lower risk.

Topics: Adenocarcinoma; Adenoma; Adenomatous Polyposis Coli; Antibodies, Monoclonal; Cell Differentiation; Cell Transformation, Neoplastic; Colon; Colonic Neoplasms; Epithelium; Humans; Hyperplasia; Intestinal Mucosa; Keratins

The flow cytometric (FCM) analysis of carcinomas is often hampered by the presence of stromal and inflammatory cells in the cell suspensions obtained from such neoplasms. Therefore, an FCM method was developed to distinguish epithelial from nonepithelial cells by using polyclonal and monoclonal antibodies to (cyto)keratins, the epithelial type of intermediate filament proteins. Using a model system of cultured bladder carcinoma (T24) and leukemia (MOLT-4) cells, we tested our hypothesis and procedures by labeling cell mixtures with these antibodies. After incubation with an appropriate intermediate filament antibody and propidium iodide staining, the DNA content and distribution of T24 cells could be analyzed separately from MOLT-4 cells. When applied to cell suspensions of endometrial carcinomas, bladder carcinomas and Grawitz tumors, only the epithelial (primarily carcinoma) cells were stained for cytokeratin; these cells could thus be analyzed separately from stromal, inflammatory and other nonepithelial cells. In this way, a more accurate FCM analysis of the malignant fraction within a tumor can be achieved.

Topics: Adenocarcinoma; Carcinoma, Transitional Cell; Cell Cycle; Cells, Cultured; DNA, Neoplasm; Epithelium; Flow Cytometry; Humans; Immunologic Techniques; Intermediate Filament Proteins; Keratins; Urinary Bladder Neoplasms; Vimentin

The occurrence and coexpression of the cytoskeletal proteins vimentin and cytokeratins were studied in malignant mesotheliomas and pulmonary carcinomas. For this purpose a double immunoenzyme staining with monoclonal antibodies was developed which made it possible to visualize vimentin and cytokeratins simultaneously within the same cell. A clear distinction between stromal cells (vimentin only) and tumour cells was also obtained. A total of 12 mesotheliomas (six mixed type and six epithelioid type) and 13 carcinomas (eight adenocarcinomas and five large cell undifferentiated carcinomas) were studied. The results revealed a clear difference between mesotheliomas and adenocarcinomas: 11 of 12 mesotheliomas showed coexpression of vimentin and cytokeratins in at least 50% of the tumour cells, while in seven of the eight adenocarcinomas none or only a few cells could be seen with this coexpression. In the undifferentiated large cell carcinomas three of five expressed both components, but in less than 25% of the cells. It is concluded that a reliable double immunoenzyme staining of vimentin and cytokeratins can be used as an additional means to distinguish malignant mesothelioma from pulmonary adenocarcinoma.

Topics: Adenocarcinoma; Antibodies, Monoclonal; Diagnosis, Differential; Humans; Immunoenzyme Techniques; Keratins; Lung Neoplasms; Mesothelioma; Peritoneal Neoplasms; Pleural Neoplasms; Staining and Labeling; Vimentin

One hundred cutaneous tumors were investigated immunohistopathologically for the expression of intermediate filament (IF) proteins. Epithelial tumors, such as basocellular and squamous cell carcinomas, cutaneous adnexal tumors, and metastatic carcinomas showed keratin positivity in a varying number of tumor cells with two keratin antibodies with different specificities. Neoplastic cells of fibrohistiocytic tumors, pigmented nevi, melanomas, hemangiomas, glomus tumors, and lymphomas were positive for vimentin, but not for keratin or desmin. Cutaneous leiomyomas and leiomyosarcomas, on the other hand, were positive for desmin. The results show that the typing of IFs enables the differential diagnosis between carcinomas and sarcomas or melanomas, epidermal appendage tumors, and mesenchymal tumors, and between fibrohistiocytic and leiomyocytic tumors, and therefore are of diagnostic value in histopathologic problems of the skin.

Topics: Adenocarcinoma; Adenoma, Sweat Gland; Antibodies, Monoclonal; Carcinoma, Adenoid Cystic; Carcinoma, Basal Cell; Carcinoma, Renal Cell; Carcinoma, Squamous Cell; Desmin; Diagnosis, Differential; Fluorescent Antibody Technique; Hemangioma; Histiocytoma, Benign Fibrous; Histocytochemistry; Humans; Intermediate Filament Proteins; Keratins; Leiomyoma; Melanoma; Neoplasm Metastasis; Nevus, Pigmented; Skin Neoplasms; Vimentin

Adenosquamous carcinomas of the intestine are rare tumours, especially those occurring in the small bowel. We report the first case of a metastasizing adenosquamous carcinoma of the ileum in a 74 year old male. The tumour mainly consisted of squamous cells, many of which reacted with antikeratin antibody. A review of the pertinent literature is given.

Topics: Adenocarcinoma; Aged; Carcinoembryonic Antigen; Carcinoma, Squamous Cell; Histocytochemistry; Humans; Ileal Neoplasms; Immunoenzyme Techniques; Keratins; Lymphatic Metastasis; Male

The adenocarcinoma cell line HSG from human salivary gland, which proliferates in vitro or in nude mice, was examined by the immunoperoxidase method for the expression of three different types of intermediate-sized filaments (IFs) and of specific antigens such as carcinoembryonic antigen, S-100 protein, secretory component, lactoferrin, myosin, tropomyosin, and actin. The cultured HSG cells were found to express three different types of IFs defined by antibodies to keratin, vimentin, and desmin. In HSG cells proliferating in vitro at 34 degrees C and 37 degrees C but not at 39 degrees C, the expression of tropomyosin and carcinoembryonic antigen was observed, although myosin and S-100 protein were not detected. The expressions of actin, lactoferrin, and secretory component were restricted to cultured HSG cells at 39 degrees C and 37 degrees C, respectively. Transplantation of HSG cells into nude mice resulted in the establishment of a nude mouse system with malignant characteristics such as invasion and metastasis. The expression of IFs in the primary tumors was restricted to keratin and desmin IFs, whereas coexpression of keratin, vimentin, and desmin IFs was observed in some neoplastic cells present in the metastatic tumors in regional lymph nodes and lung. In addition, expression of actin, myosin, tropomyosin, and S-100 protein was found in the metastatic tumors, whereas myosin and S-100 protein were not detected in the primary tumors. Moreover, the metastatic tumors were almost occupied by the neoplastic cells with oncocytic changes, although oncocytic change was not found in the cultured HSG cells and their primary tumors.

Topics: Adenocarcinoma; Animals; Antigens, Neoplasm; Carcinoembryonic Antigen; Cell Line; Cytoskeleton; Desmin; Female; Humans; Keratins; Mice; Mice, Inbred BALB C; Mice, Nude; Neoplasm Transplantation; S100 Proteins; Salivary Gland Neoplasms; Secretory Component; Transplantation, Heterologous; Vimentin

Digestion of primary breast cancers and their metastases with collagenase yields cell clusters which can be selectively isolated from stromal cells and from the less malignant-looking epithelium of the primary tumors by their failure to attach as rapidly to collagen gel. Continued passage in culture of one preparation of cell clusters has yielded a continuously growing cell strain, termed Ca2-83. This strain continues to grow mainly as cell clusters with doubling times of 10 to 14 days, although some clusters eventually adhere to plastic substrata. Two morphological extremes of cell were observed, smaller polygonal or cuboidal cells and larger, often-multinucleated cells which contain fat droplets. Cell clusters grew in a gland-like pattern similar to those of the original carcinoma and formed small nodules in 50% of recipient nu/nu mice. Both morphological forms of Ca2-83 in culture or in tumor nodules stained immunocytochemically with epithelial cell-specific antisera to epithelial membrane antigens and to human keratins but not to laminin or actin. Cultures of Ca2-83 failed to synthesize laminin under conditions where its synthesis was observed in a rat myoepithelial cell line. Ultrastructural analysis of the cell clusters has identified microvilli coated with epithelial membrane antigens and junctional complexes typical of secretory epithelia in both morphological forms, but no characteristics of myoepithelial cells or basement membranes were observed. The DNA content of the cultures increased in response to serum, a bovine pituitary fraction, and insulin. Numbers of cell clusters were also increased in the presence of culture medium exposed to preadipocytes, myoepithelial- or mesothelial-like cells/stromal cells, or to prostaglandin E2.

Topics: Actins; Adenocarcinoma; Animals; Breast Neoplasms; Cell Line; Culture Media; DNA, Neoplasm; Epithelium; Female; Growth Substances; Histocytochemistry; Hormones; Humans; Keratins; Laminin; Mice; Mice, Nude; Middle Aged