bromochloroacetic-acid and Carcinoma

Ameloblastic carcinoma is a malignant odontogenic neoplasm that has been reported only rarely in veterinary species. A 16-y-old Arabian crossbred mare was presented for evaluation of a hard mass on the body of the mandible, with evidence of osteolysis on radiographs. Incisional biopsies revealed an invasive neoplasm comprised of spindloid epithelial cells with a high mitotic count and partial dual cytokeratin-vimentin immunoreactivity. The horse was euthanized because of rapid tumor progression 3 mo after presentation. Postmortem evaluation revealed partial obliteration of the mandible by a large, firm-to-hard, tan, locally destructive and invasive mass with no gross or histologic evidence of metastasis. Postmortem histology revealed a poorly differentiated epithelial neoplasm with variably prominent features suggestive of odontogenic histogenesis: a plexiform ribbon architecture, infrequent basilar palisading with antibasilar nuclei, rare basilar cytoplasmic clearing, subepithelial matrix hyalinization, and partial dual cytokeratin-vimentin immunoreactivity. Features of malignancy included regions of necrosis, pronounced cellular atypia, a high mitotic count, extensive tissue invasion and local tissue destruction, and extension of neoplastic cells beyond the margins of the mandibular bone. Collectively, these features are most consistent with mandibular ameloblastic carcinoma. Including our case described here, ameloblastic carcinoma has been reported in only 5 horses. The microscopic features reported most consistently are dual cytokeratin-vimentin immunoreactivity, a high mitotic count, and basilar palisading. Ameloblastic carcinoma should be considered as a differential diagnosis for rapidly growing, locally invasive masses arising from the dentate jaw of horses.

Topics: Ameloblastoma; Animals; Carcinoma; Female; Horse Diseases; Horses; Keratins; Mandibular Neoplasms; Odontogenic Tumors; Vimentin

To present the clinicopathologic features of two cases of luteinized thecomas with sclerosing peritonitis (LTSP), characterize the cellular proliferation in the sclerosing peritonitis (SP), and review the literature.. The clinical, laboratory, and imaging data, operative findings, and pathology materials were reviewed and summarized. Samples of the SP were stained with keratin AE1/AE3, vimentin, CD34, calretinin, smooth muscle actin, ER/PR, CD10 and desmin. A literature search was performed to identify cases of LTSP for comparison.. A total of 43 cases of LTSP syndrome were identified. Frequent clinical features included ascites (74%), abdominal pain (35%), bowel obstruction (42%), and bilateral masses (84%). We isolated a distinct form of ovarian luteinized thecoma (thecomatosis) and peculiar sclerosing peritonitis (SP). IHC analysis shows a proliferation of specialized (vimentin+/keratin+/CD34+) submesothelial fibroblasts (SMF) with patchy expression of calretinin and hormone receptors.. LTSP syndrome is a rare entity presenting with abdominal pain, bowel obstruction, ascites, ovarian masses, and SP containing specialized (vimentin+/keratin+/CD34+) SMF. LTSP must be distinguished from abdominal cocoon, isolated SP, Meigs' syndrome, and peritoneal carcinomatosis. The importance of recognizing the diagnosis is stressed, as failure to manage this disease conservatively leads to significant morbidity and mortality. The SP and bowel obstruction may persist for months, even after resection of the tumours, resulting in extended medical therapy. Based on the immunophenotype of the peritoneal lesions, strategies to elucidate 'targeted' pharmacologic agents that could inhibit the proliferation of specialized (vimentin+/keratin+/CD34+) SMF may be of benefit.

Topics: Adult; Antigens, CD34; Antineoplastic Agents; Carcinoma; Disease Management; Female; Fibroblasts; Humans; Intestinal Obstruction; Keratins; Meigs Syndrome; Middle Aged; Ovarian Neoplasms; Ovariectomy; Peritoneal Fibrosis; Peritoneal Neoplasms; Thecoma; Treatment Outcome; Vimentin

Angiosarcoma may rarely arise near an inert foreign body material including vascular grafts and metal joint prostheses. Sixteen such cases have been reported since 1972 but mostly in the radiologic or surgical literature without detailed histologic or molecular analyses. We herein describe the clinicopathologic and molecular features of 2 new cases and reanalyzed 3 previously reported cases of angiosarcoma that developed in association with Dacron grafts for vascular repair (n=3) or related to orthopedic metal prostheses for joint replacement (n=2). All patients were men aged 50 to 84 years (median, 71 years). Mean time to development of angiosarcoma was 9 years (range, 4.6-17 years). Symptoms were recurrent bleeding/loosening of prosthesis for suspected infection (in the joint prosthesis cases) and fatigue, weight loss, and abdominal symptoms in the Dacron-associated cases. Four patients died of disease within 1 to 24 months (mean, 8 months). One patient was alive after radical surgery, radiochemotherapy, and embolization of pulmonary metastases (17 months). Histologically, all tumors were high-grade epithelioid neoplasms with a predominant solid growth pattern and variable vasoformation. All tumors expressed CD31, ERG, FLI-1, and variably pancytokeratin (diffuse in 3 cases), but none expressed D2-40, MDM2, or CDK4. Fluorescence in situ hybridization analysis revealed no MDM2 or CDK4 alterations. MYC was expressed in all cases, but only 1 case was MYC amplified by fluorescence in situ hybridization. Angiosarcomas are exceedingly rare fatal complications of long-standing metal and Dacron prostheses. Awareness of their morphology and frequent cytokeratin expression is necessary to avoid misdiagnosis as metastatic carcinoma. Limited awareness of their existence explains delayed clinical diagnosis in most of cases. Absence of MDM2/CDK4 alterations underlines their distinction from intimal-type sarcomas.

Topics: Aged; Aged, 80 and over; Biomarkers, Tumor; Blood Vessel Prosthesis; Blood Vessels; Carcinoma; Diagnosis, Differential; Hemangiosarcoma; Humans; Immunohistochemistry; In Situ Hybridization, Fluorescence; Joint Prosthesis; Joints; Keratins; Male; Middle Aged; Polyethylene Terephthalates

Tissue based research requires a background in human and veterinary pathology, developmental biology, anatomy, as well as molecular and cellular biology. This type of comparative tissue biology (CTB) expertise is necessary to tackle some of the conceptual challenges in human breast stem cell research. It is our opinion that the scarcity of CTB expertise contributed to some erroneous interpretations in tissue based research, some of which are reviewed here in the context of breast stem cells. In this article we examine the dissimilarities between mouse and human mammary tissue and suggest how these may impact stem cell studies. In addition, we consider the differences between breast ducts vs. lobules and clarify how these affect the interpretation of results in stem cell research. Lastly, we introduce a new elaboration of normal epithelial cell types in human breast and discuss how this provides a clinically useful basis for breast cancer classification.

Topics: Animals; Carcinoma; Cell Differentiation; Cell Lineage; Female; Flow Cytometry; Histology, Comparative; Humans; Immunohistochemistry; Keratins; Mammary Glands, Animal; Mammary Glands, Human; Mice; Stem Cells

The functional role of IKKα in vivo is pretty complicated, largely due to its diverse functions through cell autonomous and non-autonomous manners. In addition, most of the studies on IKKα were derived from animal models, whether these findings hold true in human tumors remain unclear. Here we examined the expression of IKKα in nasopharyngeal carcinoma, which includes non-keratinizing carcinoma and keratinizing squamous cell carcinoma, and lung squamous cell carcinoma with keratinization and non-keratinization. We demonstrated that IKKα expression was almost negative in keratinizing cancer and higher expression of IKKα was found in non-keratinizing cancer, and that IKKα expression correlated with cellular differentiation of tumors in non-keratinizing nasopharyngeal carcinoma. These findings demonstrate that IKKα is diversely expressed in keratinizing and non-keratinizing carcinomas in the same type of cancer.

Topics: Biomarkers, Tumor; Carcinoma; Carcinoma, Squamous Cell; Cell Differentiation; Gene Expression Regulation, Enzymologic; Gene Expression Regulation, Neoplastic; Humans; I-kappa B Kinase; Kaplan-Meier Estimate; Keratins; Lung Neoplasms; Nasopharyngeal Carcinoma; Nasopharyngeal Neoplasms; Phenotype; Prognosis; Time Factors

This is the first part of a 3-part comprehensive review of intraosseous carcinoma of the jaws. We have outlined 4 groups of intraosseous carcinoma of the jaws (metastatic, salivary-type, odontogenic, and primary intraosseous carcinoma), emphasizing the need for accurate diagnosis and the problems associated with changing classification systems, standardization of diagnostic criteria and nomenclature, and the accuracy of existing literature. In this first part, the features of metastatic and the very rare salivary-type carcinomas of the jaws are examined with particular emphasis on histologic and immunohistochemical characteristics, diagnostic difficulties, and uncertainties.

Topics: CA-125 Antigen; Carcinoma; Humans; Immunohistochemistry; Jaw Neoplasms; Keratins; Mandibular Diseases; Maxillary Diseases; Odontogenic Cysts; Salivary Gland Neoplasms; Transcription Factors

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

Myoepithelial carcinoma with predominantly clear cell morphology is rare. A review of the literature identified 15 unequivocal cases, only two of which were of minor salivary gland origin. A case of minor salivary gland clear cell myoepithelial carcinoma of the retromolar region in a 70-year-old man is presented. It is important to recognize the clinicopathologic features of this unusual tumor, because of its histological similarity to several other primary and metastatic clear cell tumors and its aggressive behavior.

Topics: Aged; Carcinoma; Follow-Up Studies; Humans; Keratins; Male; Membrane Proteins; Neoplasm Invasiveness; S100 Proteins; Salivary Gland Neoplasms; Salivary Glands, Minor; Serine Proteinase Inhibitors; Serpins; Vimentin

Topics: Antigens, CD; Biomarkers, Tumor; Carcinoma; Chromogranins; Humans; Keratins; Neoplasm Proteins; Neoplasm Staging; Thymoma; Thymus Neoplasms

Malignant rhabdoid tumor, first described in the kidney of young infants, is a rare and highly aggressive neoplasm of controversial histogenesis that has been reported at many other sites, including the gastrointestinal tract. However, malignant rhabdoid tumor of the small intestine is very rare, with only seven cases published to date. We report a 70-year-old man who presented with abdominal pain and weight loss, and showed a perforated jejunal mass with disseminated metastases by imaging. The patient underwent partial jejunectomy and biopsy of a liver metastasis. Microscopically, the tumor was characterized by neoplastic cells with vesicular nuclei, large nucleoli and abundant eccentric cytoplasm with hyaline globular intracytoplasmic inclusions. Immunohistochemically, the neoplasm coexpressed vimentin and epithelial antigens (AE1/AE3, Cam 5.2, CK34betaE12, CK19 and EMA), most of them showing a peculiar immunostaining pattern in relation to the globular inclusions. Ultrastructurally, the inclusions corresponded to paranuclear whorls of intermediate filaments. The patient received postoperative chemotherapy but died 9 months after surgery. In summary, we report the exceptional case of an undifferentiated carcinoma of the jejunum with rhabdoid phenotype. As with tumors at other sites, recognition of rhabdoid morphology in small intestine neoplasms is of significance because the prognosis is extremely poor.

Topics: Aged; Anion Exchange Protein 1, Erythrocyte; Biomarkers; Biopsy; Carcinoma; Cell Nucleolus; Fatal Outcome; Humans; Hyalin; Immunohistochemistry; Inclusion Bodies; Jejunal Neoplasms; Jejunum; Keratins; Liver; Liver Neoplasms; Male; Neoplasm Proteins; Rhabdoid Tumor; Vimentin

Miscellaneous primary tumors of the uterine cervix are rare. Markers which can be utilized to detect these tumors are very few and in most cases, have not been clinically validated. The information provided in this article will help in developing strategies to discover novel markers and initiate translational research in this ignored area. Based on the reported studies, cytokeratin markers are common in many tumors and few of these rare cancers demonstrate human papilloma-virus (HPV) and Epstein Bar virus (EBV) infection. Due to the very low prevalence of these tumors, epidemiological studies have not been conducted and the etiology of these tumors is largely unknown.

Topics: Biomarkers, Tumor; Carcinoma; Cell Transformation, Neoplastic; Female; Humans; Immunohistochemistry; Keratins; Lipoma; Melanoma; Neurilemmoma; Rare Diseases; Sarcoma; Uterine Cervical Neoplasms

Anaplastic carcinoma of the pancreas is a rare undifferentiated variant of ductal adenocarcinoma, which commonly displays sarcomatoid spindle-cell and pleomorphic growth patterns. Anaplastic carcinoma of the pancreas associated with mucinous cystic neoplasm has rarely been reported.. Here we report a unique case of an anaplastic carcinoma of the pancreas in association with a mucinous cystadenocarcinoma in a 70-year-old woman. The anaplastic component of this tumor is predominantly composed of spindle cells and highly pleomorphic cells that mimic a spindle cell sarcoma. The spindle neoplastic cells have strong expression of vimentin and mucin 1 and focal strong positivity of CK7 and CK20. Scattered osteoclast-like giant cells are admixed with the spindle cells with positivity for CD68 but not epithelial or other mesenchymal markers. Focal squamoid differentiation is present. Adjacent to the solid anaplastic tumor is a classic mucinous cystadenocarcinoma, which has strong reactivity to mucin 1, CA 19-9, epithelial membrane antigen (EMA), CK19, CK8/18, carcinoembryonic antigen and CK7. The peri-cystic tissue and the septa consist of an ovarian-type stroma that is strongly positive for CD10. Focal areas with pancreatic intraepithelial neoplasia IB (PanIN-IB) changes are seen in the adjacent normal pancreatic tissue.. The anaplastic carcinoma of the pancreas is of epithelial origin with various microscopic features, and the scattered osteoclast-like giant cells in the tumor are reactive cells of histiocytic origin.

Topics: Adenocarcinoma, Mucinous; Aged; Carcinoma; Female; Humans; Keratins; Mucin-1; Pancreatic Neoplasms; Vimentin

Immunohistochemistry has become an important tool in the diagnosis of ovarian tumors. This article reviews the role of immunohistochemistry in the differential diagnosis of the three main categories of ovarian tumors, with emphasis on recently developed antibodies. In the surface epithelial stromal category the most common problem is its discernment from metastasis. The use of differential cytokeratins, primarily CK7 and CK20, as well as Cdx-2, beta-catenin, and P504S in differentiating between metastatic adenocarcinoma, particularly of colorectal origin, and primary ovarian carcinoma is discussed. Dpc4 may be useful in distinguishing pancreatic from ovarian mucinous carcinomas, because up to 55% of pancreatic carcinomas lack Dpc4 expression, whereas the differential expression of mucin genes may be helpful in distinguishing between primary ovarian mucinous and metastatic tumors. Urothelial markers (thrombomodulin and uroplakin III) and renal cell carcinoma markers (CD10 and renal cell carcinoma marker) can be helpful in the diagnosis of metastatic urothelial and renal cell tumors to the ovary. The roles of inhibin, calretinin, CD99, and other recently described markers in the diagnosis of sex cord-stromal tumors are reviewed. The uses of OCT-4 (POU5F1) (a new highly sensitive and specific marker of dysgerminoma and embryonal carcinoma), CD30, and c-kit are also discussed.

Topics: Biomarkers, Tumor; CA-125 Antigen; Carcinoma; Diagnosis, Differential; Female; Germinoma; Humans; Immunohistochemistry; Keratins; Neoplasm Metastasis; Ovarian Neoplasms; Racemases and Epimerases; Sex Cord-Gonadal Stromal Tumors; Trans-Activators

Sinonasal undifferentiated carcinoma is a rare and extremely malignant tumor of the paranasal sinuses. Historically, treatment outcomes have been poor. This review presents recent data on the management of sinonasal undifferentiated carcinoma and examines treatment trends that may result in improved locoregional control and survival.. Patients who receive aggressive multimodality treatments have improved outcomes. In particular, a chemoradiotherapy regimen including concurrent platinum-based chemotherapy given preoperatively or postoperatively to patients with resectable disease seems to result in better disease-free survival. Neoadjuvant chemotherapy, although strongly advocated by some, is currently not offered by many. Although surgery seems to be an important part of the treatment for sinonasal undifferentiated carcinoma, its ideal timing, either upfront or after radiotherapy, remains uncertain.. Overall, outcomes for sinonasal undifferentiated carcinoma are poor. An aggressive approach using surgery, platinum-based chemotherapy, and radiation seems to offer the greatest chance for significant locoregional control and survival.

Topics: Carcinoma; Chemotherapy, Adjuvant; Disease-Free Survival; Humans; Immunohistochemistry; Keratins; Neoplasm Invasiveness; Paranasal Sinus Neoplasms; Prognosis; Radiotherapy, Adjuvant; Risk Factors

To evaluate the clinical and pathologic findings in two patients with prior breast carcinoma who underwent diagnostic vitrectomy for vitreous opacities and preretinal membrane.. The clinical histories and ophthalmic findings in two patients were reviewed. Vitrectomy specimens from the patients were processed by cytospin and standard tissue techniques, stained with hematoxylin and eosin, and examined immunohistochemically for cytokeratins. The original breast carcinoma specimens were reviewed.. The vitreous in both patients contained malignant cells with cytologic features consistent with metastatic carcinoma. Immunohistochemical stains were positive for cytokeratins in the cells. The cytologic findings in the vitreous cells resembled the primary breast carcinoma.. Breast carcinoma may metastasize to the vitreous, most likely via the retina. The clinical manifestations include vitreous cell and preretinal membrane.

Topics: Aged; Aged, 80 and over; Breast Neoplasms; Carcinoma; Eye Neoplasms; Female; Humans; Immunohistochemistry; Keratins; Middle Aged; Staining and Labeling; Vitreous Body

Sarcomatoid carcinoma of the small bowel is rare; to our knowledge, 19 cases have been reported to date in the English literature under several names. We report an additional case occurring in the jejunum of a 55-year-old man. The tumor was a polypoid 7.5-cm mass, which infiltrated the full thickness of the intestinal wall and the serosa of an adhesed loop of small bowel. On microscopic examination, the neoplasm was composed of sheets of spindle cells; focally, an anaplastic component was present, including tumor giant cells with bizarre nuclei. On immunohistochemical stains, tumor cells were positive for cytokeratin 7, cytokeratin AE1/AE3, vimentin, and focally, epithelial membrane antigen. No staining for cytokeratin 20 was found. Sarcomatoid carcinoma must be kept in mind in the differential diagnosis of malignant spindle cell tumors of the small bowel. As consensus regarding the terminology of these rare tumors is being reached, immunohistochemical stains are essential for accurate diagnosis.

Topics: Carcinoma; Cell Nucleus; Diagnosis, Differential; Fatal Outcome; Humans; Jejunal Neoplasms; Keratin-7; Keratins; Male; Middle Aged; Mucin-1; Neoplasm Proteins; Sarcoma; Vimentin

A COMPLEX SITUATION: Carcinomas of unknown primary site (CUP) represent at least 3% of cancers in adults. This group is heterogenic and difficult to treat, the central element of which is permanent discussions between the physician and the anatomopathologist. SPECIFIC CLINICAL FORMS: The physician must rapidly identify certain entities of good prognosis or particular treatment: cervical lymph node metastases, axillary adenopathies from occult breast cancer, primary papillary peritoneal carcinomatosis, and median line syndrome. OTHER THAN IN THESE SITUATIONS: Present recommended diagnosis strategy is limited and non-invasive (histological review with immunohistochemistry, measurement of alphaFP, beta-HCG, PSA, chest X ray, mammography, tomography of abdomen and pelvis). Positron emission scintigraphy would merit further evaluation.

Topics: alpha-Fetoproteins; Biomarkers, Tumor; CA-125 Antigen; CA-19-9 Antigen; Carcinoma; Chorionic Gonadotropin, beta Subunit, Human; Diagnosis, Differential; Female; Humans; Immunohistochemistry; Keratins; Male; Middle Aged; Mucin-1; Neoplasms, Unknown Primary; Prostate-Specific Antigen; S100 Proteins

Although first described over a decade ago, the rare entity of mesothelial lymph node inclusions (nonneoplastic mesothelial cells involving lymph node sinuses) is not well-known among pathologists. Unlike most lymph node inclusions such as Müllerian inclusions or nevus cells, which usually occur in the capsule of the lymph node, mesothelial cells involve the lymph node sinus, mimicking metastatic carcinoma or metastatic mesothelioma. The spectrum of histologic findings ranges from a few mesothelial cells, perhaps only detectable by immunohistochemical stains, to a massive distention of the lymph node sinus with abundant mesothelial cells. Mesothelial-cell inclusions in lymph nodes are usually found in mediastinal lymph nodes of patients with pleural and/or pericardial effusions. It is hypothesized that the effusion, due to whatever cause, allows for mesothelial-cell migration into the submesothelial lymphatics and regional lymph nodes. To our knowledge, cytologic findings on aspiration biopsy and intraoperative smear preparations of a lymph node with mesothelial-cell inclusions have never been described. Familiarity with this entity is important in preventing misdiagnosis of malignancy.

Topics: Biopsy, Fine-Needle; Calbindin 2; Carcinoma; Diagnosis, Differential; Disease-Free Survival; Epithelium; Female; Humans; Immunoenzyme Techniques; Inclusion Bodies; Keratin-7; Keratins; Lymph Nodes; Middle Aged; S100 Calcium Binding Protein G

Two cases of invasive carcinoma developing in extragonadal endometriosis are presented. Each case had a different clinical course. In addition to routine histopathologic studies immunohistochemical studies to assess the expression of cytoceratin and glycoprotein CD-44 were performed. In both cases CK-7 expression was higher in malignancy then in the endometrioid tissue. Very high expression of CD-44 protein (marker of metastatic potential) was found in patients with poor progress of the disease.

Topics: Abdomen; Adult; Biomarkers, Tumor; Carcinoma; Cell Transformation, Neoplastic; Endometriosis; Female; Gene Expression Regulation, Neoplastic; Humans; Hyaluronan Receptors; Keratin-7; Keratins; Perineum; Skin Neoplasms; Up-Regulation

A 78-year-old Japanese man with undifferentiated carcinoma of the common bile duct is presented. Upon gross examination, the common bile duct was found to be obstructed by a nodule measuring 10 x 10 mm. Microscopically, the nodule was ill-defined and composed of atypical spindle-shaped and pleomorphic tumor cells. The spindle-shaped cells proliferated in a whirled or interlacing pattern simulating a sarcoma, and the pleomorphic tumor cells had abundant eosinophilic cytoplasm and bizarre nuclei. Histochemically, a few tumor cells contained mucosubstances stained with the alcian blue (AB) method in their cytoplasm. Immunohistochemically, the tumor cells were diffusely positive for CAM5.2 and AE1/AE3. The histological diagnosis was undifferentiated carcinoma (spindle cell carcinoma) of the common bile duct. Other than our patient, only four other cases of undifferentiated carcinoma in the extrahepatic bile duct have been reported in the literature.

Topics: Aged; Anion Exchange Protein 1, Erythrocyte; Biomarkers; Carcinoma; Common Bile Duct Neoplasms; Humans; Immunohistochemistry; Keratins; Male

Although spindle cell carcinoma (SC) is a common neoplasm in the oral cavity, upper respiratory tract, and other head and neck areas, its occurrence in the vulva is rare. We report a case of this rare condition with immunohistochemical, ultrastructural, and human papillomavirus (HPV) testing. The neoplastic cells were positive for vimentin, keratins (AE1-AE3, keratin 902, and keratin 903), and epithelial membrane antigen. Ultrastructurally, they showed primitive junctions and tonofilaments. HPV testing by polymerase chain reaction was negative. In addition, we review the clinicopathologic findings of the four well-documented cases of vulvar SC that have been reported previously in the English language literature.

Topics: Aged; Biomarkers, Tumor; Carcinoma; DNA, Viral; Fatal Outcome; Female; Humans; Immunohistochemistry; Intercellular Junctions; Intermediate Filaments; Keratins; Lichen Sclerosus et Atrophicus; Mucin-1; Neoplasm Proteins; Papillomaviridae; Polymerase Chain Reaction; Vimentin; Vulvar Neoplasms

We report the case of a 57-year-old immunocompromised man with a pilomatrix carcinoma in his left forearm. Pilomatrix carcinoma is the rare malignant counterpart of pilomatrixoma. It has a potential for local recurrence and can metastasise to distant sites. We discuss the differential diagnosis of this rare tumour, and the difficulty in distinguishing this lesion from an atypical proliferating pilomatrixoma. Ultrastructural features of pilomatrix carcinoma are also discussed.

Topics: Carcinoma; Desmosomes; Diagnosis, Differential; Hair Diseases; Humans; Immunoenzyme Techniques; Intermediate Filaments; Keratins; Male; Middle Aged; Mucin-1; Pilomatrixoma; Skin Neoplasms

Oncocytic schneiderian papillomas (OSPs) are uncommon benign neoplasms that arise from the sinonasal schneiderian epithelium. Malignancies arising in OSPs are rare, and, to our knowledge, only 14 such instances have been reported in the medical literature. We report 2 additional cases--a small cell carcinoma and a sinonasal undifferentiated carcinoma arising in OSPs and presenting synchronously with the benign neoplasm. The potential for malignant transformation in OSPs is small, but warrants that these papillomas be completely excised to exclude a coexisting carcinoma.

Topics: Aged; Biomarkers; Biopsy; Carcinoma; Humans; Immunohistochemistry; Keratins; Male; Middle Aged; Nasal Mucosa; Nose Neoplasms; Papilloma; Paranasal Sinuses

Extraocular sebaceous carcinoma is an uncommon neoplasm usually localized on the head and neck. We report a case of sebaceous carcinoma of the axillary skin with a highly aggressive behavior. The patient was a 43-year-old black man who developed multiple cutaneous and lymph node metastases shortly after the excision of primary sebaceous carcinoma of the axillary skin. Many neoplastic aggregations were identified within the lumina of the dermal lymphatic vessels in the excised specimen of the primary neoplasm. Although extraocular sebaceous carcinoma has been traditionally considered a less aggressive neoplasm than its ocular counterpart, a review of the literature and this case demonstrate that extraocular sebaceous carcinoma may also lead to disseminated metastatic disease.

Topics: Axilla; Carcinoma; Diagnosis, Differential; Humans; Immunohistochemistry; Keratins; Ki-67 Antigen; Lymphatic Metastasis; Male; Middle Aged; Mucin-1; Sebaceous Gland Neoplasms; Skin Neoplasms

This is Part 2 of a three-part review and deals with tumorigenic cell lines. Several immortalized and malignant adult human prostatic epithelial cell lines have been recently developed. The three most widely used carcinoma cell lines-DU-145, PC-3, and LNCaP-developed between 1977 and 1980, have greatly contributed to our current understanding of prostate cancer. Before a cell line can be accepted as having prostatic epithelial origin, some basic characteristics must be established. Expression of specific cytokeratins but absence of desmin and factor VIII should be first determined to establish epithelial origin. Responsiveness to androgens and expression of androgen receptor and prostate-specific antigen should be examined under stringent culture conditions to establish prostatic epithelial origin. Response to growth factors and expression of their receptors facilitates further characterization of cell behavior. Cell lines immortalized by human papillomaviruses (HPVs) are of special interest because HPVs are involved in a variety of anogenital cancers and may also play a role in prostate carcinogenesis. Malignant transformation of HPV-18 immortalized cells with the ras oncogene provides cell systems for investigating the multistep process of carcinogenesis. Each cell line has some unique characteristics, whether it arose directly from a carcinoma or resulted from immortalization with Simian virus 40 (SV40) or HPV, or was transformed in vitro by oncogenes. Comparisons of these characteristics should facilitate elucidation of the mechanisms involved in the initiation, promotion, and progression of prostate cancer. These cell lines will further serve as useful models for investigating tumor progression, invasion, metastasis, new therapeutic strategies, drug resistance, and its reversal and chemoprevention. The nontumorigenic cell lines were discussed in Part 1 [1]. This review summarizes the characteristics of several currently available tumorigenic, adult human prostatic epithelial cell lines.

Topics: Antigens, Neoplasm; Antigens, Surface; Carcinoma; Cell Line; Cell Transformation, Neoplastic; Epithelium; Glutamate Carboxypeptidase II; Growth Substances; Humans; Immunohistochemistry; Keratins; Male; Papillomaviridae; Prostate; Prostatic Neoplasms; Receptors, Androgen; Tumor Cells, Cultured

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

Sarcomatoid transitional cell carcinoma of the renal pelvis is a rare neoplasm with only 7 well illustrated examples reported. These tumours can assume a partial or complete spindle cell pattern of growth, leading to the erroneous classification as sarcomas. We describe the clinic-pathologic features of five additional examples of sarcomatoid carcinoma of the renal pelvis observed in three males and two females. The age ranged from 65-to-82 years-old (mean 71.6). All these patients were treated by nephrectomy and died of disease between 6 and 20 months (mean 11.2) after the onset of symptoms. An immunohistochemical study demonstrated coexpression of keratins, epithelial membrane antigen and vimentin. The image DNA ploidy of all the tumours showed an aneuploid pattern.

Topics: Aged; Aged, 80 and over; Carcinoma; Carcinoma, Transitional Cell; Female; Humans; Immunohistochemistry; Keratins; Kidney Neoplasms; Kidney Pelvis; Male; Mucin-1; Ploidies; Vimentin

The clinical and pathologic features of a breast tumor with unusual morphology in a 69-year-old woman are presented. Spindle cell carcinoma is considered one of the variants of metaplastic carcinoma and is commonly described in the upper aerodigestive tract, but it is relatively rare in the breast. This case is uniquely different from the usual cases of spindle cell carcinoma because of the lack of squamous differentiation or a recognizable infiltrating ductal component at the light microscopic level. With immunohistochemical stains using keratin and actin, a rather prominent network of infiltrating compressed ductal structures became apparent. These immunohistochemical features are consistent with the current concept of myoepithelial origin for metaplastic carcinomas. Although mention has been made in the literature of cases in which this "bland" carcinoma could be confused with benign nonneoplastic conditions, few illustrated examples exist. The prognosis for this particular subgroup of metaplastic carcinoma may be somewhat better than that for ordinary ductal carcinoma. For prognostic purposes, this entity should be distinguished from other metaplastic carcinomas and sarcomas, but more importantly, it should be differentiated from lesions such as nodular fasciitis, reactive granulation tissue, and fibromatosis, with which it may be confused histologically.

Topics: Actins; Aged; Breast Neoplasms; Carcinoma; Cell Differentiation; Female; Humans; Immunohistochemistry; Keratins

There is a great deal of confusion in the literature as to whether or not true angiosarcomas of the thyroid exist or whether these are all anaplastic carcinomas of the thyroid which have an angiosarcomatoid appearance. Due to the fact that undifferentiated carcinomas of this organ can strikingly resemble various sarcomas it is recommended that great care should be taken prior to qualify as an angiosarcoma a malignant thyroid tumor. A lot of viewpoints have been expressed so far in literature concerning this theme, and they can be summarized as follows. On one side and not admitting the existence of angiosarcoma in this location there are opinions which think of it as a "variant" of undifferentiated carcinoma (a pure carcinoma with a pseudovascular pattern or a carcinoma with an intermingled non-neoplastic reactive vascular component), or as a neoplasm in transition from epithelial to endothelial differentiation ("mesenchymal neometaplasia"), or as a carcinoma with aberrant expression of endothelial markers, or as a carcinoma with a non-specific uptake of endothelial antigens(e.g. from serum in case of F-VIII R-Ag positivity). On the other side there are opinions in favor of the existence of such an entity, based upon light microscopy features coupled with immunocytochemical results (endothelial antigens expression without or with cytokeratins expression) and with the possible support of electron microscopy. Anyway ultrastructural findings of specific markers (Weibel-Palade bodies, pericellular basal lamina, tight junctions, subplasmalemmal pinocytotic vesicles) according to some authors are not a prerequisite: so poorly differentiated neoplasma can fail to show those histogenetic markers.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Aged; Antigens, Differentiation, Myelomonocytic; Biomarkers, Tumor; Carcinoma; Cell Adhesion Molecules; Cell Differentiation; Endothelium; Hemangiosarcoma; Humans; Keratins; Lectins; Male; Neoplasm Proteins; Plant Lectins; Platelet Endothelial Cell Adhesion Molecule-1; Thyroid Neoplasms; Vimentin; von Willebrand Factor

Immunohistochemical analysis of 9 choroid plexus papillomas (CPPs) and 3 choroid plexus carcinomas (CPCs) using a panel of antibodies against glial fibrillary acidic protein (GFAP), cytokeratin (CK), epithelial membrane antigen (EMA), S-100 protein, vimentin (vim), and neuron specific enolase (NSE) is presented. Focal positivity was observed for GFAP in 11, vimentin in 7, cytokeratin in 2 and EMA in 3 cases. Diffuse and intense immunoreactivity for S-100 protein was seen in all papillomas, however, unreactive areas were noted in carcinomas. All cases exhibited focal to diffuse NSE positivity. Location and type of the tumour and age of the patient did not influence the staining pattern except for predominant S-100 positivity in papillomas. The significance of these findings is discussed in relation to the differential diagnosis or immunoreactivity patterns of these tumours.

Topics: Adult; Carcinoma; Child; Child, Preschool; Choroid Plexus Neoplasms; Female; Glial Fibrillary Acidic Protein; Glioma; Humans; Infant; Keratins; Male; Membrane Glycoproteins; Middle Aged; Mucin-1; Mucins; Phosphopyruvate Hydratase; S100 Proteins; Sensitivity and Specificity; Vimentin

Intermediate filaments (IFs; diameter, about 10 nm) are cytoplasmic cytoskeletal structures found in most vertebrate cells. Their protein subunits comprise a large multi-gene family of related proteins, which make it possible to divide IFs into seven separate classes whose expression is cell-type-dependent. The most important IF classes are cytokeratin (CK) filaments (epithelial cells), vimentin filaments (mesenchymal cells), desmin filaments (muscle cells), glial filaments (astrocytes), and neurofilaments (nerve cells). As the specificity of expression of IF proteins is retained in malignant tumors, they are suitable as histological markers of differentiation (tumor markers). The protein subunits of the epithelial CK filaments are unusually diverse, and within the various types of epithelia, their expression is differentiation specific. Until recently, the catalog of human CKs comprised 19 related, yet distinct polypeptides (CKs 1-19; Moll et al., 1982a); CK 20 can now be added to this list. On the basis of sequence relationships, two CK subfamilies can be delineated (CKs 9-20 = type I; CKs 1-8 = type II). Any given epithelial cell exhibits a characteristic, differentiation-dependent combination of two or more CK polypeptides, with type-I and -II polypeptides always occurring in stoichiometric amounts (i.e., as "pairs"), because the basic structural unit of the CK filaments is a heterotypical tetramer complex. On the basis of their main tissue distribution patterns, it is possible further to subdivide these polypeptides into CKs typical of stratified squamous epithelia (CKs 1-6, 9-17) and those typical of simple columnar epithelia (CKs 7, 8, 18-20); these CKs exhibit differential expression patterns in the various types of squamous and columnar epithelia. The actual characterization of the novel CK 20 as a CK initially proved to be rather difficult, as this cytoskeletal protein, which can be biochemically isolated from cells of the intestinal epithelium (M(r) 46,000; previously called "IT protein"), exhibits no reaction with numerous well-known CK antibodies in Western blots. However, a series of other characteristics typical of CKs could be demonstrated. Thus, IT protein was found, in vitro (nitrocellulose-blot binding test, native gel electrophoresis), to for heterotypical complexes with the type-II CK 8, and these complexes were able to reconstitute themselves into typical IFs in vitro. Chymotrypsin-cleaving experiments revealed the presence of a resi

Topics: Animals; Biomarkers; Biomarkers, Tumor; Carcinoma; Epithelial Cells; Epithelium; Humans; Keratins

Cutaneous metastasis from gastric carcinoma is uncommon. We describe a patient with a metastasis from gastric carcinoma to a congenital melanocytic nevus. The diagnosis was confirmed by positive immunohistochemical staining for cytokeratin 20 and lack of cytokeratin 7.

Topics: Carcinoma; Collagen; Cytoplasm; Female; Hair; Humans; Keratins; Melanocytes; Middle Aged; Neoplasms, Multiple Primary; Nevus, Pigmented; S100 Proteins; Skin Neoplasms; Stomach Neoplasms; Sweat Glands; Vimentin

Malignant cutaneous cylindroma is a rare tumor. It has been described in 26 cases, both in the solitary form and in the autosomal dominant inherited multiple tumor form. The authors present two new cases that occurred in one family with a history of multiple cylindromas.. Clinical and histopathologic data of both tumors were compared with those of 26 other cases in the literature. Immunohistochemical examinations were performed.. The malignant tumors were distinguished from the benign lesions by rapid growth, long-standing ulceration, or bleeding. Histopathologic examination showed a well-differentiated carcinoma in one patient and a poorly differentiated tumor in the other. In the latter, lymph node metastasis developed, and the patient died 2.5 years later. Histopathologic criteria of malignancy included cell pleomorphism, frequent mitoses and loss of jigsaw pattern, peripheral palisading, hyaline sheaths, and dual cell population.. These observations are in accord with those in the literature. Malignant cutaneous cylindroma developed more often in the multiple tumor form than in the single tumor form. Malignant cylindroma is an aggressive carcinoma with a tendency to local destructive growth and metastases.

Topics: Aged; Antigens, Neoplasm; Carcinoma; Carcinoma, Adenoid Cystic; Cell Transformation, Neoplastic; Cytoplasm; Female; Humans; Hyalin; Keratins; Lymphatic Metastasis; Male; Membrane Glycoproteins; Mucin-1; S100 Proteins; Skin Neoplasms

The histologic classification for odontogenic carcinomas is still under revision; thus, the differentiation between the terms "malignant ameloblastoma" and "ameloblastic carcinoma" has not been definitely stated. Nevertheless, it is recommended to reserve the former for those lesions that, in spite of an apparently innocuous histology, have given origin to metastatic growths, and to apply the latter for those ameloblastomas in which there is histologic evidence of malignancy in the primary, recurrent or metastatic lesions. A case of an ameloblastic carcinoma in the mandible is presented. Histologically, it was characterized by areas with features of a typical ameloblastoma and areas with anaplastic appearances.

Topics: Ameloblastoma; Carcinoma; Cell Nucleolus; Cell Nucleus; Collagen; Cytoplasm; Humans; Keratins; Male; Mandibular Neoplasms; Middle Aged; Neoplasm Recurrence, Local

An extremely rare case of mucoepidermoid carcinoma of the thyroid in a 56-year-old woman is presented. The patient clinically having Hashimoto's thyroiditis was noted a nodule in her neck. The tumor was sited in the midportion of the left lobe of the thyroid, and histologically it showed both squamous features and mucin production. The squamous cells were arranged in solid sheets with horny pearls and the mucous cells tended to line dilated duct-like elements. Ultrastructurally, the epidermoid cells had aggregates of tonofilaments and well-developed desmosomal attachments, and the mucous cells contained numerous mucin granules in their cytoplasm. Immunohistochemical studies revealed that cytokeratin antibodies showed positivity for both the lining cells and squamous cells, whereas carcinoembryonic antigen positivity was found in the lining cells and intraluminal material. The tumor cells were negative for thyroglobulin, calcitonin, vimentin, chromogranin, and neuron-specific enolase. These unusual histologic and immunohistochemical features are suggestive of a tumor related to the so-called "solid cell nest" of the thyroid.

Topics: Carcinoembryonic Antigen; Carcinoma; Female; Humans; Immunoenzyme Techniques; Keratins; Microscopy, Electron; Middle Aged; Mucins; Prognosis; Staining and Labeling; Thyroid Neoplasms; Thyroiditis, Autoimmune

Topics: Animals; Carcinoma; Cell Differentiation; DNA Probes; Keratins; Mice; Papilloma; Precancerous Conditions; Skin Neoplasms

Topics: Antibodies, Monoclonal; Carcinoma; Cross Reactions; Diagnosis, Differential; Epitopes; Humans; Immunohistochemistry; Keratins; Neoplasms; Pathology, Surgical; Vimentin

Topics: Antigens, Neoplasm; Biomarkers, Tumor; Carcinoma; Epithelium; Humans; Intermediate Filaments; Keratins; Peptides; Tissue Polypeptide Antigen; Vimentin

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

Keratin protein immunohistochemistry is a powerful diagnostic tool whose role has already been firmly established in many surgical pathology laboratories. Recent studies of the biology of keratin proteins have defined the heterogeneity of keratin protein expression among various epithelial tissues and their tumors and provide the basis for understanding the immunoreactivity of epithelial tumors with various keratin antibodies. Successful execution of the procedure requires attention to technical details such as the fixation of tissue, use of proteolytic enzymes such as trypsin for formalin-fixed tissues, and the choice of the appropriate antibody and controls. Broadly reactive polyclonal and monoclonal antibodies to keratins have been remarkably useful in identifying poorly differentiated and undifferentiated carcinomas. Monoclonal antibodies of restricted specificity and monospecific antibodies to keratin are under development and may prove helpful in defining the organ of origin of metastatic carcinomas. Keratin protein immunohistochemistry supplements existing information used by pathologists in diagnosis, and the immunohistochemical results should be interpreted in the light of the clinical findings, gross and microscopic pathology, and the results of any other special studies.

Topics: Animals; Antibodies; Antibodies, Monoclonal; Bone Neoplasms; Carcinoid Tumor; Carcinoma; Humans; Immunoassay; Keratins; Neoplasms; Sarcoma; Soft Tissue Neoplasms

Most mammalian nucleated cells contain a cytoplasmic fibril system called intermediate filaments. Unlike other cytoskeletal proteins, the subunit proteins of intermediate filaments show a remarkable cell-type-specificity in their expression: mesenchymal, muscle, epithelial, glial and neuronal cells containing each their cell type specific filaments. In this review we discuss the possibilities to use antibodies to these filaments in the diagnosis and histogenetic analysis of human tumors. This approach is based on findings which indicate that these filaments retain their cell-type specific expression also in tumors.

Topics: Antibodies; Carcinoma; Cytoskeleton; Desmin; Glial Fibrillary Acidic Protein; Glioma; Humans; Intermediate Filaments; Keratins; Mesothelioma; Neoplasms; Rhabdomyosarcoma; Sarcoma; Vimentin

A panel of monoclonal antibodies to human intermediate filament proteins was tested on an unselected series of 246 neoplasms. The antibody panel includes two different anti-cytokeratin antibodies, an anti-vimentin antibody, and an anti-neurofilament antibody (Gown and Vogel, Am J Pathol 114:309, 1984). The studies were done on Carnoy's or methacarn-fixed, paraffin-embedded tissue. When used as a panel, they can unequivocally distinguish carcinomas, melanomas, and lymphomas. All carcinomas react with at least one of the anti-cytokeratin antibodies, and carcinomas can be subtyped based upon the pattern of reactivity with the two anti-cytokeratin antibodies. Melanomas react only with the anti-vimentin antibody, and lymphomas react with none of the antibodies. Neural and neuroendocrine tumors can be identified with the anti-neurofilament antibody. A minority of neoplasms, including lymphomas, seminomas, and some sarcomas, do not react with any of the antibodies. These antibodies are reliable diagnostic reagents that are useful in distinguishing different categories of human tumors.

Topics: Antibodies, Monoclonal; Antibody Specificity; Carcinoma; Cytoskeleton; Humans; Intermediate Filament Proteins; Keratins; Melanoma; Neoplasms; Nervous System Neoplasms; Vimentin

The cytoskeleton (CSK) of eukaryotic cells is composed of a complex interconnected network of filaments which is important in a wide variety of cellular functions including changes in cell shape, cell motility, mitosis, anchorage-dependent growth, and the localization of cellular organelles such as mitochondria, polyribosomes, and secretory granules. The various proteins comprising the cytoskeleton include actin in microfilaments, tubulin in microtubules, and the heterogeneous group of intermediate filament proteins that are associated with different cell types (keratin in epithelial cells, vimentin in fibroblasts, desmin in muscle cells, glial filament protein in glial cells, and the neurofilament protein subunits in neural tissue). Many other proteins in glial cells, and the neurofilament protein subunits in neural tissue). Many other proteins are closely associated with the cytoskeleton and influence its organization. In neoplastic cells, the expression of these different CSK proteins, especially the intermediate filament proteins, reflects their morphologic and functional differentiation. The carcinomas contain keratin; identification of individual keratin components may allow further sub-classification of carcinomas which is consistent with their tissue of origin. The sarcomas of muscle origin contain desmin. Vimentin is found primarily with cells of mesenchymal origin, but may coexist with other intermediate filament proteins in other tumors. One example is the coexistence of keratin and vimentin in tumors, such as mesotheliomas, which are derived from epithelial cells of embryonic origin. Glial fibrillary acidic protein is the most specific marker for glial tumors. Tumors of neural origin are characterized by the presence of neurofilament subunits. Therefore, analysis of CSK composition would be useful in diagnosis of clinical specimens and aid in studies of lineage relationships of neoplasms. Although no consistent differences in cytoskeletal structure between neoplastic and normal cells have been identified so far, the presence of more subtle biochemical alterations in the cytoskeletal structure of neoplastic cells that contributes to malignant behavior has not been ruled out. Since the cytoskeletal network plays an important role in cell shape and cell locomotion, which in turn are thought to be involved in growth control, invasion, and metastasis, further work is directed at identifying the various alterations in cytoskeletal architecture that

Topics: Actin Cytoskeleton; Actins; Animals; Astrocytes; Carcinoma; Cell Differentiation; Cell Division; Cell Transformation, Neoplastic; Cytoskeletal Proteins; Cytoskeleton; Desmin; Epithelium; Glial Fibrillary Acidic Protein; Glioma; Granulocytes; Humans; Intermediate Filament Proteins; Keratins; Leukemia; Lymphoma; Macrophages; Microtubules; Molecular Weight; Muscles; Neoplasm Metastasis; Neoplasms; Neoplasms, Nerve Tissue; Neurons; Sarcoma; Tissue Distribution; Vimentin

A wide variety of human neoplasms were examined by immunocytochemical and ultrastructural techniques. In most, one intermediate filament (IF) type was expressed reflecting the tissue of origin. However, multiple classes of intermediate filaments were regularly found in a subgroup of these tumors. We chose to subdivide them into those with a complex or mixed growth pattern, and those which showed a more "monomorphic" histologic growth pattern. This latter group is the subject of this paper. Regular coexpression of cytokeratin and vimentin was observed in tumors of endometrial, thyroid, ovarian and renal origin, and coexpression of cytokeratin and neurofilament was observed in a subgroup of neuroendocrine tumors. Immunocytochemical/ultrastructural correlation demonstrated few, if any, observable intermediate filaments in tumors expressing only low molecular weight cytokeratin, whereas vimentin and neural filament characteristically were randomly dispersed or formed whorled bundles of cytoplasmic filaments. The potential diagnostic usefulness of these observations in surgical pathology is discussed.

Topics: Carcinoid Tumor; Carcinoma; Carcinoma, Small Cell; Cytoskeleton; Endocrine System Diseases; Female; Humans; Intermediate Filaments; Keratins; Kidney Neoplasms; Lung Neoplasms; Ovarian Neoplasms; Thyroid Neoplasms; Uterine Neoplasms; Vimentin

Topics: Animals; Carcinoma; Cytoplasm; Digestive System; Embryonic and Fetal Development; Epidermal Cells; Female; Humans; Hyperplasia; Keratins; Male; Melanocytes; Neuroblastoma; Neurosecretory Systems; Rats; Skin; Skin Neoplasms

Immunofluorescence and immunoperoxidase (peroxidase-antiperoxidase, PAP) techniques for the demonstration of neural and non-neural cell markers are contributing greatly to increase the diagnostic accuracy of difficult tumors of the central nervous system. Well characterized nervous system markers include glial fibrillary acidic (GFA) protein, the three protein subunits of neurofilaments, neuron-specific enolase (NSE), myelin basic protein, and S-100 protein. The most important and reliable of these is GFA protein, which is widely in use for the immunohistochemical diagnosis of tumors of the glioma group. Its many practical applications are reviewed and illustrated. Other neural markers, in particular the specificity of NSE and S-100 protein, need to be critically evaluated. Problems related to the immunohistochemical diagnosis of central neuroepithelial tumors of putative neuroblastic origin remain complex and still need to be resolved. Non-neural markers, such as vimentin, desmin, cytokeratins, Factor VIII, alpha-fetoprotein, human chorionic gonadotropin, and immunoglobulins have well defined, although more restricted, applications in surgical neuropathology.

Topics: alpha-Fetoproteins; Antibodies, Monoclonal; Antigens; Carcinoma; Central Nervous System Diseases; Chorionic Gonadotropin; Cytoskeleton; Desmin; Factor VIII; Fluorescent Antibody Technique; Glial Fibrillary Acidic Protein; Histocytochemistry; Humans; Immune Sera; Immunoenzyme Techniques; Immunoglobulins; Intermediate Filament Proteins; Keratins; Lymphoma; Medical Oncology; Meningeal Neoplasms; Myelin Basic Protein; Neoplasm Metastasis; Neoplasms; Neoplasms, Germ Cell and Embryonal; Neurology; Oligodendroglia; Phosphopyruvate Hydratase; S100 Proteins; Sarcoma; Vascular Diseases; Vimentin; von Willebrand Factor

Topics: Carcinoembryonic Antigen; Carcinoma; Diagnosis, Differential; Female; Histocytochemistry; Humans; Immunoenzyme Techniques; Immunologic Techniques; Keratins; Melanoma; Mesenchymoma; Paget Disease, Extramammary; Protein Precursors; S100 Proteins; Vulvar Neoplasms

In most cell types intermediate or 10-mm filaments (IF) are a major cytoskeletal organization and, thus, directly or indirectly influence the structural appearance of the cytoplasm. In line with the cell type-specific expression patterns of different IF proteins in normal animal and human tissue, IF typing distinguishes the major tumor groups, as documented by results with several hundred human tumors classified by conventional histologic methods. Carcinomas are characterized by cytokeratins, sarcomas of muscle cells by desmin, nonmuscle sarcomas by vimentin, and gliomas by glial fibrillary acidic protein. Furthermore, certain tumors originating from the sympathetic nervous system, e.g., ganglioneuroblastoma, pheochromocytoma, and at least some neuroblastomas, are characterized by the presence of neurofilaments. Carcinomas can often be further subdivided with regard to their possible derivation by examining their cytokeratin profiles. The IF type characteristic of the cell of origin seems to be kept not only in the primary tumor but usually also in solid metastases. In general, tumors do not acquire additional IF types. Therefore, IF typing can provide an unambiguous and rapid characterization in certain cases, that are difficult to diagnose by conventional techniques. Some useful examples are the small cell tumors of childhood and the discrimination between undifferentiated carcinoma and lymphoma. IF typing of a few tumors has already led to a revision or reconsideration of the original light microscopic diagnosis. The combined results indicate that at least certain carcinomas, as well as certain other tumor types, seem to arise by the selective multiplication of a particular and identifiable cell type present in the normal tissue. The procedure is not restricted to tumor material. IF typing of Mallory bodies, Alzheimer's disease tangles, certain myopathies, and the cells of the amniotic fluid offers further interesting applications. Thus, IF typing should become a valuable new tool both in histology and surgical pathology.

Topics: Amniotic Fluid; Animals; Carcinoma; Cells, Cultured; Cytoskeleton; Desmin; Embryo, Mammalian; Fluorescent Antibody Technique; Ganglioneuroma; Glial Fibrillary Acidic Protein; Glioma; Humans; Intermediate Filament Proteins; Keratins; Muscular Diseases; Neoplasm Metastasis; Neoplasms; Neuroblastoma; Pheochromocytoma; Sarcoma; Vimentin

The authors assessed the detection of sentinel lymph nodes in patients with esophageal squamous cell carcinoma (SCC) using technetium-99m colloidal rhenium sulfide. They studied whether an analysis of sentinel lymph nodes using cytokeratin (CK) immunohistochemistry increased the accuracy of staging.. The authors observed 25 patients with thoracic esophageal carcinomas who underwent radical esophagectomy. The day before surgery, technetium-99m colloidal rhenium sulfide was injected into the submucosa at four sites around the primary tumor. Lymphoscintigraphy was performed. Esophagectomy and regional lymph node dissection were performed 17 hours after the technetium-99m injection. After surgery, the resected lymph nodes were evaluated by CK staining.. Lymphoscintigraphy detected sentinel lymph nodes in 92% of the patients (23 of 25 patients). The accuracy of sentinel lymph node was 91.3% (21 of 23 patients), the sensitivity was 86.7% (13 of 15 patients), and the false-negative rate was 8.7% (2 of 23 patients). A comparison of the number of sentinel lymph nodes and clinicopathologic factors showed that there was a significant association between the number of sentinel lymph nodes and lymph node status (P < 0.01), pathologic stage (P < 0.05), and the number of metastatic lymph nodes (P < 0.05). Occult metastasis was detected by CK staining in 14 (56%) of the 25 patients and in 23 (1.7%) of 1406 lymph nodes. Because the 2 false-negative (sentinel lymph node-negative and nonsentinel lymph node-positive) patients who had occult metastases in the sentinel lymph nodes, the accuracy of sentinel lymph node evaluation using CK staining was 100% (23 of 23).. Lymphatic mapping with technetium-99m colloidal rhenium sulfide was used to identify the lymphatic basin and was feasible in patients with esophageal SCC. An analysis of sentinel lymph nodes using CK immunohistochemistry increased the accuracy of sentinel lymph node.

Topics: Aged; Carcinoma; Esophageal Neoplasms; Esophagectomy; False Negative Reactions; Female; Humans; Immunochemistry; Keratins; Lymphatic Metastasis; Male; Middle Aged; Radionuclide Imaging; Radiopharmaceuticals; Rhenium; Sensitivity and Specificity; Sentinel Lymph Node Biopsy; Technetium Compounds

The detection of isolated tumor cells (ITC) in the bone marrow of patients with epithelial malignancies is an independant prognostic factor for several entities as breast cancer, colorectal cancer or non-small lung cancer. However, with conventional immunocytology using Ficoll density gradient and APAAP staining, only a small proportion of the bone marrow samples can be scanned for cytokeratin-positive (CK+) cells. To improve detection rates, we evaluated the enrichment of ITC by magnetic activated cell sorting (MACS) compared to regularly stained cytospins. Recovery experiments with a CK+ breast cancer cell line (SKBR3) were performed to calculate the MACS enrichment rate. Bone marrow was obtained by aspiration from 20 patients with carcinomas of epithelial origin and from 17 controls. ITC were enriched and stained with magnetically labeled CAM 5.2 antibodies directed to cytokeratin 7 and 8. MACS of SKBR3 seeded in peripheral blood revealed average recovery rates of 62% and 48% and average enrichment factors of 104-fold and 8139-fold of the CK+ cells after one and after two separations, respectively. After immunomagnetic enrichment, CK+ cells were detected in 16 of 20 (80%) cancer patients, whereas only 7 (35%) patients showed CK+ cells without magnetic enrichment (P = 0.002). Ten of twelve (83%) patients with metastatic disease (stage M1) and six of eight (75%) patients without any overt metastases (M0) had CK+ cells in their bone marrow. None of the negative controls showed any CK+ cells. Enrichment with magnetically labeled anti cytokeratin antibodies increases the detection rate of epithelial cells in bone marrow of cancer patients compared to immunocytology.

Topics: Adult; Aged; Aged, 80 and over; Biomarkers; Biomarkers, Tumor; Bone Marrow Neoplasms; Breast Neoplasms; Carcinoma; Carcinoma, Non-Small-Cell Lung; Colonic Neoplasms; Female; Humans; Immunohistochemistry; Keratins; Lung Neoplasms; Magnetics; Male; Middle Aged; Prospective Studies; Tumor Cells, Cultured; Urinary Bladder Neoplasms

Lymph node (LN) metastasis is one of the most significant prognostic factor in colorectal cancer. In fact, therapeutic decisions are based on LN status. However, multiple studies have reported on the limitations of the conventional pathological LN examination techniques, and therefore, the actual number of patients with LN positive colorectal cancer is probably underestimated. We assume that lymphatic tumor dissemination follows an orderly sequential route. We report here a simple and harmless coloration technique that was recently elaborated, and that allows us to identify the sentinel LN(s) (SLN) or first relay LNs in colorectal cancer patients. The main endpoint of this clinical trial is the feasibility of the technique.. Twenty patients treated by surgery for a colic cancer were admitted in this protocol. A subserosal peritumoral injection of lymphazurin 1% was performed 10 min before completing the colic resection. A pathologist immediately examined the specimens, harvested the colored SLN, and examined them by serial cuts (200 microm) with H&E staining, followed by immunohistochemical staining (AE1-AE3 cytokeratin markers), when serial sections were classified as cancer free.. The preoperative identification of the SLN was impossible in at least 50 of the cases, however, SLNs were identified by the pathologist in 90% of cases. In two patients (10%) SLN was never identified. The average number of SLN was 3.9. Immunohistochemical analysis of the SLN has potentially changed the initial staging (from Dukes B to Dukes C) for 5 of the 20 patients (25%). On the other hand, there was one patient (5%) with hepatic metastasis from adenocarcinoma for whom SLN pathology was negative for metastasis (skip metastasis).. SLN biopsy is readily feasible with identification of SLN in at least 90% of patients with colorectal cancers. Our results indicate that 45% of patients initially staged as Dukes B had tumor cells identified in their SLN when these were subjected to our protocol. This represented a 25% upgrading rate when our complete study population is considered. However, controversy persist about the clinical significance and metastatic potential of these often very small clusters of tumor cells.

Topics: Biomarkers, Tumor; Carcinoma; Colonic Neoplasms; Humans; Immunohistochemistry; Keratins; Lymph Node Excision; Lymphatic Metastasis; Patient Care Planning; Preoperative Care; Rosaniline Dyes; Sentinel Lymph Node Biopsy

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

We describe a case of a myoepithelial carcinoma of the superficial parotid gland in a 46-year-old male harboring a novel CTCF::NCOA2 gene fusion. To our knowledge, this novel gene fusion has not been described previously in myoepithelial carcinoma. A 46-year-old male patient presented with a mass involving the superficial left parotid gland with extension into the external auditory canal (EAC) and erosion of the conchal cartilage. Histologically, the neoplasm was composed of uniform spindled, epithelioid/ovoid cells arranged in cords and nests within hyalinized to myxoid stroma. On immunohistochemistry (IHC), the tumor cells demonstrated patchy and variable staining for low molecular weight cytokeratin (CAM5.2), pan-cytokeratin (OSCAR), and S-100. Overall, the morphological and immunohistochemical attributes supported a locally aggressive tumor of myoepithelial differentiation consistent with myoepithelial carcinoma. Molecular analysis using a custom 115-gene gene panel by targeted RNA sequencing, showed an in-frame CTCF::NCOA2 fusion. In addition to reporting this novel fusion in myoepithelial carcinoma, we also discuss relevant differential diagnosis, and provide a brief review of NCOA2 gene function in both normal and neoplastic contexts.

Topics: Carcinoma; Humans; Keratins; Male; Middle Aged; Myoepithelioma; Nuclear Receptor Coactivator 2; Parotid Gland; Parotid Neoplasms

The tumor formerly known as "cauda equina paraganglioma" was recently renamed as cauda equina neuroendocrine tumor (CENET) based on distinct biological and genetic properties. Nevertheless, it remains insufficiently understood. For this study, we retrieved CENETs (some previously reported), from the pathology files of 3 institutions; we examined their immunohistochemical profile, including common neuroendocrine tumor-associated hormones and transcription factors. We identified 24 CENETs from 7 female and 17 male adult patients, with a median age of 47 years. Six included neurofilament-positive ganglion cells. All tumors tested were positive for INSM1, synaptophysin, chromogranin A, SSTR2, and CD56 as well as at least 1 keratin (AE1/AE3, CAM5.2); CK7 and CK20 were negative. Glial fibrillary acidic protein was negative, except for peripheral nontumoral elements. S100 protein was variable but mainly expressed in scattered sustentacular cells. All but 1 tumor tested were positive for HOXB13; several stained for SATB2, and all tumors were consistently negative for GATA3. All tumors tested were negative for transcription factors found in various other epithelial neuroendocrine neoplasms including TTF1, CDX2, PIT1, TPIT, SF1, and PAX8; staining for T-brachyury was negative. Four of 5 CENETs tested had at least focal tyrosine hydroxylase reactivity. Serotonin expression was detected in all 21 tumors tested; it was diffusely positive in 5 and had variable positivity in the remainder. A few tumors had scattered cells expressing gastrin, calcitonin, pancreatic polypeptide, and peptide YY, while glucagon, adrenocorticotropic hormone, and monoclonal carcinoembryonic antigen were negative. PSAP expression was found focally in 4 of 5 tumors examined. SDHB was consistently intact; ATRX was intact in 14 tumors and showed only focal loss in 3. The median Ki-67 labeling index was 4.5% (range: 1% to 15%). We conclude that CENET represents a distinct neuroendocrine neoplasm; the subset with ganglion cells qualifies for designation as composite gangliocytoma/neuroma-neuroendocrine tumor (CoGNET) as defined in the 2022 WHO classification of neuroendocrine neoplasms. In addition to INSM1, chromogranin, synaptophysin, and keratins, the most characteristic finding is nuclear HOXB13 expression; a subset also express SATB2. Serotonin is the most common hormone expressed. The cytogenesis and pathogenesis of these lesions remains unclear.

Topics: Adult; Biomarkers, Tumor; Carcinoma; Cauda Equina; Female; Humans; Keratins; Male; Middle Aged; Neuroendocrine Tumors; Paraganglioma, Extra-Adrenal; Repressor Proteins; Serotonin; Synaptophysin; Transcription Factors

Extranodal follicular dendritic cell sarcomas are infrequent diagnostically challenging tumors. Because of their rarity, heterogeneous histomorphologic features and variable histologic grades a significant number of extranodal lesions are prone to be misdiagnosed. Even though they have a characteristic immunoprofile, expression of a range of nonspecific markers is well documented. Even though they are typically negative for keratins, few authors have reported lesions expressing keratin. Keratin expressing tumors are more likely to be misinterpreted by pathologists further deterring their inclusion in the differential diagnosis. We report an intraabdominal mesenteric follicular dendritic cell sarcoma in a 44-year-old male that immunophenotypically expressed keratin antigens. The lesion showed a high-grade pleomorphic epithelioid appearance and the initial differential diagnosis included lymphoma, sarcomas, melanoma, and carcinomas. Follicular dendritic cell sarcoma was not considered. Expression of epithelial membrane antigen and keratin further deterred the diagnosis which was reached only after extensive use of immunomarkers. The tumor cells expressed CD21, CD23, and D2-40. Morphologically, the tumor showed some thymoma-like features with occasional TDT-expressing background T-lymphocytes. These features were hints to reconsider our differential diagnosis to include follicular dendritic cell tumors. Awareness of this aberrant staining of epithelial immunomarkers and attention to certain clues should encourage pathologists to consider this entity. Speculative assumptions may explain this unusual keratin expression in some lesions. The histomorphologic and immunohistochemical heterogeneity may suggest different variants and grades of follicular dendritic cell sarcomas. The prevalence, importance, and histogenesis of keratin expression in follicular dendritic cell sarcomas warrant further studies.

Topics: Adult; Biomarkers, Tumor; Carcinoma; Dendritic Cell Sarcoma, Follicular; Dendritic Cells, Follicular; Diagnosis, Differential; Humans; Keratins; Male; Sarcoma

This article contains detailed protocols for the simultaneous flow cytometric identification of tumor cells and stromal cells and measurement of DNA content of formalin-fixed, paraffin-embedded (FFPE) tissues. The vimentin-positive stromal cell fraction can be used as an internal reference for accurate DNA content assessments of FFPE carcinoma tissues. This allows clear detection of keratin-positive tumor cells with a DNA index lower than 1.0 (near-haploidy) and of keratin-positive tumor cells with a DNA index close to 1.0 in overall DNA aneuploid samples, thus improving DNA ploidy assessment in FFPE carcinomas. Furthermore, the protocol is useful for studying molecular genetic alterations and intratumor heterogeneity in archival FFPE samples. Keratin-positive tumor cell fractions can be sorted for further molecular genetic analysis, while DNA from the sorted vimentin-positive stromal cells can serve as a reference when normal tissue of the patient is not available. © 2023 The Authors. Current Protocols published by Wiley Periodicals LLC. Basic Protocol: Multiparameter DNA content analysis of FFPE carcinomas Alternate Protocol 1: Immunocytochemistry for keratin and vimentin, and DNA labeling for blue and red excitation Alternate Protocol 2: Immunocytochemistry for keratin and vimentin, and DNA labeling for blue excitation Support Protocol: Sorting cell population from FFPE carcinomas.

Topics: Carcinoma; DNA; Flow Cytometry; Humans; Keratins; Paraffin Embedding; Ploidies; Vimentin

Molecular analysis of poorly differentiated/undifferentiated sinonasal neoplasms has resulted in identification of a growing number of genetically defined tumors. SMARCA4-deficient sinonasal carcinoma is one such recently described entity that emerged from within sinonasal undifferentiated carcinoma (SNUC), neuroendocrine carcinoma (NEC), and teratocarcinosarcoma (TCS).. To identify SMARCA4-deficient sinonasal carcinomas from a large institutional cohort of poorly differentiated/undifferentiated carcinomas and evaluate their clinicopathologic features.. SMARCA4/BRG1 immunohistochemistry was performed on all tumors diagnosed as SNUC, poorly differentiated carcinoma, NEC, and TCS during a 12-year period. SMARCA2/BRM and INSM1 immunostaining was performed in SMARCA4-deficient cases.. Twelve SMARCA4-deficient sinonasal carcinomas were identified among 299 cases. Morphologically, 5 cases were large cell NEC, 2 cases were small cell NEC, and 5 were TCS. SMARCA4 loss was diffuse and complete in 10 cases, while 2 cases showed focal retention. Most cases showed diffuse cytokeratin staining accompanied by weak, usually focal staining for chromogranin and synaptophysin. INSM-1 showed negativity in most cases. All cases showed retained SMARCA2 expression. IDH1/2 mutation was absent in all cases analyzed. Four of 7 patients died of disease, and aggressive multimodality treatment provided better outcome.. SMARCA4-deficient sinonasal carcinomas are morphologically akin to sinonasal poorly differentiated NECs and TCS, display cytokeratin positivity and only focal staining for neuroendocrine markers, and have aggressive biological behavior. Inclusion of SMARCA4 in the immunohistochemical panel for diagnostic workup of all sinonasal NEC and TCS phenotypes will facilitate their early recognition. Comprehensive germline and somatic mutational analyses of these tumors are necessary for further insights into their molecular pathogenesis.

Topics: Biomarkers, Tumor; Carcinoma; Carcinoma, Neuroendocrine; DNA Helicases; Humans; Immunohistochemistry; Keratins; Maxillary Sinus Neoplasms; Nuclear Proteins; Repressor Proteins; Transcription Factors

Cutaneous myoepithelial neoplasms are a heterogenous group of neoplasms with mixed tumors typically affecting the head and myoepitheliomas showing a predilection for the extremities. Their malignant counterparts, myoepithelial carcinoma, and malignant mixed tumor are exceptionally rare in the skin, and the morphologic criteria for malignancy are only poorly defined. The aim of the present study was to characterize the clinicopathologic features of myoepithelial neoplasms presenting on acral skin. The clinical and histopathologic features of 11 tumors were recorded, and follow-up was obtained. Immunohistochemistry was performed for S100, SOX10, glial fibrillary acidic protein, keratins, epithelial membrane antigen, p63, p40, smooth muscle actin, desmin, and PLAG1. The tumors mainly affected the feet of adults (range: 26 to 78 y; median: 47 y) with a predilection for the great toe and a male predominance of 1.8:1. Most tumors (91%) displayed a lobular architecture composed of solid and nested growth of epithelioid cells with plasmacytoid features in a myxoid or angiomatous stroma. Scattered cytologic atypia and rare duct differentiation were frequently noted. Three tumors with confluent cytologic atypia, infiltrative growth, and lymphovascular invasion were classified as malignant. By immunohistochemistry, the tumors were positive for S100, SOX10, keratins AE1/AE3, CK5/6 and CK7, and PLAG1. Local recurrence and bilateral pulmonary metastasis were observed in a patient presenting with a histopathologically benign-appearing tumor. Two patients with malignant tumors experienced local recurrences, and 1 developed metastasis to soft tissue, lung, and mediastinal lymph nodes. All patients are currently alive, all but 1 with no evidence of disease after a median follow-up interval of 96 months (range: 2 to 360 mo). In conclusion, acral myoepithelial neoplasms show distinctive and reproducible histopathologic and immunohistochemical features. They are best regarded as a distinctive subset of mixed tumors with features reminiscent of their salivary gland counterparts. While most tumors pursue a benign disease course, histopathologic features appear to be a poor indicator of prognosis.

Topics: Adenoma, Pleomorphic; Adult; Aged; Biomarkers, Tumor; Carcinoma; Female; Humans; Immunohistochemistry; Keratins; Male; Middle Aged; Myoepithelioma; Skin Neoplasms

Sentinel lymph nodes are widely accepted in the treatment of endometrial carcinoma. Whereas surgical aspects are well studied, the pathological work-up in terms of grossing, frozen section, and the so-called ultra-staging is still a matter of debate. This results in conflicting national or center-based recommendations. In a series of consecutive 833 sentinel lymph nodes from 206 patients in endometrial carcinomas, we compared three different grossing techniques and the use of frozen section in terms of anatomy, detection rates, and survival. In total, 42 macro-metastases, 6 micro-metastases, and 25 nodes with isolated tumor cells were found. Lymph nodes affected at least with micro-metastasis were about 0.5cm enlarged. Detection rates in lamellation technique increased with a step of 5.9% to 8.3% in comparison to bi-valved or complete embedding. The lamellation technique presented with a slight beneficial prognosis in pN0 subgroup (OS, p=0.05), which besides size effects might be attributed to trimming loss. In frozen section, this effect was less pronounced than expected (OS, p=0.56). Ultra-staging only revealed additional micro-metastases and isolated tumor cells. Exclusively, macro-metastases showed poor survival (p<0.001). In multivariate analysis, T-stage, subtype, and lympho-vascular invasion status outperformed this staging parameter significantly. Grossing of sentinel lymph nodes is the most essential step with evidence to prefer lamellation in 2 mm steps. Step sectioning should consider widely spaced protocols to exclude macro-metastases. Frozen sections might add value to the intra-operative assessment of endometrial carcinoma in selected cases. The excellent biological behavior of cases with isolated tumor cells might question the routine application of pan-cytokeratin as ultra-staging method.

Topics: Carcinoma; Endometrial Neoplasms; Female; Frozen Sections; Humans; Keratins; Lymph Node Excision; Lymphatic Metastasis; Neoplasm Staging; Sentinel Lymph Node; Sentinel Lymph Node Biopsy

Although the primary origin of some carcinomas may be obscure to clinicians, its identification is crucial as it affects prognosis and treatment (especially novel targeted therapies). Immunohistochemistry (IHC) may be helpful in identifying the primary origin of carcinomas. This retrospective survey aimed to evaluate the frequency and accuracy of each IHC marker used to determine the origin of carcinomas.. The review of pathology department archives revealed 307 cases of cancer of unknown primary origin (CUP) between 2015 and 2020, which were accessible in the department archives. Demographic information, site of biopsy, clinical and pathologic diagnoses, and IHC results of the patients were collected.. The patients included 157 (51.15%) men and 150 (48.85%) women. The age of the patients ranged from 14 to 92 years, including 106 (34.5%) expired cases. In 27% of cases, the primary origin of carcinoma remained unknown. The agreement between pathologic and clinical diagnoses was 59%. The most common pattern of cytokeratin (CK) expression in CUP was CK7+/CK20- (55.3%), followed by CK7-/CK20- (19%), CK7+/CK20+ (15%), and CK7-/CK20+ (10.7%), respectively.. The IHC analysis may improve the diagnosis of CUPs. However, the origin of some cases remains unknown despite an IHC analysis, thereby necessitating the use of more diagnostic procedures or gene expression studies for reaching a definitive diagnosis.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Biomarkers, Tumor; Carcinoma; Colorectal Neoplasms; Female; Humans; Immunohistochemistry; Intermediate Filament Proteins; Keratin-20; Keratin-7; Keratins; Male; Middle Aged; Neoplasms, Unknown Primary; Retrospective Studies; Staining and Labeling; Young Adult

Topics: Biomarkers, Tumor; Carcinoma; China; DNA Helicases; Female; Gastrointestinal Tract; Humans; Keratins; Male; Nuclear Proteins; Retrospective Studies; Transcription Factors

The tumor-stroma ratio (TSR) determined by pathologists is subject to intra- and inter-observer variability. We aimed to develop a computational quantification method of TSR using deep learning-based virtual cytokeratin staining algorithms. Patients with 373 advanced (stage III [n = 171] and IV [n = 202]) gastric cancers were analyzed for TSR. Moderate agreement was observed, with a kappa value of 0.623, between deep learning metrics (dTSR) and visual measurement by pathologists (vTSR) and the area under the curve of receiver operating characteristic of 0.907. Moreover, dTSR was significantly associated with the overall survival of the patients (P = 0.0024). In conclusion, we developed a virtual cytokeratin staining and deep learning-based TSR measurement, which may aid in the diagnosis of TSR in gastric cancer.

Topics: Adult; Aged; Carcinoma; Deep Learning; Female; Follow-Up Studies; Gastrectomy; Humans; Image Processing, Computer-Assisted; Kaplan-Meier Estimate; Keratins; Male; Middle Aged; Neoplasm Staging; Observer Variation; Risk Assessment; ROC Curve; Stomach; Stomach Neoplasms; Treatment Outcome

Extraskeletal Ewing sarcoma presenting as intra-abdominal or pelvic disease in adult female patients is very rare and may lead to diagnostic difficulty due to clinical and histologic overlap with Mullerian adenocarcinomas, which are far more common. We report a case of an intra-abdominal Ewing sarcoma in a postmenopausal female patient whose clinical and radiological presentation closely resembled that of peritoneal carcinomatosis. Biopsy of an omental nodule revealed numerous histologic features suggestive of a Mullerian carcinoma, including gland-like rosettes, strong, diffuse PAX8 immunoreactivity and cytokeratin expression. After excluding other differential diagnostic considerations, the possibility that this might represent an intra-abdominal Ewing sarcoma was entertained. Reverse transcriptase polymerase chain reaction testing demonstrated the presence of an EWSR1-ERG fusion transcript, confirming the diagnosis. The differential diagnostic considerations when dealing with this unusual clinical scenario and the uncommon yet important pitfall of PAX8 immunoreactivity in Ewing sarcoma are discussed.

Topics: Abdomen; Adenosarcoma; Carcinoma; Diagnosis, Differential; Female; Gene Fusion; Humans; Keratins; Middle Aged; Mullerian Ducts; PAX8 Transcription Factor; Peritoneal Neoplasms; Postmenopause; RNA-Binding Protein EWS; Sarcoma, Ewing; Transcriptional Regulator ERG

Myoepithelial tumors comprise a group of mesenchymal lesions that show heterogeneous histomorphological features, including dual epithelial, neural, and myoid differentiation. Cutaneous myoepithelioma is a rare neoplasm that is composed primarily of myoepithelial cells and represents one end of a histopathological spectrum of cutaneous myoepithelial neoplasms including chondroid syringoma and myoepithelial carcinoma. These tumors display a wide histopathological spectrum and immunophenotypical profile often showing epithelial and myoepithelial differentiation. In this series, we studied 35 cases of cutaneous myoepitheliomas. Our cases highlighted the broad histopathological range where most cases showed a non-infiltrative and non-encapsulated tumor exclusively located in the dermis and with no subcutaneous involvement. The majority of our cases had a solid growth pattern (syncytial pattern) and the remainder of cases had a multinodular growth pattern. The tumor cells were epithelioid in 23 cases, spindled in eight cases and there was a mixture of epithelioid and spindled cells in four cases. Mitotic figures ranged from 0 to 5 per 10 HPF. By immunohistochemistry epithelial membrane antigen (EMA) was expressed in 59% of cases S100 was positive in 88% of cases, CAM 5.2 was positive in 16% of cases, AE1/AE3 was positive in 44% of cases, p63 was positive in 17% of cases, smooth muscle actin was positive in 38% of cases, desmin was positive in 6% of cases, calponin was positive in 22% of cases, and glial fibrillary acidic protein was positive in 36% of cases. In addition, there were five cases without EMA, keratin, or p63 expression that only showed S100 expression. We describe a large series of cutaneous myoepitheliomas delineating their histomorphological spectrum and immunophenotypical profile. Awareness of some of the unusual histopathological features and the heterogeneous immunohistochemical may pose difficulties for the diagnosis.

Topics: Actins; Adenoma, Pleomorphic; Adult; Anion Exchange Protein 1, Erythrocyte; Awareness; Biomarkers; Biomarkers, Tumor; Calcium-Binding Proteins; Calponins; Carcinoma; Chloride-Bicarbonate Antiporters; Desmin; Diagnosis, Differential; Female; Glial Fibrillary Acidic Protein; Humans; Immunohistochemistry; Immunophenotyping; Keratins; Male; Membrane Proteins; Microfilament Proteins; Mucin-1; Myoepithelioma; S100 Proteins; Skin Neoplasms

The nature of endometrial morular metaplasia (MorM) is still unknown. The nuclear β-catenin accumulation and the not rare ghost cell keratinization suggest a similarity with hard keratin-producing odontogenic and hair matrix tumors rather than with squamous differentiation. We aimed to compare MorM to hard keratin-producing tumors. Forty-one hard keratin-producing tumors, including 26 hair matrix tumors (20 pilomatrixomas and 6 pilomatrix carcinomas) and 15 odontogenic tumors (adamantinomatous craniopharyngiomas), were compared to 15 endometrioid carcinomas with MorM with or without squamous/keratinizing features. Immunohistochemistry for β-catenin, CD10, CDX2, ki67, p63, CK5/6, CK7, CK8/18, CK19, and pan-hard keratin was performed; 10 cases of endometrioid carcinomas with conventional squamous differentiation were used as controls. In adamantinomatous craniopharyngiomas, the β-catenin-accumulating cell clusters (whorl-like structures) were morphologically similar to MorM (round syncytial aggregates of bland cells with round-to-spindled nuclei and profuse cytoplasm), with overlapping squamous/keratinizing features (clear cells with prominent membrane, rounded squamous formations, ghost cells). Both MorM and whorl-like structures consistently showed positivity for CD10 and CDX2, with low ki67; cytokeratins pattern was also overlapping, although more variable. Hard keratin was focally/multifocally positive in 8 MorM cases and focally in one conventional squamous differentiation case. Hair matrix tumors showed no morphological or immunophenotypical overlap with MorM. MorM shows wide morphological and immunophenotypical overlap with the whorl-like structures of adamantinomatous craniopharyngiomas, which are analogous to enamel knots of tooth development. This suggests that MorM might be an aberrant mimic of odontogenic differentiation.

Topics: beta Catenin; Biomarkers, Tumor; Carcinoma; Case-Control Studies; Cell Differentiation; Craniopharyngioma; Endometrial Neoplasms; Female; Humans; Immunohistochemistry; Keratins; Metaplasia; Odontogenesis; Pilomatrixoma; Pituitary Neoplasms

Biphenotypic sinonasal sarcoma (BSNS) is a rare, low grade spindle cell sarcoma, recently recognized in the WHO classification of head and neck tumors, which is characterized by a dual myogenic and neural differentiation and recurrent gene fusions, often involving PAX3-MAML3, and less commonly PAX3 fusions with other partners such as NCOA1, NCOA2, or WWTR1. Yet, in about 4% of tumors no gene rearrangements are identified. Herein, we describe a RREB1-MKL2 fusion in a BSNS lesion occurring in a 73-year-old female patient with a right maxillo-ethmoidal angle lesion. The polypoid, moderately cellular tumor with infiltrative submucosal growth was composed of fascicles of relatively bland spindle cells embedded in a loose collagenous matrix. The tumor cells showed moderate amounts of eosinophilic cytoplasm with indistinct borders and uniform, pale, ovoid to slender nuclei. The slowly proliferating neoplastic cells co-expressed smooth muscle actin and S100, and showed focal nuclear positivity for ß-catenin, while lacking staining for cytokeratins, desmin, myogenin, caldesmon, glial fibrillary acid protein, and SOX-10. Molecular analysis by targeted RNA-based next-generation sequencing identified an in-frame fusion between exon 8 of RREB1 and exon 11 of MKL2, a genetic event that was reported to be a molecular hallmark of ectomesenchymal chondromyxoid tumor. Gene rearrangements in both genes were independently verified by fluorescence in situ hybridization (FISH). To evaluate its recurrent potential an additional group of 15 fusion negative BSNS were tested for abnormalities in RREB1 and MKL2 genes by FISH, but no additional positive cases were identified.

Topics: Actins; Aged; beta Catenin; Carcinoma; DNA-Binding Proteins; Female; Humans; Keratins; Nose Neoplasms; Oncogene Proteins, Fusion; Phenotype; SOXE Transcription Factors; Transcription Factors

High levels of the intermediate filament protein keratin 17 (K17) are associated with poor prognoses for several human carcinomas. Studies in mouse models have shown that K17 expression is positively associated with growth, survival, and inflammation in skin and that lack of K17 delays onset of tumorigenesis. K17 occurs in the nucleus of human and mouse tumor keratinocytes where it impacts chromatin architecture, gene expression, and cell proliferation. We report here that K17 is induced following DNA damage and promotes keratinocyte survival. The presence of nuclear K17 is required at an early stage of the double-stranded break (DSB) arm of the DNA damage and repair (DDR) cascade, consistent with its ability to associate with key DDR effectors, including γ-H2A.X, 53BP1, and DNA-PKcs. Mice lacking K17 or with attenuated K17 nuclear import showed curtailed initiation in a two-step skin carcinogenesis paradigm. The impact of nuclear-localized K17 on DDR and cell survival provides a basis for the link between K17 induction and poor clinical outcomes for several human carcinomas.

Topics: 9,10-Dimethyl-1,2-benzanthracene; Active Transport, Cell Nucleus; Animals; Carcinogenesis; Carcinoma; Cell Nucleus; Cell Survival; DNA Breaks, Double-Stranded; DNA Repair; Female; Gene Knockout Techniques; HeLa Cells; Humans; Intravital Microscopy; Keratin-17; Keratinocytes; Keratins; Male; Mice, Knockout; Neoplasms, Experimental; Time-Lapse Imaging

Deviations from the classic melanocytic immunophenotype in melanoma can present a diagnostic challenge. PAX8 and PAX2 are common markers for renal or Müllerian differentiation. While most PAX8+ or PAX2+ carcinomas are seldom confused with melanoma, some cases may show a more ambiguous immunophenotype, especially when MiTF family altered renal cell carcinoma (MiTF-RCC) is in the differential diagnosis. Neither PAX8 nor PAX2 expression has been reported in melanoma to date. We aimed to better characterize PAX8, PAX2, and cytokeratin immunoreactivity in a large series of melanomas.. Tissue microarrays consisting of 263 melanomas were immunostained for PAX8, PAX2, and cytokeratin and graded by an h-score.. PAX8 expression was seen in 7.9% of melanomas and was significantly associated with spindle cytomorphology. PAX2 was positive in one (0.4%) melanoma. Cytokeratin positivity was seen in three (1.2%) cases and was associated with metastases.. PAX8 is expressed in a subset of melanomas and may be strong/extensive. As PAX8 positivity does not exclude a diagnosis of melanoma, it should be used in conjunction with other immunohistochemical markers, such as cytokeratin and PAX2, when melanoma, MiTF-RCC, and other PAX8+ tumors are in the differential diagnosis.

Topics: Biomarkers, Tumor; Carcinoma; Diagnosis, Differential; Humans; Immunohistochemistry; Keratins; Melanoma; Melanoma, Cutaneous Malignant; PAX2 Transcription Factor; PAX8 Transcription Factor; Skin Neoplasms

The adrenal glands are one of the most common sites of malignant tumor metastasis. However, metastatic adrenal carcinoma of unknown primary origin with localized adrenal gland involvement is an extremely rare condition. Herein, we reported two cases of carcinoma of unknown primary origin with isolated adrenal metastasis. In the first case, back pain was the trigger; while in the second case, the triggers were low fever and weight loss. Metabolic abnormalities such as hypertension and obesity were not detected in either case. Neither patient had relevant previous medical histories, including malignancy. However, both had a long-term history of smoking. Systemic imaging studies revealed only adrenal tumors and surrounding lesions. Primary adrenocortical carcinoma was initially suspected, and chemotherapy including mitotane was considered. However, due to difficulty in complete resection of the tumor, core needle tumor biopsies were performed. Histopathological examination of biopsy specimens led to the diagnosis of carcinoma of unknown primary origin with isolated adrenal metastasis. In both cases, additional laboratory testing showed high levels of serum squamous cell carcinoma-related antigen and serum cytokeratin fragment. Malignant lesions confined to the adrenal glands are rare. As in our cases, it could be occasionally difficult to differentiate non-functioning primary adrenocortical carcinoma from metastatic adrenal carcinoma of unknown primary origin localized to the adrenal gland. If the lesion is unresectable and there are elevated levels of several tumor markers with no apparent hormonal excess, core needle tumor biopsy should be considered to differentiate the primary tumor from the metastatic tumor.

Topics: Adrenal Gland Neoplasms; Adrenocortical Carcinoma; Antigens, Neoplasm; Biopsy, Needle; Carcinoma; Diagnosis, Differential; Humans; Keratins; Male; Middle Aged; Neoplasms, Unknown Primary; Serpins

Topics: Biomarkers, Tumor; Biopsy; Carcinoma; Humans; Immunohistochemistry; Keratins; Male; Neoplasm Grading; Predictive Value of Tests; Prostatic Neoplasms; Racemases and Epimerases; Risk Assessment; Risk Factors; Transcription Factors; Tumor Suppressor Proteins

A case of a primary lung carcinoma with histologic and immunohistochemical features of a mammary carcinoma is presented. The patient is a 72-year-old man who presented with symptoms of cough and dyspnea. Diagnostic imaging showed a bronchial tumor in the left lower lobe that was surgically resected by a left lower lobectomy. The tumor was characterized by a homogenous cellular proliferation composed of small to medium-sized cells with round nuclei and inconspicuous nucleoli. Multiple immunohistochemical stains were performed, and the tumor was notably positive for estrogen receptor, progesterone receptor, GATA3, and pan-keratin, while molecular analysis showed somatic mutation in

Topics: Aged; Biomarkers, Tumor; Carcinoma; DNA-Binding Proteins; GATA3 Transcription Factor; Humans; Keratins; Lung Neoplasms; Male; Mutation; Receptors, Estrogen; Receptors, Progesterone; Transcription Factors

Feline mammary tumors are usually malignant and aggressive carcinomas. Most cases are simple monophasic carcinomas (1 epithelial population), and additional phenotyping is usually not needed. In this study, we describe 10 malignant mammary tumors from 9 female cats that had unusual histomorphology: they appeared biphasic, with 2 distinct cell populations. Initially, they were morphologically diagnosed as either carcinosarcoma (1/10) or malignant pleomorphic tumor (9/10) of the mammary gland, as the latter did not match any previously described histological subtype. Immunohistochemistry (IHC) was performed for pancytokeratin, cytokeratins 8 and 18, cytokeratin 14, cytokeratins 5 and 6, vimentin, p63, calponin, alpha-smooth muscle actin, Ki-67, ERBB2, estrogen receptor alpha, and progesterone receptor. In 7 of 10 cases, the biphasic nature was confirmed and, on the basis of the IHC results, they were classified as carcinoma and malignant myoepithelioma (4/10), ductal carcinoma (1/10), and carcinosarcoma (2/10). The other 3 of 10 cases were monophasic based on IHC. In the cases of carcinoma and malignant myoepithelioma, the malignant myoepithelial cells were 100% positive for vimentin (4/4) and variably positive for p63, calponin, and cytokeratins (4/4). These findings show that, although rare, biphasic mammary carcinomas do occur in cats. In dogs and humans, tumors composed of malignant epithelial and myoepithelial cells have a less aggressive behavior than certain simple carcinomas, and therefore, their identification might also be clinically significant in the cat.

Topics: Animals; Biomarkers, Tumor; Calcium-Binding Proteins; Calponins; Carcinoma; Carcinoma, Ductal; Carcinosarcoma; Cat Diseases; Cats; Dogs; Female; Immunohistochemistry; Keratins; Mammary Neoplasms, Animal; Microfilament Proteins; Myoepithelioma; Sarcoma; Vimentin

The proliferation-associated biomarker Ki67 has potential utility in breast cancer, including aiding decisions based on prognosis, but has unacceptable inter- and intralaboratory variability. The aim of this study was to compare the prognostic potential for Ki67 hot spot scoring and global scoring using different digital image analysis (DIA) platforms.. An ER+/HER2- breast cancer cohort (n = 139) with whole slide images of sequential sections stained for hematoxylin-eosin, pancytokeratin and Ki67, was analyzed using two DIA platforms. For hot spot analysis virtual dual staining was applied, aligning pancytokeratin and Ki67 images and 22 hot spot algorithms with different features were designed. For global Ki67 scoring an automated QuPath algorithm was applied on Ki67-stained whole slide images. Clinicopathological data included overall survival (OS) and recurrence-free survival (RFS) along with PAM50 molecular subtypes.. We show significant variations in Ki67 hot spot scoring depending on number of included tumor cells, hot spot size, shape and location. The higher the number of scored tumor cells, the higher the reproducibility of Ki67 proliferation values. Hot spot scoring had greater prognostic potential for RFS in high versus low Ki67 subgroups (hazard ratio (HR) 6.88, CI 2.07-22.87, p = 0.002), compared to global scoring (HR 3.13, CI 1.41-6.96, p = 0.005). Regarding OS, global scoring (HR 7.46, CI 2.46-22.58, p < 0.001) was slightly better than hot spot scoring (HR 6.93, CI 1.61-29.91, p = 0.009). In adjusted multivariate analysis, only global scoring was an independent prognostic marker for both RFS and OS. In addition, global Ki67-based surrogate subtypes reached higher concordance with PAM50 molecular subtype for luminal A and B tumors (66.3% concordance rate, κ = 0.345), than using hot spot scoring (55.8% concordance rate, κ = 0.250).. We conclude that the automated global Ki67 scoring is feasible and shows clinical validity, which, however, needs to be confirmed in a larger cohort before clinical implementation.

Topics: Antigens, Neoplasm; Automation; Breast Neoplasms; Carcinoma; Disease-Free Survival; Estrogens; Female; Follow-Up Studies; Humans; Image Processing, Computer-Assisted; Kaplan-Meier Estimate; Keratins; Ki-67 Antigen; Middle Aged; Neoplasm Proteins; Neoplasms, Hormone-Dependent; Prognosis; Proportional Hazards Models; Receptor, ErbB-2; Receptors, Estrogen; Reproducibility of Results; Retrospective Studies

Malignant vascular neoplasms such as epithelioid hemangioendothelioma (EHE) and angiosarcoma (AS) can arise within the liver. The aim of this study was to study the expression of keratins CK7, AE1/AE3 and OSCAR in primary hepatic EHE and AS. 9 cases of hepatic EHE and 13 cases of hepatic AS were stained with ERG, CK7, keratin AE1/AE3 and keratin OSCAR. Their expression was graded as 1+ (1-25% of tumor cells positive), 2+ (26-50%), 3+ (51-75%) or 4+ (>75%). ERG was positive in all 9 (100%) EHEs and all 13 (100%) ASs. CK7 was positive in 5/9 (56%) EHEs (2, 1+; 1, 2+; 1, 3+; 1, 4+) and 1/13 (8%) AS (2+). Keratin OSCAR was positive in 6/9 (67%) EHEs (5, 1+; 1, 2+) and 4/13 (31%) ASs (2, 1+; 1, 2+; 1, 4+). Keratin AE1/AE3 was positive in 6/9 (67%) EHEs (3, 1+; 3; 2+) and 4/13 (31%) ASs (2, 1+; 1, 2+; 1, 4+). Overall, 6/ 9 (67%) EHEs were positive for at least one keratin marker, of which 5 were positive for all 3 keratins (AE1/AE3, OSCAR and CK7) while 1 was positive only for 2 keratins (OSCAR and AE1/AE3). 4/13 (31%) of ASs were positive for both keratins OSCAR and AE1/AE3, of which 1 case was also positive for CK7. Aberrant keratin expression is common in primary hepatic EHEs (67%) and ASs (31%). Awareness of this diagnostic pitfall is important for avoiding misdiagnosis of these primary hepatic malignant vascular tumors as carcinomas.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Biomarkers, Tumor; Carcinoma; Diagnosis, Differential; Female; Hemangioendothelioma, Epithelioid; Hemangiosarcoma; Humans; Keratins; Liver Neoplasms; Male; Middle Aged; Young Adult

Cytokeratin-positive interstitial reticulum cells (CIRCs), which are a subgroup of fibroblastic reticular cells (FRCs), are known to be present in the lymph nodes. There have been only a few cases of tumors derived from CIRCs.. We have reported a new case involving a CIRC tumor in a 75-year-old man and reviewed the literature. The resected mediastinal lymph nodes showed epithelial-like proliferation of large atypical round and polygonal epithelioid cells. The tumor cells expressed CK8, CK18, CAM5.2, AE1/AE3, epithelial membrane antigen, vimentin, fascin, and some FRC markers, which is consistent with the diagnosis of a CIRC tumor. Following chemotherapy, the CIRC tumor was observed to have responded very well and became difficult to confirm on imaging, but a small cell lung carcinoma developed 12 months later. Chemoradiotherapy was performed, but the patient passed away 29 months after the initial diagnosis. The autopsy revealed the recurrence of the CIRC tumor, residual small cell lung carcinoma, and a very small latent carcinoma of the prostate. The relapsed CIRC tumor cells had a spindle shape; they were highly pleomorphic and had invaded the superior vena cava.. We first reported autopsy findings of CIRC tumors and demonstrated the transformation of the tumor from the epithelioid cell type to the spindle cell type.

Topics: Animals; Biomarkers, Tumor; Carcinoma; Diagnosis, Differential; Epithelioid Cells; Humans; Immunohistochemistry; Keratins; Lymph Node Excision; Lymph Nodes; Vena Cava, Superior

Eight cases of primary thymic epithelial neoplasms corresponding to 7 thymomas and 1 thymic carcinoma with sebaceous differentiation are presented. The patients are 5 men and 3 women between the ages of 45 and 63 years (average, 54 years) who presented with nonspecific symptoms related to their mediastinal mass. All patients underwent complete surgical resection of the mediastinal mass. Grossly, all the tumors were described as round to oval measuring from 3.5 to 6.0 cm in greatest diameter. In 4 cases, the tumors were described as with infiltrative borders. Histologically, 1 tumor corresponded to thymic carcinoma characterized by irregular islands of tumors cells showing cellular atypia and mitotic activity. Six of the 7 thymomas showed mixed histologies corresponding to spindle cell, lymphocyte predominant, and mixed lymphocyte/epithelial types (World Health Organization types A, B1, and B2). One thymoma was mixed lymphocyte/epithelial (World Health Organization type B2). The areas of sebaceous differentiation characterized by clusters or strands of epithelial cells with ample clear cytoplasm were present within the lymphocytic component, whereas in the thymic carcinoma, the areas of sebaceous differentiation were identified within the epithelial component of the tumor. Follow-up information was obtained in 5 patients, showing that the patient with thymic carcinoma died 20 months after initial diagnosis, whereas the patients with thymoma whether encapsulated or minimally invasive remained alive without recurrence 12 to 24 months after initial diagnosis. The current cases represent an unusual feature that occasionally may be seen in thymomas and thymic carcinomas.

Topics: Biomarkers, Tumor; Carcinoma; Cell Differentiation; Female; Humans; Immunohistochemistry; Keratins; Male; Middle Aged; Perilipin-2; Thymoma; Thymus Neoplasms

The aim of this study was to clarify the quantitative and qualitative differences in tumour budding identification between haematoxylin and eosin (H&E) staining and immunohistochemical (IHC) staining for cytokeratin, and to estimate the respective clinical impacts in stage II colorectal cancer.. We retrospectively examined 314 surgically resected cases of stage II colorectal cancer, and assessed tumour budding on serial section slides with H&E staining and IHC staining for cytokeratin. Tumour budding counts based on cytokeratin-stained slides were strongly correlated with those based on H&E-stained slides, and had higher detection and reproducibility. On the basis of receiver operating characteristic analyses, the optimal cut-off values of budding counts for relapse-free survival (RFS) were 7 and 16 in a ×200 microscopic field with H&E and IHC staining, respectively. With these cut-off values, tumour budding based on H&E staining had a significant correlation with RFS (80.3% and 93.2% of 5-year RFS in the high-budding group and the low-budding group, respectively), and similar results were observed for IHC staining (79.9% and 91.7%, respectively). The Akaike Information Criterion value for RFS with H&E staining was favourable as compared with that with IHC staining.. Tumour budding counts based on cytokeratin-stained slides showed higher detection and better reproducibility, but did not have as satisfactory clinical impacts as those based on H&E staining.

Topics: Adult; Aged; Aged, 80 and over; Carcinoma; Colorectal Neoplasms; Eosine Yellowish-(YS); Female; Humans; Immunohistochemistry; Keratins; Male; Middle Aged; Neoplasm Staging; Prognosis; Reproducibility of Results; Retrospective Studies; ROC Curve; Staining and Labeling

We report the case of a 94-year-old man with a rapidly growing nodule on the preauricular area, which on histology showed a poorly differentiated spindle cell tumor with negative p63 and p40 antibody immunostains, negative high- and low-molecular-weight cytokeratins albeit for a focal expression of cytokeratin AE1/AE3. Spindle cell melanoma, angiosarcoma, and leiomyosarcoma were excluded. We explore the diagnostic approach to this challenging conundrum. Certain authors have suggested that sarcomatoid carcinoma and atypical fibroxanthoma (AFX) may lie within a spectrum of "sarcoma-like tumors of the head and neck" and that they may all run a similarly indolent clinical course. However, AFX appears to remain a diagnosis of exclusion, and expert consensus is that by definition AFX cannot express any cytokeratin antigens.

Topics: Aged, 80 and over; Biomarkers, Tumor; Carcinoma; Diagnosis, Differential; Face; Hemangiosarcoma; Humans; Keratins; Leiomyosarcoma; Male; Melanoma; Mohs Surgery; Skin; Skin Neoplasms

Differentiating between malignant phyllodes tumors and metaplastic spindle cell carcinomas could be problematic, especially on core biopsies. Immunohistochemical staining for cytokeratin cocktail and p63 has been utilized to differentiate between these tumor types. Forty-three phyllodes tumors (27 benign, 6 borderline, and 10 malignant) and 22 metaplastic carcinomas, consisting at least 80% of spindle cells, were identified. At least 4 tissue blocks from each phyllodes tumor were subjected to immunohistochemical staining for cytokeratin cocktail and p63. The immunohistochemical profiles for the spindle cells in metaplastic carcinoma were reviewed. Phyllodes tumor was diagnosed in the younger age group (mean age 41 y) with a larger tumor size (mean size 6.6 cm), compared with metaplastic spindle cell carcinoma (mean age 62.7 y, mean size 3.4 cm). Focal expression (5% of the tumor cells) of cytokeratin cocktail and p63 was identified in the stroma of 2 of 10 malignant phyllodes tumors in a scattered/patchy pattern. The stroma of benign and borderline phyllodes tumors was negative for these markers. In metaplastic spindle cell carcinomas, cytokeratin cocktail was negative in 2 of 15 cases and very focally positive in another 3 cases, whereas p63 was negative in one case and focally positive in another case. There can be anomalous, focal expression of cytokeratin and p63 in the stroma of malignant phyllodes tumors, whereas metaplastic spindle cell carcinoma can occasionally have cytokeratin and/or p63-negative staining or have very focal positivity. Caution should be exercised when relying on these markers for confirming a diagnosis, especially on core biopsies.

Topics: Adolescent; Adult; Aged, 80 and over; Carcinoma; Diagnosis, Differential; Humans; Immunohistochemistry; Keratins; Limit of Detection; Membrane Proteins; Metaplasia; Middle Aged; Phyllodes Tumor

Topics: Aged; Biomarkers; Carcinoma; Duodenal Neoplasms; Humans; Keratins; Liver Neoplasms; Male; Positron Emission Tomography Computed Tomography; Vimentin

The sinonasal cavities harbour a variety of rare tumour types. Many carry a poor prognosis while therapeutic options are limited. Histopathological classification can be difficult, especially for poorly differentiated tumours such as olfactory neuroblastoma (ONB), sinonasal neuroendocrine carcinoma (SNEC) and sinonasal undifferentiated carcinoma (SNUC). We analysed Affymetrix OncoScan genome-wide copy number profiles of these three tumour types, both as originally diagnosed and as regrouped by their cytokeratin (Ck) and neuroendocrine (Ne) expression pattern, aiming to find a relation between phenotype and genotype. According to the original histopathological classification our series consisted of 24 ONB, 11 SNEC and 19 SNUC, while immunohistochemistry indicated 11 Ck-Ne+/ONB, 18 Ck+Ne+/SNEC, 24 Ck+Ne-/SNUC, and 1 Ck-Ne-/unclassified. As originally diagnosed, the three tumour types showed similar copy number profiles. However, when regrouped by Ck/Ne immunostaining we found a distinct set of gains and losses; Ck-Ne+/ONB harboured few and predominantly whole chromosomes abnormalities, Ck+Ne+/SNEC carried both gains and losses in high frequency, and Ck+Ne-/SNUC showed mostly gains. In addition, each tumour carried a number of unique chromosomal deletions. Genome-wide copy number profiling supports the value of immunohistochemical CkNe staining of ONB, SNEC and SNUC for tumour classification, which is important for prognosis and therapeutic decision-making.

Topics: Biomarkers, Tumor; Carcinoma; Carcinoma, Neuroendocrine; Cell Differentiation; Esthesioneuroblastoma, Olfactory; Gene Expression Profiling; Genotype; Humans; Keratins; Maxillary Sinus Neoplasms

Prostate carcinoma (PC) is the second most diagnosed cancer in men population worldwide. The small amount of the tissue in prostate needle biopsy is often sufficient for the correct interpretation. Novel antibodies, as ERG, could add to the diagnostic value of IHC study in analysing difficult core biopsies.. The aim of the present study was to establish a diagnostic use of ERG in a work-up of prostate needle biopsies containing minute PC, individually and in combination with AMACR/34βE12.. From total number of 1710 consecutive prostate needle biopsies based on HE stain 114 biopsies containing minute PC. Selected biopsies were incubated with anti-ERG, AMACR and 34βE12 antibodies using immunohistochemical technique.. Among 98 selected biopsies, 57 showed positive and 41 negative ERG staining. AMACR staining was positively expressed in 86 of the cases and completely absent in remaining 12. In 9 of the AMACR-negative cases the final diagnosis was establish by manifestation of ERG expression in the tumour foci. 95 of the biopsies demonstrated lack of 34βE12 expression and only 3 cases showed weak patchy staining. Among these cases 2 were ERG-positive.. ERG antibody could be especially helpful in the cases with controversial expression of AMACR and 34βE12.

Topics: Aged; Aged, 80 and over; Biomarkers, Tumor; Biopsy, Needle; Carcinoma; Humans; Immunohistochemistry; Kallikreins; Keratins; Male; Middle Aged; Prostate-Specific Antigen; Prostatic Neoplasms; Racemases and Epimerases; Transcriptional Regulator ERG

Metaplastic breast carcinoma (MBC) is a rare type of invasive breast carcinoma, and chondroid differentiation is even rarer. Here we report a case of MBC with extensive chondroid differentiation in a 38-year-old woman who presented with a lump in her left breast. Ultrasound findings were most compatible with those of giant fibroadenoma. A histopathological examination revealed a malignant lesion comprising neoplastic epithelial cells arranged in solid nests, with large areas of chondroid differentiation. Neoplastic chondroid cells exhibited a positive reaction for S-100, patchy positive reaction for pan-cytokeratin (AE1/AE3) and negative reaction for epithelial membrane antigen. Both carcinomatous and chondroid cells exhibited p53 overexpression. Sentinel lymph node biopsy revealed no tumorous involvement.

Topics: Adult; Breast Neoplasms; Carcinoma; Cell Differentiation; Diagnosis, Differential; Female; Fibroadenoma; Humans; Keratins; Metaplasia; Neoplasm Invasiveness; Treatment Outcome; Tumor Suppressor Protein p53; Ultrasonography, Mammary

Topics: Breast Neoplasms; Carcinoma; Carcinoma, Ductal, Breast; Diagnosis, Differential; Female; Fibrocystic Breast Disease; Humans; Immunohistochemistry; Keratins; Neoplasm Proteins; Neoplasm Recurrence, Local; S100 Proteins; Triple Negative Breast Neoplasms

Topics: Adnexa Uteri; Adnexal Diseases; Carcinoma; Cysts; Diagnosis, Differential; Eyebrows; Female; Humans; Keratins; Middle Aged; Skin; Skin Diseases

Triple-negative breast carcinomas (TNBCs) correspond to a molecular heterogeneous disease defined by lack of estrogen and progesterone receptor expression, and the absence of overexpression and/or amplification of HER2. Recent data indicate that clinical outcome in TNBC is affected by tumor-infiltrating lymphocytes, suggesting that they can benefit from immunotherapies. We selected 116 consecutive premenopausal patients with TNBC to compare the immunohistochemical profile of the group rich in tumor-infiltrating lymphocytes with those without this characteristic.. We reviewed all the original histological sections to assess pathological features, and to select a representative area for tissue microarrays and immunohistochemical study. Estrogen and progesterone receptors, HER2 and Ki-67 were evaluated in whole histological sections. The following markers were analyzed in tissue microarrays sections: androgen receptor, cytokeratin 5/6, cytokeratin 14, epidermal growth factor receptor (EGFR), vimentin, p16, claudin-3, -4, and -7, p63, and aldehyde dehydrogenase isoform 1 (ALDH1). Lymphocyte-predominant breast cancer (LPBC) was defined by the presence of more than 50% of lymphocytes in the intratumoral stroma.. Twenty-six (22.4%) patients present tumors classified as LPBC and 90 (77.6%) as non-LPBC. The two groups were similar regarding age of patients, tumor grade and Ki-67 positive cells. LPBC cases presented lower frequency of expression of the basal cytokeratins, EGFR, and basal-like immunoprofile. There was a trend to higher expression of ALDH1 by stromal intratumoral cells. The expression of all other markers were similar in the two groups.. Lymphocyte-predominant TNBC in premenopausal patients are mostly of non-basal phenotype.

Topics: Adult; Aldehyde Dehydrogenase 1 Family; Biomarkers, Tumor; Brazil; Carcinoma; Claudins; Cyclin-Dependent Kinase Inhibitor p16; ErbB Receptors; Female; Humans; Immunohistochemistry; Isoenzymes; Keratins; Lymphocytes, Tumor-Infiltrating; Membrane Proteins; Middle Aged; Premenopause; Receptors, Androgen; Retinal Dehydrogenase; Retrospective Studies; Triple Negative Breast Neoplasms; Vimentin

Pulmonary sarcomatoid carcinoma (PSC) is a rare malignancy.. A total of 69 patients with PSC treated at a single institution in southern China with long-term follow-up were evaluated in this study. We analyzed the clinical characteristics, immunohistochemical profiles, epidermal growth factor receptor mutation status, K-RAS mutation status, treatments, and prognosis.. PSC mainly occurred in young male patients with a history of smoking. Most patients received multimodality treatments and the majority had early-stage disease. The median survival time was 19.1 months, and the 5-year survival rate was 17.4%. The patients without distant metastasis, with normal or higher body mass index (≥18.5), with normal hemoglobin, with smaller tumor size (≤4 cm), and those who received complete resection had significantly better overall survival (P<0.05). The patients with pleomorphic carcinoma had much worse prognosis. In a Cox regression model, M stage, pathology, and having received a complete resection were independent prognostic factors (P<0.05).. PSC is a unique lung malignancy with poor prognosis. Patients receiving complete resection had better prognosis, likely a reflection of early-stage disease. Neither neoadjuvant nor adjuvant chemotherapy improved patient survival for those with early-stage disease. The retrospective design and small sample size limited the generalizability. Future multicenter collaborations may be necessary to determine the optimal treatment.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Carcinoma; Carcinoma, Giant Cell; Carcinosarcoma; Combined Modality Therapy; Disease-Free Survival; ErbB Receptors; Female; Follow-Up Studies; Humans; Keratins; Lung Neoplasms; Male; Middle Aged; Mucin-1; Nuclear Proteins; Prognosis; Proto-Oncogene Proteins p21(ras); Pulmonary Blastoma; S100 Proteins; Survival Rate; Thyroid Nuclear Factor 1; Transcription Factors; Vimentin; Young Adult

A case of combined micropapillary and plasmacytoid urothelial carcinoma (UC) of the urinary bladder is presented for a 74-year-old male who was admitted to the hospital with gross hematuria and multifocal papillary bladder tumors. Abdominal computed tomography showed a large enhancing mass on the left lateral and anterior wall of the urinary bladder, which was highly suspicious for extravesicular extension and focal extension of the anterior lesion to the pubic bone. In voided urine, cancer cells were scattered as micropapillae or nests as well as single cells on the low power view. On a higher power view, micropapillae or nests were composed of pleomorphic, high grade tumor cells with an inverted nuclear arrangement and with acinar structures occasionally identified. Single cells were discohesive and large with a thick cytoplasm and eccentrically located nuclei. Histologically, the tumor from the resected bladder showed diffusely infiltrating micropapillae or nests with a surrounding halo and dense singly-scattered plasmacytoid cells. Immunohistochemically, the cancer cells were positive for cytokeratin-7 and cytokeratin-20 but negative for S-100, leukocyte common antigen, and vimentin. At the time of radical cystectomy, severe adhesions and peritoneal metastases were found and the surgery was discontinued. The patient received systemic chemotherapy, but died of bladder cancer 14 months after surgery.

Topics: Acinar Cells; Aged; Biomarkers, Tumor; Carcinoma; Cell Nucleus; Cytoplasm; Humans; Keratins; Male; S100 Proteins; Urinary Bladder Neoplasms

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

Triple-negative breast cancers (TNBC) comprise a heterogeneous subgroup of tumors with a generally poor prognosis. Subclassification of TNBC based on genomic analyses shows that basal-like TNBCs, specifically the basal A or BL2 subtype, are characterized by the expression of ΔNp63, a transcription factor that has been attributed a variety of roles in the regulation of proliferation, differentiation, and cell survival. To investigate the role(s) of p63 in basal-like breast cancers, we used HCC1806 cells that are classified as basal A/BL2. We show that these cells endogenously express p63, mainly as the ΔNp63α isoform. TP63 gene knockout by CRISPR resulted in viable cells that proliferate more slowly and adhere less tightly, with an increased rate of migration. Analysis of adhesion-related gene expression revealed a complex set of alterations in p63-depleted cells, with both increased and decreased adhesion molecules and adhesion substrates compared to parental cells expressing p63. Examination of the phenotype of these cells indicated that endogenous p63 is required to suppress the expression of luminal markers and maintain the basal epithelial phenotype, with increased levels of both CK8 and CK18 and a reduction in N-cadherin levels in cells lacking p63. On the other hand, the level of CK5 was not decreased and ER was not increased, indicating that p63 loss is insufficient to induce full luminal-type differentiation. Taken together, these data demonstrate that p63 exerts multiple pro-oncogenic effects on cell differentiation, proliferation and adhesion in basal-like breast cancers.

Topics: Antigens, CD; Cadherins; Carcinoma; Cell Adhesion; Cell Differentiation; Cell Line, Tumor; Cell Proliferation; CRISPR-Cas Systems; Epithelial Cells; Female; Gene Expression Regulation, Neoplastic; Gene Knockout Techniques; Humans; Keratins; Neoplasm Proteins; Phenotype; Protein Isoforms; Transcription Factors; Triple Negative Breast Neoplasms; Tumor Suppressor Proteins

To identify cutoff values of markers that correlate with the histopathologic diagnosis of ameloblastic carcinoma (AC) and/or the increased recurrence potential of ameloblastoma (AB).. Immunohistochemical expression (IHCE) of 9 selected markers were investigated in 18 non-recurrent ameloblastomas (NRABs), 6 recurrent ameloblastomas (RABs), and 5 ACs.. No significant difference in IHCE of K6, K8, K16, K17, K18, K19, maspin, or syndecan-1 was observed among study groups. α Smooth muscle actin (α-SMA)-positive area in central epithelial cells significantly differentiated between AB and AC (P = .017; t -test). Ki-67 score significantly differentiated between AB and AC (P < .005; t -test) and between AC and RAB (P = .015; ANOVA/post hoc).. Ki-67 score of 75 cells/HPF (ROC curve) is a potential indicator of AC. Clinical recurrence of AB may be predicted by α-SMA expression pattern. Syndecan-1 and α-SMA may indicate a higher aggressive potential of AB when expressed in the stroma.

Topics: Actins; Ameloblastoma; Biomarkers, Tumor; Carcinoma; Humans; Immunohistochemistry; Jaw Neoplasms; Keratins; Ki-67 Antigen; Neoplasm Recurrence, Local; Prognosis; Serpins; Syndecan-1

Prostate carcinoma (PC) is the second most diagnosed cancer in men worldwide. Prostate tissue in needle biopsy expresses a wide variety of architectural patterns some of which are difficult to interpret. Immunohistochemical markers, such as AMACR, p63 and 34βE12 that are currently used in diagnosing prostate cancer, are of great value, but often their interpretation is ambiguous. In 2005 Tomlins et al. identified an emerging marker, erythroblastosis E26 rearrangement gene (ERG), which is a member of the family of genes encoding erythroblast-transformation specific transcription factors (ETS) with frequent expression in PC.. The aim of this study was to investigate the expression of ERG in benign mimickers of PC in needle biopsies and its diagnostic value alone and in combination with AMACK and 34βE12.. Of the selected 46 biopsies, two were eventually diagnosed as PC Gleason score 6 as they were simultaneously ERG and AMACR-positive and 34βE12-negative. One case was considered atypical. The remaining 43 biopsies were diagnosed as benign cases: simple atrophy in 13 cases, partial atrophy in 11, adenosis in 9, basal cell hyperplasia in 3, post-atrophic hyperplasia in 3, clear cell hyperplasia in 2 and sclerotic adenosis in 2 cases. None of the 43 benign cores showed evidence of ERG expression.. ERG could be preferably used in diagnosing prostate needle biopsies, lesions that are hard to interpret and controversial expression of AMACR/34βE12.

Topics: Aged; Aged, 80 and over; Atrophy; Biopsy, Large-Core Needle; Carcinoma; Diagnosis, Differential; Humans; Immunohistochemistry; Keratins; Male; Middle Aged; Prostate; Prostatic Hyperplasia; Prostatic Neoplasms; Racemases and Epimerases; ROC Curve; Transcriptional Regulator ERG

Epithelial-mesenchymal transition (EMT) is a critical process for cancer metastasis and recurrence. Metformin, an effective oral antidiabetic drug, has been associated with decreased cancer risk and mortality. In this pilot study, we started to evaluate the effect of metformin on EMT in vivo and in vitro in endometrial cancer (EC).. Endometrial cancer cell lines and freshly isolated EC tumor specimens were used to assess EMT after metformin treatment. Cell lines were subjected to wound healing and AlamarBlue assays to determine cell migration and cell proliferation; messenger RNA levels were measured by real-time reverse transcriptase (RT) quantitative polymerase chain reaction (PCR), and protein levels were measured by Western blots to detect EMT marker expression.. Protein expression and messenger RNA of E-cadherin was found to be increased (P = 0.02 and 0.04, respectively) in 30 EC tumor specimens of diabetic patients treated with metformin compared with 20 EC tumor specimens of diabetic patients treated with other antidiabetic agents. In vitro, metformin reduced cell migration at 5 mM for 48 hours, as determined by the wound healing assay in EC cell lines (Ishikawa, 45% reduction; HEC50, 40% reduction), whereas more than 90% of the cells remained viable on the AlamarBlue assay. Metformin reduced EMT in the cell lines and regulated the expression of the EMT-related epithelial markers, E-cadherin and Pan-keratin; the mesenchymal markers, N-cadherin, fibronectin, and vimentin; and the EMT drivers, Twist-1, snail-1, and ZEB-1.. Tumors of patients on metformin have increased E-cadherin expression, and metformin decreases EMT in EC cell lines in vitro, suggesting clinical biological relevance of metformin in women with EC.

Topics: Adult; Aged; Aged, 80 and over; Cadherins; Carcinoma; Cell Line, Tumor; Cell Movement; Diabetes Mellitus, Type 2; Drug Screening Assays, Antitumor; Endometrial Neoplasms; Epithelial-Mesenchymal Transition; Female; Humans; Hypoglycemic Agents; Keratins; Metformin; Middle Aged; Pilot Projects; Retrospective Studies

Mammary analogue secretory carcinoma (MASC) is a recently described salivary gland tumour that harbours the recurrent ETV6-NTRK3 translocation. This is the first series of MASC cases identified in the historic cohort of carcinomas of salivary glands with clinical/pathological correlation and follow-up data. We reviewed 183 primary carcinomas of major and minor salivary glands resected at the Medical University of Gdańsk, Poland, between 1992 and 2012. Based on morphology and immunohistochemistry, cases suspicious for MASC were selected, and the diagnosis was confirmed by fluorescence in situ hybridization (FISH) for ETV6 rearrangement and by RT-PCR for the ETV6-NTRK3 fusion transcript. Seven carcinomas met the criteria of MASC, as they exhibited a typical appearance with solid/microcystic and papillary architecture and intraluminal secretions, and cells completely devoid of basophilic cytoplasmic zymogen granules indicative of true acinar differentiation. The only paediatric case was an unencapsulated tumour composed of macrocystic structures covered by a mostly single but, focally, double layer of cells with apocrine morphology. In all cases, the neoplastic cells revealed immunoreactivity for S100, mammaglobin, cytokeratin CK7, CK8, STAT5a and vimentin. FISH for ETV6 gene rearrangement was positive in six out of seven cases, and RT-PCR was positive in three cases. MASC is a new entity of malignant epithelial salivary gland tumours not included in the 2005 WHO Classification of Head and Neck Tumours. There is a growing body of evidence that it is not as rare as was assumed, as is also indicated by our series (3.8 %). In most cases, MASC shares some microscopic features with AciCC, adenocarcinoma/cystadenocarcinoma NOS and low-grade MEC. In rare cases, MASC with high-grade transformation may mimic the morphological appearances of high-grade salivary gland malignancies, such as salivary duct carcinoma.

Topics: Adolescent; Adult; Aged; Biomarkers, Tumor; Breast Neoplasms; Carcinoma; ETS Translocation Variant 6 Protein; Female; Follow-Up Studies; Gene Fusion; Gene Rearrangement; Humans; Keratins; Male; Middle Aged; Proto-Oncogene Proteins c-ets; Receptor, trkC; Repressor Proteins; Retrospective Studies; S100 Proteins; Salivary Gland Neoplasms; STAT5 Transcription Factor; Translocation, Genetic; Tumor Suppressor Proteins; Vimentin; Young Adult

To study epithelial mesenchymal transition (EMT) in breast cancer, molecules such as PRL-3, Snail, Cytokeratin and Vimentin involved in EMT were evaluated.. In this study, m-RNA expression of PRL3 and Snail by RT PCR, protein expression of PRL-3, Snail, Cytokeratin and Vimentin by immunohistochemistry were evaluated on paraffin-embedded tissue sections of 100 patients with breast cancer.. PRL3 m-RNA expression (above cut off level > 2487301.00) and PRL-3 protein expression was noted in 52% and 70% of breast carcinoma patients, respectively. The higher incidence of PRL3 protein than m-RNA expression could be due to post translation modification. Further, Snail m-RNA expression (above cut off level > 1285142.00) and Snail protein expression was noted in 53% and 54% of breast cancer patients respectively and Snail protein expression was found significantly higher in patients with pre-menopausal status. The loss of cytokeratin expression in 32% and gain of vimentin expression in 17% was noted in these patients. Vimentin expression was found significantly higher in patients with stage IV disease, BR score 4 and PR negativity. In multivariate survival analysis, Vimentin expression found as strong indicator of biologically aggressive breast cancer predicting reduced disease free survival (DFS) and overall survival (OS).. In our study reveals that Vimentin expression emerged as significant biomarker for predicting reduced DFS and OS in breast cancer. The study proposes routine evaluation of Vimentin with other predictive parameters can allow use of EMT inhibitors with conventional therapy to revert EMT in breast cancer.

Topics: Adenocarcinoma, Mucinous; Adult; Breast Neoplasms; Carcinoma; Carcinoma, Ductal, Breast; Carcinoma, Lobular; Carcinoma, Medullary; Carcinoma, Papillary; Disease-Free Survival; Epithelial-Mesenchymal Transition; Female; Humans; Immunohistochemistry; Kaplan-Meier Estimate; Keratins; Middle Aged; Neoplasm Grading; Neoplasm Proteins; Neoplasm Staging; Prognosis; Protein Tyrosine Phosphatases; Retrospective Studies; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Snail Family Transcription Factors; Transcription Factors; Vimentin

Undifferentiated carcinoma of the esophagus is a rare histologic variant of esophageal carcinoma. Using criteria based on studies of undifferentiated carcinomas arising at other sites, we have collected 16 cases of resected esophageal undifferentiated carcinomas. Patients ranged in age from 39 to 84 years (mean, 65.5 years) and were predominantly male (94%). The tumors were characterized by an expansile growth pattern of neoplastic cells organized in solid sheets and without significant glandular, squamous, or neuroendocrine differentiation. The neoplastic cells had a syncytial-like appearance, little intervening stroma, and patchy tumor necrosis. In a subset of cases, the tumor cells adopted a sarcomatoid (n = 2), rhabdoid (n = 1), or minor component (<5%) of glandular morphology (n = 3). In 1 case, reactive osteoclast-like giant cells were found interspersed among the neoplastic cells. Lymphovascular invasion, perineural invasion, and lymph node metastases were identified in 88%, 56%, and 81% of cases, respectively. In 12 (75%) specimens, the background esophageal mucosa was notable for Barrett esophagus. Consistent with the epithelial nature of these neoplasms, cytokeratin positivity was identified in all cases. In addition, SALL4 expression was present in 8 (67%) of 12 cases. Follow-up information was available for 15 (94%) of 16 patients, all of whom were deceased. Survival after surgery ranged from 1 to 50 months (mean, 11.9 months). Before death, 67% patients had documented locoregional recurrence and/or distant organ metastases. In summary, esophageal undifferentiated carcinomas are aggressive neoplasms and associated with a high incidence of recurrence and/or metastases and a dismal prognosis.

Topics: Adult; Aged; Aged, 80 and over; Alcohol Drinking; Anemia; Barrett Esophagus; Biomarkers, Tumor; Carcinoma; Carcinoma, Squamous Cell; Comorbidity; Deglutition Disorders; Esophageal Neoplasms; Esophageal Squamous Cell Carcinoma; Female; Follow-Up Studies; Gastroesophageal Reflux; Humans; Immunohistochemistry; In Situ Hybridization; Keratins; Lymphatic Metastasis; Male; Middle Aged; Neoplasm Invasiveness; Neoplasm Recurrence, Local; Neoplasm Staging; Neoplasms, Second Primary; Prognosis; Smoking; Survival Rate; Transcription Factors; Treatment Outcome

Nasopharyngeal carcinoma (NPC) is an aggressive disease and tends to involve surrounding tissues, and biomarkers for better management are yet to be identified.. One hundred and fifty tissue samples with NPC diagnosis were were investigated using pan cytokeratin (CK) and epithelial membrane protein 2 (EMP2) antibodies.. Immunohistochemical expression of CK was identified in 144/150 (96%) and of EMP2 in 120/150 (80%).. There is a high loss of EMP2 in NPC, especially high grade examples. Loss of CK expression is also linked to high grade NPC types.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Biomarkers, Tumor; Carcinoma; Female; Follow-Up Studies; Humans; Immunoenzyme Techniques; Keratins; Male; Membrane Glycoproteins; Middle Aged; Nasopharyngeal Carcinoma; Nasopharyngeal Neoplasms; Neoplasm Grading; Prognosis; Retrospective Studies; Young Adult

Well-characterized, low-passage, primary cell cultures established directly from patient tumors are an important tool for drug screening because these cultures faithfully recapitulate the genomic features of primary tumors. Here, we aimed to establish these cell cultures from primary endometrial carcinomas (ECs) and to develop subcutaneous and orthotopic xenograft models as a model to validate promising treatment options for EC in the in vivo setting.. Primary cell cultures of EC tumors were established and validated by analysing histologic and genetic characteristics, telomerase activity, and in vitro and in vivo growth characteristics. Using these primary cell cultures, subcutaneous and orthotopic mouse models were subsequently established.. We established and characterized 7 primary EC cell cultures and corresponding xenograft models of different types of endometrioid tumors. Interestingly, we observed that the chance to successfully establish a primary cell culture seems higher for microsatellite instable than microsatellite stable tumors. For the first time, we also established an orthotopic murine model for EC derived from a primary cell culture. In contrast to EC cell lines, grafted tumor cultures preserved the original tumor structure and mimicked all histologic features. They also established abdominal and distant metastases, reflecting the tumorigenic behavior in the clinical setting. Remarkably, the established cell cultures and xenograft tumors also preserved the genetic characteristics of the primary tumor.. The established EC cultures reflect the epithelial genetic characteristics of the primary tumor. Therefore, they provide an appropriate model to investigate EC biology and apply high-throughput drug screening experiments. In addition, the established murine xenograft models, in particular the orthotopic model, will be useful to validate promising therapeutic strategies in vivo, as the grafted tumors closely resemble the primary tumors from which they were derived. Microsatellite instable status seems to determine the success rate of establishing primary cell cultures.

Topics: Adult; Aged; Animals; Carcinoma; Cell Proliferation; Disease Models, Animal; Endometrial Neoplasms; Female; Humans; Keratins; Mice; Mice, Nude; Microsatellite Instability; Microsatellite Repeats; Middle Aged; Neoplasm Transplantation; Primary Cell Culture; Receptors, Estrogen; Receptors, Progesterone; Tumor Cells, Cultured; Vimentin

Controversies remain regarding the cell type from which human prostate cancer originates, and many attempts have been made to identify the cellular origin of canine prostate cancer but without definitive proof. This study aims to evaluate the expression of luminal (androgen receptor [AR], cytokeratin [CK]8/18) and basal (CK14, CK5) cell markers in different histologic subtypes of canine prostatic carcinoma (PC) and to suggest the most likely tumor-initiating cells. Normal prostates (n = 8) were characterized by AR+CK8/18+ luminal cells and few CK5+ basal cells, while CK14 was absent. Similar pattern was observed in all 35 prostates with benign prostatic hyperplasia, except few scattered CK14+ basal cells in 13 samples (37.14%). AR was localized in the nucleus of both normal and hyperplastic cells. In 34 samples of PC, the following growth patterns were identified: cribriform (44.12%), solid (32.35%), small acinar/ductal (20.59%), and micropapillary (2.94%). Most PCs expressed AR and CK8/18, while CK5 and CK14 expression was observed in 25% and 20% of cases, respectively. AR revealed a variable intracellular distribution, both nuclear and cytoplasmic. Solid PC was characterized by an undifferentiated or aberrant phenotype with a reduced expression of AR and CK8/18, increased number of CK14+ cells, and 7 antigen expression patterns. This study demonstrated a predominance of differentiated luminal cell types in canine prostatic tumors, although the role of basal cells in prostate carcinogenesis should also be considered. Moreover, few scattered CK5+ cells in AR+CK8/18+ tumors identified the existence of intermediate cells, from which neoplastic transformation may alternatively commence.

Topics: Animals; Biomarkers, Tumor; Carcinoma; Cell Differentiation; Dogs; Immunohistochemistry; Keratins; Male; Neoplastic Stem Cells; Prostate; Prostatic Neoplasms; Receptors, Androgen

Low-grade fibromatosis-like spindle cell carcinoma is a rare tumor in the breast, and represents a variant of the very heterogeneous group of metaplastic carcinomas of the breast. These tumors warrant distinction because of their resemblance to pure fibromatosis, their propensity for local recurrence, and their favorable prognosis among the metaplastic carcinomas of the breast. The diagnosis is potentially challenging, particularly on core needle biopsies, because of the morphologic overlap with other low-grade spindle cell lesions. Recognition of a proliferation of cytologically bland spindle cells with areas of epithelial differentiation in combination with immunohistochemistry using antibodies against cytokeratins and myoepithelial markers should aid in producing a definitive diagnosis. These tumors can be locally aggressive with an increased incidence of local recurrence, but the potential for lymph node or distant metastasis is low. Complete excision with adequate margins is considered curative in the majority of cases.

Topics: Biopsy; Breast; Breast Neoplasms; Carcinoma; Diagnosis, Differential; Fibroma; Humans; Immunohistochemistry; Keratins; Neoplasm Grading; Prognosis; Vimentin

Microcystic adnexal carcinoma (MAC), syringomatous carcinoma (SC) and "Squamoid eccrine ductal carcinoma" (SEDC) are rare sclerosing adnexal tumours.. To understand the histogenesis of these tumours and possible clinical implications.. We conducted a retrospective study of 30 cases, 18 MAC, 5 SC and 7 SEDC reviewed and classified by a panel of dermatopathology experts, with immunohistochemical analysis of keratins, including K77, a new keratin specific of eccrine ducts, and PHLDA1 expressed in adnexal structures.. There was a strong female predominance, with only five cases occurring in men. Patients with MAC and SC were younger (mean age 56 and 47 years) than those with SEDC (mean age 81 years). The most common localization was the cheek in SC and SEDC and the periocular area in MAC. Two cases of SEDC were found in organ transplant patients. No recurrence or metastases were observed after complete surgery of MAC, or SC (mean follow-up 7.2 years and 4.7 years), whereas one case of SEDC recurred and another could not be fully excised. MAC and SC had similar histological features, except for cysts. In MAC, calcifications, granulomas, connection to follicles, keratin expression pattern, PHLDA1 positivity and K77 negativity indicated a follicular histogenesis, whereas in SC, K77 positivity and keratin expression pattern were consistent with a differentiation towards eccrine apparatus. SEDC was composed of strands centred by ducts and nests with squamous differentiation and displayed K77 ductal positivity in all cases, a finding consistent with an eccrine origin.. Our study demonstrated that MAC and SC have similar clinical characteristics, although histogenesis differs and show arguments for the individualization of SEDC.

Topics: Adult; Aged; Aged, 80 and over; Carcinoma; Facial Neoplasms; Female; Humans; Keratins; Male; Middle Aged; Neoplasm Recurrence, Local; Retrospective Studies; Sweat Gland Neoplasms; Transcription Factors; Young Adult

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

Chemoresistance is a common mode of therapy failure for many cancers. Tumours develop resistance to chemotherapeutics through a variety of mechanisms, with proteins serving pivotal roles. Changes in protein conformations and interactions affect the cellular response to environmental conditions contributing to the development of new phenotypes. The ability to understand how protein interaction networks adapt to yield new function or alter phenotype is limited by the inability to determine structural and protein interaction changes on a proteomic scale. Here, chemical crosslinking and mass spectrometry were employed to quantify changes in protein structures and interactions in multidrug-resistant human carcinoma cells. Quantitative analysis of the largest crosslinking-derived, protein interaction network comprising 1,391 crosslinked peptides allows for 'edgotype' analysis in a cell model of chemoresistance. We detect consistent changes to protein interactions and structures, including those involving cytokeratins, topoisomerase-2-alpha, and post-translationally modified histones, which correlate with a chemoresistant phenotype.

Topics: Antigens, Neoplasm; Blotting, Western; Carcinoma; Chromatography, Liquid; DNA Repair; DNA Topoisomerases, Type II; DNA-Binding Proteins; Drug Resistance, Multiple; Drug Resistance, Neoplasm; Female; HeLa Cells; Histone Code; Histones; Humans; Immunoprecipitation; Keratins; Mass Spectrometry; Microscopy, Fluorescence; Phenotype; Protein Interaction Maps; Uterine Cervical Neoplasms

Epithelial myoepithelial carcinoma (EMC) of the lung is a very rare tumor that is characterized by biphasic differentiation of epithelial and myoepithelial cells. Current discussion about this entity focuses on the malignant potential of the tumor and the role of myoepithelial cells in diagnosis and patient prognosis. This study reports five EMC cases in the lung and discusses issues related to EMC prognosis.. The five EMC cases were diagnosed and collected at the Samsung Medical Center (Seoul, Korea) from 1998 to 2012. Four patients with EMC were received a lobectomy and one patient was given a bronchoscopy to excise the tumor. All cases were evaluated with hematoxylin and eosin and immunohistochemical staining, which included S-100 protein, smooth muscle actin, TTF-1, cytokeratin, vimentin, and p27 analysis.. All cases revealed biphasic differentiation of epithelial and myoepithelial tumor cells with various stromal patterns. One of the cases contained predominantly myoepithelial and focal epithelial differentiation, and the tumor showed recurrence and metastasized to the chest wall. This was the first case of metastatic pulmonary EMC. Therefore, we suggest that EMC of the lung has a malignant potential, and that myoepithelial tumor cells may be associated with a pulmonary EMC prognosis.

Topics: Actins; Aged; Bronchial Neoplasms; Carcinoma; Cell Differentiation; Cyclin-Dependent Kinase Inhibitor p27; DNA-Binding Proteins; Epithelial Cells; Female; Humans; Immunohistochemistry; Keratins; Male; Middle Aged; Myoepithelioma; Prognosis; S100 Proteins; Tracheal Neoplasms; Transcription Factors; Treatment Outcome; Vimentin

Cervical cancer is the seventh most common malignancy in both genders combined and the third most common cancer in women. Despite significant progress in treatments, cervical cancer is not completely curable. Therefore, further research is necessary in this area. Animal models are one of the most practical tools in the field of cancer research. The present study aimed to characterize the growth behavior and surface markers of HeLa cells after heterotopic and systemic inoculation to athymic nude mice.. Ten 6-week old female athymic C57BL/6 nude mice were used in this study. HeLa cells were inoculated into the flank or tail vein. The tumor volume was calculated and growth curves were drawn. Tumor-bearing mice were sacrificed and the lesions obtained after harvesting were analyzed in a pathology lab. Subsequently, one slide per tumor was stained with hematoxylin and eosin (H&E) and other slides were stained immunohistochemically by cytokeratins (CK), vimentin, P53, CD34, and Ki-67.. Tumor take rate, mean doubling time and latency period were 94.4%, 5.29 ± 3.57 days and 15.27 days, respectively. H&E results revealed highly malignant hyperchromatin epithelial cells. Immunohistochemical examination of the heterotopic tumors indicated greater expression of CK and less expression of vimentin compared to the metastatic ones. Sixty percent of cells were P53-positive and more than 80% were Ki-67-positive. CD34 expression indicated the intensity of angiogenesis in tumor.. This study represents a comprehensive description of a HeLa xenograft model for in vivo investigations, enabling researchers to assess new treatments for cervical cancer.

Topics: Animals; Antigens, CD34; Carcinoma; Disease Models, Animal; Female; HeLa Cells; Heterografts; Humans; Immunohistochemistry; Keratins; Ki-67 Antigen; Lung Neoplasms; Mice; Mice, Inbred C57BL; Mice, Nude; Time Factors; Tumor Burden; Tumor Suppressor Protein p53; Uterine Cervical Neoplasms; Vimentin

Undifferentiated (anaplastic) carcinoma with rhabdoid features is a rare and aggressive subtype of pancreatic carcinoma. Here, we report the clinical, histological, and immunohistochemical phenotypes in six autopsy cases of anaplastic carcinoma with rhabdoid features. The patients ranged between 44 and 76 years of age (median, 61 years) and consisted of four males and two females. All patients except one case died within 3 months of diagnosis, as these tumors were found at an advanced stage and were chemoresistant. At autopsy, tumor masses measuring 4-22 cm in maximum diameter were mainly located in the pancreatic body and tail. Microscopically, all cases showed anaplastic carcinoma with rhabdoid features that were discohesive with round to polygonal eosinophilic cytoplasm with occasional inclusions, and that had vesicular nuclei, and prominent nucleoli. Immunohistochemistry showed that the rhabdoid cells, particularly the inclusions, were strongly positive for pan-cytokeratin (AE1/AE3) and vimentin. Meanwhile, downregulation or aberrant cytoplasmic localization with focal aggregation of E-cadherin, β-catenin, and EMA were frequently observed in the rhabdoid cells. Moreover, the intracytoplasmic inclusions were labeled with selective autophagy-related molecules including p62/SQSTM1, ubiquitin, and kelch-like ECH-associated protein 1 (KEAP1). In addition, nuclear factor erythroid 2-related factor 2 (NRF2) and overexpression of its target molecule multidrug resistance-associated protein 1 (MRP1) were commonly observed in the rhabdoid cells. Therefore, these results suggest that p62-mediated aggregation of ubiquitinated intermediate filaments and membranous proteins is an important phenomenon in the rhabdoid phenotype. Indeed, the ubiquitinated aggregates of p62 and KEAP1 would induce activation of NRF2 and upregulation of MRP1, leading to potential chemoresistance of anaplastic carcinoma with rhabdoid features.

Topics: Adult; Aged; Autopsy; Biomarkers, Tumor; Carcinoma; Drug Resistance, Neoplasm; Female; Humans; Immunohistochemistry; Keratins; Male; Middle Aged; Multidrug Resistance-Associated Proteins; Pancreatic Neoplasms; Vimentin

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

Although several studies have shown that the presence of acellular mucin pools in surgical specimens with rectal carcinomas examined after preoperative chemoradiotherapy indicated complete response to therapy, the proper meaning of these pools has yet to be elucidated. The aims of this study were to analyze the immunoprofile of acellular mucin pools and to review the relevant literature.. In 30 consecutive rectal cancers that were preoperatively treated with chemoradiotherapy, the clinicopathologic features were correlated with the immunoexpression of AE1/AE3 keratin and carcinoembryonic antigen (CEA).. Acellular mucin pools were present in all the cases, independently by their preoperative histological aspect. In remnant tumors (n=20), they were present at the invasion front and were marked by CEA. In cases without remnant tumor cells (n=10), they also displayed CEA positivity. In 2 of the 10 cases, isolated tumor cells were identified after multilevel sectioning of paraffin-embedded blocks.. The presence of acellular mucin pools in surgical specimens of rectal cancers cannot be interpreted as an indicator of complete response to radiotherapy if at least 10 multilevel sections are performed in at least three tumor blocks per case, and CEA negativity is not proved.

Topics: Aged; Carcinoembryonic Antigen; Carcinoma; Chemoradiotherapy; Female; Humans; Keratins; Male; Middle Aged; Mucins; Preoperative Period; Rectal Neoplasms

Mammary analogue secretory carcinoma (MASC) is a newly described rare salivary gland tumor, which shares morphologic features with acinic cell carcinoma, low-grade cystadenocarcinoma, and secretory carcinoma of the breast. This is the first reported case of MASC of an accessory parotid gland detected by aspiration biopsy with radiologic and histologic correlation in a 34-year-old patient. Sonographically-guided aspiration biopsy showed cytologic features mimicking those of low-grade mucoepidermoid carcinoma, including sheets of bland epithelial cells, dissociated histiocytoid cells with intracytoplasmic mucinous material, and spindle cells lying in a web-like matrix. Histologic sections showed a circumscribed tumor with microcystic spaces lined by bland uniform epithelial cells and containing secretory material. The tumor cells expressed mammaglobin and BRST-2. The cytologic features, differential diagnosis, and pitfalls are discussed. The pathologic stage was pT1N0. The patient showed no evidence of disease at 1 year follow-up.

Topics: Adult; Biomarkers, Tumor; Biopsy, Needle; Breast Neoplasms; Carcinoma; Carcinoma, Mucoepidermoid; Diagnosis, Differential; Female; Humans; Image-Guided Biopsy; Keratins; Mammaglobin A; Neoplasm Staging; Parotid Neoplasms; Ultrasonography; Vimentin

Topics: Carcinoma; Diagnosis, Differential; Female; Humans; Immunohistochemistry; Keratins; Lymphoma, Large-Cell, Anaplastic; Middle Aged; Neoplasms, Unknown Primary

Progression of oral carcinomas associates with aberrant activation and inactivation of molecules that work in established or unknown pathways. Although mucosa‑associated lymphoid tissue 1 (MALT1) expressed in normal oral epithelium is inactivated in the aggressive subset of carcinomas with worse prognosis, phenotypic changes of carcinoma cells upon the loss of expression is unknown. We performed a proteomic analysis to identify MALT1‑regulated proteins in oral carcinoma cells. Four different keratins were included in the ten most abundantly changed proteins. K8/18 were upregulated in MALT1 stably‑expressing carcinoma cells and K5/14 in MALT1‑marginal control cells. K8/18 upregulation and K5/14 downregulation were MALT1 dose‑dependent and observed in a series of oral carcinoma cells. MALT1 suppressed cell proliferation (0.52-fold, P<0.01) and its dominant-negative form stimulated it (1.33-fold, P<0.01). The decreased proliferation associated with reduction of cyclin D1, which was recovered by the short interfering RNA against MALT1. Taken together, loss of MALT1 expression alters keratin expression and enhances proliferation of carcinoma cells, and may progress oral carcinomas into the advanced state.

Topics: Carcinoma; Caspases; Cell Line, Tumor; Cell Proliferation; Cyclin D1; Epithelium; Gene Expression Regulation, Neoplastic; Humans; Keratins; Mouth Neoplasms; Mucosa-Associated Lymphoid Tissue Lymphoma Translocation 1 Protein; Mucous Membrane; Neoplasm Proteins; Proteomics; Up-Regulation

Topics: Actins; Antigens, CD34; Biomarkers, Tumor; Carcinoma; Diagnosis, Differential; Female; Humans; Keratins; Mesoderm; Myxoma; Neoplasms, Germ Cell and Embryonal; Neprilysin; Proto-Oncogene Proteins c-bcl-2; Vaginal Neoplasms; Young Adult

Spindle cell carcinoma (SpCC) is a rare tumor consisting of spindle cells which express cytokeratin. Despite recent advances in immunohistochemical and genetic studies, precise histogenesis of SpCC is still controversial and this tumor had been referred to with a wide range of names (in the past): carcinosarcoma, pseudosarcoma, sarcomatoid carcinoma, pseudosarcomatous carcinoma, and collision tumor. Recently, the authors experienced an extremely rare case of SpCC arising from the stomach. A 64-year-old male presented with unintended weight loss and hematochezia. Endoscopic examination revealed a fistulous tract between the stomach and the transverse colon which was made by direct invasion of SpCC of the stomach to the colon. Histologically, the tumor was positive for both vimentin and cytokeratin but negative for CD117, CD34, actin, and desmin. Herein, we report a case of SpCC arising from the stomach that formed a fistulous tract with the colon which was diagnosed during evaluation of hematochezia and weight loss.

Topics: Antineoplastic Agents; Brain Neoplasms; Carcinoma; Colon, Transverse; Endoscopy, Digestive System; Fistula; Gastrointestinal Hemorrhage; Humans; Keratins; Magnetic Resonance Imaging; Male; Middle Aged; Stomach Neoplasms; Tomography, X-Ray Computed; Weight Loss

Nasopharyngeal carcinoma is the predominant tumor type arising in the nasopharynx with cervical lymph nodes present in 60-90% of all cases at the time of presentation. The most frequent pathological varieties include squamous cell carcinoma well-differentiated keratinizing, moderately differentiated non-keratinizing and an undifferentiated type. We present a case of non-keratinizing undifferentiated carcinoma of the nasopharynx with parapharyngeal and middle cranial fossa space involvement in an 18-year-old male who has been admitted in our hospital for recurrent right ear otitis media. Symptoms consisted in mild conductive hearing loss, trigeminal V2 nerve anesthesia, right ear tinnitus, mild dysphagia, mild dysphonia, right hypoglossal nerve paralysis and right Claude Bernard-Horner's syndrome. Clinical examination revealed no lymph node masses, chest X-ray corresponding to a normal thoracic image. Cranial contrast enhanced CT scan showed a non-homogenous mass of 5.4/4.5/5.5 cm from the level of the right rhinopharyngeal wall, extending in the right parapharyngeal space, invading the right middle cranial fossa. Cranial MRI with contrast enhancement revealed a rhino- and parapharyngeal mass of 5.5/4.6/5.3 cm with intracerebral extension in the right cavernous sinus, right internal carotid artery being engulfed by the tumor mass with partial compression. Several lymph node masses of 1.7/1.2 cm were also revealed. We performed rhinopharyngeal biopsy, right tympanotomy and grommet tube insertion. The tissue specimens were processed with routine histological technique. Subsequent immunohistochemical reactions for pan-cytokeratin AE1/AE3 and leukocytes common antigen were performed. The histological examination of routine stained slides showed that malignant tumor cells had a syncytial pattern of growth in a background of small lymphocytes. The positivity of tumor cells for pan-cytokeratin established the final diagnosis of non-keratinizing undifferentiated carcinoma. The age of onset, the clinical signs and symptoms and minimum involvement of lymph nodes represents the particular aspects of the case.

Topics: Adolescent; Carcinoma; Giant Cells; Humans; Keratins; Magnetic Resonance Imaging; Male; Nasopharyngeal Carcinoma; Nasopharyngeal Neoplasms

Sarcomatoid carcinoma of the urinary bladder is a rare entity, whose histogenesis and biological behavior remain controversial. The cytological literature on sarcomatoid carcinoma in voided urine is very scarce. Clinically, the diagnosis of this tumor can be made by computed tomography (CT), magnetic resonance imaging (MRI), cytology, and biopsy material. In this study, cytology, histopathology, and radiological imaging were employed in order to reach a diagnosis of sarcomatoid carcinoma. CT imaging showed increased thickness of the bladder wall associated to a polypoid mass. MRI showed a 4-cm sized, broadly necked polypoid mass with calcification and ulceration at the right side of the bladder wall. T2W1 imaging showed low signal. Voided urinary cytology showed a scattered cellular presentation. The tumor cells had a high nucleo- cytoplasmic ratio, with elongated cytoplasm with faint with indistinct cytoplasm border. The nucleus was oval to round, with large and irregular nucleoli and irregular nuclear membrane. These tumor cells were positive for cytokeratin (CKAE1/AE3), vimentin, p53, carcinoembryonic antigen (CEA), α1-smooth muscle actin (SMA) by the immunoperoxidase staining. Histopathology showed spindle-shaped and clumped large tumor cells with abundant cytoplasm. Mitotic figures were frequently seen and varied from area to area (50% of the tumor cells were positive for MIB1).

Topics: Actins; Aged; Carcinoembryonic Antigen; Carcinoma; Cytodiagnosis; Epithelial Cells; Female; Humans; Keratins; Magnetic Resonance Imaging; Tomography, X-Ray Computed; Tumor Suppressor Protein p53; Urinary Bladder Neoplasms; Vimentin

Nasopharyngeal carcinoma (NPC) is rare in western countries albeit affected by common and unrelated phenomena: smoking less in men, more in women and immigration from China and North Africa. We studied trends in NPC incidence, tumour morphology, survival and mortality in order to assess progress against this cancer.. A trend analysis was performed with nationwide incidence and survival data (from The Netherlands Cancer registry in 1989-2009), followed by analysis of mortality (data from Statistics Netherlands) covering the period 1970-2009, and calculating estimated percentages of change (EAPC) in both. According to the WHO classification we distinguished keratinizing SCC (WHO-I), differentiated (WHO-IIA) and undifferentiated (WHO-IIB) non-keratinizing carcinoma.. NPC incidence significantly decreased since 1989, especially in males (EAPC 1989-2009: -1.3; 95% CI: -2.5, -0.2) and in patients with keratinizing SCC (WHO-I) (EAPC: -3.6; 95% CI: -5.3, -1.8). By contrast, the incidence of differentiated non-keratinizing tumours (WHO-IIA) significantly increased in the same period (EAPC: 9.6; 95% CI: 5.6, 13.5). One- and three-year relative survival, as an indicator of disease-specific survival increased slightly from 79% to 81% and from 57% to 65% since 1989. NPC mortality significantly decreased since 1970 (EAPC: -1.2; 95% CI: -1.8, -0.5) and more pronounced since 1989 (EAPC: -3.0; 95% CI: -4.3, -1.6).. During the past two decades, the incidence of NPC in The Netherlands decreased mainly by less keratinizing, supposedly smoking-related NPC (WHO-I). However, the incidence of non-keratinizing NPC (WHO-IIA, B) increased, most likely due to EBV infection and thus related to higher immigration levels of people from high-incidence areas.

Topics: Adolescent; Adult; Age Factors; Aged; Aged, 80 and over; Carcinoma; Carcinoma, Squamous Cell; Child; Disease-Free Survival; Emigration and Immigration; Epstein-Barr Virus Infections; Female; Humans; Incidence; Keratins; Male; Middle Aged; Nasopharyngeal Neoplasms; Neoplasm Staging; Netherlands; Registries; Sex Factors; Smoking; Survival Rate; Young Adult

Topics: Aged, 80 and over; Carcinoma; Carcinoma, Basal Cell; Carcinoma, Squamous Cell; Cell Transformation, Neoplastic; Humans; Immunohistochemistry; Keratins; Ki-67 Antigen; Male; Skin Neoplasms; Tumor Suppressor Protein p53

A 13-year-old castrated male Labrador retriever dog presented with a mass caudal to the first molar of his left mandible. Although the tumor was excised, a recurrent tumor was detected one month later and resected. Both tumors displayed invasive growth and were composed of neoplastic proliferation arranged in irregular lobules, nests and cords continuous with mucosal epithelium. The most prominent feature of the tumors was the presence of many proliferating spindle cells admixed with palisading basal-like cells, acanthocytes and stellate cells. In immunohistochemical examinations, the spindle cells were found to be positive for vimentin; cytokeratin AE1/AE3, 5/6, 14 and 19; and p63. The other neoplastic cells were positive for all of these markers shown above except vimentin. Based on these findings, the tumors were diagnosed as spindle cell ameloblastic carcinoma.

Topics: Ameloblastoma; Animals; Carcinoma; Dog Diseases; Dogs; Immunohistochemistry; Jaw Neoplasms; Keratins; Male; Neoplasm Recurrence, Local; Vimentin

Epithelial-myoepithelial carcinoma (EMC) is a rare low-grade salivary gland malignancy of presumed intercalated duct origin comprising 1% of all salivary gland tumours. High grade transformation (HGT) in EMC is a recently recognised entity with only a few cases reported in the literature. The authors report an additional case of EMC with HGT involving the submandibular gland. The patient was a 60-year-old woman who requested examination of the rapid growth of a mass in the left submandibular area, which she had first noticed 20 years previously. Histologically, the tumour had two distinct carcinomatous components. One component had features of a low grade EMC. The second component consisted of polygonal cells, arranged in a solid and nested pattern, with marked nuclear pleomorphism, brisk mitotic activity, and frequent necrosis. The Ki-67 labelling index of the EMC component was 9%, and that of the high grade component was 40%. The patient developed multiple pulmonary metastases 15 months after surgery. The aggressive behaviour of EMC with HGT suggests that it is important to recognise this variant of EMC to avoid misdiagnosis and inappropriate treatment.

Topics: Calcium-Binding Proteins; Calmodulin-Binding Proteins; Calponins; Carcinoma; Cell Nucleus; Cell Transformation, Neoplastic; Cytoplasm; Diagnostic Errors; Female; Follow-Up Studies; Humans; Keratins; Ki-67 Antigen; Lung Neoplasms; Membrane Proteins; Microfilament Proteins; Middle Aged; Mitotic Index; Necrosis; Neoplasm Invasiveness; Submandibular Gland Neoplasms

We report a case of carcinoma ex pleomorphic adenoma of a sublingual gland in a 70-year-old man. Under a clinical diagnosis of benign salivary gland tumor, excision of the mass with the sublingual salivary gland in an en bloc fashion via an intraoral approach was performed. Histopathologically, there was a rupture of the fibrous capsule and diffuse cell-rich sheets composed of myoepithelial cells with round nuclei were also seen. Immunohistochemically, the cells that composed of cell rich sheets were positive to smooth muscle actin. Final diagnosis of myoepithelial carcinoma ex pleomorphic adenoma was made.

Topics: Adenoma, Pleomorphic; Aged; Carcinoma; Diagnosis, Differential; Glial Fibrillary Acidic Protein; Humans; Keratins; Male; Myoepithelioma; Neoplasm Invasiveness; S100 Proteins; Sublingual Gland Neoplasms

Cutaneous epithelioid and spindle cell neoplasms occasionally pose a significant diagnostic challenge on purely histologic grounds. Given the substantial clinicopathologic overlap between these lesions, especially in small biopsies, the use of immunohistochemical studies are essential. We evaluated the utility of a battery of immunohistochemical markers, including podoplanin (D2-40), CD10, p63, and wide-spectrum cytokeratin, for distinguishing cutaneous epithelioid and spindle cell tumors. A total of 81 cases, including 42 atypical fibroxanthoma (AFX), 13 spindle cell melanoma, 10 sarcomatoid carcinoma, 9 leiomyosarcoma (LMS), and 7 leiomyoma, formed the basis of our study. Immunohistochemical results were as follows-AFX: CD10 (35 of 42), p63 (1 of 42), CK (1 of 42), and podoplanin (19 of 42); spindle cell melanoma: CD10 (7 of 13), p63 (0 of 13), CK (0 of 13), and podoplanin (2 of 13); sarcomatoid carcinoma: CD10 (5 of 10), p63 (7 of 10), CK (4 of 10), and podoplanin (7 of 10); LMS: CD10 (4 of 9), p63 (0 of 9), CK (2 of 9), and podoplanin (1 of 9); and leiomyoma: CD10 (0 of 7), p63 (0 of 7), CK (0 of 7), and podoplanin (1 of 7). Our findings showed that the combination of certain immunohistochemical markers may be a useful adjunct in the evaluation of epithelioid and spindle cell tumors of the skin. In this study, we found that a combination of wide-spectrum cytokeratin and p63 are most helpful in the distinction of sarcomatoid carcinomas from other tumors; however, there remains a substantial minority of cases of sarcomatoid carcinoma that will consistently demonstrate negative staining for these markers. We also found that CD10 and podoplanin (D2-40) have limited diagnostic utility in epithelioid and spindle cell tumors of the skin; however, a strong and diffuse pattern of staining will favor the diagnosis of AFX. Caution should also be observed in the diagnosis of spindle cell malignant melanoma because some cases may express CD10, p63, and podoplanin while being nonreactive to S100 protein. Awareness of the limitations of the use of these stains and familiarity with their staining patterns in spindle and epithelioid cell tumors of the skin are extremely important because the prognostic and therapeutic implications for such neoplasms may be quite different.

Topics: Adult; Aged; Aged, 80 and over; Antibodies, Monoclonal, Murine-Derived; Biomarkers, Tumor; Carcinoma; Diagnosis, Differential; Epithelioid Cells; Female; Humans; Immunohistochemistry; Keratins; Male; Membrane Glycoproteins; Middle Aged; Neprilysin; Predictive Value of Tests; Sarcoma; Skin Neoplasms; Transcription Factors; Tumor Suppressor Proteins; Wisconsin; Young Adult

Feline mammary carcinomas are highly aggressive neoplasms. Several mechanisms are thought to be involved in their progression, including the loss of epithelial adhesion molecules. The present study was carried out on 21 adenomas and 139 mammary carcinomas. Of the carcinomas, 66 were not reported to have metastasized, while the remaining 73 had evidence of regional lymph node metastasis at the moment of diagnosis. The relationship was examined between the expression of the E-cadherin-β-catenin complex and basal (CK5/6, CK14) and luminal (CK8/18) cytokeratin expression. In the medical literature, carcinomas expressing basal cytokeratins are reported as having a poor prognosis in human breast cancer. Results revealed that preservation of the expression of E-cadherin and β-catenin is a significant feature of carcinomas without metastasis, whereas carcinomas with metastasis reveal the loss of one or both adhesion molecules. Additionally, basal cytokeratin expression was statistically associated with the presence of regional metastasis. Furthermore, the expression of E-cadherin-β-catenin was significantly correlated with the high expression of CK18 and low expression of CK5/6.

Topics: Adenoma; Animals; beta Catenin; Biomarkers, Tumor; Cadherins; Carcinoma; Cat Diseases; Cats; Female; Immunohistochemistry; Keratins; Lymphatic Metastasis; Mammary Neoplasms, Animal; Neoplasm Grading; Vimentin

Keratins are intermediate filament family proteins which are predominantly expressed in the epithelial cells. Most of the studies which evaluate the status of keratins in clinical samples of the oral cavity are based on the identification of their presence and localization by immunohistochemistry using monoclonal antibodies. It is very well known that many monoclonal/polyclonal antibodies show cross-reactivity with the other closely related or non-related proteins. This cross-reactivity might be the result of epitope similarity, but it is not always necessary. Therefore studies done with only antibody based techniques can mislead interpretation unless they are validated with additional techniques like mass-spectrometry. In this investigation we have evaluated the status of keratin 18 in cancer of buccal mucosa using 1DE, 2DE and western blotting with monoclonal antibody to keratin 18. The patterns emerging showed aberrant as well as differential expression of K18 in adjacent normal versus tumor tissue samples of buccal mucosa. Mass spectrometry analysis of the immunodetected spots however revealed that it is keratin 13. Thus this study emphasizes the necessity of validation of antibody based findings when dealing with proteins of a large family having similarity/homology in amino acid sequence.

Topics: Amino Acid Sequence; Antibodies; Antibody Specificity; Carcinoma; Cross Reactions; False Positive Reactions; Humans; Immunohistochemistry; Keratins; Mass Spectrometry; Microdissection; Mouth Neoplasms; Sensitivity and Specificity; Tissue Extracts

Accurate detection and analysis of circulating tumor cells plays an important role in the diagnosis and treatment of metastatic cancer treatment.. A cell microarray chip was used to detect spiked carcinoma cells among leukocytes. The chip, with 20,944 microchambers (105 µm width and 50 µm depth), was made from polystyrene; and the formation of monolayers of leukocytes in the microchambers was observed. Cultured human T lymphoblastoid leukemia (CCRF-CEM) cells were used to examine the potential of the cell microarray chip for the detection of spiked carcinoma cells. A T lymphoblastoid leukemia suspension was dispersed on the chip surface, followed by 15 min standing to allow the leukocytes to settle down into the microchambers. Approximately 29 leukocytes were found in each microchamber when about 600,000 leukocytes in total were dispersed onto a cell microarray chip. Similarly, when leukocytes isolated from human whole blood were used, approximately 89 leukocytes entered each microchamber when about 1,800,000 leukocytes in total were placed onto the cell microarray chip. After washing the chip surface, PE-labeled anti-cytokeratin monoclonal antibody and APC-labeled anti-CD326 (EpCAM) monoclonal antibody solution were dispersed onto the chip surface and allowed to react for 15 min; and then a microarray scanner was employed to detect any fluorescence-positive cells within 20 min. In the experiments using spiked carcinoma cells (NCI-H1650, 0.01 to 0.0001%), accurate detection of carcinoma cells was achieved with PE-labeled anti-cytokeratin monoclonal antibody. Furthermore, verification of carcinoma cells in the microchambers was performed by double staining with the above monoclonal antibodies.. The potential application of the cell microarray chip for the detection of CTCs was shown, thus demonstrating accurate detection by double staining for cytokeratin and EpCAM at the single carcinoma cell level.

Topics: Antibodies, Monoclonal; Antigens, Neoplasm; Carcinoma; Cell Adhesion Molecules; Cell Line, Tumor; Cell Separation; Epithelial Cell Adhesion Molecule; Humans; Keratins; Leukocytes; Microscopy, Fluorescence; Neoplasm Metastasis; Neoplasms; Neoplastic Cells, Circulating; Oligonucleotide Array Sequence Analysis; Polystyrenes; Reproducibility of Results; T-Lymphocytes

The study of proto-oncogene Her-2/neu using the fluorescence in situ hybridization (FISH) technique in routinely paraffin-embedded formalin-fixed tissue has become commonplace over the past decade and mandatory among invasive breast cancer expressing a score 2+ by immunohistochemical analysis of c-erbB2 protein. The patient's eligibility for treatment with the biological drug trastuzumab/herceptin is based on the evidence of a Her-2/neu proto-oncogene amplification (ratio Her-2/neu/CEP-17>2.2). However, although the exclusion is declared in the absence of Her-2/neu gene amplification (ratio Her-2/neu/CEP-17 <1.8) according to the American Society of Clinical Oncology/College of American Pathologists recommendations, there are borderline cases (1.82.2) that need to be investigated (eg, ductal carcinoma in situ with microinvasion, metastatic breast cancer). In such cases with Her-2/neu genetic heterogeneity it is difficult to count the nuclear signals in the areas of invasive tumor using fluorescence. The availability of a Fluorescence Immunophenotyping and Interphase Cytogenetics as a Tool for Investigation of Neoplasms technique, based on the simultaneous evaluation of immunostaining with anticytokeratins (CKAE1/AE3 and CK19), together with FISH for Her-2/neu gene status [it is therefore useful and of current applicability in breast cancer blocks (formalin-fixed and paraffin-embedded)], permits a more easy identification of even single neoplastic cells by immunofluorescence and then a better evaluation of Her-2/neu status gene by the FISH technique, as shown in our study.

Topics: Antibodies, Monoclonal, Humanized; Breast Neoplasms; Carcinoma; Female; Gene Amplification; Genotype; Humans; Immunohistochemistry; Immunophenotyping; In Situ Hybridization, Fluorescence; Keratins; Molecular Targeted Therapy; Patient Selection; Proto-Oncogene Mas; Receptor, ErbB-2; Trastuzumab

Topics: Adult; Antigens, CD20; Carcinoma; Diagnosis, Differential; DNA Nucleotidylexotransferase; Female; Follow-Up Studies; Humans; Keratins; Lymphoma; Male; Middle Aged; Necrosis; Seminoma; Thymoma; Thymus Neoplasms; Tuberculosis

The description of the histological features and the immunohistochemical and molecular analyses of a case of cribriform-morular variant of papillary thyroid carcinoma in an 8-year-old girl with a family history of adenomatous polyposis is presented. The neoplasm was multifocal and bilateral, with a mixed pattern of solid, trabecular, and morular areas. The neoplasm showed angioinvasive behavior, extracapsular infiltration with extension to the perythyroidal muscles, and lymph node metastases. Tumor cells were positive for CAM 5.2, cytokeratins 5/6, TTF-1, HBME-1, galectin-3, and β-catenin. In addition, the molecular tests did not reveal BRAF mutations, RET/PTC rearrangement, APC mutation, or KRAS mutation.

Topics: beta Catenin; Biomarkers; Biomarkers, Tumor; Carcinoma; Carcinoma, Papillary; Child; Disease-Free Survival; DNA Mutational Analysis; DNA-Binding Proteins; DNA, Neoplasm; Female; Galectin 3; Humans; Immunohistochemistry; Keratins; Neck Dissection; Thyroid Cancer, Papillary; Thyroid Neoplasms; Thyroidectomy; Transcription Factors; Treatment Outcome

Recent studies have suggested that some ovarian and pelvic serous carcinomas could originate from the fimbriated end of the distal fallopian tube. To test this hypothesis, we immortalized a normal human fallopian tube epithelial (FTE) cell line by using retrovirus-mediated overexpression of the early region of the SV40 T/t antigens and the human telomerase reverse transcriptase subunit (hTERT). These immortalized FTEs were then transformed by ectopic expression of oncogenic human HRAS (V12) . Tumorigenicity of the immortalized and/or transformed cells was subsequently tested by anchorage-independence growth assay and inoculation into nude mice via subcutaneous and intraperitoneal injection. As expected, the HRAS (V12) -transformed FTEs produced tumors through both subcutaneous and intraperitoneal injections, whereas no tumor growth was observed in immortalized FTEs. Unexpectedly, histopathological examination of tumors resulting from subcutaneous as well as intraperitoneal injections revealed largely poorly differentiated mucinous adenocarcinoma mixed with undifferentiated carcinoma. The tumor implants invaded extensively to the liver, colon, spleen, omentum, adrenal gland and renal capsule. Immunohistochemical staining of tumor cells showed positive staining for the epithelial cell markers cytokeratin AE1/AE3 and Müllerian lineage marker PAX8. Our study demonstrates that FTEs can generate poorly differentiated mucinous adenocarcinoma mixed with undifferentiated carcinoma through genetic modifications. Thus, we provide the first experimental evidence that fimbrial epithelial cells of the fallopian tube could be a potential source of ovarian mucinous adenocarcinoma.

Topics: Adenocarcinoma, Mucinous; Animals; Antigens, Polyomavirus Transforming; Carcinoma; Carcinoma, Ovarian Epithelial; Cell Line, Transformed; Cell Transformation, Neoplastic; Epithelial Cells; Fallopian Tubes; Female; Humans; Immunohistochemistry; Keratins; Mice; Mice, Nude; Neoplasms, Glandular and Epithelial; Ovarian Neoplasms; Paired Box Transcription Factors; PAX8 Transcription Factor; Proto-Oncogene Proteins p21(ras); Telomerase

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

Epithelioid angiosarcoma of the parotid gland is rare, and may pose a great diagnostic challenge. We report a case of primary epithelioid angiosarcoma in a 64-year-old male without history of radiation. The histopathological findings demonstrated a high grade epithelioid neoplasm. Immunostaining showed that the tumor was positive for the pan-cytokeratin, p63, cytokeratin18, Vimentin and vascular markers CD31, and was negative for CD34, cytokeratin5/6, cytokeratin7, cytokeratin20, CD68, CD30, S-100, HMB45, desmin, α-SMA and CD45. The tumor was diagnosed as an epithelioid angiosarcoma. To our knowledge, this is the first reported case of angiosarcoma which showed common positivity for cytokeratin and p63. In addition to cytokeratin, p63 is considered a useful marker for carcinoma. The co-expression of cytokeratin and p63 in epithelioid angiosarcoma represents a diagnostic pitfall. Thus, using a panel of antibodies is essential for distinguishing this tumor from poorly differentiated carcinoma. Virtual slides: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/6548916707504750.

Topics: Biomarkers, Tumor; Biopsy; Carcinoma; Diagnosis, Differential; Epithelioid Cells; Hemangiosarcoma; Humans; Immunohistochemistry; Keratins; Male; Middle Aged; Parotid Neoplasms; Predictive Value of Tests; Transcription Factors; Tumor Suppressor Proteins

Altered cell motility is considered to be a key factor in determining tumor invasion and metastasis. Epidermal growth factor (EGF) signaling has been implicated in this process by affecting cytoskeletal organization and dynamics in multiple ways. To sort the temporal and spatial regulation of EGF-dependent cytoskeletal re-organization in relation to a cell's motile behavior time-lapse microscopy was performed on EGF-responsive gastric carcinoma-derived MKN1 cells co-expressing different fluorescently labeled cytoskeletal filaments and focal adhesion components in various combinations. The experiments showed that EGF almost instantaneously induces a considerable increase in membrane ruffling and lamellipodial activity that can be inhibited by Cetuximab EGF receptor antibodies and is not elicited in non-responsive gastric carcinoma Hs746T cells. The transient cell extensions are rich in actin but lack microtubules and keratin intermediate filaments. We show that this EGF-induced increase in membrane motility can be measured by a simple image processing routine. Microtubule plus-ends subsequently invade growing cell extensions, which start to accumulate focal complexes at the lamellipodium-lamellum junction. Such paxillin-positive complexes mature into focal adhesions by tyrosine phosphorylation and recruitment of zyxin. These adhesions then serve as nucleation sites for keratin filaments which are used to enlarge the neighboring peripheral keratin network. Focal adhesions are either disassembled or give rise to stable zyxin-rich fibrillar adhesions which disassemble in the presence of EGF to support formation of new focal adhesion sites in the cell periphery. Taken together the results serve as a basis for modeling the early cytoskeletal EGF response as a tightly coordinated and step-wise process which is relevant for the prediction of the effectiveness of anti-EGF receptor-based tumor therapy.

Topics: Actins; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antineoplastic Agents; Carcinoma; Cell Movement; Cetuximab; Epidermal Growth Factor; ErbB Receptors; Focal Adhesions; Gene Expression; Humans; Keratins; Microtubules; Paxillin; Phosphorylation; Pseudopodia; Signal Transduction; Stomach Neoplasms; Time Factors; Time-Lapse Imaging; Tumor Cells, Cultured; Zyxin

To investigate the importance of expression of the NUT gene and its rearrangement in diagnosing NUT midline carcinoma (NMC) of the upper respiratory tract; and to evaluate the prevalence, histological features and differential diagnosis of NMC of the upper respiratory tract.. One-hundred and sixty-three small cell malignant tumors of the upper respiratory tract were reviewed at the Beijing Tongren Hospital, Capital Medical University over a 20-year period. These cases included poorly-differentiated squamous cell carcinomas (n = 31), undifferentiated carcinoma (n = 1), non-keratizing undifferentiated nasopharyneal carcinomas (n = 60), small cell neuroendocrine carcinomas (n = 6) and non-epithelial small round cell malignant tumors (n = 65). The clinical and pathologic features were investigated. All cases were subjected to Epstein-Barr virus encoded RNA (EBER) in situ hybridization and NUT monoclonal antibody immunohistochemical staining. Cases positive for NUT immunohistochemistry and negative for EBER in situ hybridization were submitted for fluorescent in situ hybridization (FISH) for rearrangements in both BRD4 and NUT genes, and immunohistochemical staining for a set of cytokeratins (AE1/AE3, CK7, CK8), p63,and neuroendocrine markers (NSE, Syn, CgA, S-100 protein, CD56).. Three cases of poorly-differentiated squamous cell carcinomas and one case of undifferentiated carcinoma showed diffuse nuclear immunohistochemical staining with antibody against NUT. These positive cases approximately accounted for 12.5% (4/32) of this group, 4.1% (4/98) of the malignant epithelial carcinomas and 2.5% (4/163) of all small round cell malignant tumors in the study. The age of these patients were 42 - 59 years. Other groups were all negative for NUT immunohistochemistry. These four cases also stained for antibodies against cytokeratins and p63, but were negative for neuroendocrine markers and not associated with EBV infection. Only two of these four cases showed rearrangements of the NUT and BRD4 genes by FISH. These two patients died within one year. The other two patients that did not demonstrate NUT rearrangement by FISH were alive and did not have an aggressive clinical course, surviving 40 and 12 months respectively.. NMC is a rare small round cell malignant tumor in the upper respiratory tract. Only in the groups of primary poorly differentiated squamous cell carcinoma and undifferentiated carcinoma were positive for NUT immunohistochemical staining and NUT rearrangement by FISH. NMC typically occurs in midline organs, and affects the sinonasal tract. It is not associated with EBV infection. There is difference in the clinical course and prognosis among NMC patients. NUT immunohistochemical staining and NUT gene rearrangement analysis can differentiate NMC from other small cell tumors in the upper respiratory tract.

Topics: Adult; Antibodies, Monoclonal; Carcinoma; Carcinoma, Squamous Cell; Cell Cycle Proteins; Female; Gene Expression Regulation, Neoplastic; Gene Rearrangement; Humans; Keratins; Male; Maxillary Sinus Neoplasms; Membrane Proteins; Middle Aged; Neoplasm Proteins; Nose Neoplasms; Nuclear Proteins; Oncogene Proteins; Oncogene Proteins, Fusion; Transcription Factors

Predictive tools for local recurrence (LR) of rectal cancer are needed. This study assessed the predictive value of tumour budding detected by MNF-116 and laminin-5 γ2 chain (Ln-5 γ2).. In a case-control study, the surgical specimens of 48 patients with LR after from primary resection of rectal carcinoma and 82 control patients matched for gender and preoperative radiation from a population of 1180 patients operated with total mesorectal excision were studied. The presence of budding was examined using immunohistochemistry with Ln-5 γ2 and pan-cytokeratin staining with MNF-116.. Tumour budding counts ranged from 0 to 106 buds (mean 43, median 38) for all patients. Significantly more tumours with more than 35 buds were seen in the LR than in the control group (67 vs 44%; P = 0.02). The spread of budding was also more extensive in the LR than in the control group (63 vs 49%, P = 0.03). In a multivariate analysis with tumour, node, metastasis stage, MNF-116-stained budding was an independent predictor of local failure (P = 0.02). The budding frequency was higher in irradiated tumours in comparison with tumours that had not received irradiation (mean 53 vs 38, P = 0.03). For Ln-5 γ2, more tumours with ≥ 10 buds were seen in the group with LR than among the control patients, but this difference was not statistically significant (73 vs 57%; P = 0.09). No additive value was found in the multivariate logistic regression model when Ln-5 γ2-stained budding frequency was added to MNF-116 and tumour, node, metastasis stage. The agreement between budding frequency determined by MNF-116 and Ln-5 γ2 was moderate, with a κ-coefficient of 0.34 (0.16-0.51).. Tumour budding determined by MNF-116 staining may serve as a predictive marker for LR in rectal cancer.

Topics: Adult; Aged; Aged, 80 and over; Biomarkers, Tumor; Carcinoma; Case-Control Studies; Female; Humans; Immunohistochemistry; Keratins; Laminin; Male; Middle Aged; Multivariate Analysis; Neoplasm Recurrence, Local; Predictive Value of Tests; Rectal Neoplasms; Staining and Labeling

A high lactate content in malignant head and neck cancer (Head and neck squamous cell carcinomas, HNSCC) is associated with a higher risk of metastatic spread and lower overall patient survival. However, until present, the underlying mechanisms are not clearly understood. Here, a systematic comparison of glucose metabolism in HNSCC and homologous normal tissue is presented for the first time.. The concentrations of glucose, lactate and ATP were measured in cryobiopsies of 29 human HNSCC and of 9 normal mucosa using bioluminescence imaging. The protein expression of lactate dehydrogenase (LDH) was analyzed by Western blotting.. Tumors own a higher content of lactate and LDH in comparison with normal tissues. However, within the tumor group, the grade of LDH expression shows substantially strong variation and overlap with normal values. Furthermore, LDH expression was not correlated with tumor lactate content. Investigating a small subpopulation, patients with a short-term survival had significantly higher tumor lactate levels compared to patients with long-term survival.. The data provide clear evidence of an enhanced glycolysis in tumors compared to normal tissue. This may partially but not completely attributable to an elevated expression of LDH. High tumor lactate levels may be predictive for restricted patient survival. In conclusion, lactate measurements, for example non-invasively with MRT, should be advanced for use in clinical routine as a supportive tool for tumor diagnosis and prognosis.

Topics: Adenosine Triphosphate; Adult; Aged; Aged, 80 and over; Biomarkers, Tumor; Blotting, Western; Carcinoma; Carcinoma, Squamous Cell; Female; Gene Expression Regulation, Enzymologic; Gene Expression Regulation, Neoplastic; Gingiva; Glucose; Glycolysis; Head and Neck Neoplasms; Humans; Keratins; L-Lactate Dehydrogenase; Lactic Acid; Luminescence; Male; Middle Aged; Neoplasms, Squamous Cell; Predictive Value of Tests; Prognosis; Squamous Cell Carcinoma of Head and Neck

Reactive renal tubular cells show features of an atypical repair reaction. Differentiation between reactive renal tubular cells and low-grade urothelial carcinoma (LG-UC) cells can therefore be a diagnostic challenge based on morphology alone. In this study, we evaluated the diagnostic utility of vimentin and a high-molecular-weight cytokeratin antibody (clone 34ßE12) in differentiating reactive renal tubular cells from LG-UC.. We evaluated voided urine cytology and surgical specimens from 40 patients with renal disease, and 17 patients with LG-UC. All slides were stained with vimentin and 34ßE12.. In the reactive renal tubular cells in voided urine cytology, vimentin showed strong cytoplasmic staining in 39/40 (97.5%) cases, but all were negative for 34ßE12. LG-UC cells showed positive staining for 34ßE12 in 3/17 (17.6%) cases, whereas none were positivity for vimentin. The reactive renal tubular cells of histological specimens in the renal disease group demonstrated positive for vimentin in all 40 cases and all were negative for 34ßE12. The LG-UC group showed abnormal staining for 34ßE12 in 4/17 (23.5%) cases, whereas none were positive for vimentin.. Vimentin expression in urine cytology can help to distinguish reactive renal tubular cells from LG-UC. However, 34ßE12 does not appear to be a useful adjunct to distinguish these two groups in voided urine cytology.

Topics: Biomarkers, Tumor; Carcinoma; Cytodiagnosis; Diagnosis, Differential; Humans; Keratins; Kidney Neoplasms; Kidney Tubules; Neoplasm Staging; Urinary Bladder Neoplasms; Urothelium; Vimentin

The searching of the reliable and repeatable immunohistochemical markers in the differential diagnosis of the thyroid's differentiated follicular epithelial neoplasms has been continuing. Recently, the studies have majored on immunohistochemical markers such as high-molecular weight cytokeratin (HMW-CK), galectin-3, cytokeratin 19, and p27. We aimed to evaluate the differences of the expressions of the proliferating cell nuclear antigen (PCNA), thyroid transcription factor-1 (TTF-1), Ki-67, p63, p53, and HMW-CK among the papillary thyroid carcinomas (PTCs), follicular carcinomas (FCs), and follicular adenomas (FAs). Thirty-nine patients with the diagnoses of the PTC, FC, and FA in the archives of the Izmir Tepecik Training and Research Hospital Pathology Laboratory registries in between 2004 and 2009 were included in the study. Immunohistochemical stains for PCNA, TTF-1, Ki-67, p63, p53, and HMW-CK were applied. The results were analyzed statistically by using Statistical Package for the Social Sciences (SPSS) for Windows 16.0 program (SPSS Inc., IBM, Somers, New York, USA). In all 3 groups, all tumors showed PCNA and TTF-1 positivity. Ki-67 proliferation index varied in a wide range in all groups. Although it was not statistically significant, 19 of 39 tumors (7 PTCs, 2 FCs, and 10 FAs) were stained with p63. The results of the immunoreactivity seen in PTCs with p53 (41.2%) and HMW-CK (52.9%) were statistically significant. The tumors in the other 2 groups (FC and FA) showed no reactivity with HMW-CK. Although the differential diagnosis of the thyroid follicular neoplasms are based on the histologic and cytomorphological criteria, p53 and HMW-CK positivity might be undertaken in favor of the diagnosis of the PTC.

Topics: Adenoma; Adolescent; Adult; Age Distribution; Aged; Biomarkers, Tumor; Carcinoma; Carcinoma, Papillary; Child; Diagnosis, Differential; Female; Humans; Immunohistochemistry; Keratins; Ki-67 Antigen; Male; Membrane Proteins; Middle Aged; Molecular Weight; Nuclear Proteins; Proliferating Cell Nuclear Antigen; Sex Distribution; Thyroid Cancer, Papillary; Thyroid Neoplasms; Thyroid Nodule; Thyroid Nuclear Factor 1; Transcription Factors; Tumor Suppressor Protein p53; Young Adult

Spindle cell thymomas are an uncommon subset of thymomas that have been regarded as benign by some. There are no comprehensive immunohistochemical studies focusing on this histological variant of thymoma. Therefore, our knowledge on the variability of its immunohistochemical profile is limited. Thirty cases of spindle cell thymomas were reviewed and immunohistochemical studies performed using antibodies against pancytokeratin, cytokeratin 5/6 (CK5/6), CK7, CK20, thyroid transcription factor-1 (TTF-1), S-100, CD34, chromogranin, synaptophysin, epithelial membrane antigen (EMA), calretinin, desmin, smooth muscle actin (SMA), and Bcl-2. The percentage and intensity of staining were evaluated and scored. The neoplastic thymic epithelial cells were diffusely positive for CK and CK5/6 and negative for CK20, S-100, chromogranin, and desmin in all 30 cases. Eighty three percent of cases showed variable reactivity for CK7 and Bcl-2. Although 97% of cases showed focal staining for calretinin, 23% for synaptophysin, and 13% for SMA, only a single case was TTF-1 positive. An interesting staining pattern was observed for CD34 and EMA, which stained the fibrous bands in some of the cases. EMA only reacted with the epithelial cells of 1 case. Spindle cell thymomas display a strong epithelial immunohistochemical phenotype as demonstrated by their reactivity for CK and CK5/6. However, tumor cells may also show positive staining for calretinin, Bcl-2, and synaptophysin and rarely for SMA and TTF-1, which can pose a problem in the evaluation of small mediastinoscopic biopsies in separating these tumors from other more aggressive neoplasms of either epithelial or mesenchymal origin.

Topics: Adult; Aged; Biomarkers, Tumor; Calbindin 2; Carcinoma; Diagnosis, Differential; Female; Humans; Immunohistochemistry; Keratins; Male; Middle Aged; Neoplasm Staging; Predictive Value of Tests; Proto-Oncogene Proteins c-bcl-2; S100 Calcium Binding Protein G; Sensitivity and Specificity; Thymus Neoplasms

To study the clinicopathologic features, immunophenotypes and differential diagnosis of thyroid carcinoma showing thymus-like differentiation (CASTLE).. The clinical and pathologic features of 8 cases of CASTLE were reviewed. Immunohistochemical study was performed using a panel of antibodies. In-situ hybridization for Epstein-Barr virus-encoded RNA (EBER) was also carried out.. There were altogether 4 males and 4 females. The age of the patients ranged from 25 to 57 years (mean = 48.8 years). All of them presented with painless mass at the anterior neck. Two patients also complained of hoarseness of voice. On CT scan, the tumor had a low density with contrast enhancement. Seven cases were located in the mid to lower pole and the remaining one in the upper pole of thyroid gland. Four cases were relatively circumscribed. The other 4 cases showed evidence of extrathyroidal invasion. Grossly, the tumor had a nodular or lobulated appearance and was gray-white in color, with a mean diameter of 4.3 cm. Microscopically, the tumor was infiltrative and consisted of islands, nests or lobules of epithelial cells separated by thick fibrous septa. The fibrous stroma showed various degree of lymphoplasmacytic infiltration, resulting in a prominent lymphoepithelioma-like pattern in 3 cases. Two cases showed squamoid differentiation, mimicking thymic Hassall corpuscles. Immunohistochemically, the tumor was consistently positive for cytokeratins, CD5, bcl-2, p63 and CD117. CEA was variably expressed. The staining for thyroglobin and TTF1 was negative. There was no labeling for EBER in all the cases. Two patients experienced local recurrence at 22 months and 12 years after surgery, respectively. They were treated with re-resection. All patients remained well on follow up. The duration of follow up ranged from 4 to 55 months.. CASTLE is a low-grade thyroid carcinoma with the morphologic features and immunophenotypes overlapping with those of thymic carcinoma. Awareness of this rare entity is important to both the pathologists and clinicians.

Topics: Adenoma; Adult; Carcinoma; CD5 Antigens; Cell Differentiation; Disease-Free Survival; Female; Follow-Up Studies; Humans; Keratins; Male; Middle Aged; Neoplasm Recurrence, Local; Proto-Oncogene Proteins c-bcl-2; Reoperation; Thymus Gland; Thymus Neoplasms; Thyroid Neoplasms; Tomography, X-Ray Computed

Topics: Adenocarcinoma, Clear Cell; Adult; Carcinoma; Carcinoma, Mucoepidermoid; Carcinoma, Renal Cell; Diagnosis, Differential; Humans; Keratins; Male; Nasal Cavity; Nose Neoplasms; S100 Proteins

Although patients with Stage I colorectal cancer show an excellent prognosis, a few of them die of metastatic disease. In this subgroup of individuals, the search of occult metastasis might reveal that early dissemination of tumor cells could be the cause of cancer progression.. Through a Cancer Registry, we selected all patients with Stage I disease who died of metastatic tumor; a total of 32 patients were identified and in 25 of them paraffin-embedded material was available. The group was matched to 70 Stage I patients with favorable prognosis (controls). In cases and controls resected lymph nodes were cut, and micrometastases were searched using pan-cytokeratin antibodies.. Micrometastases were detected in 18 of 25 (72%) Stage I patients who died of the disease, while they were almost absent among controls (1 of 70, p < 0.001 by χ(2) test). Vascular invasion and tumor budding were more frequent among Stage I patients with an unfavorable prognosis than in controls. By regression analyses, micrometastases (HR 12.3, CI 4.8-32) and vascular invasion (HR 3.5, CI 1.4-8.5) maintained an independent association with prognosis (cancer-specific survival).. Micrometastasis in the lymph nodes can be revealed in the majority of patients with early colorectal cancer who die of tumor progression, while they appear extremely rare in Stage I individuals with good prognosis. The selection of patients through histology (vascular invasion) and search of occult metastatic cells might represent a way to identify individuals who might benefit from adjuvant chemotherapy.

Topics: Aged; Blood Vessels; Carcinoma; Case-Control Studies; Colorectal Neoplasms; Female; Humans; Keratins; Lymph Nodes; Lymphatic Metastasis; Male; Middle Aged; Neoplasm Invasiveness; Prognosis; Proportional Hazards Models; Regression Analysis

Cutaneous myoepithelial tumors form a clinicopathological spectrum ranging from mixed tumor to myoepithelioma and myoepithelial carcinoma. Recently, EWSR1 rearrangement has been described in a subset of soft tissue myoepithelial tumors, whereas the cutaneous counterparts showed this aberration in a minority of cases. This raises the question whether cutaneous myoepithelial tumors have comparable genetic alterations. We examined 18 cases of cutaneous myoepithelial tumors arising in 7 female and 11 male patients (age range, 34-86 years; mean, 58 years). Eight mixed tumors occurred at the head, and one at the scrotum. Six myoepitheliomas arose at the extremities, and one case each at the back and head. One myoepithelial carcinoma occurred at the cheek. The tumor size ranged from 0.3 to 1.7 cm (mean, 1.0 cm). All mixed tumors and three myoepitheliomas were limited to the dermis. Four myoepitheliomas and the myoepithelial carcinoma involved the subcutis. Mixed tumors and myoepitheliomas were composed of myoepithelial cells with a variable cytomorphology, architecture and stromal background. Ductal structures were seen by definition in mixed tumors. The myoepithelial carcinoma represented an infiltrative dermal neoplasm consisting of atypical spindle cells. Immunohistochemically, all cases tested were positive for EMA and calponin, whereas S100, CK, ASMA and GFAP were expressed in 90%, 80%, 78% and 50% of the cases tested, respectively. By fluorescent in situ hybridization analysis, 7 out of 16 cases (44%) exhibited EWSR1 rearrangement. Four of them were mixed tumors, two were myoepitheliomas and one was a myoepithelial carcinoma, confirming that these lesions represent a spectrum of dermal myoepithelial tumors. Follow-up information, available for five patients (including the patient with a myoepithelial carcinoma), revealed no evidence of disease in all cases (range, 6-72 months). Our study provides a genetic relationship of myoepithelial tumors of the skin with their counterparts in soft tissue, bone and visceral localization by sharing EWSR1 rearrangement.

Topics: Adult; Aged; Aged, 80 and over; Autoantibodies; Biomarkers, Tumor; Calcium-Binding Proteins; Calmodulin-Binding Proteins; Calponins; Carcinoma; Female; Gene Rearrangement; Germany; Humans; Immunohistochemistry; In Situ Hybridization, Fluorescence; Keratins; Male; Microfilament Proteins; Middle Aged; Mucin-1; Myoepithelioma; Nerve Tissue Proteins; RNA-Binding Protein EWS; RNA-Binding Protein FUS; RNA-Binding Proteins; S100 Proteins; Skin Neoplasms; Tumor Burden

The presence of para-aortic lymph node metastasis in biliary cancer negatively impacts prognosis. The present study aims to immunohistochemically identify and evaluate the clinical significance of para-aortic lymph node micrometastases in 66 patients who had undergone curative resection of biliary cancer.. We used an antibody against cytokeratins 7 and 8 (CAM5.2) to immunostain 529 para-aortic lymph nodes that were negative according to conventional analysis from 66 patients with biliary cancer.. We detected CAM5.2-positive occult carcinoma cells in para-aortic lymph nodes from 3 (5%) of the 66 patients and in 3 (0.6%) of the 529 para-aortic lymph nodes. One of the 3 patients also had micrometastasis in the regional lymph nodes. All 3 patients with para-aortic lymph node micrometastasis are alive at 45, 48 and 90 months after surgery despite having locally advanced cancer.. Occult cancer cells were identified in para-aortic lymph nodes from 5% of patients with node-negative biliary cancer, yet these patients have survived over the long term. The presence of para-aortic nodal micrometastasis might not have an influence on survival. However, further studies using a greater number of patients are required to support this notion.

Topics: Adult; Aged; Aged, 80 and over; Bile Duct Neoplasms; Bile Ducts, Intrahepatic; Biomarkers; Carcinoma; Cholangiocarcinoma; Female; Gallbladder Neoplasms; Humans; Immunohistochemistry; Kaplan-Meier Estimate; Keratins; Lymph Nodes; Lymphatic Metastasis; Male; Middle Aged; Prognosis; Retrospective Studies

Angiogenesis is believed to be essential for the growth of metastatic tumors in the brain. We analyzed the vascularization of tumors formed by 4 epithelial cell lines (C38, ZR75, HT25, and H1650) and a fibrosarcoma (HT1080) cell line injected into the brains of mice. No peritumoral angiogenesis was observed. Tumors apparently acquired their vasculature by incorporation of native vessels. Vessel density was lower, but vessel diameter and vascular cell proliferation were higher within all tumors versus those in the peritumoral tissue. There was an inverse correlation between the number of incorporated vessels and vascular cell proliferation. Epithelial tumors with pushing growth patterns had lower vessel density and elevated vascular cell proliferation compared with invasive tumors. The incorporated vessels retained their normal structure, with the exception of astrocyte foot processes that were replaced by tumor cells. Attachment to the vascular basement membrane led to the differentiation of the ZR75 breast cancer cells. In the HT1080 metastases, there was intussusceptive angiogenesis, that is, the fibrosarcoma cells that were attached to the vessel caused lumen splitting and filled the developing pillars. Branching angiogenesis was not observed either in the tumors or in control cerebral wounds. These data suggest that sprouting angiogenesis is not needed for the incipient growth of cerebral metastases and that tumor growth in this model is a result of incorporation of host vessels.

Topics: Angiopoietin-1; Animals; Brain Neoplasms; Breast Neoplasms; Bromodeoxyuridine; Carcinoma; Cell Line, Tumor; Cell Proliferation; Colorectal Neoplasms; Disease Models, Animal; DNA-Binding Proteins; Electron Microscope Tomography; Female; Glial Fibrillary Acidic Protein; Humans; Keratins; Lamins; Mice; Mice, Inbred C57BL; Neoplasm Transplantation; Neovascularization, Pathologic; Platelet Endothelial Cell Adhesion Molecule-1; Quinolines; Receptor, Platelet-Derived Growth Factor beta; Thiazoles; Vascular Endothelial Growth Factor A

Oral spindle cell carcinoma (SpCC) is a rare variant of oral squamous cell carcinoma (SCC). The aims of this study were to compare the clinicopathologic and immunohistochemical features of oral SpCC with conventional oral SCC.. Five cases of oral SpCC and 10 cases of oral SCC (five well-differentiated and five poorly differentiated) were evaluated through conventional hematoxylin and eosin staining and immunohistochemical reactions to cytokeratins (CK), vimentin, desmin, smooth muscle actin, muscle-specific actin, S-100 protein, epithelial membrane antigen (EMA), p53, and ki-67.. Oral SpCC showed predilection for males on their sixth decade of life, presenting clinically as painful infiltrative ulcers or ulcerated exophytic polypoid masses, preferably located on the alveolar mucosa. Mesenchymal markers were expressed in the spindle cell but not in the carcinomatous component of SpCC, and it was negative in all SCC. CKs AE1/AE3, 6, 14, and EMA were positive on both carcinomatous and spindle cell components of most SpCCs. These tumors also presented higher p53 and ki-67 expression and no CK 1 expression in contrast to well-differentiated SCC.. Oral SpCC presented a different clinical profile than conventional SCC and histopathologic features and p53 and ki-67 expression closer to poorly differentiated SCC. Besides mesenchymal markers, CK AE1/AE3, 6, 14, and EMA expression on spindle cells may be useful as an adjunct on microscopical differential diagnosis of SpCC.

Topics: Actins; Adult; Age Factors; Aged; Carcinoma; Carcinoma, Squamous Cell; Desmin; Female; Humans; Immunohistochemistry; Keratin-13; Keratin-14; Keratin-6; Keratin-8; Keratins; Ki-67 Antigen; Male; Middle Aged; Mouth Neoplasms; Mucin-1; S100 Proteins; Sex Factors; Tumor Suppressor Protein p53; Vimentin

Spontaneous salivary gland tumors in rats are rare. The authors report a poorly differentiated carcinoma of a submandibular gland in a ten-week-old rat that was positive for vimentin. Microscopically, the neoplastic cells showed a diffuse growth pattern in most areas of the tumor mass and a nestlike structure in a part of the peripheral area. Immunohistochemically, the cells were positive for keratin and vimentin but not for alpha-smooth muscle actin. Ultrastructurally, desmosome-like structures were observed. Based on these findings, the tumor was diagnosed as a poorly differentiated carcinoma. The origin of the neoplastic cells would be either acinar or ductal cells. This suggests that acinar or ductal cells have the potential to transform into vimentin-expressing cells.

Topics: Animals; Carcinoma; Keratins; Male; Rats; Rats, Sprague-Dawley; Rodent Diseases; Submandibular Gland Neoplasms; Toxicity Tests; Vimentin

First described in 1969, syringoid eccrine carcinoma (SEC) is a rare cutaneous tumor with some controversy regarding its correct definition. It consists of solid nests and small cords in a dense fibrocollagenous stroma. As it is rare, its clinical appearance is not well characterized and its biological behaviour is not defined. It usually affects skin of the scalp, extremities and more rarely, other sites. It behaves as locally aggressive tumor but metastases are rare. Although there have been some previous reports describing clinical presentation and management of SEC in the skin, there has been no previous reports describing clinical findings and management of this tumor in the external auditory canal. We report a case of a 57-year-old female with small solitary mass in left external auditory canal associated with discharge, severe itching and bleeding on manipulation. Complete local excision is the recommended method for diagnosis and treatment of this tumor in the external auditory canal. This extremely rare case serves as a springboard for the diagnosis as well as the management of SEC in external auditory canal.

Topics: Biomarkers, Tumor; Carcinoma; Ear Canal; Ear Neoplasms; Eccrine Glands; Female; Humans; Immunoenzyme Techniques; Keratins; Middle Aged; Neoplasm Invasiveness; Neoplasm Staging; Scalp; Sweat Gland Neoplasms

The presence of pleomorphic tumor giant cells in thyroid carcinomas of follicular cell origin is always worrisome for the pathologist as they first of all refer to anaplastic carcinoma, one of the most aggressive human malignancies. However, non-anaplastic pleomorphic giant cells are well described in other thyroid diseases, most often benign. In this paper, we describe four cases of papillary thyroid carcinoma displaying pleomorphic tumor giant cells with features that differ from those of anaplastic carcinoma. Pleomorphic giant cells were admixed with the underlying thyroid carcinoma and constituted from 5% to 25% of the tumor. Cytologically, they had an abundant eosinophilic cytoplasm with large and irregular nuclei. Compared to pleomorphic giant cells of anaplastic carcinoma, they reproduced the growth pattern of the underlying carcinoma, had a low mitotic index without necrosis or inflammation, and were reactive with thyroglobulin and thyroid-specific transcription factor-1 and strongly and diffusely positive for cytokeratin AE1/AE3. After 16-84 months of follow-up, patients are relapse-free and still alive. These cases show that pleomorphic tumor giant cells arising in papillary thyroid carcinomas do not always represent dedifferentiation and progression to anaplastic carcinoma. Distinction among these processes is critical as their treatment and prognosis are very different.

Topics: Adult; Carcinoma; Carcinoma, Papillary; DNA-Binding Proteins; Female; Giant Cells; Humans; Immunohistochemistry; Keratins; Male; Middle Aged; Thyroid Neoplasms; Transcription Factors

Topics: Aged; Antigens, CD; Carcinoma; Diagnosis, Differential; Diagnostic Errors; Gastrectomy; Gastrointestinal Stromal Tumors; Humans; Immunohistochemistry; Keratins; Male; Stomach Neoplasms

We report on a patient with obstructive jaundice caused by recurrence of gastric carcinoma in the wall of an extrahepatic bile duct more than 5 years after gastrectomy who was treated with pancreaticoduodenectomy. Histopathologic examination of the surgically resected specimen revealed a poorly differentiated adenocarcinoma with focal signet ring cells in the wall of the common bile duct which was histologically similar to the primary gastric carcinoma. To confirm the diagnosis, immunohistochemical staining was performed with antibodies against cytokeratins (CK7, CK20) and mucin peptide core antigens (MUC5AC, MUC6, MUC2). Based on the expression patterns of this monoclonal antibody panel, the final diagnosis of the common bile duct tumor was an isolated local recurrence of the gastric carcinoma. The patient has survived for more than 26 months after pancreaticoduodenectomy without recurrence.

Topics: Bile Ducts, Extrahepatic; Carcinoma; Female; Humans; Immunohistochemistry; Jaundice, Obstructive; Keratins; Medical Oncology; Middle Aged; Mucins; Pancreaticoduodenectomy; Recurrence; Stomach Neoplasms; Tomography, X-Ray Computed; Treatment Outcome

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

Topics: Breast Neoplasms; Carcinoma; Female; Fibroma; Humans; Keloid; Keratin-5; Keratins; Lymphatic Metastasis; Metaplasia; Middle Aged

Metaplastic breast carcinoma (MBC) is a rare subtype of breast cancer characterized by coexistence of carcinomatous and sarcomatous components. Snail is a nuclear transcription factor incriminated in the transition of epithelial to mesenchymal differentiation of breast cancer. Aberrant Snail expression results in lost expression of the cell adhesion molecule E-cadherin, an event associated with changes in epithelial architecture and invasive growth. We aimed to identify the utility of Snail, and of traditional immunohistochemical markers, in accurate MBC classification and to evaluate clinicopathologic characteristics and outcome.We retrospectively reviewed 34 MBC cases from January 1997 to September 2007. The control group contained 26 spindle cell lesions. Immunohistochemistry used Snail, p63, epidermal growth factor receptor (EGFR), OSCAR, and wide spectrum cytokeratin (WS-KER). Negative was a score less than 1%. We found that Snail and EGFR are sensitive (100%) markers with low specificity (3.8% and 19.2%) for detecting MBC. p63 and WS-KER are specific (100%), with moderate sensitivity (67.6% and 76.5%); OSCAR is sensitive (85.3%) and specific (92.3%). A combination of any 2 of the p63, OSCAR, and WS-KER markers increased sensitivity and specificity. MBCs tended to be high-grade (77%), triple negative (negative for estrogen receptor, progesterone receptor, and HER2) [27/33; 81.8%], and carcinomas with low incidence of axillary lymph node involvement (15%), and decreased disease-free [71% (95%CI: 54%, 94%) at 3 yrs.) and overall survival. A combination of p63, OSCAR and WS-KER are useful in its work-up. On the other hand, Snail is neither a diagnostic nor a prognostic marker for MBC.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Biomarkers, Tumor; Breast Neoplasms; Carcinoma; Case-Control Studies; Disease-Free Survival; ErbB Receptors; Female; Humans; Immunohistochemistry; Kaplan-Meier Estimate; Keratins; Male; Metaplasia; Middle Aged; Minnesota; Neoplasm Staging; Predictive Value of Tests; Receptor, ErbB-2; Receptors, Cell Surface; Receptors, Estrogen; Receptors, Progesterone; Retrospective Studies; Sensitivity and Specificity; Snail Family Transcription Factors; Time Factors; Transcription Factors; Treatment Outcome; Young Adult

Topics: Aged; Carcinoma; Cell Differentiation; Humans; Immunohistochemistry; Keratins; Male; Prostate; Urothelium

Topics: Actins; Adult; Carcinoma; Diagnostic Errors; Epithelioid Cells; Female; Humans; Immunohistochemistry; Keratins; Ovarian Neoplasms; Sex Cord-Gonadal Stromal Tumors; Tomography, X-Ray Computed; Vimentin

To evaluate the diagnostic utility of alpha-methylacyl CoA racemase (P504S) & HMWCK (34beta E12) in morphologically difficult prostate cancer.. A total of 1034 cases were reviewed and divided into benign (585) malignant (399) and suspicious (50). Immunohistochemistry with HMWCK and AMACR was done on the 50 suspicious cases along with controls.. Forty nine suspicious cases were resolved by using both markers where as 1 case was resolved by further support with CD68. The original diagnosis was changed in 15 of 50 (30%) suspicious cases from benign to malignant, one case from benign to high grade PIN and in one case from malignant to benign. Change of diagnosis was seen in 17 of 50 (34%) suspicious cases with a significant p value of 0.002. The overall diagnosis was changed in 17 of 1034 cases (1.64%) of prostatic disease (p < 0.001).. A combination of HMWCK and AMACR is of great value in combating the morphologically suspicious cases and significantly increasing the diagnostic accuracy in prostate cancer. Although, in this study the sensitivity and specificity of HMWCK and AMACR were high, yet it should be used with caution, keeping in mind all their pitfalls and limitations.

Topics: Aged; Aged, 80 and over; Biomarkers, Tumor; Biopsy; Carcinoma; Case-Control Studies; Humans; Immunohistochemistry; India; Keratins; Male; Middle Aged; Molecular Weight; Predictive Value of Tests; Prostatectomy; Prostatic Neoplasms; Racemases and Epimerases; Sensitivity and Specificity

The differential diagnosis of pleural sarcomatoid mesothelioma (SM) from lung sarcomatoid carcinoma (LSC) invading parietal pleura and chest wall is a challenging issue. The aim of this study was to identify useful antibodies that can be used for the differential diagnosis of pleural SM from LSC.. Forty-five cases of pleural SM and 27 cases of LSC were immunohistochemically analysed by using 15 commercially available antibodies, including D2-40 and antibodies to calretinin, thrombomodulin, Wilms' Tumour 1, carcinoembryonic antigen (CEA), Napsin A, thyroid transcription factor (TTF)-1, pan-cytokeratin, CAM5.2, epithelial membrane antigen, Ber-EP4, MOC-31, alpha-smooth muscle actin, h-caldesmon and desmin. The results revealed that D2-40 positivity was significantly higher in pleural SM (86.7%) than in LSC (25.9%). The positivity of the adenocarcinoma markers, including CEA, Napsin A, and TTF-1, was low even in LSC.. Evaluating the positivity and degree of staining of the well-known mesothelial marker D2-40 could be applied to differentiate pleural SM from the sarcomatoid component of LSC, in addition to assessing clinical and radiological information.

Topics: Adult; Aged; Aged, 80 and over; Antibodies, Monoclonal; Antibodies, Monoclonal, Murine-Derived; Biomarkers; Biomarkers, Tumor; Carcinoma; Diagnosis, Differential; Humans; Immunohistochemistry; Keratins; Lung Neoplasms; Mesothelioma; Middle Aged; Pleural Neoplasms

Transforming growth factor-beta1 (TGF-beta1), a cytokine involved in various stages of cancer, is produced as a latent complex and requires processing to become active. We have determined total and active TGF-beta1 levels in homogenates of colorectal neoplasia. In contrast to total TGF-b levels, showing a stepwise increase in the mucosa-adenoma-carcinoma sequence, active TGF-beta1 levels are increased only in carcinomas but not in premalignant adenomas. Furthermore, solely active TGF-beta1 levels are associated with the stage of the carcinomas and worse patient prognosis. Active TGF-beta1 levels correlated significantly with plasminogen activator inhibitor (PAI)-1, alpha-smooth muscle actin (SMA) and several matrix-remodeling proteinases. Interestingly, SMA levels are also significantly increased in colorectal carcinomas but not in adenomas, suggesting that despite the enhanced total TGF-beta1 levels, myofibroblast accumulation is not (yet) occurring in these premalignant neoplasias. The correlation between active TGF-beta1 and SMA expression in tumors indicates that tumor-promoting myofibroblasts might arise as a result of increased TGF-beta1 activation. These data underline the significance of the interaction between malignant cells and (myo)-fibroblasts in the tumor microenvironment, modulating the biologic behavior of colorectal cancer.

Topics: Actins; Adenoma; Biomarkers, Tumor; Carcinoma; Colorectal Neoplasms; Desmin; Enzyme-Linked Immunosorbent Assay; Female; Fibroblasts; HT29 Cells; Humans; Immunohistochemistry; Keratins; Male; Muscle, Smooth; Plasminogen Activator Inhibitor 1; Reproducibility of Results; Sensitivity and Specificity; Smad2 Protein; Transforming Growth Factor beta1; Urokinase-Type Plasminogen Activator; Vimentin

We compared the protein expression pattern of triple-negative breast carcinomas (HER2-, ER-, PR-) versus those being positive for HER2 and negative for the hormone receptors (HER2+, ER-, PR-) by 2-D DIGE and mass spectrometry. We obtained differential expression patterns for several glycolytic enzymes (as for example MDH2, PGK1, TKT, Aldolase1), cytokeratins (CK7, 8, 9, 14, 17, 19), further structure proteins (vimentin, fibronectin, L-plastin), for NME1-NME2, lactoferrin, and members of the Annexin family. Western blot analysis and immunohistochemistry were conducted to verify the results. The identified marker proteins may advance a more detailed characterization of triple-negative breast cancers and may contribute to the development of better treatment strategies.

Topics: Biomarkers, Tumor; Breast Neoplasms; Carcinoma; Cell Line, Tumor; Female; Gene Amplification; Gene Expression Profiling; Humans; Immunohistochemistry; Keratins; Mass Spectrometry; Proteins; Proteome; Proteomics; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization

Differentiation of true metastases from cytokeratin (CK)-positive nonepithelial cells by immunohistochemistry occasionally may be difficult in the evaluation of sentinel lymph nodes (SLNs) for occult breast carcinoma metastases. In this study, we evaluated estrogen receptor (ER) immunostaining superimposed on CK as a method for the confirmation of metastasis when CK immunostaining alone was equivocal. We performed sequential ER staining on previously CK-stained slides on 15 axillary SLNs from breast cancer patients: 5 SLNs with known metastatic carcinoma (positive controls), 6 known negative SLNs (negative controls), and 4 test cases (3 SLNs in which CK-positive cells were equivocal for malignancy and 1 SLN in which metastasis was obvious, but contained focal weakly CK-positive signet ring cells). The primary tumor in all cases expressed ER in >50% of cells. Only 3 of 5 positive controls showed metastatic cells with dual CK/ER staining. CK-positive reticulum cells in all negative controls were ER negative. Three test cases showed dual CK/ER staining in the equivocal cells. The case with signet ring cells showed strong ER staining in the nonsignet ring cells and weaker staining in the signet ring cells. We conclude that dual CK/ER staining can be useful in SLNs when CK staining alone is equivocal, particularly when the primary tumor is known to have high expression of ER. Although dual ER/CK positivity helps to confirm metastasis, negative ER staining does not exclude metastatic disease.

Topics: Breast Neoplasms; Carcinoma; Female; Humans; Immunohistochemistry; Keratins; Lymphatic Metastasis; Receptors, Estrogen; Sentinel Lymph Node Biopsy

Topics: Actins; Aged; Biomarkers, Tumor; Breast Neoplasms; Carcinoma; Carcinosarcoma; Diagnosis, Differential; ErbB Receptors; Female; Hemangiosarcoma; Humans; Keratins; Membrane Proteins; Metaplasia; Neoplasm Proteins; Phyllodes Tumor; Stromal Cells; Syringoma

Meningiomas and breast cancers are common tumors among women in the fifth to seventh decade. However, metastasis from breast cancer to an intracranial meningioma is rare. A 63-year-old woman presented with headache, nausea and vomiting, and progressive right hemiparesis for one month. She had undergone a right modified radical mastectomy in another hospital 10 years prior. At that time, the pathological diagnosis was infiltrating ductal carcinoma. She required adjuvant radiotherapy and chemotherapy for a local recurrence 7 years later. On admission to our hospital, cranial CT scans showed a brightly enhancing, irregularly shaped lesion over the left high parietal lobe with surrounding parenchymal edema. Histopathological examination of the lesion revealed two distinct tumor types, meningioma and metastatic carcinoma of breast tissue origin. Although meningiomas have well-known radiological features, other tumors, including metastases from breast cancers may simulate them. In the clinical setting of previously diagnosed breast cancer, prompt craniotomy for removal of meningioma-like intracranial lesions is recommended to avoid missing the diagnosis of breast cancer metastasis which carries a poorer prognosis than meningioma and requires a different treatment strategy.

Topics: Aged, 80 and over; Breast Neoplasms; Carcinoma; Female; Humans; Keratins; Meningeal Neoplasms; Meningioma; Tomography, X-Ray Computed

A 5-year-old, male Bichon-Frise dog presented with a cutaneous mass in the basal region of the auricle. Histologically, the cutaneous neoplasm was comprised of lobules with solid cellular proliferation separated by thin fibrous septa. Neoplastic cells varied in size, with moderate to abundant amounts of PAS-positive cytoplasm, large nuclei and prominent nucleoli. Immunohistochemical examinations showed that tumor cells were positive for pan-cytokeratin (CK) (AE1/AE3 and CAM5.2), CK8 and CK18, but negative for pan-CK (KL1), CK7, CK14, CK16 and CK20. Double-labeled immunofluorescence testing indicated that neoplastic cells frequently co-expressed CK and vimentin, suggesting divergent differentiation of tumor cells. Based on these findings, the tumor was diagnosed as canine clear cell adnexal carcinoma.

Topics: Animals; Carcinoma; Dog Diseases; Dogs; Gene Expression Regulation, Neoplastic; Keratins; Male; Skin Neoplasms

Thyroid gland angiomatoid tumors are an extremely aggressive neoplasms with varied histological patterns and features of endothelial differentiation. The histogenesis of thyroid angiomatoid tumors has been controversial for many years: these tumors may be either a variant of anaplastic carcinoma, or an angiosarcoma. We report a case of thyroid angiomatoid tumor in a 68-year-old woman. We also discuss, through a review of the literature, the pathologic criteria that could be used to distinguish between angiosarcoma and anaplastic carcinoma of the thyroid.

Topics: Aged; Carcinoma; Diagnosis, Differential; Epithelial Cells; Female; Hemangiosarcoma; Humans; Immunohistochemistry; Keratins; Thyroid Neoplasms

Isolated disseminated tumour cells (DTC) are regarded as surrogate markers for minimal residual disease in breast cancer. Characterisation of these cells could help understand the known limitations of adjuvant therapy. Of particular interest is their oestrogen-receptor (ER) status because endocrine adjuvant therapy remains a cornerstone of breast cancer treatment.. Bone marrow (BM) aspirates from 254 patients with primary breast cancer were included in this study. A double immunofluorescence staining procedure was established for the identification of cytokeratin (CK) positive/Eralpha-positive cells. ERalpha status of the primary tumour was assessed immunohistochemically using the same antibody against ERalpha.. In 107 of 254 (42%) breast cancer patients, CK-positive cells could be detected in the BM. More than one DTC in the BM was observed in 38 of the 107 patients. The number of detected cells ranged between 1 and 55 cells per 2 x 10(6) mononuclear cells. DTCs demonstrated ERalpha positivity in 12% of the patients. The ERalpha expression was heterogeneous in 10 of the 38 (26%) patients with more than one DTC. The concordance rate of ERalpha status between primary tumour and DTC was 28%. Only 12 of 88 patients with ERalpha-positive tumours also had ERalpha-positive DTCs.. Primary tumours and DTCs displayed a concordant ERalpha status in only 28% of cases. Most of the DTCs were ERalpha negative despite the presence of an ERalpha-positive primary tumour. These findings further underline the distinct nature of DTCs and may explain the failure rates seen in conventional endocrine adjuvant therapy.

Topics: Adult; Aged; Antineoplastic Agents, Hormonal; Bone Marrow; Breast Neoplasms; Carcinoma; Cell Line, Tumor; Chemotherapy, Adjuvant; Epithelial Cells; Estrogen Receptor alpha; Estrogens; Female; Fluorescent Antibody Technique, Direct; Humans; Keratins; Middle Aged; Neoplasm Proteins; Neoplasm, Residual; Neoplasms, Hormone-Dependent

Immunocytology substantially improves the diagnostic accuracy of conventional cytology in the diagnosis of carcinomatous effusions. Due to the unequivocal characterization of the various cell populations, a sensitivity of 92% and specificity of 100% was achieved by immunocytology, examining samples of 1234 serous effusions.. Cytology plays a central role in the aetiological clarification of serous effusions. The sensitivity of this method for the diagnosis of carcinomatous effusions varies between 40% and 80%. The aim of the present study was to investigate whether immunocytology substantially improves the diagnostic quality of the cytological examination in the diagnosis of carcinomatous effusions.. Consecutive serous effusions were examined by conventional cytology and by immunocytology. The immunocytological examination was performed on smears, using a standard panel of three antibodies against pancytokeratin, human epithelial antigen 125 and calretinin.. Altogether, 1234 effusion samples were examined. A total of 603 effusions were caused by carcinomas, five by malignant mesotheliomas, 11 by malignant lymphomas and 615 by non-malignant disorders. In conventional cytology, carcinomatous effusions were correctly diagnosed in 314 samples, corresponding to a sensitivity of 52%. In 31 specimens (5%) tumour cells without further specification were described and in 161 samples (27%) the presence of tumour cells was suspected (84% overall sensitivity). A total of 97 carcinomatous effusions (16%) were diagnosed false-negatively and 50 (8%) of the 615 non-malignant effusions false-positively (92% specificity). In immunocytology, 561 carcinomatous samples were correctly diagnosed, representing a sensitivity of 93%. In six cases (1%) the presence of tumour cells was suspected. A total of 36 carcinomatous effusions (6%) were diagnosed false-negatively (94% over-all sensitivity). Out of the 615 non-malignant specimens, there were no false-positive diagnoses (100% specificity).. Immunocytology is a simple, cost-effective, routinely practicable method which substantially improves the diagnostic accuracy of conventional cytology in the diagnosis of carcinomatous effusions. Therefore, we recommend the use of immunocytology in all those cases where cytology on its own is not completely unequivocal.

Topics: CA-125 Antigen; Calbindin 2; Carcinoma; Cytodiagnosis; Exudates and Transudates; Humans; Immunohistochemistry; Keratins; Neoplasms; S100 Calcium Binding Protein G; Sensitivity and Specificity

The 6th edition of the TNM classification has recently defined "sentinel nodes (SN)," "micrometastasis," and "isolated tumor cells (ITC)." The present study examines the frequency and proliferative activity of such metastases with focus on the SNs of gastric cancer.. We enrolled 133 patients with cT1-2 tumors (cT1: 104, cT2: 29) and mapped SNs. Lymph node metastases were examined by routine histology and by immunohistochemistry with anti-cytokeratin. We used the Ki-67 antibody to detect the primary tumor and lymph node metastases to evaluate proliferative activity.. The number of patients with SNs metastases and metastatic SNs was 19 and 52, respectively. The frequencies of macrometastasis, micrometastasis, and ITC were 48%, 25%, and 27%, respectively. Ki-67 expression in the tumor closely correlated with lymphatic invasion (P = 0.0001), venous invasion (P < 0.0001), and lymph node metastasis (P < 0.0001). Cells in 96% of macrometastases, 92% of micrometastases, and 29% of ITCs were Ki-67 positive.. We showed that micrometastasis and some ITCs in SNs had proliferative activity. We suggest that micrometastasis and ITCs should be removed, especially during SN navigation surgery, until their clinical significance is clarified.

Topics: Carcinoma; Cell Differentiation; Cell Division; Gastrectomy; Humans; Immunohistochemistry; Keratins; Ki-67 Antigen; Lymph Node Excision; Lymph Nodes; Lymphatic Metastasis; Sentinel Lymph Node Biopsy; Stomach Neoplasms

Topics: Carcinoma; Diagnosis, Differential; Female; Humans; Keratins; Middle Aged; Ovarian Neoplasms; Prognosis; Sarcoma

We report a case of a primary lymphoepithelioma-like carcinoma of the skin (LELCS) associated with scar from a previous excision of basal cell carcinoma. The patient was a 68-year-old female with a 3.0 mm skin-colored pearly papule on her forehead that developed over 2-3 months. The patient had a history of a basal cell carcinoma in the same location, which was completely excised 1 year earlier. A biopsy and subsequent excision of the tumor were performed. The tumor consisted of small islands of large pleomorphic mitotically active epithelioid cells surrounded by a very dense lymphoplasmacytic infiltrate. The tumor was associated with dermal scar. There was no connection of tumor with the unremarkable epidermis. Immunohistochemical examination showed that the epithelioid tumor cells were positive for pan-cytokeratin and epithelial membrane antigen, supporting the morphologic impression of LELCS. The lesion was negative for Epstein-Barr virus. Retrospective review of the original excision specimen confirmed the diagnosis of an ordinary basal cell carcinoma. Forty-five cases of LELCS have been reported to date. We report the first case of LELCS to arise in the scar from an excision of a cutaneous malignancy.

Topics: Aged; Biomarkers, Tumor; Carcinoma; Carcinoma, Basal Cell; Cicatrix; Female; Humans; Keratins; Mohs Surgery; Mucin-1; Neoplasms, Second Primary; Skin Neoplasms

Carcinomas are widely thought to derive from epithelial cells with malignant progression often associated with an epithelial-mesenchymal transition (EMT). We have characterized tumors generated by spontaneously transformed human mesenchymal cells (TMC) previously obtained in our laboratory. Immunohistopathological analyses identified these tumors as poorly differentiated carcinomas, suggesting that a mesenchymal-epithelial transition (MET) was involved in the generation of TMC. This was corroborated by microarray and protein expression analysis that showed that almost all mesenchymal-related genes were severely repressed in these TMC. Interestingly, TMC also expressed embryonic antigens and were able to integrate into developing blastocysts with no signs of tumor formation, suggesting a dedifferentiation process was associated with the mesenchymal stem cell (MSC) transformation. These findings support the hypothesis that some carcinomas are derived from mesenchymal rather than from epithelial precursors.

Topics: Animals; Carcinoma; Cell Dedifferentiation; Cell Transformation, Neoplastic; Cells, Cultured; Epithelial Cells; Humans; Keratins; Male; Mesenchymal Stem Cells; Mice; RNA, Messenger; Vimentin

Microglandular adenosis (MGA) of the breast is widely known as a benign lesion that can mimic invasive carcinoma. In situ and invasive carcinomas have been described as arising in MGA, but which cases of MGA will progress to carcinoma is unclear. Criteria for distinguishing uncomplicated MGA, MGA with atypia (AMGA), and carcinoma arising in MGA (MGACA) are not standardized. The primary objective of this study was to illustrate the clinical, histopathologic, and immunophenotypical characteristics of MGA, AMGA, and MGACA in an effort to provide criteria for distinguishing the 3 types. We retrospectively identified 108 cases seen at M.D. Anderson Cancer Center between 1983 and 2007 that had a diagnosis of MGA. Of the 108 cases, 65 cases had available material for review. Inclusion criteria were glands of MGA expressing S-100 protein and lacking myoepithelial layer (smooth muscle actin negative). Eleven out of 65 cases qualified to have an MGA component; myoepithelial layer was detected in the remaining 54 cases and were classified as adenosis. Out of the 11 MGA patients, there were 3 patients with uncomplicated MGA, 2 had AMGA, and 6 had MGACA. Staining indices for the cell cycle markers p53 and Ki-67 were used to compare the 3 tumor categories. Additional staining for other tumor markers [estrogen and progesterone receptors, HER2, epidermal growth factor receptor (EGFR), c-kit, CK5/6, and CK18] were performed. Patient demographics, tumor radiologic features, and clinical follow-up data were collected for all cases. Multiple invasive histologic components were identified in each of the MGACA cases. All invasive MGACAs had a duct-forming component. In addition, basal-like component was present in 2 cases, aciniclike in 2, matrix producing in 4, sarcomatoid in 1, and adenoid cystic in 1. All tumors had strong and diffuse CK8/18 and EGFR expression but no estrogen receptor, progesterone receptor, HER2 (ie, triple negative), or CK5/6 expression. C-kit was focally expressed in 2 of the MGACAs. Ki-67 and p53 labeling indices was < 3% in all MGAs, 5% to 10% in the AMGAs, and > 30% in MGACAs. In a follow-up ranging from 14 days to 8 years, none of the MGA cases recurred. One of the AMGA cases recurred as invasive carcinoma in a background of AMGA after 8 years following incomplete excision of the lesion. Three out of 6 MGACA cases (50%) required multiple consecutive resections ending up with mastectomy due to involved margins by invasive or in situ carcinoma. Two ou

Topics: Actins; Adult; Aged; Biomarkers, Tumor; Breast Neoplasms; Carcinoma; Carcinoma in Situ; Cell Transformation, Neoplastic; Diagnosis, Differential; Diagnostic Errors; Disease Progression; ErbB Receptors; Female; Fibrocystic Breast Disease; Humans; Immunohistochemistry; Keratins; Ki-67 Antigen; Mastectomy; Middle Aged; Neoplasm Invasiveness; Precancerous Conditions; Proto-Oncogene Proteins c-kit; Receptor, ErbB-2; Receptors, Estrogen; Receptors, Progesterone; Retrospective Studies; S100 Proteins; Texas; Time Factors; Treatment Outcome; Tumor Suppressor Protein p53

The introduction of radiochemotherapy for treatment of advanced cervical cancers represents a new chapter in surgical pathology. The study group included 50 women with a histological diagnosis of advanced cervical carcinoma (43 squamous, 3 adenosquamous, 2 adenocarcinoma, 1 glassy cell, and 1 undifferentiated; International Federation of Gynecology and Obstetrics stage Ib-III) receiving a platinum-based chemotherapy concomitant with external beam radiotherapy before radical surgery. We evaluated the amount of residual neoplastic tissue, depth of invasion, presence of neoplastic embolism, number of metastatic lymph nodes, and alterations of the nonneoplastic stroma and epithelium. We observed neoplastic masses larger than 0.3 cm (no pathological response, pR2) in 14 cases (28%), single or multiple microscopic neoplastic residual (partial pathological response, pR1) in 24 cases (48%), and no invasive neoplastic cells (complete pathological response, pR0) in 12 cases (24%). Residual neoplastic cells showed a wide pattern of alterations such as cytoplasmic eosinophilia, vacuolation, and foamy appearance; the nuclei were enlarged and irregular with clumped chromatin. The mitotic activity was scanty. In some cases, multinucleated neoplastic giant cell coexisted with reactive foreign body-like giant cells. The stroma was fibrous containing inflammatory cells, fibrinous debris, cholesterol clefts, hemosiderin pigments, and microcalcifications. In just 2 cases, we found lymph node metastases. The pathologist has to distinguish neoplastic residuals from reactive changes. In most cases, morphological criteria are sufficient to make a diagnosis, but sometimes, the use of immunohistochemistry (keratins and CD68) is a mandatory method to reveal the nature of the lesion.

Topics: Adult; Aged; Antigens, CD; Antigens, Differentiation, Myelomonocytic; Biomarkers, Tumor; Carcinoma; Carcinoma, Adenosquamous; Carcinoma, Squamous Cell; Cervix Uteri; Combined Modality Therapy; Female; Humans; Hysterectomy; Keratins; Middle Aged; Neoadjuvant Therapy; Uterine Cervical Neoplasms

In routine practice, gastrointestinal stromal tumor (GIST) can usually be identified with relative ease on the basis of a rather simple immunohistochemical panel besides its characteristic morphology. Still, serious differential diagnostic problems may arise because of the heterogeneity of these tumors in both morphologic appearance and clinical behavior. In our case, we present a metastatic, ulcerative, hemorrhagic GIST with epithelioid appearance, which displayed diffuse pan cytokeratin (AE1/AE3) positivity beside CD117 expression. As carcinomas may also be CD117-positive, definitive diagnosis was confirmed by the detection of a hexanucleotide deletion in the exon 11 of c-kit. This case demonstrates that although gastric carcinoma more commonly ulcerates or causes hemorrhage than GIST, keratin-positive GIST should also be considered from a differential diagnostic point of view. In these cases, c-kit mutation analysis may be necessary.

Topics: Carcinoma; Diagnosis, Differential; DNA Mutational Analysis; Exons; Female; Gastrointestinal Stromal Tumors; Gene Deletion; Humans; Keratins; Middle Aged; Proto-Oncogene Proteins c-kit; Sequence Deletion; Stomach Neoplasms

Cutaneous spindle cell squamous carcinoma is an uncommon variant of squamous cell carcinoma in which keratinocytes infiltrate the dermis as single cells with elongated nuclei rather than as cohesive nests or islands, and signs of keratinization of conventional squamous cell carcinoma are insubstantial or nonexistent. Spindle cell carcinoma must be distinguished from spindle cell/desmoplastic melanoma, cutaneous leiomyosarcoma, atypical fibroxanthoma (AFX), and scar. In instances when there is no definitive evidence of squamous differentiation, immunohistochemical studies may confer diagnostic discrimination. Twenty-four cases consisting of 12 spindle cell squamous cell carcinomas, 3 AFXs, 3 leiomyosarcomas, 3 desmoplastic melanomas, and 3 scars were evaluated with a battery of immunohistochemical stains, with the specificity and sensitivity of each marker calculated. The immunohistochemical battery consisted of S-100, desmin, CD68, and smooth muscle actin and cytokeratins P KER (keratins predominantly of molecular weight 56 and 69 kd) and low-molecular weight keratin (CAM 5.2), AE1/AE3, p63, and 34 beta E12 (CK903). Spindle cell squamous carcinomas were negative for S-100, CD68, smooth muscle actin, and desmin with the exception of 2 cases with weak staining for smooth muscle actin. 34 beta E12 provided positive results for each spindle cell squamous carcinoma. The other cytokeratin stains were less sensitive for spindle cell squamous carcinoma than 34 beta E12. The final immunohistochemical results were as follows: 34 beta E12 (12/12, 100%), p63 (10/12, 80%), AE1/AE3 (8/12, 67%), low-molecular weight keratin (7/12, 58%), and P KER (4/12, 33%). The 3 AFXs were positive for CD68 and negative for all other stains, whereas the 3 leiomyosarcomas stained positively for desmin and smooth muscle actin and negatively for all other stains. The 3 melanomas stained positively for S-100 and negatively for all other immunohistochemistry. The scars were negative for all stains. In conclusion, our study of 34 beta E12 proved most promising in distinguishing spindle cell squamous carcinoma from the histologic mimickers, AFX, spindle cell melanoma, scar, and leiomyosarcoma.

Topics: Adult; Aged; Aged, 80 and over; Biomarkers, Tumor; Carcinoma; Carcinoma, Squamous Cell; Cicatrix; Diagnosis, Differential; Female; Histiocytoma, Benign Fibrous; Humans; Immunohistochemistry; Keratinocytes; Keratins; Leiomyosarcoma; Male; Melanoma; Middle Aged; Predictive Value of Tests; Skin Neoplasms

Rhabdoid tumours (RTs) are rare but highly aggressive tumours of childhood. Their rarity and their miscellaneous locations make the diagnosis particularly challenging for pathologists. Central nervous system and peripheral RTs have been associated with biallelic inactivation of the hSNF5/INI1/SMARCB1 (hSNF5/INI1) tumour suppressor gene. Immunohistochemistry (IHC) with a monoclonal anti-hSNF5/INI1 antibody has recently been proposed as an efficient diagnostic tool for RTs. We have conducted a retrospective study of 55 tumours referred to our institution with a suspicion of RT. This analysis included pathological review, IHC with anti-hSNF5/INI1 antibody, and molecular investigation using quantitative DNA fluorescent analysis and sequencing of the nine exons of hSNF5/INI1. The molecular lesion could be detected in 37 of the 39 cases exhibiting negative staining for hSNF5/INI1. In the two discrepant cases, the lack of detection of genetic abnormality was probably owing to the presence of a high number of non-tumour cells in the samples. This indicates that hSNF5/INI1 IHC is very sensitive and highly specific for the detection of hSNF5/INI1 loss-of-function. Among the 38 cases with typical RT histological features, six failed to exhibit hSNF5/INI1 mutation and stained positive for hSNF5/INI1. This strongly supports the evidence of a second genetic locus, distinct from hSNF5/INI1, associated with RT. Conversely, seven tumours with histological features poorly compatible with RT stained negative for hSNF5/INI1; they nevertheless exhibited an age of onset and a clinical behaviour similar to RT. This suggests that hSNF5/INI1 inactivation is not strictly limited to typical RT but characterizes a wider family of hSNF5/INI1-deficient tumours. Consequently, we believe that anti-hSNF5/INI1 IHC should be performed widely, even when the pathological characteristics are not typical. The molecular investigation should be performed in infants when a rhabdoid predisposition syndrome is suspected.

Topics: Adult; Biomarkers, Tumor; Carcinoma; Child, Preschool; Choroid Plexus Neoplasms; Chromosomal Proteins, Non-Histone; DNA Mutational Analysis; DNA-Binding Proteins; Female; Gene Deletion; Genetic Markers; Humans; Immunohistochemistry; In Situ Hybridization, Fluorescence; Infant; Keratins; Kidney Neoplasms; Male; Point Mutation; Retrospective Studies; Rhabdoid Tumor; SMARCB1 Protein; Transcription Factors; Vimentin

Salivary duct carcinoma (SDC) is an uncommon malignant tumor, characterized by aggressive behavior and poor prognosis. SDC usually arises from ductal epithelium of the major salivary glands, and it is quite infrequent elsewhere. We present a rare case of a 73-year-old man with SDC, which is possibly originated from the paranasal sinuses or the lacrimal system. Microscopic evaluation revealed that the tumor cells, with pleomorphic nuclei and abundant eosinophilic cytoplasm, formed cell nests and duct-like structure. A cribriform growth pattern was also seen. Immunohistochemical staining was positive for cytokeratins (CAM 5.2 and 34betaE12), gross cystic disease fluid protein 15 (GCDFP-15), and androgen receptor protein, while p63 and involucrin were negative. The patient already had multiple metastasis of the tumor in the lung at diagnosis, and he could not undergo definitive surgical procedures, because of severe restrictive lung disease. Although SDC in the sinonasal tract is quite rare, SDC should be in the differential diagnosis in these regions, due to its aggressive behavior and poor prognosis.

Topics: Aged; Biomarkers; Carcinoma; Diagnosis, Differential; Humans; Immunohistochemistry; Keratins; Male; Neoplasms, Second Primary; Paranasal Sinus Neoplasms; Prognosis; Salivary Ducts; Salivary Gland Neoplasms; Tomography, X-Ray Computed

The objective was to determine the additional value of pathologic examination using three-level sectioning and immunocytokeratin (ICK) staining of sentinel lymph node (SN) biopsies in cT1-2N0M0 breast carcinoma patients regarding lymph node staging and eligibility of systemic therapy taking primary tumor characteristics in account.. SN slides of 277 patients out of a total group of 961 patients known to have tumor-positive SNs detected by three-level sectioning and ICK staining were re-examined. Haematoxylin-eosin (HE) slide level three was scanned for tumor deposits, and when present, extra capsular extension, maximum tumor diameter and number of positive SNs was noted. In addition, slides of the axillary dissection of non-SNs were reviewed, with determination of metastasis size and number of positive non-SNs. Primary tumor characteristics (grade, diameter, estrogen receptor) were recorded.. In the single-HE examination, 26 cases SN micrometastasis and 6 macrometastasis were missed, 3 cases of micrometastasis were incorrectly classified as isolated tumor cells, and 9 patients with macrometastasis were misclassified as micrometastasis. In addition, in the tumor-negative single-HE examination, additional axillary lymph node dissection (ALND) revealed 6 cases of non-SN metastasis. Taking primary tumor factors into account for adjuvant systemic therapy, 21 patients would have been denied the choice for systemic therapy if single-HE examination was carried out only.. Single-HE examination of SN may result in a reduction of locoregional and systemic treatment according to treatment guidelines then current in the Netherlands.

Topics: Adult; Aged; Aged, 80 and over; Breast Neoplasms; Carcinoma; Eosine Yellowish-(YS); Female; Hematoxylin; Humans; Immunohistochemistry; Keratins; Lymph Nodes; Male; Middle Aged; Neoplasm Metastasis; Sentinel Lymph Node Biopsy

Topics: Biomarkers, Tumor; Carcinoma; Cell Differentiation; Dysgerminoma; Female; Humans; Immunohistochemistry; Keratins; Ki-1 Antigen; Middle Aged; Octamer Transcription Factor-3; Ovarian Neoplasms

There were investigated 22 cases from which the thymic tissue was removed either during surgery for cardiovascular malformations (n = 14), or for myasthenia gravis (n = 8). Histological sections were stained with routine morphologic methods, and immunohistochemistry was performed for cytokeratin, CD20, CD3, and S100 protein. Aspects characteristic for thymus involution were found in 11 cases without myasthenia gravis and in all cases with myasthenia gravis. Morphological changes of the thymus of involution are age-dependent. There were characterized stages of involution, with special reference to cortical - medulla inversion, lymphocyte depletion and sequestration. In advanced-stage of involution, epithelial cells are arranged in cords or compact islands, and could mimic a thymoma or a metastatic carcinoma. The immunohistochemical profile is similar but not identical to the active thymus. We noticed a decreased expression of cytokeratin, and a reduced number of CD3, CD20, and S100 positive cells. Morphologic and immunohistochemical peculiarities of the thymus of involution are discussed in relation with the specific pathology of the organ.

Topics: Adolescent; Adult; Antigens, CD20; Atrophy; Carcinoma; Cardiovascular Abnormalities; CD3 Complex; Child; Child, Preschool; Diagnosis, Differential; Humans; Infant; Infant, Newborn; Keratins; Lymphatic Diseases; Middle Aged; Myasthenia Gravis; Thymus Gland; Thymus Neoplasms

Determination of multidrug resistance (MDR) activity of tumor cells could provide important information for the personalized therapy of cancer patients. The functional calcein assay (MultiDrug Quant Assay, Solvo Biotechnology, Budaörs, Hungary) has been proven to be clinically valuable in hematological malignancies by determining the transporter activity of MDR protein 1 (MDR1, ATP-binding cassette protein [ABC] B1, P-glycoprotein-170) and MDR-related protein 1 (MRP1, ABCC1). In this study, we evaluated if the same functional test was adaptable for the analysis of MDR activity in solid tumors. For this purpose, tissue specimens of human colorectal cancer samples were subjected to limited enzymatic digestion by collagenase to provide a single-cell suspension; dead cells were excluded by 7-aminoactinomycin D staining, and epithelial cancer cells were detected by Cy5-conjugated anti-BerEP4 monoclonal antibody. The transporter functions of MDR1 and MRP1 in viable epithelial cells were assessed by flow cytometry detecting the intracellular accumulation of calcein dye after exposing cells to various MDR inhibitors. Collagenase disintegration preserved the MDR activity and the antigenicity of tumor cells. Thus using the extended calcein assay provided sufficient viable and functionally active tumor cells from surgical biopsies to determine the functional MDR activity. In conclusion, the newly described modified calcein assay may be applicable for evaluating the MDR phenotype in solid tissue specimens from colorectal forceps biopsy to surgical samples.

Topics: Animals; Antibodies, Monoclonal; Antigens, Neoplasm; Antigens, Surface; ATP Binding Cassette Transporter, Subfamily B, Member 1; Biomarkers; Biopsy; Body Fluids; Carcinoma; Cell Separation; Cell Survival; Fluoresceins; Fluorescent Antibody Technique; Humans; Keratins; Leukemia P388; Neoplasms

Metastatic carcinoma, which is a common malignant tumor seen in the central nervous system is often difficult to distinguish from glioblastoma multiforme. In general, neoplastic cells maintain fidelity in the expression of parent cell intermediate filament and immunohistochemistry remains the mainstay in diagnosis. A panel consisting of GFAP (usually positive for astrocytic tumors) and cytokeratin (usually positive for metastatic carcinomas) is most commonly used for this purpose. However, co-expression of two or more classes of intermediate filament proteins by neoplasms is a widespread phenomenon and there are reports of glial neoplasms expressing keratin markers. Our aims and objectives were to analyse the expression of both cytokeratin and GFAP in different glial tumors and metastatic carcinomas. Cases were collected for a period of two years. All the cases were diagnosed as primary or metastatic intracranial tumors. Formalin-fixed paraffin-embedded thin sections were taken on egg-albumin coated slides and immunostaining with GFAP and polyclonal cytokeratin was done. Forty-five tumors were analysed, including 35 glial neoplasms and 10 metastatic carcinomas of which 7 of the 32 astrocytic neoplasms (22%) showed focal immunoreactivity with pancytokeratin. All of the glial tumors but none of the metastatic carcinomas were positive with GFAP. So our conclusion was that co-expression of GFAP and CK is a fairly common phenomenon, especially in case of undifferentiated and high grade gliomas and this must be kept in mind while differentiating these cases from metastatic carcinoma, as CK positivity does not rule out the diagnosis of a glial neoplasm. Further studies with an expanded panel of CK is most useful for this.

Topics: Astrocytoma; Biomarkers, Tumor; Brain Neoplasms; Carcinoma; Diagnosis, Differential; Glial Fibrillary Acidic Protein; Glioblastoma; Glioma; Humans; Immunohistochemistry; Keratins; Oligodendroglioma

Breast cancer, a whole body disease, can metastasize at early stage. This study was to explore the correlation of peripheral blood cancer cell (PBCC) content to distant metastasis of breast cancer.. The PBCC content of 65 breast cancer patients and 8 healthy donors was detected by multi-parameter flow cytometry (FCM) with CD45 and cytokeratin staining.. Cancer cells were detected in peripheral blood samples from 57 of the 65 patients; the positive rate was 87.7%. No cancer cell was found in peripheral blood samples from healthy donors. The positive rate of PBCCs was correlated to T stage (r=0.271,P=0.017) and N stage (r=0.393, P=0.002). The patients were followed for 5 years; 2 were lost. Distant metastasis was found in 25 patients with PBCCs. In contrast, no metastasis was found in 8 patients without PBCCs (P<0.05).. Preoperative PBCC content is closely related to distant metastasis of breast cancer. The detection of PBCCs might be useful for individual treatment decision for breast cancer.

Topics: Adult; Aged; Breast Neoplasms; Carcinoma; Female; Fibroma; Flow Cytometry; Follow-Up Studies; Humans; Keratins; Leukocyte Common Antigens; Liver Neoplasms; Lung Neoplasms; Middle Aged; Neoplasm Staging; Neoplastic Cells, Circulating; Young Adult

Lymph nodes estimated as pNO in conventional morphological studies could have focuses of carcinoma cells with a diameter of < or =2 mm referred to as micrometastases (pN+). Matrix metalloproteinases (MMPs) are proteolytic family of endopeptidases which are capable to degrading components of the extracellular matrix and play an important role in cancer invasion and metastases. The aim of this study was to investigate MT1-MMP expression in carcinoma of the larynx and analyze morphological parameters to relate the expression to CKs in pN0 lymph nodes.. To presented the direct correlation between 6 morphological features of tumor front and the probability of micrometastases and prediction of prognosis 22 patients operated for squamous cell carcinoma of the larynx were analyzed. The total score of TFG, chosen clinicomorphological features and grade of matrix metalloproteinase membrane type 1 staining in tumor front were analyzed to predict the presence of micrometastases and prognosis. Immunohistochemical methods with a panel of CKs antigens in lymph nodes and MT1-MMP expression in tumor tissue were per-lymph nodes. There was no significant relationship for immunoexpression of MT1-MMP and positive poliCKs stain.. The results of study suggest that extended traditional pathologic evaluation by features from the TFG classification could aid in diagnosis of micrometastases. The positive expression of poliCKs in the pN0 lymph nodes appears to play an important role in determining prognosis in patients with carcinoma of the larynx.

Topics: Aged; Carcinoma; Carcinoma, Squamous Cell; Disease Progression; Female; Gene Expression Regulation, Neoplastic; Humans; Keratins; Laryngeal Neoplasms; Lymph Nodes; Lymphatic Metastasis; Male; Matrix Metalloproteinase 14; Middle Aged; Prognosis

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

Topics: Aged; Carcinoma; Diagnosis, Differential; Female; Giant Cells; Hemangioendothelioma; Humans; Immunohistochemistry; Keratins; Leiomyosarcoma; Liver Neoplasms; Osteoclasts; Thrombosis; Vena Cava, Inferior

Mucinous tubular and spindle cell carcinoma of the kidney is a new diagnostic entity. We present the pathologic and genomic characteristics of three such low-malignant tumors. Two of the tumors were found in women aged 19 and 52 years, the third tumor was found in an 80-year-old man, and the tumor stages were pT2N0MX, pT2NXMX, and pT1NXMX, respectively. Findings by immunohistochemistry were similar but not identical for the three cases; markers for both proximal and distal parts of the nephron were expressed in each tumor, a finding that is in agreement with data from previous studies. The Ki-67-labeling index was below 5 in all three cases. Two of the tumors were predominantly hypodiploid (DNA-indexes 0.77 and 0.80), whereas the third tumor was hypertriploid (1.57) as measured by DNA-image cytometry. From the latter tumor live cells were available making it possible to establish its karyotype: 62-70,XXX,+del(X)(q11),-1,+2,+4,-5,-6,+7,-8,-9,-10,-11,+12,-13,-14,-15,+16,+17,+18,-19,+20,+21,-22[cp15]. Interphase fluorescence in situ hybridization analyses with centromere-specific probes for chromosomes 1, 3, 4, 6, 7, 9, 10, 17, 18, 20, and X showed that the two hypodiploid tumors had disomic and monosomic chromosome populations, whereas the karyotyped, near-triploid tumor was dominated by trisomic chromosome populations. Comparative genomic hybridization analysis was normal for the karyotyped tumor but abnormal for the two others. We conclude that multiple numerical chromosome aberrations may be a feature of mucinous tubular and spindle cell carcinomas of the kidney, but beyond that no clear-cut karyotypic aberration pattern is so far discernible.

Topics: Adenocarcinoma, Mucinous; Adult; Aged, 80 and over; Carcinoma; Carcinoma, Renal Cell; Chromosome Aberrations; DNA, Neoplasm; Female; Genome, Human; Humans; Immunohistochemistry; In Situ Hybridization, Fluorescence; Karyotyping; Keratin-7; Keratins; Kidney Neoplasms; Male; Middle Aged; Mucin-1; Nucleic Acid Hybridization; Vimentin

Topics: Aged; Carcinoma; Carcinoma, Medullary; CD5 Antigens; Cell Differentiation; Choristoma; Diagnosis, Differential; Female; Humans; Immunohistochemistry; Keratins; Male; Middle Aged; Thymoma; Thymus Gland; Thyroid Gland; Thyroid Neoplasms

A real-time reverse transcriptase-polymerase chain reaction (RT-PCR) method for detection of cytokeratin 20-positive cells in blood characterized by two novel features was developed and tested on 99 patients with colorectal cancer, 110 with breast cancer, and 150 healthy subjects. To optimize the specificity and sensitivity of the method, two novel features were used. First, a primer overlapping two adjacent exons was generated to inhibit nonspecific amplification both in healthy donors and cancer patients; second, a non-end-point first-round amplification was used to increase sensitivity. The number of first-round cycles was chosen to reach the highest level of sensitivity while conserving quantitative characteristics. PCR efficiency increased from 88.9% in single-round RT-PCR to 99.0% in nested real-time RT-PCR. To establish sensitivity and specificity of the method, HT29 cells were serially diluted with normal blood. Detection limit improved from 100 HT29 cells (single-round RT-PCR) to 1 to 10 cells (nested real-time RT-PCR) per 3 ml of whole blood. None of the healthy subjects was positive, whereas 22 and 29% of all colorectal and breast cancer patients, respectively, had cytokeratin 20 cell equivalents in blood. The association between cytokeratin 20 cell equivalents and metastasis was statistically significant for breast (P = 0.026) but not colorectal cancer patients (P = 0.361). Negativity of all 150 healthy controls examined confers diagnostic potential to the method.

Topics: Biomarkers, Tumor; Breast Neoplasms; Carcinoma; Colorectal Neoplasms; Humans; Keratin-20; Keratins; Polymerase Chain Reaction; Reverse Transcriptase Polymerase Chain Reaction; RNA, Neoplasm; Sensitivity and Specificity; Tumor Cells, Cultured

Topics: Actinomycosis; Aged; Carcinoma; Humans; Immunohistochemistry; Keratins; Laryngeal Diseases; Laryngeal Neoplasms; Male; Tracheal Diseases

Detection of micrometastatic disease is an interesting area in non-small cell lung cancer (NSCLC). We conducted a study to determine whether the detection of mediastinal lymph node spread by immunohistochemical (IHC) analysis offers some prognosis with respect to patients' disease-free survival or not.. Between 1997 and 2003, twenty-one early stage lung cancer patients underwent complete resection with mediastinoscopy and systemic nodal dissection. Four hundred and twenty-six paraffin-embedded lymph node sections from 21 patients were analyzed. Epithelial specific-antigen Ab-9 and Keratin-Pan Ab-1 were used as IHC marker.. Based on nodal spread four of the 21 patients (19.04%) were up-staged after IHC analysis. Two patients with stage IB (T2N0) up-staged to stage IIIA (T2N2); two patients staged as IIB (T2N1) up-staged to IIIA (T2N2). Statistical analysis showed that the lymphatic dissemination detected with IHC analysis was associated with reduced disease-free survival (DFS) (p = 0.002).. Our study provides some indication that patients with lymphatic micrometastasis have a reduced DFS. Before creating a new TNM staging system, more information is needed to understand the prognostic impact of micrometastatic dissemination.

Topics: Antibodies, Neoplasm; Biomarkers, Tumor; Carcinoma; Female; Follow-Up Studies; Humans; Immunohistochemistry; Keratins; Lung Neoplasms; Lymph Nodes; Lymphatic Metastasis; Male; Middle Aged; Neoplasm Staging; Retrospective Studies

Metaplastic breast carcinoma is very rare, and metaplastic carcinoma with chondroid differentiation is even rarer. Here, we report a case of metaplastic carcinoma with extensive chondroid differentiation mimicking chondrosarcoma that was challenging to diagnose. The tumor was characterized by an abundant chondromyxoid matrix. The definitive area of classic invasive ductal carcinoma was minimal. The peripheral portion of the tumor showed increased cellularity with pleomorphism and definitive invasive growth. Tumor cells in the chondrosarcomatous areas were diffusely immunoreactive for S-100 protein, patchy positive for cytokeratin, but negative for epithelial membrane antigen (EMA). Tumor cells in carcinomatous areas were diffusely positive for cytokeratin, S-100 protein, and patchy positive for EMA. In both areas, tumor cells were negative for smooth muscle actin (SMA) and CD34, while oncoprotein p53 was overexpressed. When pathologists encounter breast tumors with chondroid differentiation, careful sampling and immunohistochemistry for cytokeratin and SMA are most helpful to differentiate metaplastic carcinoma from malignant phyllodes tumor and malignant adenomyoepithelioma.

Topics: Actins; Antigens, CD34; Breast Neoplasms; Carcinoma; Cell Differentiation; Female; Humans; Immunohistochemistry; Keratins; Metaplasia; Middle Aged; Mucin-1; Muscle, Smooth; Neoplasm Metastasis; S100 Proteins

We have used a recently described model in which a ras oncogene is expressed in cytokeratin 5 (K5)-expressing cells on doxycycline administration to explore the effects of this oncogene in salivary glands of adult mice. Inducible expression of a mutated K-ras gene under the control of the K5 promoter led to the development of hyperplastic and dysplastic epithelial lesions and carcinomas, with an incidence of 100% and a minimum latency of a week. All major salivary glands were affected, as well as a set of previously undescribed buccal accessory salivary glands located on the apex of the masseter muscle, close to the oral angle. The tumors appear to arise from the cytokeratin 5-positive basal cell compartment. Myoepithelial cells participated in the hyperplasias but not in carcinomas, because the tumors are negative for smooth muscle actin. Carcinomas did not accumulate immunoreactive p53 but are positive for p63, as assayed by immunohistochemistry using an antibody against the N terminus of DeltaN p63, a splice variant of p63 that can inhibit p53 transcriptional activity. In this study, we provide evidence that the ras oncogene, targeted to a specifically sensitive cell compartment within the salivary glands, can trigger a series of event that are sufficient for full carcinogenesis.

Topics: Animals; Carcinoma; Carcinoma, Squamous Cell; Cell Proliferation; Cheek; Female; Fibroadenoma; Gene Expression Regulation, Neoplastic; Genes, ras; Keratins; Male; Mice; Mice, Transgenic; Mouth Mucosa; Promoter Regions, Genetic; Salivary Gland Neoplasms; Salivary Glands; Submandibular Gland

Topics: Biomarkers, Tumor; Biopsy, Needle; Breast Neoplasms; Carcinoma; Cell Nucleus; Female; Humans; Keratins; Middle Aged; Ultrasonography, Mammary

This study is aimed at establishing a sensitive approach to detect disseminated tumor cells in peripheral blood and evaluate its clinical significance. A total of 198 blood samples including 168 from colorectal carcinoma (CRC) patients and 30 from healthy volunteers were examined by quantitative real-time reverse transcription-polymerase chain reaction (RT-PCR) to evaluate the expression of carcinoembryonic antigen (CEA), cytokeratin 20 (CK20) and cytokeratin 19 (CK19) mRNA. CEA mRNA was detected in 35.8% of patients and 3.3% of controls, CK20 mRNA in 28.3% of patients and 6.7% of controls, and CK19 mRNA in 41.9% of patients and 3.3% of controls. CEA and CK20 mRNA positive ratio increased with the advancing Dukes stages, but there was no significant difference in positive ratio between any two stages (P>0.05). Also, relatively high positive ratio of CEA, CK20 and CK19 mRNA expression was observed in some CRC patients with earlier Dukes stages. A higher positive ratio was obtained when two or three detection markers were combined compared to a single marker. Our study indicates that quantitative real-time RT-PCR detection for CEA, CK20 and CK19 mRNA in peripheral blood is a valuable tool for monitoring early stage dissemination of CRC cells in blood circulation.

Topics: Adult; Aged; Aged, 80 and over; Biomarkers, Tumor; Carcinoembryonic Antigen; Carcinoma; Colorectal Neoplasms; Female; Humans; Keratin-20; Keratins; Male; Middle Aged; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Sensitivity and Specificity

Topics: Aged; Biomarkers, Tumor; Carcinoma; Desmin; Female; Humans; Immunohistochemistry; Keratins; Laryngeal Neoplasms; Male; Middle Aged; Vimentin

To investigate whether immunohistochemically demonstrated lymph node micrometastasis has a survival impact in patients with advanced gallbladder carcinoma (pT2-4 tumors).. The clinical significance of immunohistochemically detected lymph node micrometastasis recently has been evaluated in various tumors. However, few reports have addressed this issue with regard to gallbladder carcinoma.. A total of 1476 lymph nodes from 67 patients with gallbladder carcinoma (pN0, n = 40; pN1, n = 27) who underwent curative resection were immunostained with monoclonal antibody against cytokeratins 8 and 18. The results were correlated with clinical and pathologic features and with patient survival.. Lymph node micrometastases were detected immunohistochemically in 23 (34.3%) of the 67 patients and in 37 (2.5%) of the 1476 nodes examined. Of the 37 nodal micrometastases, 21 (56.8%) were single-cell events, and the remaining 16 were clusters. Five micrometastases were detected in the paraaortic nodes. Clinicopathologic features showed no significant associations with the presence of lymph node micrometastases. Survival was worse in the 27 patients with pN1 disease than in the 40 with pN0 disease (5-year survival; 22.2% vs. 52.6%, P = 0.0038). Similarly, survival was worse in the 23 patients with micrometastasis than in the 44 without micrometastasis (5-year survival; 17.4% vs. 52.7%, P = 0.0027). Twenty-eight patients without any lymph node involvement had the best prognosis, whereas survival for the 11 patients with both types of metastasis was dismal. The grade of micrometastasis (single-cell or cluster) had no effect on survival. The Cox proportional hazard model identified perineural invasion, lymph node micrometastasis, and microscopic venous invasion as significant independent prognostic factors.. Lymph node micrometastasis has a significant survival impact in patients with pN0 or pN1 gallbladder carcinoma who underwent macroscopically curative resection. Extensive lymph node sectioning with keratin immunostaining is recommended for accurate prognostic evaluation for patients with gallbladder carcinoma.

Topics: Adult; Aged; Aged, 80 and over; Biomarkers, Tumor; Carcinoma; Female; Gallbladder Neoplasms; Humans; Immunohistochemistry; Keratins; Lymph Nodes; Lymphatic Metastasis; Male; Middle Aged; Prognosis; Survival Analysis; Survival Rate

Cytokeratin 5 and p63 have been described as basal and myoepithelial cell markers in human breast. Mixed tumors of the canine mammary gland have been associated with a myoepithelial origin. Cytokeratin 5 expression has not been evaluated in these tumors. We investigated the relation between cytokeratin 5 and p63 double-immunohistochemical expression in 23 mixed tumors of the canine mammary gland (10 benign mixed tumors and 13 carcinomas arising from benign mixed tumors) and their origin. Cytokeratin 5 and p63 co-expression was observed in myoepithelial cells of benign mixed tumors, as well as in squamous differentiation of carcinoma arising from benign mixed tumors. Though a few interstitial spindle cells of the mesenchymal components expressed both p63 and cytokeratin 5, the basal epithelial cells were labeled only by cytokeratin 5. The co-expression of p63 and cytokeratin 5 in myoepithelial cells and squamous differentiation suggest that, like in human breast, cytokeratin 5 can also be considered a myoepithelial- and squamous-cell differentiating marker in canine tumors. The presence of some interstitial spindle cells stained for p63 and cytokeratin 5 might be associated with a myoepithelial origin of the mesenchymal component of mixed tumors of the canine mammary gland. Moreover, contrary to p63, basal epithelial cells were labeled by cytokeratin 5, indicating that cytokeratin 5 may not represent an exclusive myoepithelial cell marker but also a basal epithelial cell marker in canine mixed tumors. According to these data, basal epithelial cells may be related to the origin of the epithelial component of mixed tumors of the canine mammary gland.

Topics: Animals; Biomarkers, Tumor; Carcinoma; Dog Diseases; Dogs; Female; Genes, Tumor Suppressor; Immunohistochemistry; Keratins; Mammary Neoplasms, Animal; Retrospective Studies; Tumor Suppressor Proteins

Breast carcinomas expressing basal epithelium cytokeratins constitute a tumor subgroup that is typically hormone receptor negative and shows a distinct gene expression profile. Based on variable basal cytokeratin immunostaining patterns, we hypothesized that the "basal phenotype" tumor group may comprise more than one biological entity.. Basal cytokeratins 5 and 14 (CK5/14) were stained by immunohistochemistry and the percentage of positive cells was defined by image analysis. The results thus obtained were compared with clinicopathologic characteristics and relapse-free survival.. Of the 506 breast tumors, 53 (10.5%) showed immunoreactivity for CK5/14. Basal cytokeratin expression showed up as two microscopically distinguishable subtypes, i.e., a uniformly positive type ("basal") and a partially positive type ("basoluminal") often displaying a checkerboard-type intratumoral heterogeneity. These subgroups could also be separated with a third basal cytokeratin (CK17, P < 0.0001). Both basal and basoluminal subtypes were hormone receptor negative and of high grade, but differed with respect to the Ki-67 labeling index (P = 0.0014), vimentin (P = 0.005), and c-kit (P = 0.02), which were more frequently expressed in basal than in basoluminal tumors. In contrast, the amplification of HER-2 was found almost exclusively in the basoluminal subgroup (P = 0.009). Compared with the basal tumors, basoluminal tumors associated with significantly shorter relapse-free survival (P = 0.01), which was not explained by their more frequent HER-2 amplification.. We conclude that the intratumoral heterogeneity in basal cytokeratin expression can be used to define two distinct breast cancer subtypes, basal and basoluminal, with distinctive features related to proliferation activity, oncogene and biomarker status, and patient survival.

Topics: Aged; Breast Neoplasms; Carcinoma; Cohort Studies; Disease-Free Survival; Female; Gene Expression Regulation, Neoplastic; Humans; Image Processing, Computer-Assisted; Keratin-14; Keratin-5; Keratins; Male; Middle Aged; Prognosis

Carcinoma showing thymus-like differentiation (CASTLE) is a rare intrathyroidal neoplasm, a member of a tumor family probably arising from ectopic thymus or branchial pouch remnants. Thyroid solid cell nests (SCNs) may also be derived from branchial pouch remnants. SCNs express p63, carcinoembryonic antigen (CEA), and high molecular weight keratin (HMWK). To determine whether CASTLE and SCNs derive from similar embryologic origins/lines of differentiation, and to better differentiate CASTLE from other thyroid neoplasms, we compared p63, CD5, HMWK, and CEA staining of CASTLE and SCNs with other thyroid and thymic lesions. Seven CASTLE, 11 SCNs, 10 thymic carcinoma, 11 invasive thymoma, 12 thymoma, 28 papillary thyroid carcinoma, 4 thyroid squamous cell carcinoma, 2 childhood sclerosing carcinoma, 4 follicular adenoma, 6 follicular carcinoma, 4 poorly differentiated carcinoma, and 20 lymphocytic thyroiditis cases were analyzed. In normal thyroid, only SCNs stained for p63, HMWK, and CEA. The only CD5-positive cells in normal thyroid were T cells. Thymomas and normal thymus stained similarly to SCNs. All CASTLE and thymic carcinomas exhibited diffuse p63 and HMWK staining and all CASTLE cases and the majority of thymic carcinomas were positive for CEA and CD5. In contrast, none of the other thyroid neoplasms examined exhibited consistent staining for all 4 markers studied. These findings provide further evidence that CASTLE is distinct from other thyroid neoplasms, is probably of thymic origin, and may arise from branchial pouch remnants, the thyroid SCNs. Moreover CD5, HMWK, CEA and p63 can be used to help distinguish CASTLE from other thyroid neoplasms.

Topics: Adult; Aged; Biomarkers, Tumor; Carcinoembryonic Antigen; Carcinoma; CD5 Antigens; Cell Lineage; Choristoma; Diagnosis, Differential; Female; Humans; Immunohistochemistry; Keratins; Male; Membrane Proteins; Middle Aged; Thymus Gland; Thyroid Gland; Thyroid Neoplasms

A 70-year-old Japanese man presented with a 5-year history of refractory indolent onycholysis of the little finger of the right hand. Roentgenograms did not show involvement of the bone. Histological examination revealed an epithelial tumor consisting of lobular masses varying in size. The tumor was composed of keratinocytes varying in atypicality and showed infiltrative growth into the dermis but not into the phalangeal bone. The tumor had cystic structures composed of eosinophilic amorphous keratin and a surrounding thin layer of keratinocytes. Characteristically, the epithelium in the center of the tumor abruptly changed into amorphous keratin without the formation of intervening keratohyaline granules. From these findings, the mass was diagnosed as onycholemmal carcinoma. Immunohistochemically, the tumor showed a keratin profile comparable to that of the nail bed epithelium and a smaller number of Ki-67-positive proliferating tumor cells compared with those of a previous case of onycholemmal carcinoma.

Topics: Aged; Biopsy; Carcinoma; Cell Proliferation; Humans; Keratins; Male; Nail Diseases; Skin Neoplasms

The Goseki system is a new gastric carcinoma classification system that classifies gastric carcinomas as grade I (intestinal type), grade II (mucinous type), grade III (mucin-poor, diffuse infiltrating type), and grade IV (signet ring cell type). The main advantage of the Goseki classification may be to separate these distinct entities into different groups. CK7 is not observed in normal gastric mucosa but can be detected in chronically inflamed gastric mucosa and coexists with incomplete intestinal metaplasia. CK20 can be observed in the superficial foveolar epithelium and mature goblet cells. The aim of this study was to examine the cytokeratin expression profiles in gastric carcinomas that are classified according to both the Goseki and Lauren systems. CK7, CK8, CK19, and CK20 were applied to the paraffin sections of 66 gastric carcinoma cases. The cytokeratin expression patterns were grouped as CK20+/CK7+, CK20+/CK7-, CK20-/CK7+, or CK20-/CK7-. The results were examined statistically. CK20 immunoreactivity was observed in 18%, 24%, and 31% of grade I, III, and IV cases, respectively. The CK20+/CK7- pattern was observed in 20% of the grade IV and 66.7% of the grade II carcinomas and was not observed in grade I or grade III tumors (P<0.0001). Goseki grade III and IV carcinomas originate from superficial gastric mucosa, but grade III carcinomas are poorly differentiated. Goseki grade II carcinomas have a specific immunophenotype other than intestinal-type gastric tumors. The Goseki classification seems to be superior in identifying poorly and well-differentiated forms of diffuse infiltrating carcinomas and mucinous carcinomas.

Topics: Adult; Aged; Biomarkers, Tumor; Carcinoma; Chi-Square Distribution; Female; Humans; Immunohistochemistry; Keratins; Male; Middle Aged; Neoplasm Staging; Stomach Neoplasms

Epithelial myoepithelial carcinoma (EMC) is a rare low grade malignant salivary gland neoplasm that most commonly occurs in the parotid gland but can also arise in minor salivary glands. We report a case of primary epithelial myoepithelial carcinoma of minor salivary gland in a 25 year old women who presented with swelling left cheek of one year duration and bilateral submandibular lymphadenopathy. A mass causing erosion of mandible, thyroid cartilage and masseter muscle was identified on CT scan. This was excised and histological examination revealed a mixture of ductal structures consisting of inner dark cells and outer clear cells seen in solid sheets. Immunohistochemical analysis showed the clear cells to be weakly positive for S100 and smooth muscle actin (SMA) and ductal cells to be positive for cytokeratin (CK) and epithelial membrane antigen (EMA). The characteristic morphological and immunohistochemical features aided in the diagnosis of epithelial myoepithelial carcinoma.

Topics: Actins; Adult; Carcinoma; Female; Humans; Keratins; Lymph Nodes; Lymphatic Metastasis; Mandible; Mucin-1; Myoepithelioma; S100 Proteins; Salivary Gland Neoplasms; Salivary Glands

To study the value of immunocytochemical study for cyclin D1, c-erbB-2, Ki-67, p21(CIP1/WAF1) and 34betaE12 in fine needle aspiration cytology (FNAC) diagnosis of mammary lesions.. One hundred and thirty-five cases of breast diseases, all with FNAC performed and follow-up histologic correlation available, were enrolled into the study. These included 43 cases of benign non-proliferative diseases, 45 cases of benign proliferative diseases and 47 cases of mammary carcinoma. Immunostaining for cyclin D1, c-erbB-2, Ki-67, p21(CIP1/WAF1) and 34betaE12 was carried out on FNAC smears and paraffin sections of the corresponding biopsy specimens. The statistical significance was analyzed using SPSS11.5 software.. No statistically significant difference was observed in the expression of cyclin D1, c-erbB-2, Ki-67, p21(CIP1/WAF1) and 34betaE12 within the groups of benign non-proliferative and benign proliferative breast diseases. On the other hand, a significant difference in immunostaining results was found between benign breast lesions and mammary carcinoma (P < 0.001). A panel of cyclin D1, 34betaE12 and c-erbB-2 immunostaining is highly sensitive and specific in confirming the diagnosis of mammary carcinoma in FNAC samples. A positive reaction for cyclin D1 and c-erbB-2, when coupled with a negative reaction for 34betaE12, showed to be the most reliable supportive evidence for the malignant cytologic diagnosis. When taking the results of either cyclin D1 or 34betaE12 immunostaining into consideration, the sensitivity and specificity for diagnosing carcinoma was 95.7% and 94.3% respectively. On the other hand, when any of the three immunostains suggested carcinoma, the diagnostic sensitivity and specificity became 97.9% and 92.0% respectively. If the immunostaining results of any two of the three markers suggested carcinoma, the diagnostic sensitivity and specificity became 72.3% and 100% respectively. Within the carcinoma group, the degree of expression of cyclin D1, p21(CIP1/WAF1) and 34betaE12 showed little difference amongst different cytologic grades (according to Robinson cytologic grading system). There were however differences in expression of c-erbB-2 and Ki-67. Highest expression rate was observed in grade 3 carcinoma, while lowest expression rate was observed in grade 1 carcinoma (only in 40.0% and 33.3% of cases respectively). Whenever either cyclin D1 positivity or 34betaE12 negativity was demonstrated, the diagnostic accuracy for grade 1 and grade 2 carcinoma was 93.3% and 96.2 % respectively.. Immunocytochemical study using a panel of antibodies for cyclin D1, c-erbB-2, and 34betaE12 has significant diagnostic value in distinguishing between benign breast diseases and mammary carcinoma in FNAC samples. Cyclin D1 and 34betaE12 are especially useful in confirming the cytologic diagnosis of low-grade cancer.

Topics: Biopsy, Fine-Needle; Breast; Breast Diseases; Breast Neoplasms; Carcinoma; Cyclin D1; Diagnosis, Differential; Female; Humans; Immunohistochemistry; Keratins; Receptor, ErbB-2

High grade prostatic intraepithelial neoplasia (PIN) and atypical adenomatous hyperplasia (AAH) are discussed to be precursors of prostate cancer (PC). Unlike high grade PIN the relation between AAH and PC is however unclear. In the present study we analyzed AAH, accompanying prostate carcinomas and carcinomas of the transitional zone after microdissection using comparative genomic hybridization (CGH) and multipelx-PCR with 10 microsatellite polymorphic markers. In every case non-neoplastic prostatic tissue was investigated for the same allelic imbalances. Two AAH showed allelic imbalances in multiplex-PCR. These imbalances did not correlate with the corresponding tumours and furthermore were different to the LOH found in the investigated prostate tumours of the transitional zone. One AAH showed loss on chromosome 22q. We found allelic imbalances in over 50% of non-neoplastic tissue adjacent to prostatic carcinoma. Our findings support the idea that AAH does not seem to be linked closely to PC and should not be considered as an obligate premalignant lesion.

Topics: Aged; Biomarkers, Tumor; Carcinoma; Chromosomes, Human, Pair 22; Cytogenetic Analysis; Humans; Karyotyping; Keratins; Loss of Heterozygosity; Male; Middle Aged; Nucleic Acid Hybridization; Polymerase Chain Reaction; Prostate; Prostatic Hyperplasia; Prostatic Neoplasms

Topics: Biopsy; Bone Marrow; Breast Neoplasms; Carcinoma; Female; Follow-Up Studies; Humans; Keratins; Neoplasm Metastasis; Neoplasm, Residual; Neoplastic Cells, Circulating; Practice Patterns, Physicians'; Time Factors

Isolated tumor cells are often found in the regional lymph nodes of colorectal cancer, although their prognostic significance has not been established yet. This study was performed to investigate the correlation between the presence of isolated tumor cells in lymph nodes and the histopathologic characteristics of colorectal cancers and, thus, to determine which factors are associated with isolated tumor cells.. We used immunohistochemistry with anticytokeratin antibody to examine 2,784 lymph nodes in 109 patients with node-negative colorectal cancers. The clinicopathologic features of the tumors with isolated tumor cells were compared with those without isolated tumor cells. The frequency, number, and level of the isolated tumor cells also were assessed.. Isolated tumor cells were detected in 335 lymph nodes (12 percent) from 71 patients (65.1 percent). Those tumors having isolated tumor cells in lymph nodes, compared with those not having isolated tumor cells, were characterized by large tumor size, high T stage (pT3 and pT4), angiolymphatic invasion, perineural invasion, absence of peritumoral lymphocytic response, microsatellite instability-negative phenotype, and tumor budding. Multivariate analysis showed that those factors independently associated with the presence of isolated tumor cells were high T stage, tumor budding, and microsatellite instability-negative phenotype. Among the 71 patients with high T stage and microsatellite instability-negative phenotype, tumors with isolated tumor cells were characterized by a high frequency of tumor budding compared with tumors without isolated tumor cells (85 vs. 36.4 percent). In a further study, the degree of budding, which was assessed by an immunohistochemical study of gamma2 chain of laminin-5, was closely related to the number and location of isolated tumor cells. Moreover, we found that most of the isolated tumor cells in the regional lymph nodes also expressed gamma2 chain of laminin-5.. Our results suggested that isolated tumor cells are derived from undifferentiated cancer cells or small clusters ("budding") at the invasive front. Thus, tumor budding may be used as an indicator of isolated tumor cells in lymph nodes with node-negative colorectal cancers.

Topics: Adult; Aged; Aged, 80 and over; Analysis of Variance; Carcinoma; Chi-Square Distribution; Colorectal Neoplasms; Humans; Immunohistochemistry; Keratins; Logistic Models; Lymphatic Metastasis; Male; Middle Aged; Neoplasm Staging; Predictive Value of Tests; Prognosis; Sensitivity and Specificity

A 49-year-old woman underwent hysterectomy and bilateral adnexectomy after the diagnosis of a right ovarian tumor with paraaortic and pelvic lymph node metastases. The pathological diagnosis was undifferentiated carcinoma of the ovary. After the operation, a bladder tumor was discovered during the evaluation for microscopic hematuria. The bladder tumor was pathologically diagnosed as transitional cell carcinoma, pT1b, G3. Although the pathological findings of the bladder cancer and ovarian cancer were very similar, we could diagnose primary bladder cancer with ovary and lymph node metastases according to the immunohistochemical staining pattern of cytokeratins 7 and 20. Herein, the clinical usefulness of immunohistochemical staining using cytokeratins for making a differential diagnosis of the origin of a tumor in the pelvic cavity is demonstrated.

Topics: Biomarkers, Tumor; Carcinoma; Carcinoma, Transitional Cell; Diagnosis, Differential; Female; Humans; Immunohistochemistry; Intermediate Filament Proteins; Keratin-20; Keratin-7; Keratins; Middle Aged; Ovarian Neoplasms; Urinary Bladder Neoplasms

A spindle cell carcinoma arose three years after the seeming excision of a so-called "infiltrative" basal cell carcinoma (IBCC) in the cheek of an 87-year-old Japanese woman. The patent had no history of irradiation. The tumor was composed of short fascicles and whorling arrangements of spindle to polygonal cells without residual IBCC. Immunohistochemically, the tumor was positive for vimentin, cytokeratin 8 & 18, epithelial membrane antigen, and alpha-smooth muscle actin. Ultrastructurally, the tumor cells had tonofilaments and desmosomes. The patient died after a local recurrence with metastatic lesions in the lung and the neck lymph nodes that were indicated by CT scanning and MRI at nine months after diagnosis. This case and others support the concept that spindle cell carcinoma can pursue an aggressive clinical course.

Topics: Actins; Aged; Aged, 80 and over; Biomarkers, Tumor; Carcinoma; Carcinoma, Basal Cell; Fatal Outcome; Female; Humans; Keratins; Mucin-1; Neoplasms, Second Primary; Skin Neoplasms; Vimentin

Pleomorphic carcinoma of the lung (PCL) is characterized by a mixture of sarcomatoid and carcinoma components, and a poor prognosis. However, no immunophenotype of tumor markers has been characterized in PCL. To characterize the immunophenotype for CD99 in PCL, we performed an immunohistochemical evaluation of PCLs for thyroid transcription factor-1 (TTF-1), cytokeratin (CK) 7 and 20, and for CD99. CD99 was found to be expressed in both carcinomatous (47%) and sarcomatous components such as spindle cells (92%) and giant cells (57%). In the case of spindle cells, CK7 was expressed in 6 cases (46%) and TTF-1 in 2 cases (15%), whereas for giant cells CK7 was expressed in 8 cases (57%) and TTF-1 in one case (7%). However, CK20 was not expressed in either the carcinomatous or sarcomatous components in any case. Thus, CD99 was found to be widely expressed in both sarcomatous and carcinoma component in PCL. A clinicopathological analysis showed no direct correlation between the expression of CD99 and the clinical indices (stage, survival rate, invasion) of PCL.

Topics: 12E7 Antigen; Adult; Aged; Aged, 80 and over; Antigens, CD; Carcinoma; Cell Adhesion Molecules; Female; Humans; Immunohistochemistry; Immunophenotyping; Intermediate Filament Proteins; Keratin-20; Keratin-7; Keratins; Lung Neoplasms; Male; Middle Aged; Nuclear Proteins; Prognosis; Sarcoma; Thyroid Nuclear Factor 1; Time Factors; Transcription Factors

Recently, the rearrangement of RET proto-oncogene has been reported to be the most common genetic change in papillary thyroid carcinoma (PTC). However, its prevalence has been reported variably and its relation to clinical outcome has been controversial. The characteristic nuclear features of PTC usually render the diagnosis, but problem arises with equivocal cytologic features that are present focally. Although there remains some controversy, CK19 has been reported to be a useful ancillary tool for diagnosis of PTC. To evaluate the expression rate of RET/PTC rearrangement and CK19 in PTCs in a Korean population, we studied 115 papillary thyroid carcinomas in 3 mm-core tissue microarray based immunohistochemical analysis. The prevalence of Ret protein expression was 62.6% and the CK19 immunoreactivity was 80.9%. There was no statistically significant association between the Ret positivity and CK19 immunoreactivity, although the percent agreement of the two was relatively high. The clinicopathological variables did not correlate with the expression of Ret. In conclusion, the prevalence of Ret protein expression and its clinicopathological implications in a Korean population are not much different from those reported in previous studies. However, its detection via immunohistochemistry can be a useful diagnostic tool for diagnosing papillary thyroid carcinoma in conjunction with CK19.

Topics: Adenocarcinoma, Papillary; Adult; Carcinoma; Cell Line, Tumor; Cytoplasm; Female; Gene Expression Regulation, Neoplastic; Humans; Immunohistochemistry; Keratins; Korea; Lymphatic Metastasis; Male; Middle Aged; Oligonucleotide Array Sequence Analysis; Oncogene Proteins; Proto-Oncogene Mas; Proto-Oncogene Proteins c-ret; Receptor Protein-Tyrosine Kinases; Thyroid Neoplasms

This study aimed to investigate the role of underlying fibroblasts on morphogenesis of in vitro epithelium reconstituted with normal and neoplastic human oral keratinocytes at various stages of malignant transformation. Primary normal human oral keratinocytes (NOKs), early neoplastic/dysplastic human oral keratinocytes (DOK cell line), and neoplastic human oral keratinocytes (PE/CA-PJ 15 cell line) were organotypically grown on top of a collagen type I matrix with or without primary normal human oral fibroblasts. Morphogenesis of the reconstituted epithelia was assessed by histomorphometry, immunohistochemistry (Ki-67, cyclin D1, cytokeratin 13 (CK13), collagen IV, E-cadherin, p53, CD40), and the terminal deoxynucleotidyl transferase-mediated dUTP in situ nick end-labelling method. Reproducible in vitro models of multistage oral carcinogenesis were established. Presence of fibroblasts in the collagen matrix significantly increased cell proliferation in all three models (p<0.05), and induced an invasive pattern of growth in the neoplastic cell lines (p<0.05). In normal, but not in neoplastic oral keratinocytes fibroblasts induced the expression of CD40, and polarized the expression of E-cadherin and p53 to the basal cell layer. In both normal and early neoplastic keratinocytes (DOK cell line), fibroblasts induced the expression of CK13 and collagen IV. In the neoplastic oral keratinocytes (PE/CA-PJ 15 cell line), the presence of underlying fibroblasts did not change the expression of any of the protein markers assessed. This study showed that (1) major steps of oral carcinogenesis can be reproduced in vitro, and (2) the tight control exerted by fibroblasts on epithelial morphogenesis of in vitro reconstituted normal human oral mucosa is gradually lost during neoplastic progression.

Topics: Biomarkers; Cadherins; Carcinoma; Cell Differentiation; Cell Transformation, Neoplastic; Collagen Type IV; Epithelium; Fibroblasts; Humans; Keratinocytes; Keratins; Morphogenesis; Mouth Mucosa; Mouth Neoplasms

Sarcomatoid carcinomas are rare malignancies which represent poorly differentiated epithelial tumors that may be difficult to recognize as such. While some cases may have obvious epithelial areas, the sarcomatoid areas are poorly distinguishable from true sarcoma at the light microscopic level and, by immunohistochemistry, often show only limited staining for traditional epithelial markers such as cytokeratin or epithelial membrane antigen. This can be particularly problematic for diagnosis on small biopsy specimens. We sought to assess the diagnostic utility of several immunohistochemical markers of epithelial differentiation including p63, MOC-31, and thyroid transcription factor-1 on sarcomatoid carcinomas of the head and neck (19 cases; 'spindle cell carcinomas'), lung (19 cases), and urinary bladder (11 cases). These results were compared to immunohistochemistry for the traditional epithelial markers pan-cytokeratin and epithelial membrane antigen. Staining for p63 showed the greatest diagnostic utility, positive in 63, 50, and 36% of head and neck, lung, and urinary bladder sarcomatoid carcinomas, respectively. p63 stains were positive in many cases where immunohistochemistry was negative for both pan-cytokeratin and epithelial membrane antigen. All three alternative markers were quite specific for epithelial differentiation, each staining less than 10% of the control group of 73 various primary and metastatic sarcomas, melanomas, and benign spindle cell lesions. In conclusion, immunostaining beyond traditional pan-cytokeratin and epithelial membrane antigen may have diagnostic utility in this context.

Topics: Aged; Aged, 80 and over; Biomarkers, Tumor; Carcinoma; Diagnosis, Differential; Female; Head and Neck Neoplasms; Humans; Immunohistochemistry; Keratins; Lung Neoplasms; Male; Melanoma; Membrane Glycoproteins; Membrane Proteins; Middle Aged; Mucin-1; Nuclear Proteins; Sarcoma; Sensitivity and Specificity; Thyroid Nuclear Factor 1; Transcription Factors; Urinary Bladder Neoplasms

Adenomyoepithelial tumours and myoepithelial carcinomas of the breast are primarily defined by the presence of neoplastic cells with a myoepithelial immunophenotype. Current classification schemes are based on purely descriptive features and an assessment of individual prognosis is still problematic.. A series of 27 adenomyoepithelial tumours of the breast was analysed immunohistochemically with antibodies directed against various cytokeratins, p63, smooth muscle alpha-actin (SMA) and vimentin. Additionally, double immunofluorescence and comparative genomic hybridisation (CGH) was performed.. Immunohistochemically, all the tumours showed a constant expression of high molecular weight cytokeratins (Ck) Ck5 and Ck14, p63, SMA and vimentin. With exception of one case diagnosed as myoepithelial carcinoma, all tested tumours expressed low molecular weight cytokeratin Ck18 in variable proportions of cells. Even in monophasic tumours lacking obvious glandular differentiation in conventional staining, a number of neoplastic cells still expressed those cytokeratins. Double immunofluorescence revealed tumour cells exclusively staining for Ck5/Ck14 in the presence of other cell populations that co-expressed high molecular weight Ck5/Ck14 as well as either low molecular weight Ck8/18 or SMA. Based on morphology, we assigned the series to three categories, benign, borderline and malignant. This classification was supported by a stepwise increase in cytogenetic alterations on CGH.. Adenomyoepithelial tumours comprise a spectrum of neoplasms consisting of an admixture of glandular and myoepithelial differentiation patterns. As a key component SMA-positive cells co-expressing cytokeratins could be identified. Although categorisation of adenomyoepithelial tumours in benign, borderline and malignant was supported by results of CGH, any assessment of prognosis requires to be firmly based on morphological grounds. At present it is not yet clear, if and to what extent proposed Ck5-positive progenitor cells contribute to the immunohistochemical and morphological heterogeneity of these neoplasms of the breast.

Topics: Actins; Adult; Aged; Aged, 80 and over; Breast Neoplasms; Carcinoma; Cell Proliferation; DNA-Binding Proteins; Epithelial Cells; Female; Genes, Tumor Suppressor; Humans; Image Processing, Computer-Assisted; Immunohistochemistry; Immunophenotyping; Keratins; Microscopy, Fluorescence; Middle Aged; Myoepithelioma; Nucleic Acid Hybridization; Phosphoproteins; Prognosis; Trans-Activators; Transcription Factors; Tumor Suppressor Proteins; Vimentin

Topics: Adenocarcinoma, Mucinous; Adult; Breast; Breast Neoplasms; Carcinoma; Female; Humans; Keratins; Metaplasia; Mucin-1; S100 Proteins

Microarray studies have linked Annexin A8 RNA expression to a "basal cell-like" subset of breast cancers, including BRCA1-related cancers, that are characterized by cytokeratin 5 (CK5) and CK17 expression and show poor prognosis. We assessed Annexin A8's contribution to the overall prognosis and its expression in normal, benign, and cancerous tissue and addressed Annexin A8's physiologic role in the mammary gland.. Using microarrays and reverse transcription-PCR, the Annexin A8 expression was studied during mouse mammary gland development and in isolated mammary structures. Reverse transcription-PCR on cultured human luminal and basal cells, along with immunocytochemistry on normal and benign breast tissues, was used for cellular localization. Annexin A8's prognostic relevance and its coexpression with CK5 were assessed on tissue arrays of 1,631 cases of invasive breast cancer. Coexpression was further evaluated on a small cohort of 14 BRCA1-related breast cancers.. Annexin A8 was up-regulated during mouse mammary gland involution and in pubertal ductal epithelium. Annexin A8 showed preferred expression in cultured basal cells but predominant luminal expression in normal human breast tissue in vivo. Hyperplasias and in situ carcinomas showed a strong staining of basal cells. Annexin A8 expression was significantly associated with grade (P < 0.0001), CK5 (P < 0.0001), and estrogen receptor status (P < 0.0001); 85.7% BRCA1-related breast tumors coexpressed Annexin A8 and CK5.. Annexin A8 is involved in mouse mammary gland involution. In humans, it is a luminally expressed protein with basal expression in cell culture and in hyperplasia/ductal carcinoma in situ. Expression in invasive breast carcinomas has a significant effect on survival (P = 0.03) but is not independent of grade or CK5.

Topics: Animals; Annexins; Apoptosis; Breast Neoplasms; Carcinoma; Carcinoma, Intraductal, Noninfiltrating; Cohort Studies; Female; Gene Expression Regulation, Neoplastic; Genes, BRCA1; Humans; Immunohistochemistry; Keratins; Mammary Glands, Animal; Mice; Mutation; Oligonucleotide Array Sequence Analysis; Oligonucleotides; Phenotype; Polymerase Chain Reaction; Prognosis; Reverse Transcriptase Polymerase Chain Reaction; RNA; Time Factors; Treatment Outcome; Up-Regulation

Topics: Breast Neoplasms; Carcinoma; Diagnosis, Differential; Female; Fibroma; Humans; Keratins; Middle Aged; Vimentin

A 3-year-old, neutered, male Golden Retriever was presented for evaluation of a 10 X 9 X 5 mm, firm, red, raised, cutaneous mass located over the left cranial thorax and noted incidentally by the owner. On cytologic evaluation of a fine-needle aspirate of the mass, the interpretation was a malignant tumor with predominantly mesenchymal features. Differentials included liposarcoma, atypical amelanotic melanoma, anaplastic sarcoma, and anaplastic carcinoma. Following complete excision of the mass, a diagnosis of sebaceous adenocarcinoma was made based on histologic features, positive immunostaining for pancytokeratin, and negative staining for vimentin, Melan-A, and S-100. There was no evidence of metastasis on physical examination or thoracic radiographs, and the prognosis was good. The unique and previously unreported cytologic features of this small, sebaceous adenocarcinoma were the extreme pleomorphism, including marked anisocytosis, anisokaryosis, and multinuclearity, and the paucity of epithelial features.

Topics: Adenocarcinoma, Sebaceous; Animals; Carcinoma; Diagnosis, Differential; Dog Diseases; Dogs; Immunohistochemistry; Keratins; Liposarcoma; Male; Melanoma, Amelanotic; Sebaceous Gland Neoplasms

Histologic differentiation of primary ovarian carcinoma from colonic carcinoma metastatic to the ovary may be difficult. Cytokeratin 7 (CK7) and cytokeratin 20 (CK20) immunostaining is usually used, but these markers lack specificity for ovarian and intestinal epithelium, and overlapping results have been reported. Cdx2 is a transcription factor whose expression in normal tissues is limited to the intestinal epithelium. It is also expressed in the vast majority of colonic carcinomas and in a sizeable proportion of cases of gastric, pancreatobiliary, and ovarian mucinous carcinomas. We evaluated Cdx2, CK7, and CK20 expression in 50 ovarian carcinomas (15 serous, 20 mucinous, and 15 endometrioid), 15 colonic carcinomas metastatic to the ovaries, and 20 primary colonic carcinomas. The extent (1-25%/1+, 26-75%/2+, >75%/3+) and intensity (weak/1+, strong/2+) of staining were recorded semiquantitatively. All primary and metastatic colonic carcinomas had diffuse (3+) strong Cdx2 reactivity. All serous and endometrioid tumors were Cdx2 negative, whereas mucinous carcinomas had 1+ or 2+ immunoreactivity. All ovarian carcinomas had strong diffuse CK7 staining, whereas all colonic carcinomas were negative for CK7. CK20 stained diffusely and strongly all primary and metastatic colonic carcinomas and was 1+ or 2+ in all mucinous carcinomas, in 67% of serous carcinomas, and in 33% of endometrioid carcinomas. In conclusion, 1) Cdx2 is a highly sensitive (100%) marker for colonic carcinoma metastatic to the ovary; 2) Cdx2 is more specific than CK20 as it is not expressed by serous and endometrioid carcinomas; and 3) a limited panel of Cdx2 and CK7 helps in distinguishing colonic carcinomas metastatic to the ovaries (Cdx2+/CK7-) from primary ovarian serous (Cdx2-/CK7+), endometrioid (Cdx2-/CK7+), and mucinous (Cdx2+/CK7+) carcinomas.

Topics: Biomarkers, Tumor; Carcinoma; CDX2 Transcription Factor; Colonic Neoplasms; Diagnosis, Differential; Female; Homeodomain Proteins; Humans; Immunohistochemistry; Intermediate Filament Proteins; Keratin-20; Keratin-7; Keratins; Ovarian Neoplasms; Sensitivity and Specificity; Trans-Activators

Distinguishing primary cutaneous adnexal neoplasms (PCANs) from metastatic carcinomas (MCs) can be difficult. We study the utility of p63, CK 5/6, CK 7, and 20 expression in PCAN vs. MC.. Twenty-one PCAN with sweat gland differentiation (six benign, 15 malignant), one sebaceous carcinoma, and 15 MC (14 adenocarcinomas, one urothelial carcinoma) to skin were retrieved from the pathology files. Immunostains for p63, CK 5/6, CK 7, and CK 20 were performed and graded as follows: 1, <10; 2, 11-50; and 3 >50% of tumor cells stained.. Twenty of 22 PCAN expressed p63 and CK 5/6. Four of 15 and two of 15 MC were positive for CK 5/6 and p63, respectively. Thirteen of 22 PCAN and 13 of 15 MC were positive for CK 7, respectively. All PCAN were negative for CK 20, two of 15 MC were positive. The sensitivity and specificity for the diagnosis of PCAN were 91 and 73% for CK 5/6, 91 and 100% for p63, and 60 and 13% for CK 7, respectively.. For distinguishing PCAN from MC: (1) positivity for p63 and CK 5/6 are relatively specific and sensitive for PCAN, (2) CK 7 and 20 are neither sensitive nor specific, and (3) CK 7 positivity in PCAN was focal with a specific pattern in contrast to the diffuse positivity for MC.

Topics: Biomarkers, Tumor; Carcinoma; Fluorescent Antibody Technique, Indirect; Humans; Keratins; Membrane Proteins; Neoplasms, Adnexal and Skin Appendage; Retrospective Studies; Skin Neoplasms

This investigation, though initially designed to examine the possible influence of the Bcl-2 protein on the node-metastasizing capacity of breast carcinomas, was amplified to study the expression of this anti-apoptotic protein in normal breast lobules and hyperplastic lesions. We examined paraffin sections of 508 breast carcinomas, stained for Bcl-2, estrogen (ER) and progesterone receptors (PgR) and epithelial membrane antigen, and occasionally for other antigens as well. Only a few cells showing a strong Bcl-2 positivity spotted the tubulo-lobular units of normal resting glands, whereas such cells were relatively numerous in atrophic lobules, and very scarce in the terminally differentiated lactating breast. Columnar and usual types of hyperplasia were exclusively, or almost exclusively, composed of Bcl-2(+), ER(+) and PgR(+) cells. The foci of carcinoma in situ and those of invasive carcinomas were respectively 83% and 66% positive for Bcl-2 in at least 25% of their cells. Even among the invasive carcinomas, Bcl-2(+) cases included 83% and 87% of the ER(+) and PgR(+) cases, respectively (p=0.0001). Though there was a statistically significant inverse relation between Bcl-2 and tumor grade (p=0.0001), no significant association was found between Bcl-2 and lymph node stage. In conclusion, we suggest that normal, hyperplastic and neoplastic breast epithelial cells expressing the anti-apoptotic protein Bcl-2 are immature cells that ought to form part of the stem-cell subpopulation, which is committed to the development and to the maintenance of the normal gland and which gives rise to hyperplastic and neoplastic disorders when its proliferation is deregulated. In ductal proliferative changes Bcl-2 assays may be useful for diagnostic but not for prognostic purposes.

Topics: Aged; Apoptosis; Breast; Breast Neoplasms; Carcinoma; Cell Division; Gene Expression Regulation, Neoplastic; Humans; Hyperplasia; Immunohistochemistry; Keratins; Middle Aged; Neoplasm Metastasis; Proto-Oncogene Proteins c-bcl-2; Receptors, Estrogen; Receptors, Progesterone; Stem Cells

Cytokeratins (CKs) have been recognized for >20 years as structural marker proteins specific for epithelial cells. Recent expression profiling analyses indicate, however, that CK down-regulation may occur in breast cancer.. Here we evaluated the expression pattern of CK18 by immunohistochemical analysis of primary breast carcinomas (n = 1458) spotted on a high-density tissue microarray. The findings were correlated to histopathological risk factors and clinical outcome.. Down-regulation of CK18 (as compared to normal breast tissue) was observed in 25.4% of the tumors with a lower rate in lobular carcinomas (17.0%) than in ductal carcinomas (25.4%) or other histological entities (32.5%). CK down-regulation was significantly correlated to advanced tumor stage and high grade but not to axillary lymph node status. Kaplan-Meier survival analysis revealed CK18 as a prognostic indicator of overall survival (P = 0.015) and cancer-specific survival (P = 0.005).. Down-regulation of the luminal CK18 is not rare and a clinically relevant event in breast cancer. This finding has important implications for the use of CK18 as epithelial tumor marker. The correlations with clinical follow-up suggest that CK18 might suppress tumor progression.

Topics: Aged; Biomarkers, Tumor; Breast Neoplasms; Carcinoma; Carcinoma, Ductal; Carcinoma, Lobular; Disease Progression; Down-Regulation; Humans; Immunohistochemistry; Keratins; Lymphatic Metastasis; Middle Aged; Prognosis; Protein Array Analysis; Risk Factors; Time Factors

Based on clinical and histologic features, differentiating metastatic carcinomas from benign or malignant meningiomas usually is not difficult. Occasionally, however, in some patients without a clinical history of carcinoma, malignant meningiomas can morphologically simulate metastatic carcinoma, necessitating an immunohistochemical study for cytokeratin to make a correct diagnosis. However, the utility of immunohistochemical markers to separate malignant meningioma from metastatic carcinoma has not been investigated. The immunoperoxidase method with antigen retrieval was used to characterize the expression of three cytokeratins (AE1/AE3, CAM 5.2, and Pan cytokeratin), EMA, CEA, Ber-EP4, CD 15, and B72.3 in 12 previously diagnosed malignant meningiomas, 20 benign meningiomas, and 20 metastatic carcinomas. Cytokeratin expression was detected in 75% of malignant meningiomas, 0% of benign meningiomas, and 100% of metastatic carcinomas. While epithelial markers of Ber-EP4, CEA, B72.3 and CD-15 were positive in 90, 80, 70 and 65% of the metastatic carcinoma, respectively, they were negative in all 12 malignant meningioma examined. Vimentin immunoreactivity was seen in all benign and malignant meningiomas, and in 20% of metastatic carcinomas. Our results indicated that cytokeratin is not a reliable immunohistochemical marker to separate a malignant meningioma from metastatic carcinoma. A panel of epithelial markers including Ber-EP4, CEA, B72.3 and CD-15, and vimentin may be needed to separate malignant meningioma from metastatic carcinoma. Cytokeratin expression can be a potential pitfall for confusing a malignant meningioma with a metastatic carcinoma.

Topics: Antibodies, Neoplasm; Biomarkers, Tumor; Carcinoembryonic Antigen; Carcinoma; Diagnosis, Differential; Humans; Immunohistochemistry; Keratins; Lewis X Antigen; Meningeal Neoplasms; Meningioma; Mucin-1; Predictive Value of Tests; Vimentin

Mixed tumors of the vagina (MTsV) are rare benign neoplasms characterized by an admixture of well-differentiated epithelial cells and stromal-type cells in various proportions. In contrast to mixed tumors in other anatomic sites, the histogenesis of the vaginal tumors is unclear. We studied the immunohistochemical profile of 13 examples to explore their histogenesis and determine whether their immunohistochemical profile might be useful in the differential diagnosis. The panel of antibodies used and the number of cases studied were: AE1/3 (12), cytokeratin 7 (CK7) (13), cytokeratin 20 (CK20) (13), epithelial membrane antigen (EMA) (13), muscle actin (MA) (12), desmin (11), h-Caldesmon (13), CD10 (13), CD34 (11), CD99 (8), and S-100 (7). Eight out of 12 tumors were positive for AE1/3, 7/13 for CK7, 2/13 for CK20, and 6/13 for EMA. MA was positive in 11/12 mixed tumors, desmin in 10/11 tumors and h-Caldesmon in 5/13. All tumors were extensively positive for CD10; CD34 was positive in 7/11; and none out of eight tumors showed membranous CD99 staining. Focal S-100 immunoreactivity was seen in 1/7 tumors. These results show that MTsV coexpress epithelial and mesenchymal markers. The expression of muscle actin (usually extensive), and focal desmin and h-Caldesmon positivity suggests the presence of a smooth muscle or myoepithelial component; however, the S-100 negativity and diffuse CD10 expression argue against it. Positivity for muscle markers does not help distinguish MTsV from smooth muscle or skeletal muscle tumors. The frequent expression of CD10 negates its use in the differential diagnosis with endometrial stromal tumors, and the CD10 and CD34 expression suggests that mixed tumors may arise from a primitive pluripotential cell. MTsV are positive for h-Caldesmon and CD10, two markers that have been used in gynecologic pathology primarily to aid in establishing the smooth muscle or endometrial stromal phenotype of a neoplasm.

Topics: 12E7 Antigen; Actins; Antigens, CD; Antigens, CD34; Calmodulin-Binding Proteins; Carcinoma; Cell Adhesion Molecules; Desmin; Diagnosis, Differential; Female; Humans; Immunohistochemistry; Intermediate Filament Proteins; Keratin-20; Keratin-7; Keratins; Mucin-1; Muscle, Smooth; Neprilysin; S100 Proteins; Vaginal Neoplasms

Topics: Aged; Biopsy, Fine-Needle; Bronchiectasis; Carcinoma; Carcinoma, Basal Cell; Diagnosis, Differential; Female; Giant Cells; Granuloma; Humans; Immunohistochemistry; Keratins; Lymph Nodes; Lymphatic Metastasis; Nasopharyngeal Neoplasms; Neoplasms, Multiple Primary; Skin Neoplasms

A broad histomorphologic spectrum of ampullary carcinomas of Vater make a reproducible histologic classification difficult. Using cytokeratin immunohistochemistry, we present a new classification of ampullary carcinomas and analyze their clinical significance. Fifty-five invasive carcinomas of Vater's ampulla were histologically classified into pancreaticobiliary, intestinal, and other types. Serial sections of all carcinoma specimens were additionally stained with antibodies to cytokeratins (CK7, CK20), apomucins (MUC1, MUC2, MUC5AC), CEA, CA19-9, Ki67, and p53. Follow-up of patients from 4 months to 22 years after surgery (mean interval, 51.6 months) was evaluated. Most carcinomas of the ampulla of Vater were of immunohistochemically pancreaticobiliary type (iPT, CK7+, CK20-; 54.5%) or intestinal type (immunohistochemically intestinal type [iIT], CK7-, CK20+; 23.6%). Some carcinomas of immunohistochemically "other" type (iOT both CK7+ and CK20+ or CK7- and CK20-; 21.8%) had precursor lesions of iIT or iPT. Carcinomas positive for MUC2 or CEA were associated with iIT (MUC2, P < 0.001; CEA, P = 0.003), whereas MUC5AC-positive carcinomas were related to iPT (P = 0.005). Our classification based on cytokeratin-immunohistochemistry correlated well with the histologic classification according to published criteria (kappa-coefficient = 0.398; P < 0.001). Furthermore, histologically unusual types could be histogenetically related to pancreaticobiliary duct mucosa or intestinal mucosa. Therefore, all 4 signet-ring cell carcinomas were iIT carcinomas. Thus, cytokeratin immunohistochemistry allows a reproducible, histogenetically based categorization of ampullary carcinomas. However, neither histopathologic nor immunohistochemical subgroups significantly correlated with clinical outcome in our German collective. The overall survival was significantly shorter in males (P = 0.032) and patients with positive nodal stage (N1 < N0; P = 0.0025).

Topics: Aged; Ampulla of Vater; CA-19-9 Antigen; Carcinoembryonic Antigen; Carcinoma; Carcinoma, Signet Ring Cell; Common Bile Duct Neoplasms; Female; Follow-Up Studies; Gastric Mucins; Humans; Immunohistochemistry; Intermediate Filament Proteins; Keratin-20; Keratin-7; Keratins; Ki-67 Antigen; Male; Middle Aged; Mucin 5AC; Mucin-1; Mucin-2; Mucins; Neoplasm Staging; Tumor Suppressor Protein p53

Induced sputum, in contrast to bronchoscopic biopsies and lavages, is an easily obtained source of biological specimens. However, obtaining abnormal exfoliated cells for detailed molecular studies is limited because respiratory epithelial cells comprise only about 1% of sputum cell populations.. We developed a multiparameter flow sorting strategy to purify epithelial cells from nonepithelial sputum cells, using anti-cytokeratin antibody AE1/AE3 to recognize human epithelial cells and DAPI to stain DNA. We excluded cells with a high degree of side-scatter, which were composed predominantly of squamous cells and contaminating macrophages. The remaining cytokeratin-positive respiratory epithelial cells were then sorted based on anti-cytokeratin (PE) vs DNA (DAPI) parameters.. In this proof of principle study, the AE1AE3 cytokeratin/DNA flow sorting strategy enriched rare diploid respiratory epithelial cells from an average of 1.1% of cells in unsorted induced sputum samples to average purities of 42%. Thus, AE1AE3 flow-sorting results in a 38-fold enrichment of these cells.. We report a multiparameter flow cytometric assay to detect and enrich rare respiratory epithelial cells from induced sputum samples to average purities of 42%. With further development, this methodology may be useful as part of a molecular screening approach of populations at high risk for lung cancer.

Topics: Carcinoma; Cell Separation; Epithelial Cells; Flow Cytometry; Humans; Keratins; Lung Neoplasms; Sputum

Cyfra 21-1 is a recognised marker for epidermoid lung and head and neck carcinomas oriented to the cytokeratin 19 that is expressed particularly in malignant epithelial cells. The aims of this study were to evaluate the importance of the use of this marker in nasopharyngeal carcinoma (NPC). Our prospective study interested 41 patients (33M/8F) with a mean age of 44 years (13 to 70) with 8 of them aged less than 30 years, presenting a nasopharyngeal carcinoma histologically confirmed from September 1999 to March 2000 and 45 healthy controls without evidence neoplasm. Undifferentiated forms represent 90.2% of cases and lesions are staged T2, T3 and T4 in 2.4%, 36.6% and 61% of cases, while N1, N2 and N3 represent 9.8%, 26.8% and 41.5% of cases. A blood sample was collected from each patient and control before any treatment, as well as controls to measure Cyfra 21-1 by immunoenzymatic assay, 2 groups of patients were selected after a period varying from 4 to 37 months with a median of 29 months: 27 patients with favourable evolution (without evidence of disease after initial treatment), 12 patients with non favourable evolution (1 death, 2 cases of loco-regional relapse and 9 patients with metastatic disease). 2 patients were lost to follow-up. The results showed that the mean serum Cyfra 21-1 values were significantly higher in patients with NPC than those in controls (p = 0.001). A significant correlation was found between the serum Cyfra 21-1 level before treatment and the clinical outcome of patients (p = 0.0009). Patients having a favourable evolution have the lowest level. Seric level of Cyfra 21-1 at diagnosis of NPC may play a predictive role to evaluate the risk of metastatic disease and prognosis.

Topics: Adolescent; Adult; Aged; Antigens, Neoplasm; Biomarkers, Tumor; Carcinoma; Case-Control Studies; Female; Humans; Immunoenzyme Techniques; Keratin-19; Keratins; Male; Middle Aged; Nasopharyngeal Neoplasms; Neoplasm Recurrence, Local; Prognosis; Prospective Studies; Sensitivity and Specificity; Tunisia

Alterations in gene expression accompany cell-type-specific differentiation. In complex systems where functional differentiation depends on the organization of specific cell types into highly specialized structures (tissue morphogenesis), it is not known how epigenetic mechanisms that control gene expression influence this stepwise differentiation process. We have investigated the effect of DNA methylation, a major epigenetic pathway of gene silencing, on the regulation of mammary acinar differentiation. Our in vitro model of differentiation encompasses human mammary epithelial cells that form polarized and hollow tissue structures (acini) when cultured in the presence of basement membrane components. We found that acinar morphogenesis was accompanied with chromatin remodeling, as shown by alterations in histone 4 acetylation, heterochromatin 1 protein, and histone 3 methylated on lysine 9, and with an increase in expression of MeCP2, a mediator of DNA-methylation-induced gene silencing. DNA hypomethylation induced by treatment with 5-aza-2' deoxycytidine during acinar differentiation essentially prevented the formation of apical tissue polarity. This treatment also induced the expression of CK19, a marker of cells that are in a transitional differentiation stage. These results suggest that DNA methylation is a mechanism by which mammary epithelial differentiation is coordinated both at the tissue and cellular levels.

Topics: Acetyltransferases; Breast Neoplasms; Carcinoma; Cell Differentiation; Cell Polarity; Cells, Cultured; Chromatin Assembly and Disassembly; Chromobox Protein Homolog 5; Chromosomal Proteins, Non-Histone; DNA; DNA Methylation; DNA-Binding Proteins; Epigenesis, Genetic; Epithelial Cells; Female; Gene Expression Regulation, Developmental; Gene Silencing; Histone Acetyltransferases; Histones; Humans; Keratins; Mammary Glands, Human; Methyl-CpG-Binding Protein 2; Repressor Proteins; Up-Regulation

Substantial evidence supports that detailed analysis of the regional lymphatics will identify previously unrecognized micrometastatic disease in colorectal cancer. In order to determine whether the sentinel lymph node(s) (SLNs) harvested by ex vivo lymphatic mapping in node-negative colorectal cancer (CRC) are the most likely node(s) to harbor micrometastatic disease, we examined all nodes in CRC specimens in an identical fashion.. One hundred twenty-four specimens from patients with colorectal cancer were delivered to pathology in the fresh state and underwent ex vivo sentinel lymph node mapping. If negative by routine hematoxylin and eosin (H&E) analysis, the SLNs and non-SLNs were subjected to further analysis by level section H&E and immunohistochemical (IHC) analysis.. A mean of 30 nodes were harvested (range, 5-111). Fifty-one patients (41%) were found to be node-positive by routine H&E analysis. SLNs were identified in all but three specimens. A total of 2177 nodes were analyzed from the 66 H&E node-negative specimens (1883 non-SLNs and 294 SLNs). Overall, metastases were identified in 13 of 278 SLNs and in only 5 of 1829 non-SLNs (P <.001). Only 5 of 66 patients (7.5%) had evidence of metastatic disease in non-SLNs when the SLNs were negative. Thirteen apparently node-negative patients (19.3%) were upstaged by IHC analysis of the SLNs (P =.04).. If the SLN is negative by both H&E and IHC analysis, the probability of finding metastases in a non-SLN is remote. If microstaging is demonstrated to be prognostically relevant, focused examination should be of the SLN(s).

Topics: Adult; Aged; Aged, 80 and over; Carcinoma; Colorectal Neoplasms; Female; Hematoxylin; Humans; Immunohistochemistry; Keratins; Lymph Nodes; Lymphatic Metastasis; Male; Middle Aged; Neoplasm Staging

In order to evaluate the significance of altered expression of mucin and cytokeratin during gallbladder carcinogenesis, we characterized the expressional profiles of MUC1, MUC2, MUC5AC, MUC6, CK7 and CK20 in 33 normal mucosa, 31 adenomas, 55 dysplasias and 131 carcinomas of the gallbladder. In normal gallbladder mucosa, the expressions of MUC5AC and MUC6 were diffuse and MUC1 expression was absent. However, in adenomas, dysplasias and carcinomas, the expressions of MUC5AC and MUC6 tended to decrease, whereas MUC1 expression was elevated. MUC2 and CK20 were infrequently expressed in all of the gallbladder epithelia, but adenomas expressing MUC2 and/or CK20 were more frequently associated with carcinomas and showed a higher grade of atypia than those without these antigens. In carcinomas, MUC1 expression was related to invasive growth, lymph node metastasis and a non-papillotubular type, whereas MUC6 expression was related to non-invasive growth. CK7 was diffusely expressed in almost all lesions, but carcinomas with a loss of CK7 expression showed poor survival. In conclusion, normal gallbladder mucosa has a gastric phenotype, but during carcinogenesis and tumor progression, the gastric phenotype is gradually lost and the aberrant expression of MUC1 occurs. The intestinal phenotype is not common in the gallbladder.

Topics: Adenoma; Biomarkers, Tumor; Carcinoma; Cell Count; Gallbladder Neoplasms; Hospitals, University; Humans; Immunoenzyme Techniques; Keratins; Mucins; Phenotype; Survival Rate

Patients with undifferentiated nasopharyngeal carcinoma (NPC) have elevated serum levels of CYFRA 21-1 (CYFRA), ferritin, and beta-2-microglobulin (beta2M) compared with healthy control individuals. The prognostic value of these markers has never been validated prospectively.. Paired serum samples from 160 patients with newly diagnosed, nonmetastatic, undifferentiated NPC were collected before radiotherapy (RT) and at 4-6 weeks after the completion of RT. Pre-RT and post-RT levels of serum CYFRA, ferritin, and beta2M were analyzed and correlated with overall survival (OS), progression-free survival (PFS), time to locoregional recurrence, (TLR) and time to distant recurrence (TDR). The results of pre-RT and post-RT plasma Epstein-Barr virus (EBV) DNA levels available from a previous study were included in a Cox regression model together with age, tumor (T) classification, and lymph node (N) classification.. Sixty percent of patients had International Union Against Cancer Stage III-IV disease. At a median follow-up of 116 weeks (range, 37-239 weeks), 38 patients had disease progression. On multivariate analysis, pre-RT CYFRA and post-RT EBV DNA levels were independent predictors of poor OS, post-RT EBV DNA level and N classification predicted poor PFS and TDR; and only T classification predicted TLR. Patients who had pre-RT CYFRA levels > or = 1.5 U/mL were more likely to die (hazard ratio, 1.18; 95% confidence interval, 1.10-1.26) compared with patients who had pre-RT CYFRA levels < 1.5 U/mL. There were no associations between age, post-RT CYFRA levels and pre-RT or post-RT serum ferritin and beta2M levels, and the survival and recurrence rates on multivariate analysis.. Serum CYFRA levels taken before RT predicted reduced survival in patients with nonmetastatic, undifferentiated NPC who underwent RT.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Antigens, Neoplasm; beta 2-Microglobulin; Biomarkers, Tumor; Carcinoma; DNA, Viral; Female; Ferritins; Herpesvirus 4, Human; Humans; Keratin-19; Keratins; Male; Middle Aged; Multivariate Analysis; Nasopharyngeal Neoplasms; Predictive Value of Tests; Prognosis; Prospective Studies; Survival Analysis

We report a 75-year-old male with anaplastic carcinoma in an extrathyroid area. Thyroid remained unchanged. The patient is alive without incident of tumor recurrence at 3.5 years after total resection and at 5 years after initial symptom. The tumor developed between the sternocleidomastoid muscle and common carotid artery, and was completely separated from the thyroid. The tumor location was consistent with a branchial cyst. The tumor consisted of two parts; an upper solid tumor and a deep cystic tumor. The former showed anaplastic carcinoma with osteoclast-like giant cells. The latter was consistent with thyroid papillary carcinoma. The center was intermingled with these two carcinomas. Anaplastic carcinoma cells were positive for vimentin and papillary carcinoma cells were positive for keratin, thyroglobulin, and thyroid transcription factor-1. These results remain insufficient to find any conclusions concerning the tumor nature; either ectopic thyroid carcinoma arising from a branchial cyst or occult thyroid carcinoma metastasis. This is rare case in which thyroid anaplastic carcinoma transformed from papillary carcinoma in an extrathyroid area.

Topics: Aged; Branchioma; Carcinoma; Carcinoma, Papillary; Cell Transformation, Neoplastic; Diagnosis, Differential; Humans; Keratins; Male; Nuclear Proteins; Osteoclasts; Thyroglobulin; Thyroid Neoplasms; Thyroid Nuclear Factor 1; Tomography, X-Ray Computed; Transcription Factors; Vimentin

We evaluated the diagnostic usefulness of the 34betaE12-p63 cocktail, compared with 34betaE12 and p63 used alone, in 34 prostate needle biopsy (NBXs) and 3 transurethral resection specimens containing atypical glandular proliferations and in 18 NBXs containing unequivocal prostate carcinoma (PCa). Staining intensity; percentage of basal cells staining in benign, atypical, and malignant glands; number of benign glands lacking basal cell staining; and staining variance were analyzed. All NBXs with unequivocal PCa were negative with all 3 markers. Diagnoses were as follows for the atypical cases after staining for the 3 markers: PCa, 9; postatrophic hyperplasia, 12; high-grade prostatic intraepithelial neoplasia (HGPIN), 5; atypical adenomatous hyperplasia, 6; benign atypical proliferations, 4; and HGPIN with adjacent small atypical acinar proliferation suggestive of PCa, 1. The cocktail demonstrated consistently strong staining intensity and improved basal cell staining in morphologically benign and benign atypical glands compared with p63 and 34betaE12 alone; it had the smallest staining variance compared with 34betaE12 (F < 0.0001) and p63 (F = 0.31), although its advantage for resolving individual atypical cases was limited compared with 34betaE12 and p63 alone. Of 37 atypical cases, 1 (3%) additionally was resolved as benign using the cocktail and p63. Because the diagnosis of PCa is supported by lack of basal cell staining, the immunohistochemical analysis with highest possible sensitivity and lowest possible variability is critical to ensure that a negative reaction is true. The cocktail provides a simple, cost-effective improvement in basal cell immunohistochemical analysis of difficult prostate lesions.

Topics: Biomarkers, Tumor; Biopsy, Needle; Carcinoma; DNA-Binding Proteins; Genes, Tumor Suppressor; Humans; Immunohistochemistry; Keratins; Male; Phosphoproteins; Prostate; Prostatic Neoplasms; Staining and Labeling; Trans-Activators; Transcription Factors; Tumor Suppressor Proteins

Histopathologic classification of lung carcinoma is important, as a prognostic factor and in the evaluation of treatment modalities. Although the World Health Organization classification of lung cancer is based on routine microscopy, immunohistochemistry is an important additional aspect in modern pathologic practice. This study examines whether the main histologic types of lung carcinomas are more reliably diagnosed with immunohistochemical technique using antibodies for the lung tissue-specific antigen thyroid transcription factor-1 (TTF-1) and a panel of cytokeratin (CK) antibodies. Forty-five cases of lung cancer (12 squamous cell carcinoma, 13 small cell carcinoma, 11 adenocarcinoma, 9 large cell carcinoma [LCC]/pleomorphic carcinoma) were stained with antibodies to CK CAM5.2, CK5, CK7, CK20, and TTF-1. All 45 cases were positive with CAM5.2, 16 of 45 cases with CK5, 34 of 45 cases with CK7, 4 of 45 cases with CK20, and 29 of 45 with TTF-1. Squamous cell carcinoma (epidermoid carcinoma) had the immunophenotype CK5+/TTF-1-, and at least 20% were also positive with CK7. Most nonepidermoid tumors had the "lung-specific" phenotype CK5-/TTF-1+; all small cell carcinomas had the phenotype CK5-/CK8+/TTF-1+, all adenocarcinomas CK5-/CK7+/TTF-1+ and (more than 50%) of LCC CK5-/CK7+/TTF-1+. Thus, more than 50% of LCCs were of the same phenotype as adenocarcinomas. The immunophenotypes of the main histologic types of lung carcinoma are stable and highly reproducible. However, because of considerable overlapping, immunophenotyping should not be used alone for histopathologic classification of lung cancer, but only as an adjunct to light microscopy. It is also suggested that CK5+ lung carcinomas with basaloid features should be regarded as variants of squamous cell carcinoma and not as LCC.

Topics: Biomarkers, Tumor; Carcinoma; Humans; Immunoenzyme Techniques; Immunophenotyping; Keratins; Lung Neoplasms; Nuclear Proteins; Thyroid Nuclear Factor 1; Transcription Factors

Although immunization with tumor antigens can eliminate many transplantable tumors in animal models, immune effector mechanisms associated with successful immunotherapy of epithelial cancers remain undefined.. Skin from transgenic mice expressing the cervical cancer-associated tumor antigen human papillomavirus type 16 (HPV16) E6 or E7 proteins from a keratin 14 promoter was grafted onto syngeneic, non-transgenic mice. Skin graft rejection was measured after active immunization with HPV16 E7 and adoptive transfer of antigen-specific T cells. Cytokine secretion of lymphocytes from mice receiving skin grafts and immunotherapy was detected by enzyme-linked immunosorbent assay, and HPV16 E7-specific memory CD8+ T cells were detected by flow cytometry and ELISPOT.. Skin grafts containing HPV16 E6-or E7-expressing keratinocytes were not rejected spontaneously or following immunization with E7 protein and adjuvant. Adoptive transfer of E7-specific T-cell receptor transgenic CD8+ T cells combined with immunization resulted in induction of antigen-specific interferon gamma-secreting CD8+ T cells and rejection of HPV16 E7-expressing grafts. Specific memory CD8+ T cells were generated by immunotherapy. However, a further HPV16 E7 graft was rejected from animals with memory T cells only after a second E7 immunization.. Antigen-specific CD8+ T cells can destroy epithelium expressing HPV16 E7 tumor antigen, but presentation of E7 antigen from skin is insufficient to reactivate memory CD8+ T cells induced by immunotherapy. Thus, effective cancer immunotherapy in humans may need to invoke sufficient effector as well as memory T cells.

Topics: Adjuvants, Immunologic; Adoptive Transfer; Animals; Antigen Presentation; Carcinoma; CD8-Positive T-Lymphocytes; Cytokines; Enzyme-Linked Immunosorbent Assay; Flow Cytometry; Gene Expression Regulation, Neoplastic; Graft Rejection; Immunization, Passive; Immunotherapy, Active; Interferon-gamma; Keratin-14; Keratinocytes; Keratins; Mice; Mice, Transgenic; Oncogene Proteins, Viral; Papillomavirus E7 Proteins; Repressor Proteins; Skin Neoplasms; Skin Transplantation

Mammary tumors in mice are categorized by using morphologic and architectural criteria. Immunolabeling for terminal differentiation markers was compared among a variety of mouse mammary neoplasms because expression of terminal differentiation markers, and especially of keratins, provides important information on the origin of neoplastic cells and their degree of differentiation.. Expression patterns for terminal differentiation markers were used to characterize tumor types and to study tumor progression in transgenic mouse models of mammary neoplasia (mice overexpressing Neu (Erbb2), Hras, Myc, Notch4, SV40-TAg, Tgfa, and Wnt1), in spontaneous mammary carcinomas, and in mammary neoplasms associated with infection by the mouse mammary tumor virus (MMTV).. On the basis of the expression of terminal differentiation markers, three types of neoplasm were identified: first, simple carcinomas composed exclusively of cells with a luminal phenotype are characteristic of neoplasms arising in mice transgenic for Neu, Hras, Myc, Notch4, and SV40-TAg; second, 'complex carcinomas' displaying luminal and myoepithelial differentiation are characteristic of type P tumors arising in mice transgenic for Wnt1, neoplasms arising in mice infected by the MMTV, and spontaneous adenosquamous carcinomas; and third, 'carcinomas with epithelial to mesenchymal transition (EMT)' are a characteristic feature of tumor progression in Hras-, Myc-, and SV40-TAg-induced mammary neoplasms and PL/J and SJL/J mouse strains, and display de novo expression of myoepithelial and mesenchymal cell markers. In sharp contrast, EMT was not detected in papillary adenocarcinomas arising in BALB/cJ mice, spontaneous adenoacanthomas, neoplasms associated with MMTV-infection, or in neoplasms arising in mice transgenic for Neu and Wnt1.. Immunohistochemical profiles of complex neoplasms are consistent with a stem cell origin, whereas simple carcinomas might originate from a cell committed to the luminal lineage. In addition, these results suggest that the initiating oncogenic events determine the morphologic features associated with cancer progression because EMT is observed only in certain types of neoplasm.

Topics: Animals; Biomarkers, Tumor; Carcinoma; Cell Differentiation; Disease Models, Animal; Disease Progression; Epithelial Cells; Female; Immunohistochemistry; Intercellular Signaling Peptides and Proteins; Keratins; Mammary Neoplasms, Experimental; Mice; Mice, Inbred BALB C; Mice, Inbred C3H; Mice, Transgenic; Proteomics; Proto-Oncogene Proteins c-myc; Wnt Proteins; Wnt1 Protein

P63, a homologue of p53, was recently identified as a useful basal cell-specific marker. We compared the sensitivity and specificity of p63 with the widely used high-molecular-weight keratin 34betaE12 for the diagnosis of prostate carcinoma in needle biopsies. We selected 100 consecutive prostate carcinoma diagnosed by needle biopsies with an adequate number of cancerous glands on the slide. We chose 1 representative hematoxylin and eosin-stained slide from each case and gave it a Gleason score. The same paraffin block was retrieved for 34betaE12 and p63 stains. We compared staining patterns of 34betaE12 and p63 on both malignant glands and benign glands and recorded basal cell density (percentage of basal cells with positive staining in the benign glands). The cases were divided into 3 groups according to the Gleason score: 5 to 6 (31 cases), 7 (46 cases), and 8 to 10 (23 cases). In 20 cases, focal and patchy staining in a basal cell distribution in malignant glands (range, 1%-20%; mean, 6.6%) was demonstrated (19 by both stains and 1 by 34betaE12 only). In 1 case with a Gleason score of 9, the cancer cells, not the basal cells, were stained focally by p63 but not by 34betaE12. Higher-grade tumors demonstrated higher numbers of malignant glands with basal cell staining (1.65% for Gleason 7, 1.26% for Gleason 8-10, compared with 0.42% for Gleason 5-6). The overall specificity of the absence of basal cell staining in the malignant glands for 34betaE12 and p63 was 98.63% and 98.60%, respectively. In 17 cases, both stains revealed total absence of basal cell staining in some benign glands (range, 1%-10%; mean, 3.5%). The overall sensitivity in identifying basal cells in benign glands was 99.48% and 99.44% for 34beta12 and p63, respectively. Basal cell density was higher for 34betaE12 in comparison with p63 (92% vs. 87%). For diagnosing prostate carcinoma in the needle biopsies, p63 is as specific and sensitive Hospital as 34betaE12 and therefore can be used as a complementary basal cell-specific stain for 34betaE12 in difficult cases.

Topics: Biomarkers, Tumor; Biopsy, Needle; Carcinoma; DNA-Binding Proteins; Genes, Tumor Suppressor; Humans; Keratins; Male; Phosphoproteins; Prostate; Prostatic Neoplasms; Trans-Activators; Transcription Factors; Tumor Suppressor Proteins

Diagnostic utility of E-cadherin (E-CD) and cytokeratin (CK) subtype profiling in effusion cytology was investigated, employing immunocytochemistry on cellblock sections available from 211 metastatic carcinomas (MC), 6 mesotheliomas and 73 reactive mesothelial hyperplasias (MH). E-CD and monoclonal carcinoembryonic antigen (mCEA) stained 85% (120/141) and 65% (138/211) of MC, respectively. E-CD staining of MC was frequently heterogeneous (76/120) and absent in all anaplastic carcinomas (0/2). E-CD stained none (0/57) of MH while mCEA and epithelial membrane antigen (EMA) stained 12% (9/73) and 32% (16/32) of MH, respectively. Of 6 mesotheliomas, E-CD focally stained in 2 while mCEA stained none and EMA stained all. CK20 and CK17 stained none of MH or mesotheliomas. CK20 stained 15% of MC and CK 17 stained 22% of MC. CK5/6 and high molecular weight CK stained all mesotheliomas, 56% and 88% of MH, 26% and 39% of MC, respectively. MC showed predominant CK7+/20-expression, with the exceptions of MC from mucinous type of colon/rectum and ovary showing predominant CK20 positive. E-CD may be a useful positive marker for MC in effusion cytology, although it may focally stain in some mesotheliomas. Any positive staining for CK20 of MC suggests MC from the gastrointestinal tract or ovary among others.

Topics: Biomarkers, Tumor; Cadherins; Carcinoma; Diagnosis, Differential; Epithelium; Humans; Hyperplasia; Immunohistochemistry; Keratins; Mesothelioma

Diagnosis of renal epithelial tumours of adult is often easily made. Nevertheless, it can be difficult to distinguish clear cell carcinoma (CCC) and chromophobe carcinoma (CCHRO), or the eosinophilic variants of CCC and CCHRO with papillary carcinoma (CTP) and oncocytoma (ONCO). The objective is to study and validate immunohistochemical phenotypes of these tumours and to evaluate if they are helpful and to define a diagnostic strategy.. 310 tumours (75 CCC, 89 CTP, 50 CCHRO and 96 ONCO) were collected and put on 4 tissue-arrays blocks. Immunohistochemical stainings were performed with some usual antibodies: pancytokeratin AE1-AE3, EMA, vimentin, CD10, CK7, CK20 and RCC (Renal Cell Carcinoma).. Pancytokeratin AE1-AE3 is expressed mainly in CTP (82.5%). The cytoplasmic staining of EMA is seen in almost all CCHRO (98%) and more than half of CTP (57%). Vimentin is rather specific of CCC (54.5%) and CTP (85%) whereas it is negative in ONCO and CCHRO. CD10 is expressed in the majority of CCC (86.5%) and in some of CTP and CCHRO 65 and 39% respectively. CK7 is rather specific of CTP and CCHRO with 79 and 81.5% of positivity rate. Based on statistical analysis, we have built a diagnostical tree allowing to distinguish 79% of tumours using only three antibodies: CK7, vimentin and CD10.. CCC are CK7-/Vim-/CD10+ or CK7-/Vim+; CTP are CK7+/Vim+; CCHRO are CK7+/Vim-; and ONCO CK7-/Vim-/CD10-. In the oncocytoma/chromophobe group, ONCO are more often CK7-/EMA- and CCHRO CK7+/EMA+.

Topics: Adenoma, Oxyphilic; Adult; Aged; Aged, 80 and over; Carcinoma; Carcinoma, Papillary; Carcinoma, Renal Cell; Diagnosis, Differential; Female; Humans; Immunohistochemistry; Keratin-7; Keratins; Kidney Neoplasms; Male; Middle Aged; Neoplasms, Glandular and Epithelial; Neprilysin; Phenotype; Reproducibility of Results; Vimentin

The purpose of the study was to establish the subcutaneous model of human extrahepatic bile duct carcinoma in nude mice so as to provide a suitable model for the study of extrahepatic bile duct carcinoma. Surgical specimens of the patient with extrahepatic bile duct carcinoma were transplanted into the subcutaneous layer of nude mice. Growth curve of transplanted tumors was drawn and its morphological and biological characteristics, as well as choromosome were observed. A well differentiated mucinous adenocarcinoma model of human bile duct carcinoma in nude mice, designated as HBDCM1-ZSH (Human Bile Duct Carcinoma Model No. 1 established by Zhong Shan Hospital in April, 2001), was established via subcutaneous transplantation of the surgically resected tumor from a 56-year-old Chinese man. HBDCM1-ZSH has been maintained for 13 passages and exhibited 98.1% transplantability. Mean latent periods were 26 days. Transplanted tumors exhibited the characteristics of the original tumor in morphology and biology. Chromosomal analysis revealed numerical abnormalities ranging from 67 to 84. HBDCM1-ZSH expressed carcinoembryonic antigen (CEA), carbohydrate antigen (CA)19-9, cytokeratin (CK7, CK19, CK20), PCNA, AB and PAS. In conclusion, HBDCM1-ZSH is similar to human extrahepatic bile duct carcinoma and provides an applicable animal model for research on extrahepatic bile duct carcinoma.

Topics: Aminosalicylic Acid; Animals; Bile Duct Neoplasms; Biomarkers, Tumor; CA-19-9 Antigen; Carcinoembryonic Antigen; Carcinoma; Chromosome Banding; Chromosome Mapping; Disease Models, Animal; DNA; Humans; Immunohistochemistry; Intermediate Filament Proteins; Karyotyping; Keratin-20; Keratin-7; Keratins; Kinetics; Male; Mice; Mice, Inbred BALB C; Mice, Nude; Microscopy, Electron; Middle Aged; Neoplasm Transplantation; Proliferating Cell Nuclear Antigen; Radioimmunoassay; Time Factors; Tumor Cells, Cultured

The presence of isolated tumor cells (ITC) in the bone marrow at the time of primary diagnosis indicates an increased risk for subsequent development of distant metastases in various solid tumors. This study evaluates the prevalence and prognostic significance of ITC in patients with primary carcinoma of the cervix uteri.. We immunocytochemically analyzed bone marrow aspirates of 130 patients with newly diagnosed carcinoma of the cervix uteri for the presence of cytokeratin(CK)-positive cells from May 1994 to January 2001. We used a quantitative immunoassay with the monoclonal anti-CK antibody A45-B/B3 and evaluated 2 x 10(6) bone marrow cells per patient. Patients were followed prospectively for a median of 43 (range, 1-85) months.. Isolated tumor cells were found in the bone marrow of 38 patients (29%). The presence of ITC did not correlate with the International Federation of Gynecology and Obstetrics (FIGO) tumor stage (P = 0.61), pelvic and paraaortal lymph node involvement (P = 0.41), histopathologic grading (P = 0.67), the histologic type of the carcinoma (P = 0.93), invasion of lymph nodes (P = 0.93) and blood vessels (P = 0.92), or with menopausal status (P = 0.17). The bone marrow status at the time of primary diagnosis did not correlate with the overall survival as estimated by Kaplan-Meier analysis (P = 0.30). However, distant metastases occurred in 5% of the patients (n = 5) with negative bone marrow status and in 15% of the patients (n = 6) with positive bone marrow status (P = 0.054). The median distant disease-free survival period was 78 months (95% confidence interval 73-82) in patients with negative bone marrow status and 72 months (95% CI 61-82) in patients with positive bone marrow status (P = 0.051). Multivariate analysis revealed the presence of ITC as a significant, independent risk factor for the subsequent development of distant metastases (relative risk 3.6, P = 0.046).. Despite the locoregional predominance of cervical carcinoma at the time of primary diagnosis, the presence of ITC in the bone marrow indicates an increased risk for the development of distant metastases. This information may prove useful to stratify patients for systemic treatment.

Topics: Adult; Bone Marrow Neoplasms; Carcinoma; Combined Modality Therapy; Female; Humans; Immunoenzyme Techniques; Keratins; Lymphatic Metastasis; Middle Aged; Neoplasm Staging; Prognosis; Proportional Hazards Models; Risk Factors; Survival Analysis; Uterine Cervical Neoplasms

Topics: Aged; Aneuploidy; Biopsy; Carcinoma; Diagnosis, Differential; Diploidy; Female; Flow Cytometry; Humans; Keratins; Male; Middle Aged; Palatal Neoplasms; S100 Proteins; Salivary Ducts; Salivary Gland Neoplasms; Salivary Glands, Minor

Several immunohistochemical markers, among them calretinin, thrombomodulin (CD141), keratin 5, and mesothelin, have been documented or suggested as useful markers for positive identification of mesothelioma and to differentiate it from pulmonary adenocarcinoma; numerous studies have documented their variable specificity. However, expression of these markers in other types of lung carcinomas has not been systematically explored, although these tumors can enter in the differential diagnosis of mesothelioma. In this study we immunohistochemically evaluated 596 lung carcinomas of different types for the four above-mentioned mesothelioma markers, all of which reacted with a great majority of epithelioid mesotheliomas studied for comparison. Calretinin expression was common in giant cell carcinomas (67%), small cell carcinomas (49%), and large cell carcinomas (38%), whereas it was rare in usual adenocarcinomas but slightly more common in those with neuroendocrine differentiation (11% and 17%, respectively). Thrombomodulin was present in all keratinizing squamous carcinomas and the great majority (87%) of nonkeratinizing tumors in a membrane-staining pattern. It was moderately common in small cell (27%) and large cell carcinomas (25%) but relatively rare in adenocarcinomas (13%). Keratin 5 was expressed in all keratinizing and the great majority (87%) of nonkeratinizing squamous carcinomas, and a majority of large cell carcinomas (56%) and some small cell carcinomas (27%). It was rare in acinar adenocarcinomas (12%) and absent in those with neuroendocrine differentiation. Mesothelin was present in more than half (53%) of adenocarcinomas and a minority (13%) of large cell carcinomas but was absent in small cell carcinomas. In squamous carcinomas it was more often seen in nonkeratinizing versus keratinizing tumors (31% vs 16%). These results show that each of these "mesothelioma" markers reacts with different subsets of pulmonary carcinomas with a variable frequency; this should be considered when using these markers in the differential diagnosis of thoracic tumors.

Topics: Biomarkers, Tumor; Calbindin 2; Carcinoma; Diagnosis, Differential; Humans; Immunohistochemistry; Keratin-5; Keratins; Lung Neoplasms; Mesothelioma; Pleural Neoplasms; S100 Calcium Binding Protein G; Thrombomodulin

Sentinel Node Biopsy (SNB) is considered an accurate method of detecting axillary lymph node status in patients with small breast cancer. Combined with an accurate and rapid histopathology tool, it could spare this group of patients unnecessary Axillary Node Clearance (ANC) with its associated hazards. Intraoperative examination of SNB for cancer cells has been investigated using both Frozen Sections (FS) and Imprint Cytology (IC) stained with different stains. This study is devoted to establish a reliable and rapid protocol for immunostaining of touch imprints from SNB.. We investigated two different EPOS (Enhanced Polymer One-Step staining--DAKO) anticytokeratin antibodies, five different tissue fixatives and different incubation periods and temperatures with both positive and negative controls.. We have developed a protocol, which produced good and consistent immunostaining of touch imprints. The initial results using this protocol are concordant with those of permanent Haematoxylin and Eosin (H&E) sections.. We propose this protocol for rapid immunostaining of touch imprints of SNB.

Topics: Antibodies; Axilla; Breast Neoplasms; Carcinoma; Ethanol; Female; Fixatives; Histocytological Preparation Techniques; Humans; Immunohistochemistry; Intraoperative Care; Keratins; Lymph Nodes; Reproducibility of Results; Sentinel Lymph Node Biopsy; Solvents; Temperature; Time Factors

We collected 75 primary pulmonary carcinomas with pleomorphic, sarcomatoid, or sarcomatous elements to better define their clinical, histologic, and immunohistochemical profile. The patient's age ranged from 42 to 81 years (mean 65 years), and the male-to-female ratio was 9.7:1. Sixty-nine patients (92%) were smokers. Cough and hemoptysis were the most frequent presenting symptoms. Fifty-nine patients (65%) died of disease: only stage significantly predicts overall survival (p = 0.0273). Microscopically, based on the WHO criteria, 58 cases were classified as pleomorphic carcinoma (51 with an epithelial component, 7 composed exclusively of spindle and giant cells), 10 as spindle cell carcinoma, 3 as giant cell carcinoma, 3 as carcinosarcoma, and 1 as pulmonary blastoma. Immunohistochemically, in the tumors composed exclusively of spindle and/or giant cells, thyroid transcription factor-1 (TTF-1) and cytokeratin 7 were positive in 55% and 70% of the cases, respectively, whereas surfactant protein-A was always negative. In pleomorphic carcinomas with an epithelial component, cytokeratin 7, TTF-1, and surfactant protein-A were positive in the sarcomatoid component in 62.7%, 43.1%, and 5.9% of the cases, respectively, whereas they were always negative in the sarcomatous part of carcinosarcomas and blastoma. In the epithelial component of pleomorphic carcinomas, cytokeratin 7, TTF-1, and surfactant protein-A were positive in 76.4%, 58.8%, and 39.2% of the cases, respectively, whereas the same antibodies did not react with the epithelial component of carcinosarcomas; in the case of blastoma, the epithelial part of the tumor was positive for cytokeratin 7 and TTF-1, whereas it was negative for surfactant protein-A. Cytokeratin 20 was always negative. In our opinion, this study: 1) supports the metaplastic histogenetic theory for this group of tumors; 2) shows that cytokeratin 7 and TTF-1, but not surfactant protein-A, are useful immunohistochemical markers in this setting; 3) confirms that stage is at the moment the only significant prognostic parameter, as in conventional non-small cell lung carcinomas; and 4) shows that this group of tumors has a worse prognosis than conventional non-small cell lung carcinoma at surgically curable stages I, justifying their segregation as an independent histologic type in the WHO classification.

Topics: Adult; Aged; Aged, 80 and over; Biomarkers, Tumor; Carcinoma; Carcinosarcoma; Female; Humans; Immunohistochemistry; Intermediate Filament Proteins; Keratin-20; Keratin-7; Keratins; Lung Neoplasms; Male; Middle Aged; Nuclear Proteins; Prognosis; Pulmonary Surfactant-Associated Protein A; Survival Rate; Thyroid Nuclear Factor 1; Transcription Factors

Antibodies against high molecular weight cytokeratin (34betaE12) and p63 are frequently used basal cell markers to aid in the diagnosis of prostate cancer (Pca). Absence of a basal cell marker in an atypical lesion histologically suspicious for cancer supports a diagnosis of Pca. However, absence of basal cells demonstrable by basal cell immunohistochemistry (IHC) is not always conclusive for PCa. Some benign prostatic lesions may have inconspicuous or even lack basal cell lining focally. Technical factors such as tissue fixation and antigen retrieval techniques may also make the detection of basal cells difficult. Improving the sensitivity of current basal cell markers is critical if these tests are being used to help make diagnostic decisions in conjunction with standard histology. In this study, we test the hypothesis that that inclusion of both 34betaE12 and p63 in the same IHC reaction (basal cell cocktail) is advantageous over either marker used alone. One thousand three hundred fifty glands from 9 trans-urethral resectioned of prostate specimens with benign prostatic hypertrophy were used to study the immunostaining intensity and pattern for 34betaE12, p63, and the basal cell cocktail. Basal cell marker expression was scored as strong, moderate, weak, or negative. Basal cell staining was considered complete if 75% of the gland's circumference was positive for the basal cell marker and partial if <25% of the circumference was stained. The mean staining intensity and variance were calculated for 34betaE12, p63, and the basal cell cocktail. A paired test was used to evaluate whether the overall basal cell staining was significantly different between 34betaE12, p63, and the basal cell cocktail. F-test was used to assess the variances for 34betaE12, p63, and the basal cell cocktail. A high-density tissue microarray (TMA) comprising prostate tissue from 103 tumors from men with clinically localized Pca and a separate TMA comprising metastatic hormone-refractory Pca samples from 23 rapid autopsy cases were used to study the aberrant expression of 34betaE12 and p63 in clinically localized and poorly differentiated Pca. The prostate glands in transition zone have variable basal cell staining intensity and pattern with 34betaE12, p63, or the cocktail. Histologically, benign glands lack basal cell lining in 2%, 6%, and 2% of glands with cocktail, 34betaE12, and p63 staining, respectively. The staining variance for the cocktail is significantly smaller than th

Topics: Biomarkers, Tumor; Carcinoma; DNA-Binding Proteins; Genes, Tumor Suppressor; Humans; Immunohistochemistry; Keratins; Male; Membrane Proteins; Phosphoproteins; Prostate; Prostatic Neoplasms; Staining and Labeling; Trans-Activators; Transcription Factors; Transurethral Resection of Prostate; Tumor Suppressor Proteins

While squamous cell carcinoma and pseudocarcinomatous hyperplasia have been documented as pre-existing lesions in cases of reactive eccrine syringofibroadenoma (ESFA), to the best of our knowledge carcinoma occurring in a solitary ESFA has not yet been reported. We present one such case in a 91-year-old female who had a dome-shaped, reddish tumor on the extensor side of the left forearm.. We review the histopathological, immunophenotypical and ultrastructural findings of this tumor, including the keratin expression profile.. Histopathologically, long, branching, anastomosing, thin and thick strands of small cuboidal epithelial cells were extending from the surface epidermis into the dermis. In the center of the tumor, there were irregular-shaped nests of atypical tumor cells invading downward into the dermis. Ultrastructurally, duct-like lumina lined with cuboidal tumor cells were present in the epithelial cords. From these findings, the present case was diagnosed as solitary eccrine syringofibroadenocarcinoma (ESFAC). Keratin expression studies revealed that cells of the thick strands, except for the luminal and basal cells, were positive for differentiation-specific keratins, keratins 1 and 10, and that cells of the thin strands were positive for keratins 5 and 14.. Histopathological, immunophenotypical and ultrastructural evidence, as well as the pattern of keratin expression, suggest differentiation of the present malignant tumor towards the eccrine dermal duct. This case is the first reported case of ESFAC as far as we know.

Topics: Aged; Aged, 80 and over; Biomarkers, Tumor; Carcinoma; Cell Transformation, Neoplastic; Eccrine Glands; Female; Fibroadenoma; Humans; Immunohistochemistry; Keratins; Sweat Gland Neoplasms; Syringoma; Treatment Outcome

Epithelioid sarcoma (ES) is a rare, aggressive soft tissue tumor characterized by nodular aggregates of epithelioid and/or spindled cells that are immunoreactive to cytokeratins (CKs) and epithelial membrane antigen. ES that arises in the dermis may cause epidermal ulceration and can resemble, clinically, morphologically and immunohistochemically, cutaneous squamous cell carcinoma. CK 5/6 has recently been found to be an excellent marker of squamous cell carcinoma, including spindled variants, but it is not known if this marker can be utilized to distinguish superficial ES from cutaneous spindled squamous cell carcinoma (SSCC).. Twenty-four cases of ES with typical histologic features and 10 cases of SSCC with ultrastructural evidence of epithelial differentiation were studied. Immunohistochemical analysis using an antibody to CK 5/6 was performed. The extent of immunoreactivity was evaluated in a semiquantitative manner using the following scale: 0, < 5% of cells staining; 1+, 6-25% of cells staining; 2+, 26-50% of cells staining; 3+, 51-75% of cells staining; 4+, > 75% of cells staining.. CK 5/6 was expressed in all 10 cases of SSCC, including one case with 3+ staining and six cases with 4+ staining. In contrast, CK 5/6 staining was found only in rare tumor cells (1+ staining) in one of 24 (4%) cases of ES.. CK 5/6 staining is useful in distinguishing superficial ES from cutaneous SSCC.

Topics: Biomarkers, Tumor; Carcinoma; Carcinoma, Squamous Cell; Diagnosis, Differential; Humans; Immunohistochemistry; Keratin-5; Keratins; Sarcoma; Skin Neoplasms

PMC42-LA cells display an epithelial phenotype: the cells congregate into pavement epithelial sheets in which E-cadherin and beta-catenin are localized at cell-cell borders. They abundantly express cytokeratins, although 5% to 10% of the cells also express the mesenchymal marker vimentin. Stimulation of PMC42-LA cells with epidermal growth factor (EGF) leads to epithelio-mesenchymal transition-like changes including up-regulation of vimentin and down-regulation of E-cadherin. Vimentin expression is seen in virtually all cells, and this increase is abrogated by treatment of cells with an EGF receptor antagonist. The expression of the mesenchyme-associated extracellular matrix molecules fibronectin and chondroitin sulfate proteoglycan also increase in the presence of EGF. PMC42-LA cells adhere rapidly to collagen I, collagen IV, and laminin-1 substrates and markedly more slowly to fibronectin and vitronectin. EGF increases the speed of cell adhesion to most of these extracellular matrix molecules without altering the order of adhesive preference. EGF also caused a time-dependent increase in the motility of PMC42-LA cells, commensurate with the degree of vimentin staining. The increase in motility was at least partly chemokinetic, because it was evident both with and without chemoattractive stimuli. Although E-cadherin staining at cell-cell junctions disappeared in response to EGF, beta-catenin persisted at the cell periphery. Further analysis revealed that N-cadherin was present at the cell-cell junctions of untreated cells and that expression was increased after EGF treatment. N- and E-cadherin are not usually coexpressed in human carcinoma cell lines but can be coexpressed in embryonic tissues, and this may signify an epithelial cell population prone to epithelio-mesenchymal-like responses.

Topics: Actins; Breast Neoplasms; Cadherins; Carcinoma; Cell Adhesion; Cell Transformation, Neoplastic; Chemotaxis; Dose-Response Relationship, Drug; Epidermal Growth Factor; Extracellular Matrix Proteins; Keratins; Neoplasm Proteins; Tumor Cells, Cultured; Vimentin; Vinculin

Expression of cytokeratin 7 (CK7) and cytokeratin 20 (CK20) helps to establish the origin of biliary and metastatic carcinomas. We investigated the expression of CK7 and CK20 in inflammatory, metaplastic and neoplastic conditions of the bile ducts, and evaluated possible relationships between the CK expression pattern and extrahepatic bile duct/gallbladder carcinomas (EBDCs) or intrahepatic bile duct carcinomas (IBDCs). We used immunohistochemistry for the investigation of 48 formalin-fixed, paraffin-embedded specimens grouped as: A) lithiasic or inflamed surgically resected extrahepatic bile ducts/gallbladders: all were CK7+/CK20+; B) percutaneous liver biopsies from patients with chronic hepatitis C primary biliary cirrhosis and primary sclerosing cholangitis: all were CK7+/CK20-; C) EBDCs: all were CK7+/CK20+, except for two cases which were CK7-/CK20-; D) IBDCs: all were CK7+/CK20-, except for one case showing CK20 positivity. Metaplastic changes were seen only among specimens in groups A and C: in these cases, CK20 was either focally or diffusely expressed. Our study suggests that the expression of cytokeratins under specific stimuli can be different from normal tissues, and that sometimes CK20 expression can be related to and precede the occurrence of metaplastic alterations.

Topics: Bile Duct Diseases; Bile Duct Neoplasms; Bile Ducts, Extrahepatic; Bile Ducts, Intrahepatic; Carcinoma; Cell Transformation, Neoplastic; Gallbladder Diseases; Gallbladder Neoplasms; Gene Expression Profiling; Humans; Immunohistochemistry; Intermediate Filament Proteins; Keratin-20; Keratin-7; Keratins

Epithelial-myoepithelial carcinoma of the salivary gland is a rare, low-grade, neoplasm, composed of ductal and myoepithelial cells. We present two novel cell lines, which have been characterised by immunofluorescence, derived from an epithelial-myoepithelial carcinoma of the parotid gland. A resected mass of the parotid gland was diagnosed as an epithelial-myoepithelial carcinoma by routine histological examination. Part of the specimen was labelled with a panel of antibodies confirming the tumour type. The other part was finely minced and the explants were incubated in DMEM supplemented with penicillin and streptomycin, at 37 degrees C in a humidified 5% CO(2) atmosphere. Two cell types were identified by immunofluorescence-a small cobblestone cell, positive for AE1/AE3 and p53, and a polyhedral cell, positive for vimentin, smooth muscle markers and S-100. Herein two cell lines are presented in order to open up possibilities of new studies and a discussion of the events that culminate in this bimodal neoplasm is also performed.

Topics: Adult; Carcinoma; Cell Culture Techniques; Female; Humans; Keratins; Neoplasm Proteins; Nuclear Proteins; Parotid Neoplasms; Proto-Oncogene Proteins; Proto-Oncogene Proteins c-mdm2; Tumor Cells, Cultured; Tumor Suppressor Protein p53

To extend flow cytometry (FC) to the diagnosis of nonhematopoietic neoplasms, we have developed new flow cytometric assays to identify expression of cytokeratin, epithelial cell adhesion molecule (EpCAM)/epithelial glycoprotein-2, myogenin, and CD99. To validate these assays, we correlated the flow cytometric results with the histologic and immunohistochemical results on paraffin-embedded tissue in a series of 21 cases, including 17 carcinomas, 1 atypical carcinoid, 2 rhabdomyosarcomas, and 1 Ewing sarcoma/primitive neuroectodermal tumor (ES/PNET). Six of 7 assayed carcinomas and the carcinoid were positive for cytoplasmic cytokeratin by the flow cytometric assay. EpCAM was expressed by 11 of 12 carcinomas that were assayed by FC. Both rhabdomyosarcomas expressed myogenin by FC, and the ES/PNET case expressed CD99. Interestingly, the blast-associated antigen CD90 was expressed uniformly on the ES/PNET case and on subsets of cells in the rhabdomyosarcoma and carcinoma cases. Potential applications of the flow cytometric assay to nonhematopoietic neoplasms will include evaluating samples with limited material, monitoring disease persistence and recurrence in patients with previous diagnoses, and making rapid diagnoses in urgent cases.

Topics: 12E7 Antigen; Antigens, CD; Antigens, Neoplasm; Carcinoma; Cell Adhesion Molecules; Cell Lineage; Epithelial Cell Adhesion Molecule; Feasibility Studies; Flow Cytometry; Immunohistochemistry; Immunophenotyping; Keratins; Leukocyte Common Antigens; Myogenin; Neoplasms; Rhabdomyosarcoma; Thy-1 Antigens

Sphingosylphosphorylcholine (SPC) is a naturally occurring bioactive lipid that is present in high density lipoproteins (HDL) particles and found at increased levels in blood and malignant ascites of patients with ovarian cancer. Here, we show that incubation of human epithelial tumour cells with SPC induces a perinuclear reorganization of intact keratin 8-18 filaments. This effect is specific for SPC, largely independent of F-actin and microtubules, and is accompanied by keratin phosphorylation. In vivo visco-elastic probing of single cancer cells demonstrates that SPC increases cellular elasticity. Accordingly, SPC stimulates migration of cells through size-limited pores in a more potent manner than lysophosphatidic acid (LPA). LPA induces actin stress fibre formation, but does not reorganize keratins in cancer cells and hence increases cellular stiffness. We propose that reorganization of keratin by SPC may facilitate biological phenomena that require a high degree of elasticity, such as squeezing of cells through membranous pores during metastasis.

Topics: Actin Cytoskeleton; Carcinoma; Cell Movement; Cell Size; Cytoskeleton; Elasticity; Fluorescent Antibody Technique; Humans; Keratins; Microscopy, Electron; Neoplasm Metastasis; Pancreatic Neoplasms; Phosphorylcholine; Sphingosine; Stress, Mechanical; Tumor Cells, Cultured

This study presents a comprehensive survey and characterization of available prostate carcinoma cell lines, most of which have been widely used but are incompletely characterized.. A total of 21 cell lines were investigated, including three "classical" (DU 145, LNCaP, and PC-3) and 18 "non-classical" lines (1013L, 22Rv1, ALVA-55, ALVA-101, ARCaP, CWR-R1, DuCaP, DuPro-1, LAPC-4, MDA PCa 1, MDA PCa 2a, MDA PCa 2b, NCI-H660, PC-346C, PC-93, PSK-1, UM-SCP-1, and VCaP). Cytogenetics, DNA profiling, expression of basal, luminal, and neuroendocrine differentiation markers, and mutation analyses of the TP53 and androgen receptor (AR) genes were performed.. Based on cytogenetics and DNA profiling analyses, out of the 18 "non-classical" lines, six were confirmed to be unique, eight (in four pairs) were confirmed to be related in origin, and four lines were identified as cross-contaminants. Of this latter group, PC-93 was found to be a derivative of HeLa, whereas DuPro-1, ALVA-55, and ALVA-101 were derivatives of PC-3. The 17 genuine prostate cell lines expressed keratin 8 (K8) and K18. Nine showed AR expression, of which five harbored mutations in the AR gene. Prostate-specific antigen and DD3 were exclusively detected in AR expressing cell lines. Seven lines expressed the basal cell marker K5, three of these lines showed co-expression of AR.. This study defines a collection of 17 genuine prostate carcinoma cell lines. This collection, although small, constitutes a variety of different types and stages of prostate cancer, while it also partly reflects the heterogeneous nature of this malignancy.

Topics: Blotting, Western; Carcinoma; Cell Line, Tumor; DNA Fingerprinting; DNA, Neoplasm; Female; Humans; Immunohistochemistry; Karyotyping; Keratins; Male; Prostate-Specific Antigen; Prostatic Neoplasms; Receptors, Androgen; Reverse Transcriptase Polymerase Chain Reaction; Tumor Suppressor Protein p53

The apparently dormant breast cancer micrometastases in haemopoietic marrow are correlated with distant metastatic carcinoma dissemination. We studied in vitro interactions of carcinoma cells with adjacent stromata, using connective tissue cell cultures from breast and bone marrow samples of normal donors, comparing them to the pericancerous breast tissue and bone marrows of 12 selected patients with invasive breast carcinomas. Cancer cells were detected by immunocytochemistry and RT-PCR in all the bone marrows and in most blood samples of the studied patients. We monitored the growth and interaction of carcinoma MCF-7 cells with the stromata. The normal breast stroma sustained typical massive cancer growth. The pericancerous breast stroma induced the invasive mesenchymal pattern of growth. Normal bone marrow stroma induced the same conversion and was highly adhesive, retaining the cells in the stroma, but carcinoma patients' bone marrow stromata underwent low adhesive interactions with cancer cells, releasing them potentially into the circulation. The semi-quantitative RT-PCR indicated an enhanced expression of the hepatocyte growth factor and its receptor c-met in breast and bone marrow stromata of cancer patients. The input of cancer cells into the normal bone marrow may induce modifications of the local microenvironment, favourable for growth and release of carcinoma cells into the systemic circulation, which correlate with the poor prognosis of patients with bone marrow micrometastases.

Topics: Bone Marrow; Bone Marrow Cells; Breast Neoplasms; Carcinoma; Cell Adhesion; Cell Division; Cell Line; Coculture Techniques; DNA, Complementary; Fluorescein-5-isothiocyanate; Hepatocyte Growth Factor; Humans; Keratins; Neoplasm Metastasis; Protein Binding; Proto-Oncogene Proteins c-met; Reverse Transcriptase Polymerase Chain Reaction; RNA; Tumor Cells, Cultured

Urothelial carcinoma with gland-like lumina is an uncommon type of tumor, reported only occasionally in literature. Its diagnosis usually does not offer any difficulties, and its prognosis is determined by the accompanying classic transitional or squamous component. It is important though, not to misdiagnose it as a mixed transitional cell adenocarcinoma. In that respect, features such as the type of epithelium lining, the gland-like structures, as well as the type of luminal mucin have been used to make the diagnosis. Recently, an immunohistochemical panel of antibodies has proven helpful in differentiating primary and metastatic adenocarcinomas of urothelial tract from urothelial carcinoma with gland differentiation. In their series of 16 cases, Tamboli et al included only one case of transitional cell carcinoma with gland differentiation. We present two additional cases of urothelial carcinoma with gland-like lumina in two men, 60 and 79 years old, respectively. Both tumors were grade 2 of Ash-Bergkvist, and the stage was pT(1) in both cases. Immunohistochemical study with cytokeratins 7 and 20, and with c-erbB-2, was performed. Both tumors expressed cytokeratins 7 and 20; c-erbB-2 was only expressed in one, in spite of the same staging. Although some relation has been found in animals between gland-like lumina phenotype and expression of epidermal growth factor (the receptor of which is homologous to c-erbB-2), it seems that this relationship might not be constant in humans.

Topics: Aged; Biomarkers, Tumor; Carcinoma; Humans; Immunohistochemistry; Intermediate Filament Proteins; Keratin-20; Keratin-7; Keratins; Male; Middle Aged; Receptor, ErbB-2; Urinary Bladder Neoplasms; Urothelium

Dissemination of lymph nodes is a known prognostic factor in colorectal carcinoma. Micrometastases in lymph nodes can be missed when studied by routine techniques. We analyzed 162 lymph nodes from 30 patients with colonic carcinoma and using routine techniques, they were classified as follows: two Dukes A; nineteen Dukes B; and nine Dukes C. A patient with benign colon disease served as negative control. Lymph nodes were all sectioned in halves, with one of the halves stored in liquid nitrogen for molecular biology examination by carcinoembryonic antigen expression. The other formalin-fixed and paraffin embedded halves were saved for both pathologic and immunohistochemical examination. For Dukes A and Dukes B tumors, reverse transcriptase-polymerase chain reaction (RT-PCR) had a 50% higher sensitivity in the detection of micrometastases. The expression of carcinoembryonic antigen (CEA) was detected in all Dukes C cases, which were considered as positive controls. These results showed that RT-PCR has a higher sensitivity in the detection of micrometastases than routine techniques, including immunohistochemistry.

Topics: Adult; Aged; Aged, 80 and over; Carcinoembryonic Antigen; Carcinoma; Colorectal Neoplasms; Electrophoresis, Polyacrylamide Gel; Female; Humans; Keratins; Lymph Nodes; Lymphatic Metastasis; Male; Middle Aged; Neoplasm Staging; Prospective Studies; Reverse Transcriptase Polymerase Chain Reaction; Sensitivity and Specificity

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

We are investigating the mechanism responsible for the overexpression of the keratin 18 (K18) gene in tumorigenic clones from the SW613-S human colon carcinoma cell line, as compared with non-tumorigenic clones. We have previously shown that this mechanism affects the minimal K18 promoter (TATA box and initiation site). We report here that treatment of the cells with histone deacetylase inhibitors stimulates the activity of the promoter in non-tumorigenic cells but has no effect in tumorigenic cells, resulting in a comparable activity of the promoter in both cell types. The adenovirus E1A protein inhibits the activity of the K18 promoter specifically in tumorigenic cells. This inhibition can be reversed by an excess of CBP protein. The conserved region 1 (CR1) of E1A, which is involved in the interaction with the CBP/p300 co-activators, is necessary to the inhibitory capacity of E1A. A 79 amino acid long N-terminal fragment of E1A, encompassing the two domains of E1A necessary and sufficient for binding to CBP (N-terminus and CR1), has the same differential inhibitory capacity on the K18 promoter as wild-type E1A. Forced recruitment of GAL4-CBP fusion proteins to the K18 promoter results in a greater stimulation of its activity in non-tumorigenic than in tumorigenic cells. The histone acetyltransferase activity of CBP is essential for this differential stimulation and the presence of the CBP2 domain greatly augments the activation capacity of the fusion protein. Chromatin immunoprecipitation experiments carried out with anti-acetylated histone antibodies showed no difference in the level of histone acetylation in the region of the K18 promoter between the two cell types. The structure of chromatin in the promoter region is similar in tumorigenic and non-tumorigenic cells, as determined by mapping of DNase I hypersensitive sites and probing the accessibility of the DNA to restriction endonucleases. From all these results we conclude that alteration of an acetylation mechanism involving the CBP (or p300) protein and acting on a non-histone substrate is responsible for the higher activity of the K18 promoter in tumorigenic cells of the SW613-S cell line.

Topics: Acetylation; Acetyltransferases; Adenovirus E1A Proteins; Carcinoma; Carrier Proteins; Cell Cycle Proteins; Chromatin; Clone Cells; Colonic Neoplasms; Enzyme Inhibitors; Gene Expression Regulation, Neoplastic; Histone Acetyltransferases; Histone Deacetylase Inhibitors; Histones; Humans; Keratins; p300-CBP Transcription Factors; Promoter Regions, Genetic; Protein Structure, Tertiary; Trans-Activators; Transcription Factors; Transcriptional Activation; Tumor Cells, Cultured

A case of sarcomatoid carcinoma of the bladder is reported herein. Immunohistochemical staining with human pancytokeratin antibody was negative, while vimentin staining was strongly positive, suggesting a diagnosis of sarcoma of the bladder. Further immunohistochemical analysis revealed positivity for AE1/AE3 cytokeratins, permitting a correct diagnosis of sarcomatoid carcinoma of the bladder. It can be difficult to distinguish between sarcomatoid carcinoma, undifferentiated carcinoma and sarcoma, particularly if the biopsy specimens are of small size. In rare cases, sarcomatoid tumors may express epithelial markers different from those revealed by human pancytokeratin staining.

Topics: Aged; Carcinoma; Female; Humans; Immunohistochemistry; Keratins; Sarcoma; Urinary Bladder Neoplasms

A histopathological and immunohistochemical study of a case of nephrogenic adenoma of the bladder associated to glandular cystitis is presented with a very similar immunostaining to adenomatoid tumors in other organs and probably of a mesothelial origin. Its pathogenesis seems to correspond to a metaplastic change of the bladder's urothelium through anomalous differentiation of the reserve cells faced with different irritating agents. Because of its benign characteristics, we think that treatment can be confined to endoscopic observation and conservative technique.

Topics: Adenoma; Aged; Biomarkers, Tumor; Carcinoma; Cystitis; Diagnosis, Differential; Humans; Immunoenzyme Techniques; Keratins; Male; Metaplasia; Mucin-1; Neoplasm Proteins; Urinary Bladder Neoplasms; Urography; Urothelium; Vimentin; von Willebrand Factor

Syringoid eccrine carcinoma is an extremely rare cutaneous malignant tumor, thought to be derived from eccrine sweat apparatus. We report a case of syringoid eccrine carcinoma occurring on the scalp of a 66-year-old woman and analyzed its cytokeratin expression immunohistochemically to clarify its histogenesis. The tumor consisted mainly of numerous small cords and nests extending from the reticular dermis to the subcutaneous tissue, which formed luminal or tubular structures mimicking the nests of syringoma. Immunohistochemical analysis revealed that most tumor cells expressed simple epithelial cytokeratins (CKs 7, 8, 18, 19) suggesting their sweat secretory differentiation, and that a small number of tumor cells showed an expression of stratified epithelial cytokeratins (CKs 5, 14) suggesting their ductal differentiation. We believe that the syringoid eccrine carcinoma of our case may differentiate mainly toward the sweat secretory cells rather than toward the dermal ductal cells.

Topics: Aged; Biomarkers, Tumor; Carcinoma; Eccrine Glands; Female; Humans; Immunoenzyme Techniques; Keratins; Scalp; Sweat Gland Neoplasms; Treatment Outcome

We investigated the distribution and fate of apoptotic bodies during human development and in the adult, using an antibody (M30) that recognizes a neo-epitope formed early in the apoptotic cascade by caspase cleavage of cytokeratin 18. In the fetus, we found extensive accumulation of M30-positive, non-phagocytosed fragments in the red pulp of the spleen, subcutaneous and submucosal vessels, the interstitium of the lung, and the glomerular mesangium of the kidneys. In the liver, M30-immunoreactive fragments were found inside macrophages in the sinusoids. The number of these fragments and the intensity of the immunostaining increased with the gestational age of the fetus. In the adult, M30-positive fragments were barely detectable in normal tissues. However, many pathological situations, including both chronic degenerative processes and metastatic cancer, were associated with accumulation of M30-positive fragments in the red pulp of the spleen. In the liver and kidney, no fragments could be detected. Remarkably, 13 of the 16 patients with metastasized cancer showed pronounced accumulation of M30-positive fragments containing hematoxylin-reactive material in the red pulp of the spleen. In the non-cancerous cases, such DNA-containing fragments were only seen in 9 of 94 cases. The results show that when apoptotic activity is high, as during development in the fetus or during metastasis and other pathological processes in the adult, the phagocytic clearance of apoptotic bodies can be overloaded. These apoptotic fragments then accumulate in the spleen. The visual detection of apoptotic fragments is concluded to reflect increased cell turnover.

Topics: Adult; Apoptosis; Carcinoma; Colorectal Neoplasms; Embryo, Mammalian; Epithelium; Fetus; Humans; Immunoenzyme Techniques; In Situ Nick-End Labeling; Intestine, Small; Keratins; Liver; Macrophages; Phagocytosis; Spleen

Ten mucinous cystic ovarian tumors that contained sarcoma-like mural nodules are described. The nodules were studied by conventional and immunohistochemical methods. The sarcoma-like mural nodules occurred predominantly in middle-aged women, were multiple and sharply demarcated from the adjacent mucinous tumor, had small size, and exhibited a heterogeneous cell population. Distinction of these lesions from true sarcomatous nodules and foci of anaplastic carcinoma is important because of the worse prognosis of the two latter tumors compared with the favorable behavior of the sarcoma-like mural nodules. Six of the eight patients with follow-up information were alive and clinically free of recurrence at a mean follow-up interval of 12 years. Two patients died of other causes (thyroid and breast carcinomas). The nature of the nodules is not clear. Sarcoma-like mural nodules probably represent a reactive and self-limited phenomenon within a neoplasia. Their coexpression of vimentin and cytokeratins is consistent with an origin from submesothelial mesenchymal cells, which undergo partial transformation into epithelial cells.

Topics: Adult; Aged; Aged, 80 and over; Biomarkers, Tumor; Carcinoma; Combined Modality Therapy; Cystadenocarcinoma, Mucinous; Diagnosis, Differential; Disease-Free Survival; Female; Follow-Up Studies; Humans; Immunohistochemistry; Keratins; Ovarian Neoplasms; Sarcoma; Vimentin

Sinonasal undifferentiated carcinoma (SNUC) is a highly aggressive malignant neoplasm that is often difficult to distinguish from other poorly differentiated carcinomas arising in the sinonasal tract. To search for a differential cytokeratin (CK) expression that could be useful for diagnostic purposes, we compared the expression of a large panel of CKs in a series of 6 SNUCs, 10 poorly differentiated squamous cell carcinomas (SCCs), 10 nonkeratinizing squamous cell carcinomas (NKSCCs), and 5 nasopharyngeal-type undifferentiated carcinomas (NPTCs). SCC, NKSCC, and NPTC frequently showed immunoreactivity for CK5/CK6, CK8, CK13, and CK19. In addition, SCC and NKSCC expressed CK14, which was not detected in NPTC, and SCC expressed CK7 (60% of cases) and CK4 (30% of cases), which were absent in NKSCC and NPTC. Three NKSCCs were associated with a Schneiderian papilloma, and the results of the immunostaining were similar in the two components, with the exception of CK4 and CK7, which were expressed by the papilloma and not by the carcinoma. In contrast to other carcinomas, SNUC was characterized by the exclusive expression of CKs of simple epithelia, such as CK8 (100% of cases), CK7 (50% of cases), and CK19 (50% of cases). Thus, there are significant differences in the pattern of CK expression between SNUC, SCC, NKSCC, and NPTC, which could be of diagnostic aid. Moreover, these findings support the hypothesis that SNUC is a separate entity from SCC and NPTC of the sinonasal tract.

Topics: Adult; Biomarkers, Tumor; Carcinoma; Carcinoma, Squamous Cell; Female; Gene Expression Regulation, Neoplastic; Humans; Immunohistochemistry; Keratins; Male; Middle Aged; Nasopharyngeal Neoplasms; Nose Neoplasms; Paranasal Sinus Neoplasms

Galectin-7 is associated with p53-dependent onset of apoptosis and proliferation control/differentiation in keratinocyte development. It is also up-regulated in chemically induced rat mammary carcinogenesis. Because the levels of expression of galectin-7 have never been investigated in thyroid tumors (in contrast to those of galectin-1 and -3 associated with malignancy), we initiated analysis of the expression of galectin-7 in benign and malignant thyroid lesions together with that of cytokeratin-19 (CK19), a marker already demonstrated to be useful in diagnosing this kind of lesion. The immunohistochemical expression levels were quantitatively determined by means of computer-assisted microscopy on a series of 84 thyroid lesions including 10 multinodular goiters, 32 adenomas, and 42 carcinomas. Our data clearly indicate a marked down-regulation of galectin-7 expression in a large proportion of adenomas (including the normomacrofollicular, microfollicular, and trabecular variants) if compared with carcinomas. In accordance with results of previous studies, a marked up-regulation of CK19 expression was observed in the thyroid carcinomas, and this contrasted in particular with the low CK19 expression observed in the microfollicular adenomas. Of importance for diagnostic implications, the combination of these two markers enabled our series of microfollicular adenomas (characterized by low galectin-7 and CK19 expression) to be efficiently distinguished from the encapsulated follicular variant of papillary thyroid carcinomas (high galectin-7 and CK19 expression).

Topics: Adenoma; Carcinoma; Disease Progression; Galectins; Goiter; Humans; Immunohistochemistry; Keratins; Thyroid Gland; Thyroid Neoplasms

The reverse transcriptase-polymerase chain reaction (RT-PCR) technique is a tool capable of detecting minute quantities of circulating tumor cell-derived transcripts. Nasopharyngeal carcinoma (NPC) is a rapidly growing tumor of epithelial origin and high metastatic potential. The aim of our study is to investigate the clinical value of circulating cytokeratin-19 (CK-19) mRNA detection in NPC patients. Between June 1997 and March 1999, 57 previously untreated, advanced NPC patients without distant metastasis were uniformly treated by concurrent chemoradiotherapy. Peripheral blood samples were collected prospectively before treatment and subjected to a nested RT-PCR assay. Measures were taken to prevent contamination and pseudogene interference. PCR products of positive results were verified by restriction enzyme Hae II and direct sequencing. Under our nested RT-PCR experimental conditions, 33.3% (19/57) clinically nonmetastatic NPC patients had CK-19 mRNA in their blood. The positive detection rates of CK-19 mRNA in the peripheral blood for different stages were 20.0% for stage II, 31.6% stage III and 43.5% stage IV (p = 0.1335). After a median follow-up time of 35 months, 2 patients had recurrences of their primary tumors and 14 developed distant metastases without locoregional recurrence. Nine of 19 (47.4%) CK-19 mRNA-positive patients and 5 of 38 (13.2%) CK-19 mRNA-negative patients developed distant metastasis (p = 0.00826). The 3-year metastasis-free survival rates were 49.9% for patients with detectable CK-19 and 85.9% for those with undetectable CK-19 (p = 0.0089, log-rank test). Our data suggest that the presence of CK-19 mRNA in the peripheral blood may be a potential marker of micrometastasis for NPC.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Biomarkers, Tumor; Carcinoma; Cisplatin; False Positive Reactions; Female; Fluorouracil; Follow-Up Studies; Humans; Keratins; Life Tables; Male; Middle Aged; Nasopharyngeal Neoplasms; Neoplasm Metastasis; Neoplasm Proteins; Polymorphism, Restriction Fragment Length; Predictive Value of Tests; Prognosis; Prospective Studies; Pseudogenes; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; RNA, Neoplasm; Survival Analysis; Survival Rate; Treatment Outcome

In a number of clinical situations, especially in the context of the recent sentinel node concept, lymph-node involvement has to be determined intraoperatively. Since serious and dependable decisions are to be made according to the result of this examination, the most reliable method for the detection of tumour cells should be applied. We and others have shown previously that routine histological examination underestimates lymph-node metastases, and that immunohistochemistry (IHC) significantly improves the accuracy of staging. However, IHC has so far been difficult to apply to the intraoperative examination of cryosections since it has required too much time. We have developed a novel modification of IHC for the rapid detection of metastases of carcinomas in cryosections from lymph nodes. It is based on a unique directly labelled cytokeratin antibody, immunofluorescence, and a specially devised staining solution. This one-step staining procedure can be performed within 10 min. At the same time, its sensitivity is very high. Single tumour cells can easily be detected, and background staining is very low. The high sensitivity could result in a markedly improved reliability of sentinel node-based decisions.

Topics: Breast Neoplasms; Carcinoma; Female; Humans; Immunohistochemistry; Intraoperative Period; Keratins; Lymph Node Excision; Lymph Nodes; Lymphatic Metastasis; Sensitivity and Specificity; Staining and Labeling

Sarcomatoid carcinomas involving the intestinal tract are rare and usually associated with poor prognosis. We report a case of sarcomatoid carcinoma of the ileum, diagnosed in a 61-year-old man. The patient presented with acute intestinal occlusion. Surgical resection of the ileum was performed. At macroscopic examination, two large polypoid masses were found. Frozen section examination suggested the diagnosis of malignant stromal tumor. At histological examination, both tumors were formed by pleiomorphic, large spindle cells, presenting numerous mitoses and marked nuclear atypia. Immunohistochemical examination showed that tumor cells coexpressed vimentin and epithelial markers (cytokeratins, EMA). The final diagnosis was monomorphic sarcomatoid carcinoma. The patient deceased with metastatic disease after 3 months of follow-up. This report underlines the potential diagnostic problems raised by this unusual type of carcinoma and emphasizes the role of immunohistochemistry in assessing the correct diagnosis.

Topics: Carcinoma; Fatal Outcome; Humans; Ileum; Immunohistochemistry; Intestinal Neoplasms; Keratins; Male; Middle Aged; Sarcoma; Vimentin

Desmosomes are prominent cell adhesion structures that are major stabilizing elements, together with the attached cytoskeletal intermediate filament network, of the cytokeratin type in epithelial tissues. To examine desmosome dynamics in tightly coupled cells and in situations of decreased adhesion, fluorescent desmosomal cadherin desmocollin 2a (Dsc2a) chimeras were stably expressed in human hepatocellular carcinoma-derived PLC cells (clone PDc-13) and in Madin-Darby canine kidney cells (clone MDc-2) for the continuous monitoring of desmosomes in living cells. The hybrid polypeptides integrated specifically and without disturbance into normal-appearing desmosomes that occurred in association with typical cytokeratin filament bundles. Tracking of labeled adhesion sites throughout the cell cycle by time-lapse fluorescence microscopy revealed that they were immobile and that they maintained their structural integrity for long periods of time. Time-space diagrams further showed that desmosomal positioning was tightly controlled, even during pronounced cell shape changes, although the desmosomal arrays extended and contracted, suggesting that they were interconnected by a flexible system with intrinsic elasticity. Double-fluorescence microscopy detecting Dsc2a chimeras together with fluorescent cytokeratin 18 chimeras revealed the association and synchronous movement of labeled desmosomes and fluorescent cytokeratin filaments. Only a minor destabilization of desmosomes was observed during mitosis, demonstrated by increased diffuse plasma membrane fluorescence and the fusion of desmosomes into larger structures. Desmosomes did not disappear completely at any time in any cell, and residual cytokeratin filaments remained in association with adhesion sites throughout cell division. On the other hand, a rapid loss of desmosomes was observed upon calcium depletion, with irreversible uptake of some desmosomal particles. Simultaneously, diffusely distributed desmosomal cadherins were detected in the plasma membrane that retained the competence to nucleate the reformation of desmosomes after the cells were returned to a standard calcium-containing medium. To examine the molecular stability of desmosomes, exchange rates of fluorescent chimeras were determined by fluorescence recovery after photobleaching, thereby identifying considerable Dsc2a turnover with different rates of fluorescence recovery for PDc-13 cells (36+/-17% recovery after 30 minutes) and MDc-2 cells (6

Topics: Animals; Calcium; Carcinoma; Cell Adhesion; Cell Cycle; Cell Line; Desmocollins; Desmosomes; Dogs; Epithelial Cells; Genes, Reporter; Humans; Keratins; Liver Neoplasms; Membrane Glycoproteins; Microscopy, Electron; Microscopy, Fluorescence; Recombinant Fusion Proteins; Time Factors

Metaplastic spindle cell carcinomas may be difficult to distinguish histologically from other spindle cell lesions in the breast. Variable staining with cytokeratin immunomarkers has been reported for metaplastic carcinomas. We evaluated the diagnostic utility of anti-cytokeratin polyclonal antibody, wide spectrum screening keratin, to assess spindle cell breast lesions.. Twenty-four patients with spindle cell breast carcinoma and 31 patients with benign or malignant spindle cell tumours were studied using a panel of antibodies directed against multiple cytokeratins (AE1/AE3, CAM5.2, wide spectrum screening keratin), epithelial membrane antigen (EMA), and vimentin. Sites of origin for the 31 controls included breast, bone, and soft tissue. All but one (95.8%) metaplastic carcinomas stained positively with wide spectrum screening keratin. Only rare or focal immunoreactivity was observed with AE1/AE3 in four cases; however, sensitivity of AE1/AE3 was improved in 13 cases using steam EDTA as an antigen retrieval technique. Three cases were immunoreactive with CAM5.2 and eight cases were immunoreactive with EMA. All control cases lacked immunoreactivity with the cytokeratin panel and EMA. The spindle cells in the metaplastic breast tumours (88%) and in the controls (97%) stained with vimentin.. Wide spectrum screening keratin may be the most useful and convenient antibody in differentiating metaplastic spindle cell carcinoma from other spindle cell lesions in the breast.

Topics: Aged; Aged, 80 and over; Biomarkers, Tumor; Breast Neoplasms; Carcinoma; Female; Humans; Immunohistochemistry; Keratins; Metaplasia; Middle Aged; Mucin-1; Vimentin

Two new cell lines, designated as RK-33 and RK-45, have been successfully established by an outgrowth technique from two different larynx tumours obtained from patients after laryngectomy. Both cell lineshave been maintained incultureforover 18 monthsandrecently have reached passage number 220 (RK-33) and 110 (RK-45). The cells display an epithelial morphology and multiply with a population doubling time of about 24 h (RK-33) and about 40 h (RK-45). The epithelial nature of the cells was also confirmed by expression of cytokeratins 8 and 18. Both lines were sensitive to antiproliferative effect of the tested cytostatic agents such as methotrexate. etoposide and thiotepa, with methotrexate being the most effective. We believe that both cell lines: RK-33 and RK-45 could be a suitable model for studying larynx cancer biology, however, further characterization of their properties is needed.

Topics: Antineoplastic Agents; Blotting, Western; Carcinoma; Cell Division; Cell Line; Female; Humans; Keratins; Laryngeal Neoplasms; Male; Middle Aged

Lymph node metastasis in colorectal carcinoma is an important prognostic factor, yet the prognostic relevance of occult tumor cells in lymph nodes has not elucidated. This study was performed to investigate the correlation between isolated tumor cells in lymph nodes and malignancy potential in patients with Dukes B colorectal carcinoma and, thus, to determine whether presence of isolated tumor cells in lymph nodes has a prognostic significance.. To evaluate the incidence of isolated tumor cells in lymph nodes in patients with Dukes B colorectal carcinoma, 1,808 lymph nodes taken from 93 patients (19.4 per case) were assessed by immunohistochemical technique using a monoclonal antihuman cytokeratin (MNF 116). Clinicopathologic parameters and prognosis were compared between patients with and without isolated tumor cells.. Isolated tumor cells were identified in 54 lymph nodes from 29 patients (31.2 percent) by the immunostaining. No correlations were observed between the incidence of positive isolated tumor cells and various clinicopathologic parameters, including preoperative carcinoembryonic level, tumor site and size, histologic differentiation, pT stage, vascular invasion and lymphatic invasion, and perineural invasion. There was no difference in five-year survival estimated by Kaplan-Meier life-table method between positive and negative groups for isolated tumor cells (82.8 and 85.9 percent, respectively). Multivariate analyses showed that sex (P = 0.0236), serum carcinoembryonic level (>or= 5 ng/ml, P = 0.0002), and lymphatic vessel invasion (P = 0.0002) were significant factors in the survival time.. Immunohistochemical staining with an anticytokeratin antibody is useful in identifying isolated tumor cells in lymph nodes missed in routine hematoxylin-eosin staining, but clinically it seems to be of little prognostic value in patients with Dukes B colorectal carcinoma. Thus, this immunostaining technique does not offer a significant benefit of different strategies for additional therapy or follow-up during conventional pathologic staging using hematoxylin-eosin staining.

Topics: Adult; Aged; Antibodies, Monoclonal; Carcinoma; Colorectal Neoplasms; Female; Humans; Immunohistochemistry; Incidence; Keratins; Lymphatic Metastasis; Male; Middle Aged; Neoplasm Invasiveness; Peritoneal Neoplasms; Prognosis; Retrospective Studies; Survival Analysis

No standard method for handling and histopathologic examination of the sentinel node (SN) exists. We hypothesized that a focused examination of all nodes with serial sectioning and cytokeratin immunohistochemical staining would confirm the SN as the node most likely to harbor metastasis. Intraoperative lymphatic mapping and sentinel lymphadenectomy using blue dye and (99m)technetium-labeled sulfur colloid were performed. All nodes were stained with H&E. All tumor-free nodes underwent additional sectioning and staining with H&E and an immunohistochemical stain. Routine H&E examination detected SN metastases in 27.6% of cases. Occult SN metastases were identified in 12.7% of cases. None of the 724 non-SNs examined contained occult metastases. The SN false-negative rate was zero. This study confirms histopathologically that the SN has biologic significance as the axillary node most likely to harbor metastatic tumor Standardization of the handling, sectioning, and staining of the SN is necessary as lymphatic mapping and sentinel lymphadenectomy become integrated into the care of patients with breast cancer

Topics: Adult; Aged; Aged, 80 and over; Breast Neoplasms, Male; Carcinoma; Coloring Agents; Female; Humans; Immunohistochemistry; Keratins; Lymphatic System; Male; Middle Aged; Monitoring, Intraoperative; Radionuclide Imaging; Sentinel Lymph Node Biopsy; Technetium

Cell growth and proliferation depend on protein synthesis that is regulated, in part, by two eukaryotic translation initiation factors, eIF-4E and eIF-2alpha. These factors are transiently increased as normal cells respond to growth factors and are constitutively elevated in transformed cells. In cultured cells, eIF-4E facilitates cell cycle progression by increasing the expression of cell cycle promoting proteins including cyclin D1. Our previous study revealed elevated cyclin D1 expression in histologically more aggressive thyroid carcinomas as compared to conventional papillary carcinoma. We hypothesized that the increased cyclin D1 expression might correlate with increased eIF-4E expression. We, therefore studied the expression of eIF-4E by immunohistochemistry in 25 cases of conventional papillary carcinoma (CPC) and 28 cases of aggressive thyroid carcinomas (ATC), the latter included 11 tall cell/columnar cell variant of papillary carcinoma, 5 insular carcinomas, and 12 anaplastic carcinomas. We also analyzed the expression of eIF-2a in the same samples as this factor is usually regulated similarly to eIF-4E in cell culture models. Of the 25 CPC, 13 were eIF-4E positive (11 weakly and 2 strongly), and 19 were eIF-2a positive (14 weakly and 5 strongly). Conversely, of the 28 ATC, 25 were eIF-4E positive (4 weakly and 21 strongly), and 23 were eIF-2alpha positive (4 weakly and 19 strongly). There was a significantly increased expression of both eIF-4E (p < 0.001) and eIF-2alpha (p < 0.001) in ATC compared to CPC, suggesting that these translation initiation factors may play a role in the progression of thyroid cancer.

Topics: Antibody Specificity; Blotting, Western; Carcinoma; Carcinoma, Papillary; Cell Division; Cyclin D1; Eukaryotic Initiation Factor-2; Eukaryotic Initiation Factor-4E; Humans; Immunohistochemistry; Keratins; Peptide Initiation Factors; Thyroid Neoplasms

The aim of this study was to analyse the diagnostic value of selected glyco- and immunohistochemical probes for discrimination between mesotheliomas and metastatic carcinomas within the pleura, and to evaluate prognostic indicators in the tested panel. A panel of nine markers (five antibodies, two neoglycoproteins, and labelled hyaluronic acid) was applied to a total of 264 specimens with mesotheliomas (118 cases) and metastatic carcinomas in the pleura (146 cases); the material consisted exclusively of surgical specimens. The diagnosis obtained by standard procedures was further substantiated through a detailed follow-up and clear-cut descriptions of primary sites. The metastatic tumours originated from the lung (82 cases), breast (47 cases), colon (three cases), and kidney (two cases); in 12 cases, however, the tumour origin could not be ascertained. In detail, the probes tested included antibodies against carcinoembryonic antigen (CEA), vimentin, calretinin, mesothelial cells (HBME-1), calcyclin and keratin-5; and also biotinylated neoglycoproteins with ganglioside GM1 and N-acetyl-D-glucosamine (GlcNAc) as the ligand part, and hyaluronic acid. Carrier-immobilized ganglioside GM1 and hyaluronic acid displayed the highest specificity and sensitivity for mesotheliomas, followed by calretinin and HBME-1, whereas keratin-5 and vimentin were of low specificity (43% and 52%, respectively). Metastatic carcinomas could be discerned by CEA detection and application of GlcNAc-bearing neoglycoprotein with similar sensitivity (76% and 72%, respectively) and specificity (91% and 86%, respectively). In cases of breast carcinoma, the maximum specificity (59%) and sensitivity (67%) were low for all markers. Patients with mesothelioma survived longer than those with metastatic carcinoma, especially those with detectable binding sites for hyaluronic acid. No association of tumour type and binding properties of the other applied probes with survival of the patients could be found at a statistically significant level. It is concluded that in routine practice, the application of carrier-immobilized GM1, hyaluronic acid, and antibodies against calretinin and HBME-1 is useful for confirmation of mesothelioma, whereas the detection of CEA and GlcNAc-specific binding sites is useful for distinguishing metastatic carcinoma from mesothelioma. Despite the rather infrequent occurrence of mesotheliomas in women, particular attention should be given to exclude or confirm metastatic

Topics: Acetylglucosamine; Biomarkers, Tumor; Carcinoembryonic Antigen; Carcinoma; Diagnosis, Differential; Evaluation Studies as Topic; Female; Gangliosides; Humans; Hyaluronic Acid; Keratins; Male; Mesothelioma; Pleural Neoplasms; Sensitivity and Specificity; Vimentin

The aim of our study was to assess the clinical value of CYFRA 21-1 tumor marker and carcinoembryonic antigen (CEA) as diagnostic tools that are complementary to cytology in the diagnosis of malignant mesotheliomas.. We measured CEA and CYFRA 21-1 in the pleural effusions (PEs) and serum of 106 patients (benign lung disease, 34 patients; bronchogenic and metastatic carcinoma, 40 patients; mesothelioma, 32 patients).. CEA and CYFRA 21--1 levels were determined by means of two commercial enzyme immunoassays.. The cutoff levels of CYFRA 21--1 and CEA in malignant PEs, selected on the basis of the best diagnostic efficacy, were 41.9 ng/mL and 5.0 ng/mL, respectively. In all neoplastic PEs, CYFRA 21--1 and CEA sensitivity was 78% and 30.6%, respectively, with a specificity of 80% and 91%, respectively. The sensitivity of CYFRA 21--1 and CEA in patients with mesothelioma was 87.5% and 3.1%, respectively. The results of the CYFRA 21--1 assay were positive in 17 of 19 cases of mesothelioma (89.5%) with a negative or uncertain cytology. The association of the tumor marker assay and the cytology allowed a correct diagnosis in 30 of 32 cases of mesothelioma (93.7%).. This study suggests that CYFRA 21--1 would provide a useful parameter for the differential diagnosis between benign and malignant PE from mesothelioma when the result of cytology is negative or uncertain and the clinical context does not allow a more aggressive approach. Moreover, the association of CYFRA 21--1 with CEA could provide details for a differential diagnosis between mesotheliomas and carcinomas. In fact, an elevated CYFRA 21--1 level with a low CEA level is highly suggestive of mesothelioma, whereas high levels of CEA alone or high levels of both the markers suggest a diagnosis of malignant PE, excluding mesothelioma.

Topics: Antigens, Neoplasm; Biomarkers, Tumor; Carcinoembryonic Antigen; Carcinoma; Diagnosis, Differential; Humans; Keratin-19; Keratins; Lung Diseases; Lung Neoplasms; Mesothelioma; Pleural Effusion, Malignant; Pleural Neoplasms; Sensitivity and Specificity

Salivary duct carcinoma is an uncommon malignant salivary gland tumor that occurs predominantly in the parotid gland. Oral involvement is extremely rare, with few cases having been reported in the literature. The tumor is characterized by an aggressive behavior and has a poor prognosis. We describe a case of salivary duct carcinoma arising in the hard palate of a 63-year-old man. Immunohistochemical analysis revealed that tumor cells tested positive for cytokeratin, epithelial membrane antigen, proliferating cell nuclear antigen, Ki67, p53, laminin, and collagen IV. Despite radical surgical resection, bilateral neck dissection, and postoperative radiotherapy, liver metastases developed, and the patient subsequently died of his disease.

Topics: Carcinoma; Collagen; Fatal Outcome; Humans; Immunohistochemistry; Keratins; Ki-67 Antigen; Laminin; Liver Neoplasms; Male; Middle Aged; Mucin-1; Palatal Neoplasms; Prognosis; Proliferating Cell Nuclear Antigen; Radiotherapy, Adjuvant; Salivary Ducts; Salivary Gland Neoplasms; Salivary Glands, Minor; Tumor Suppressor Protein p53

-Cytokeratin 7 (CK7) and cytokeratin 20 (CK20) are 2 types of intermediate filament protein. Expression of CK7 is seen in the majority of primary urinary bladder carcinomas. CK20 is restricted to superficial and occasional intermediate cells of the normal urothelium of the bladder. Aberrant CK20 expression has been documented in urothelial carcinoma and has proved useful as an ancillary diagnostic aid for urinary bladder tumor. Our hypothesis is that the pattern of CK7 and CK20 expression in metastatic urothelial carcinoma duplicates the expression of the same markers in the primary tumors. Therefore, immunohistochemical staining of metastatic tumors for these 2 markers may be helpful for differential diagnosis in ambiguous metastatic tumor deposits.. -To determine the concordance of CK7 and CK20 expression in primary bladder urothelial carcinoma and the matched lymph node metastasis.. -We studied 26 patients with lymph node metastases who underwent radical cystectomy and bilateral lymphadenectomy for bladder carcinoma. Immunohistochemical staining for CK7 and CK20 was performed on formalin-fixed paraffin-embedded tissues containing primary cancers and lymph node metastases.. -In all cases, there was a concordant expression of CK20 in the primary cancer and its matched lymph node metastasis. Twelve cases (46%) showed positive CK20 immunoreactivity in the primary tumor and its matched lymph node metastases, whereas 14 cases (54%) were negative for CK20 in both the primary tumor and lymph node metastasis. All cases showed positive CK7 immunoreactivity in the primary cancers and matched lymph node metastases.. -CK20 immunoreactivity is reliably observed in metastases from bladder cancer when the primary tumor expresses CK20.

Topics: Adult; Aged; Aged, 80 and over; Carcinoma; Female; Humans; Immunohistochemistry; Intermediate Filament Proteins; Keratin-20; Keratin-7; Keratins; Lymph Nodes; Lymphatic Metastasis; Male; Middle Aged; Staining and Labeling; Tissue Distribution; Urinary Bladder Neoplasms

Flow cytometric assessment of DNA-ploidy and S-phase fraction in malignant tumors is compromised by the heterogeneity of cell subpopulations derived from the malignant and surrounding connective tissue, e.g., tumor, stromal and inflammatory cells. To evaluate the effect on quality of DNA cell cycle analysis and determination of DNA ploidy, cytokeratin labeling of epithelial cells was used for tumor cell enrichment in breast, ovarian, cervical and endometrial cancer prior to DNA analysis. In a prospective study, tumor cell subpopulations of 620 malignant tumors were labeled by a FITC-conjugated cytokeratin antibody (CK 5, 6, CK18 and CK 5, 6, 8 and CK 17, respectively) prior to flow cytometric cell cycle analysis. Compared to total cell analysis, detection rate of DNA-aneuploid tumors following cytokeratin labeling was increased from 62% to 76.5% in breast cancer, from 68% to 77% in ovarian cancer, from 60% to 80% in cervical cancer and from 30% to 53% in endometrial cancer. Predominantly in DNA-diploid tumors, a significantly improved detection of S-phase fraction of the tumor cells was shown due to the elimination of contaminating nonproliferating "normal cells". S-phase fraction following tumor cell enrichment was increased by 10% (mean) following cytokeratin staining in ovarian and endometrial cancer, by 30% in breast cancer and even by 70% in cervical cancer compared to total cell analysis. Thus, diagnostic accuracy of DNA-analysis was enhanced by cytokeratin labeling of tumor cells for all tumor entities investigated.

Topics: Biomarkers, Tumor; Breast Neoplasms; Carcinoma; DNA; Epithelial Cells; Female; Flow Cytometry; Fluorescein-5-isothiocyanate; Genital Neoplasms, Female; Humans; Keratins; Ploidies; Prospective Studies; S Phase; Sensitivity and Specificity

A case of epithelial-myoepithelial carcinoma of the parotid gland harboring p53 mutation is reported. The tumor removed from a 67-year-old Japanese female was composed of an organoid biphasic population of cells: inner dark epithelial cells were surrounded by clear myoepithelial cells. The cells were immunopositive for EMA and smooth muscle actin, respectively. Some of the epithelial cells formed solid nests. Immunostaining for proliferating cell nuclear antigen (PCNA) resulted in a higher percentage of labeled cells in the solid epithelial region than in the region with the more general biphasic pattern. Genetic analysis, including polymerase chain reaction-single strand conformational polymorphism (PCR-SSCP) and nucleotide sequencing, revealed a mutation in codon 207 (aspartic acid to glycine) of the p53 tumor-suppressor gene. To our knowledge, this is the first report of a mutation in the p53 gene in an epithelial-myoepithelial carcinoma of the salivary gland.

Topics: Actins; Aged; Base Sequence; Carcinoma; DNA Mutational Analysis; DNA, Neoplasm; Female; Genes, p53; Humans; Immunohistochemistry; Keratins; Parotid Neoplasms; Point Mutation; Proliferating Cell Nuclear Antigen

We present the first report of bladder carcinoma that demonstrates a mixture of two distinct histological patterns resembling malignant lymphoma. The patient was a 79-year-old man. One of the histological patterns was a diffuse growth of monomorphic carcinoma cells, and the other was a dense lymphoplasmacytic infiltrate, obscuring the carcinoma. The tumor cells showing both patterns expressed cytokeratin and epithelial membrane antigen, but not lymphoid markers. Careful immunohistochemical evaluation should be done when diagnosing urinary bladder carcinomas resembling lymphomas (other than primary lymphomas).

Topics: Aged; Carcinoma; Diagnosis, Differential; Humans; Immunoenzyme Techniques; Keratins; Lymphoma; Male; Mucin-1; Urinary Bladder Neoplasms

To report three patients with sinonasal undifferentiated carcinoma (SNUC) that invaded the orbit.. Retrospective small case series. The clinical, radiographic, and pathologic features of three patients with SNUC were reviewed.. Three patients with SNUC that invaded the orbit were evaluated. A biopsy was performed on the tumors, which were composed of small, hyperchromatic cells with numerous mitoses and areas of necrosis. Immunohistochemical staining was positive for cytokeratins AE1.3, epithelial membrane antigen, and neuron-specific enolase in all three tumors. Electron microscopic examination showed absence of neurosecretory granules and presence of basement membrane production. Two patients were treated with surgical resection and postoperative chemotherapy and/or radiation. One patient was treated with preoperative radiation and chemotherapy.. Sinonasal undifferentiated carcinoma is a high-grade tumor that arises in the nasal and paranasal sinuses and may invade the orbit. SNUC should be distinguished from other small, round, blue cell tumors, in particular, esthesioneuroblastoma.

Topics: Adult; Biomarkers, Tumor; Carcinoma; Female; Humans; Immunoenzyme Techniques; Keratins; Male; Maxillary Sinus Neoplasms; Middle Aged; Mucin-1; Neoplasm Invasiveness; Orbital Neoplasms; Paranasal Sinus Neoplasms; Phosphopyruvate Hydratase; Radiotherapy, Adjuvant; Retrospective Studies; Tomography, X-Ray Computed

CYFRA 21-1 is a newly developed tumor marker that is especially useful for detecting squamous cell carcinoma (SCC) of the lung. Squamous cell carcinoma antigen is a proven tumor marker that is especially useful for detecting SCC of the cervix. Our aim in this study was to compare the clinical value of CYFRA 21-1 and SCC antigen in the detection of nasopharyngeal carcinoma (NPC). Serum levels of CYFRA 21-1 and SCC antigen were measured in 80 untreated NPC patients and 77 healthy controls. The cutoff values of CYFRA 21-1 and SCC antigen, determined at the 95th percentile of the 77 healthy controls, were 2.48 ng/mL and 1.49 ng/mL, respectively. The results revealed that the mean serum value of only CYFRA 21-1 was significantly higher in the 80 NPC patients than in the 77 healthy controls, and the detection sensitivity of CYFRA 21-1 for NPC was significantly higher than that of SCC antigen. In conclusion, our results suggest that CYFRA 21-1 is a better tumor marker than SCC antigen for detection of NPC.

Topics: Adult; Aged; Aged, 80 and over; Antigens, Neoplasm; Biomarkers, Tumor; Carcinoma; Carcinoma, Squamous Cell; Female; Humans; Keratin-19; Keratins; Male; Middle Aged; Nasopharyngeal Neoplasms; Sensitivity and Specificity; Serpins

Keratin polypeptides of the nonhair type, numbered 1 through 20 in the Moll catalog, are selectively expressed in normal and neoplastic tissues. Keratin 1 (K1), the highest-molecular-weight keratin (67 kd), was generally considered specific for keratinizing squamous epithelia. However, recent studies have shown that it is an integral component of the multiprotein kininogen receptor of endothelial cells. A library of formalin-fixed, paraffin-embedded tissue samples was evaluated immunohistochemically (avidin-biotin peroxidase complex method) for K1 expression using a specific monoclonal antibody (Novocastra clone 34betaB4). The study group included a wide variety of normal tissues and 541 tumors of epithelial or mesenchymal derivation. The specificity of the antibody to K1 was verified in normal epithelial tissues, where the staining was essentially limited to the epidermis and Hassal corpuscles of the thymus and focally to other squamous epithelia. Among carcinomas, it was essentially limited to keratinizing squamous carcinomas. It was also regularly found in endothelial cells of normal capillaries, veins, and arteries. Capillary, cavernous, and venous hemangiomas often had endothelia with K1 positivity. Among the malignant vascular tumors, epithelioid hemangioendotheliomas were consistently positive (8 of 8). However, angiosarcomas had more variable expression (59 of 81 were positive), with well-differentiated tumors generally having greater reactivity than poorly differentiated examples. Mesenchymal tumors with K1 expression included schwannomas (10 of 16), epithelioid sarcomas (26 of 37), and synovial sarcomas (19 of 68). In the last 2 tumor types, K1 reactivity was detected in both epithelioid and spindled neoplastic populations. In addition to its specificity for keratinizing squamous epithelia, K1 can be immunohistochemically detected in normal vascular endothelial cells and a spectrum of vascular tumors. However, its expression in poorly differentiated vascular tumors is variable, suggesting that this marker is poorly conserved in highly transformed endothelia. The unexpected K1 immunoreactivity in nonvascular soft tissue tumors, such as synovial sarcoma, epithelioid sarcoma, and schwannomas, requires further study.

Topics: Adult; Carcinoma; Endothelium; Female; Fetus; Humans; Immunoenzyme Techniques; Keratins; Male; Mesoderm; Neoplasms; Sarcoma, Synovial; Vascular 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

The paucicellular variant of anaplastic carcinoma is an infrequent type of thyroid tumor. It was described as a tumor characterized by very low cellularity and prominent fibrosis, probably secondary to extensive infarction. These features could lead to an erroneous diagnosis of Riedel's thyroiditis. In this paper, we report the clinical and pathological features of two new cases of this unusual entity. Tumor cells were negative for thyroglobulin immunostaining and positive for keratins and p53. Although the number of reported cases is small, the cumulative data on these two cases and the previously reported ones lead us to suggest that the paucicellular variant may occur in younger patients than the conventional anaplastic thyroid carcinoma and that the tumor may be associated with a less aggressive tendency to local progression and metastasis.

Topics: Aged; Biopsy, Needle; Carcinoma; Diagnosis, Differential; Female; Fibrosis; Humans; Keratins; Male; Middle Aged; Thyroglobulin; Thyroid Neoplasms; Tumor Suppressor Protein p53

Anal gland carcinoma is a rare entity. The authors conducted a joint study of cases coded as definite or possible anal gland carcinoma from the archives of the Armed Forces Institute of Pathology and the Canadian Reference Center for Cancer Pathology.. Seven cases of potential anal gland carcinoma were identified from the Canadian files and 12 from the Armed Forces Institute of Pathology archives. Of these 19 cases, 14 had adequate material to allow clinical, histologic, and immunohistochemical analysis.. Seven of these 14 cases met a modified World Health Organization (WHO) definition of anal gland carcinoma. The mean age of these patients was 66 years (range, 60-72 years), with a male-to-female ratio of 6:1. The tumors were composed of haphazardly dispersed, small glands with scant mucin production that invaded the wall of the anorectal area with no obvious intraluminal component observed clinically or microscopically. Immunohistochemical studies were performed on all seven of these cases, revealing cytokeratin (CK) 7+/CK 20- expression in six cases, and CK 7+/CK 20+ expression in one case. The remaining seven cases showed no intraluminal component but did not meet a modified WHO definition of anal gland carcinoma. This group included three mucinous adenocarcinomas (two clinically arising in anal fistulas), all of which were CK 7+/CK 20+, and a rectal-type adenocarcinoma that was CK 7-/CK 20+. There was also a tumor interpreted as probable rectal-type adenocarcinoma that was CK 7+/CK 20+, and a tumor interpreted as probable squamous cell carcinoma that was CK 7-/CK 20-. The seventh tumor in this group, which could not be classified, was CK 7+/CK 20-.. A useful and discriminating definition of anal gland carcinoma is an anal canal tumor composed of haphazardly dispersed, small glands with scant mucin production invading the wall of the anorectal area without an intraluminal component. The glands are positive for CK 7.

Topics: Aged; Anus Neoplasms; Carcinoma; Female; Humans; Immunohistochemistry; Keratin-7; Keratins; Male; Middle Aged

The aim of the study was analysis of CK-10 expression in human skin squamous cell carcinoma (SCC) basing on immunohistochemical procedure. The study was carried out on 43 samples of skin SCC which were evaluated histopathologically with regard to 3-grade scale (G) of malignancy. In each case immunohistochemical reactions by use of ABC method were carried out in order to detect CK-10 within cancer cells. The expression of CK-10 was evaluated in accordance with arbitrary 3 grade scale: from +++ to +. The obtained results revealed affection of CK-10 expression in cancer cells. In G1 and G2 skin SCC a moderate expression of CK-10 was found and this occurred in cells grouped in nests. In G3 SCC the expression of CK-10 was very low and this was noted in single cells only. The use of immunohistochemical methods in evaluation of CK-10 expression can be a useful tool in routine histopathologic examination of tumors of epithelial origin.

Topics: Antibodies, Monoclonal; Carcinoma; Carcinoma, Squamous Cell; Humans; Immunohistochemistry; Keratins; Neoplasm Staging; Skin Neoplasms

Primary ovarian carcinomas with unusual histologic patterns can be difficult to differentiate from metastases. In this study, we reviewed 15 cases of mixed-epithelial carcinoma (12 serous, 1 serous and endometrioid, 1 endometrioid, 1 undifferentiated) with a predominant microcystic pattern and signet-ring cells. The patients' ages ranged from 31 to 78 (mean 58) years. The microcystic component in 11 patients had features of high-grade carcinoma and in 4 patients had features of low-grade carcinoma associated with areas of borderline tumor. The tumors in all 15 patients showed a predominant microcystic growth pattern composed of small cysts that were variable in size and shape. Signet-ring cells were also present in all cases (diffusely in nine cases, focally in six cases) within the neoplastic epithelial proliferation. Mucin was present in the lumina of some of the microcysts and in the cytoplasm of most of the signet-ring cells. A microcystic pattern and mucin-containing signet-ring cells can be seen as small foci or as a predominant component in primary epithelial nonmucinous ovarian carcinomas. It is important for pathologists to recognize these unusual findings in ovarian neoplasms, because they may produce a confusing apperance, even potentially suggesting a metastasis.

Topics: Adult; Aged; Carcinoma; Carcinoma, Endometrioid; Carcinoma, Signet Ring Cell; Cell Nucleus; Cystadenocarcinoma; Cystadenocarcinoma, Papillary; Cytoplasm; Female; Humans; Keratins; Middle Aged; Mucins; Ovarian Cysts; Ovarian Neoplasms

The aim of this study was to establish the cytokeratin expression profile of different types of thyroid carcinoma.. The expression of cytokeratins (CKs) 1, 4, 6, 7, 10/13, 18, 19 and 20 in 153 thyroid carcinomas were examined by immunohistochemistry.. All papillary carcinomas (n=86) and follicular carcinomas (n=19) showed expression of CK7 and CK18. The staining was often diffuse. CK19 staining was expressed in all papillary carcinomas and the staining was often diffuse. The staining was noted in 68% of follicular carcinomas and the staining was often focal. No difference in the expression was noted between the minimally invasive and widely invasive follicular carcinomas. Poorly differentiated carcinomas (n=10) showed CK7, CK18, CK19 expression in 60%, 60% and 40%, respectively. Anaplastic carcinomas (n=25) expressed CK7 in 84%, CK18 in 80%, CK19 in 76% and CK10/13 in 16%. Medullary carcinomas (n=13) showed CK7 expression in 100%, CK18 in 85% and CK19 in 77%. None of the medullary carcinomas showed diffuse positivity to CK19. All the thyroid carcinomas were negative for CKs 1, 4, 6 and 20.. Cytokeratin expression profile for each type of thyroid carcinoma was established.

Topics: Aged; Biomarkers, Tumor; Carcinoma; Diagnosis, Differential; Female; Humans; Immunohistochemistry; Intermediate Filament Proteins; Keratin-20; Keratins; Male; Middle Aged; Thyroid Neoplasms

The ability to diagnose prostate carcinoma would be improved by the detection of a tumor-associated antigen. P504S, a cytoplasmic protein, was recently identified by cDNA library subtraction in conjunction with high throughput microarray screening from prostate carcinoma. The aim of this study was to establish the pattern of expression of P504S in prostate carcinoma and benign prostatic tissue. A total of 207 cases, including 137 cases of prostate carcinoma and 70 cases of benign prostate, from prostatectomies (n = 77), prostate needle biopsies (n = 112), and transurethral prostate resections (n = 18) were examined by immunocytochemistry for P504S. P504S showed strong cytoplasmic granular staining in 100% of prostate carcinomas regardless of Gleason scores and diffuse (>75% of tumor) staining in 92% of cases. In contrast, 171 of 194 (88%) of benign prostates, including 56 of 67 (84%) benign prostate cases and 115 of 127 (91%) cases of benign glands adjacent to cancers were negative for P504S. The remainders of benign prostates were focally and weakly positive for P504S. The staining pattern of these normal glands was different and easily distinguishable from that observed in prostate carcinoma. Expression of P504S was not found in basal cell hyperplasia, urothelial cells/metaplasia and small atrophic glands that may mimic prostate carcinoma. Our findings indicate that P504S is a highly sensitive and specific positive marker for prostate carcinoma.

Topics: Antibodies, Monoclonal; Biomarkers, Tumor; Blotting, Western; Carcinoma; Humans; Immunoenzyme Techniques; Keratins; Male; Molecular Weight; Prostate; Prostatic Neoplasms; Racemases and Epimerases

The search continues to find methods to more effectively distinguish colorectal carcinoma patients who could be separated into high-risk and low-risk categories. Investigators have reported on the detection of occult micrometastases in bone marrow using antibodies to cytokeratin, which is a marker of epithelial cells but which has no tissue specificity, as opposed to villin, a cytoskeletal protein that is specifically involved in the formation of brush-border microvilli in the small intestine and colon epithelium. Specificity and sensitivity of antibody to villin (ID2C3) and antibody to cytokeratin (A45-B/B3) were first studied in normal bone marrow and in a test system in which cancer cell lines were mixed in normal bone marrow. In a preliminary study including 16 colorectal carcinoma patients, we compared the number of villin-positive cells with cytokeratin-presenting cells. As A45-B/B3, ID2C3 was determined to be sensitive enough to detect one cancer cell in 10(6) hematopoietic cells. Staining of hematopoietic cells with irrelevant antibody and a light staining of megakaryocytes with ID2C3 limited the specificity of the method. In colorectal carcinoma patients, correlation between ID2C3 and A45-B/B3 was 94%. Sensitivity and specificity of ID2C3 antibody to villin were satisfactory. Its clinical relevance must be investigated in further studies.

Topics: Aged; Aged, 80 and over; Antibodies, Monoclonal; Biomarkers, Tumor; Bone Marrow Cells; Bone Marrow Neoplasms; Carcinoma; Carrier Proteins; Colorectal Neoplasms; Female; Humans; Immunohistochemistry; Keratins; Male; Microfilament Proteins; Middle Aged; Sensitivity and Specificity; Tumor Cells, Cultured

Prostate cancer progression is associated with deregulation of genes like E-cadherin, p21/WAF1, MMP-2, VEGF, and IGF-binding protein, 3 and 5, all of which are target genes for the transcription factor activator protein 2alpha (AP-2alpha). We, therefore, hypothesize that the development/progression of prostate cancer is associated with changes in the expression of AP-2alpha.. We used immunofluorescent staining to assess the presence of AP-2alpha in normal, benign, and malignant human prostate tissues and to correlate its expression with tumor grade and stage.. We found that although AP-2alpha was expressed in normal prostate epithelium, it was not expressed in 30 prostate cancer specimens of different Gleason scores. Moreover, AP-2alpha protein was present in the luminal cell layer but not in the basal cell layer of the normal epithelium, which indicated that the loss of AP-2alpha staining in the prostate cancer specimens was not attributable to a lack of AP-2alpha-expressing cells. Further analysis demonstrated the presence of AP-2alpha in 2 (40%) of 5 atrophic normal epithelium, in 4 (24%) of 17 cases of benign prostatic hyperplasia, and in 2 (13%) of 13 cases of high-grade prostatic intraepithelial neoplasia. Loss or reduction in AP-2alpha expression was also observed in LNCaP, LNCaP-LN3, and PC3M-LN4 cell lines.. Our data demonstrate that AP-2alpha expression is associated with normal luminal differentiation and that a loss of AP-2alpha expression occurs early in the development of prostate adenocarcinoma. Loss of AP-2alpha may lead to deregulation in AP-2alpha target genes that normally regulate cellular growth and differentiation.

Topics: Biomarkers, Tumor; Carcinoma; Cell Differentiation; Disease Progression; DNA-Binding Proteins; Epithelial Cells; Fluorescent Antibody Technique; Humans; Immunohistochemistry; Keratins; Male; Prostate; Prostate-Specific Antigen; Prostatectomy; Prostatic Hyperplasia; Prostatic Neoplasms; Reference Values; Transcription Factor AP-2; Transcription Factors; Tumor Cells, Cultured

We studied cytokeratin-positive (CK+) cells in the bone marrow (BM) and tumor markers (TM) in the blood of 128 patients with primary breast cancer in order to obtain an early diagnosis of residual disease. CK+ cells of two BM aspirations were detected by immunocytochemistry (IC). To evaluate the usefulness of immunomagnetic separation (IMS) for tumor cell enrichment in clinical samples, IMS was performed prior to IC and compared with the results for IC alone. The overall CK+ rate was 34% (44/128 patients), 29% (15/51) for patients with T1 tumors, 33% (28/84) for N0 patients and 31% (26/82) for patients with G1-2 breast carcinoma. Interestingly, 67% of CK+ patients were only positive in one of the two aspirates studied. A comparison between IC alone and IMS/IC could be performed in 70/128 patients (28/70 CK+). In 6/28 patients, CK+ cells were detected by both methods, in 16/28 patients only by IC and in 6/28 patients only by IMS. At least one TM, including carcinoembryonic antigen, carbohydrate antigen 15-3 and tissue polypeptide antigen, was increased in 58/128 (45%) patients [21/58 (36%) were CK+ in the BM]. Surprisingly, levels for the extracellular domain of Her-2/neu in serum samples were within the normal range in every patient studied. After a 2-year follow-up, 7/128 patients relapsed (3/7 CK+/TM-; 2/7 CK-/TM+; 2/7 CK-/TM-). We conclude that studying two BM aspirates for CK+ cells by IC in combination with TM determination is useful for identifying patients with a higher risk for relapse, however, tumor cell enrichment techniques will have to be improved for clinical use.

Topics: Adult; Aged; Aged, 80 and over; Antibodies, Monoclonal; Biomarkers, Tumor; Bone Marrow Cells; Breast Neoplasms; Carcinoma; Female; Humans; Immunohistochemistry; Immunomagnetic Separation; Keratins; Middle Aged; Neoplasm Recurrence, Local; Neoplasm, Residual; Predictive Value of Tests; Risk Factors; Sensitivity and Specificity

Human Papillomavirus type 16 (HPV-16) is the cause of both benign lesions and ano-genital cancers. In HPV-associated cancers the transforming properties of the expressed viral E6 and E7 proteins have been revealed by a number of different assays. We have generated transgenic mice expressing HPV-16 E6/E7 genes under the control of the murine keratin 5 gene promoter, which should confer cell-type specific expression in the basal cells of squamous stratified epithelia. Transgenic mice developed thymic hyperplasia and lung neoplasia with 100% frequency, the thymus showing a size increase at 2 months and reaching the maximum dimension at 6 months, when lung carcinomas appeared. After this time the size of hyperplastic thymi decreased, while malignant formations invaded the mediastinal area. Hepatic metastasis could be also observed in some of the animals at the autopsy and death invariably occurred around 10-11 months of age.

Topics: Animals; Carcinoma; Keratin-15; Keratin-5; Keratins; Liver Neoplasms; Lung Neoplasms; Mice; Mice, Transgenic; Oncogene Proteins, Viral; Organ Size; Papillomavirus E7 Proteins; Papillomavirus Infections; Promoter Regions, Genetic; Recombinant Fusion Proteins; Repressor Proteins; Thymus Gland; Thymus Hyperplasia; Tumor Virus Infections

A 73-year-old woman had a linear yellowish plaque on the upper part of her right ear since birth. She presented because of the sudden growth of a nodule within the plaque. The plaque was waxy and yellowish, arching around the upper part of the ear. A reddish to yellowish large nodule was seen within the central part of the arc-shaped plaque; in addition, a small pigmented nodule, a small skin-colored nodule, and a few pigmented papules were observed in the anterior half of the arched plaque. Histopathologic examination revealed the large nodule to be sebaceous carcinoma, the small pigmented nodule to be trichoblastoma, the small skin-colored nodule to be sebaceoma with the features of trichoblastoma, a few pigmented papules to be superficial trichoblastomas due to primitive follicular induction, and the linear yellowish plaque to be nevus sebaceus. Although our literature search revealed scanty reports of definite cases of sebaceous carcinoma in nevus sebaceus, the presented case demonstrated the occurrence of sebaceous carcinoma in nevus sebaceus. Malignant neoplasms occurring in nevus sebaceous seem to be extremely rare, but care should be taken when a large nodule suddenly grows in a lesion of nevus sebaceus, especially in older adults. The presented case also suggested a close relation between trichoblastoma and sebaceoma. The cytokeratin staining pattern could not distinguish between sebaceous and follicular neoplasms in our case.

Topics: Aged; Carcinoma; Carcinoma, Skin Appendage; Ear Neoplasms; Ear, External; Female; Hamartoma; Humans; Immunohistochemistry; Keratins; Sebaceous Gland Neoplasms; Skin Diseases; Skin Neoplasms

A 69-year-old japanese female with epithelial myoepithelial carcinoma (EMC) in the parotid gland is reported. The tumor, 3.5 x 4.0 x 1.5 cm in size, was located in the left parotid gland. Histopathological examination of the surgically removed tumor revealed that it was composed of double-layered, tubule-like structures formed by inner eosinophilic ductal cells and outer clear cells, as well as solid clear cell nests. The unique histological finding of this tumor was that it had a cribriform-like arrangement of myoepithelial cells resembling an adenoid cystic carcinoma. On the other hand, the typical ductal and myoepithelial components of EMC showed the usual biphasic pattern and the expected immunophenotypes, with expression of low molecular weight cytokeratins, CAM 5.2 and EMA in the ductal part, and smooth muscle actin, S-100 protein, and vimentin in the myoepithelial component.

Topics: Aged; Carcinoembryonic Antigen; Carcinoma; Female; Humans; Immunohistochemistry; Keratins; Parotid Neoplasms

To develop a highly sensitive quantitative RT-PCR hybridization assay for the determination of CK-19 mRNA in peripheral blood of patients with breast cancer.. Quantification of CK-19 mRNA was based on the coamplification of CK-19 mRNA with a recombinant CK-19 RNA internal standard (CK-19 RNA-IS) through RT-PCR. The biotinylated amplification products were immobilized on steptavidin coated wells, hybridized with digoxigenin labeled probes and determined through an antidigoxigenin antibody conjugated to alkaline phosphatase by luminometric detection. The developed luminometric hybridization assay was validated with samples containing total RNA of known amounts from CK-19 expressing cells (MCF-7) in the presence of 1 microg total RNA isolated from peripheral blood mononuclear cells (PBMC) of healthy controls and a constant amount of CK-19 RNA-IS. The method was applied for the quantitative determination of CK-19 mRNA in the peripheral blood of 26 healthy volunteers, 14 patients with stage IV breast cancer and 37 patients with stage I/II breast cancer before chemotherapy.. Luminescence ratios for CK-19 mRNA and CK-19 RNA-IS were linearly related to the number of MCF-7 cells within the range of 1 to 2000 cells. The overall reproducibility of the assay (between-run) varied between 8.9% and 13.4%. The method can clearly detect CK-19 mRNA from 1 MCF-7 cell in the presence of 10(6) normal PBMC and is highly specific as none of the 26 healthy controls tested had detectable CK-19 mRNA levels, while 10 out of 14 (71.4%) and 9 out of 37 (24.3%) patients with stage IV and stage I/II breast cancer, respectively, were tested positive.. The developed quantitative RT-PCR hybridization assay for CK-19 is reproducible, highly sensitive and specific, and can be used for a large-scale prospective evaluation of clinical samples.

Topics: Adolescent; Adult; Aged; Breast Neoplasms; Carcinoma; Female; Humans; Keratins; Luminescent Measurements; Middle Aged; Molecular Probes; Nucleic Acid Hybridization; Reference Standards; Reproducibility of Results; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Sensitivity and Specificity; Tumor Cells, Cultured

Specimens from 17 head and neck tumor patients were immunohistochemically stained with monoclonal antibodies against HLA-DR, CD1a, RFD1, LAG, CD3, CD4, CD8, CD45RO, CD68, and cytokeratin to identify the nature and distribution of dendritic cells (DCs), T cells, and macrophages. Small numbers of DCs were present in all but 2 specimens. They were located between the tumor cells and in the stroma, especially in areas of inflammatory cell infiltration. Variable numbers of T lymphocytes (cytotoxic and memory type) occurred in the same locations. Numerous macrophages were found in the epithelium, in the stroma, and in the vicinity of tumor cells. The presence of DCs in head and neck tumors indicates that the organism has activated the immune surveillance system and is trying to present tumor antigens. Considering the sparsity of DCs in the malignant tissues, the T cell response can be only limited.

Topics: Antibodies, Monoclonal; Antigens, CD; Carcinoma; Dendritic Cells; Head and Neck Neoplasms; HLA-DR Antigens; Humans; Immunohistochemistry; Keratins; Langerhans Cells; Major Histocompatibility Complex

It is important to clarify the clinicopathologic characteristics of micrometastasis in lymph nodes and microinvasion in primary lesions for the treatment options with regard to submucosal gastric cancer.. We examined 1945 lymph nodes and 68 primary tumors resected from 79 patients with submucosal gastric cancer. Two consecutive sections were prepared for simultaneous staining with ordinary hematoxylin and eosin and immunostaining with anticytokeratin antibody (CAM 5.2), respectively.. The incidence of nodal involvement in 79 patients with submucosal gastric cancer increased from 13% (10/79 patients) by hematoxylin and eosin staining to 34% (27/79 patients) by cytokeratin immunostaining. Micrometastases in the lymph nodes were found in 17 of 69 patients (25%), with cancer-free nodes examined by hematoxylin and eosin. Microinvasion to the muscularis propria was found in 11 of 68 patients (16%) who were histologically diagnosed with submucosal gastric cancer. Survival analysis demonstrated a lesser 5-year survival in the patients with micrometastasis in lymph nodes (82%) and with microinvasion to muscularis propria (73%). A high incidence of nodal involvement was found in submucosal cancers of large size (> 2 cm; 43%), a depressed type (48%), lymphatic invasion (73%), and deeper submucosal invasion (submucosal 3, 53%). A higher incidence of microinvasion was found with the diffuse-type carcinoma (33%).. Cytokeratin immunostaining is useful for detecting micrometastasis and microinvasion in submucosal gastric cancer. Tumor size, macroscopic type, lymphatic invasion, and the depth of submucosal invasion are strongly associated with lymph node involvement.

Topics: Adult; Aged; Aged, 80 and over; Carcinoma; Coloring Agents; Eosine Yellowish-(YS); Female; Fluorescent Dyes; Gastric Mucosa; Hematoxylin; Humans; Immunohistochemistry; Keratins; Lymph Nodes; Lymphatic Metastasis; Male; Middle Aged; Neoplasm Invasiveness; Prognosis; Staining and Labeling; Stomach Neoplasms; Survival Analysis

Syringoid carcinoma (syringoid "eccrine" carcinoma or eccrine epithelioma) is a rare cutaneous tumor with some controversy regarding its correct definition. It may also be difficult to differentiate from its benign counterpart (syringoma), other adnexal carcinomas, and cutaneous metastasis from adenocarcinomas. We present a case of a syringoid carcinoma of the clear cell variant complemented with an immunohistochemical and ultrastructural study, the latter revealing cytoplasmic accumulation of glycogen and presence of intercellular and intracellular lumina in clear tumor cells, as well as diverse hallmarks of malignancy (i.e., perineural invasion, tumor necrosis, and deep invasion). Clear tumor cells showed cytoplasmic and membranous immunoreactivity to epithelial membrane antigen, carcinoembryonic antigen, keratins, and S-100. Our ultrastructural and immunohistochemical results support the ductal differentiation of the glycogen-filled clear cell tumor population.

Topics: Aged; Aged, 80 and over; Carcinoembryonic Antigen; Carcinoma; Female; Humans; Keratins; S100 Proteins; Scalp; Sweat Gland Neoplasms

A pilot study of a novel translational research method to simultaneously assay multiple molecular markers and DNA in fine-needle aspirates (FNA) of mammographically detected breast lesions is described. Specimen mammography-guided 20-gauge FNAs obtained from 86 lesions and 22 areas of normal tissue were analyzed by multiparameter flow cytometry for DNA content, her2/neu, transforming growth factor alpha (TGF alpha), and the epithelial marker cytokeratin (CK) simultaneously. Epithelial cell her2/neu positivity was detected in 12 of 44 (27%) of invasive ductal carcinomas and 3 of 9 (33%) ductal carcinoma in situ (DCIS), 10 of 30 (33%) benign lesions, and 4 of 22 (18%) normal tissue aspirates. All lesions and normal tissue showed a similar positive rate for TGFalpha ranging from 61 to 76%. The CK(+)TGF alpha(-)her2/neu(+) immunophenotype was more frequently positive in aneuploid tumors (22%) than all other lesions (7%) (P < 0.05). Specimen mammography-guided FNAs provide fresh cells for flow cytometric multiple marker analysis and immunophenotyping of clinically occult breast lesions and normal tissue.

Topics: Adult; Aged; Aged, 80 and over; Aneuploidy; Biomarkers, Tumor; Biopsy, Needle; Breast; Breast Neoplasms; Carcinoma; Carcinoma, Ductal, Breast; Carcinoma, Intraductal, Noninfiltrating; Carcinoma, Lobular; Diploidy; DNA; Female; Flow Cytometry; Humans; Immunophenotyping; Keratins; Mammography; Middle Aged; Pilot Projects; Receptor, ErbB-2; Transforming Growth Factor alpha

Topics: Antibodies; Carcinoma; Humans; Immunohistochemistry; Keratins; Lymphatic Metastasis; Pelvis; Urologic Neoplasms

Caspase 8 plays an essential role in the execution of death receptor-mediated apoptosis. To determine the localization of endogenous caspase 8, we used a panel of subunit-specific anti-caspase 8 monoclonal antibodies in confocal immunofluorescence microscopy. In the human breast carcinoma cell line MCF7, caspase 8 predominantly colocalized with and bound to mitochondria. After induction of apoptosis through CD95 or tumor necrosis factor receptor I, active caspase 8 translocated to plectin, a major cross-linking protein of the three main cytoplasmic filament systems, whereas the caspase 8 prodomain remained bound to mitochondria. Plectin was quantitatively cleaved by caspase 8 at Asp 2395 in the center of the molecule in all cells tested. Cleavage of plectin clearly preceded that of other caspase substrates such as poly(ADP-ribose) polymerase, gelsolin, cytokeratins, or lamin B. In primary fibroblasts from plectin-deficient mice, apoptosis-induced reorganization of the actin cytoskeleton, as seen in wild-type cells, was severely impaired, suggesting that during apoptosis, plectin is required for the reorganization of the microfilament system.

Topics: Actins; Amino Acid Sequence; Animals; Antibodies, Monoclonal; Apoptosis; Biological Transport; Breast Neoplasms; Carcinoma; Caspase 8; Caspase 9; Caspases; Cytoplasm; Enzyme Precursors; fas Receptor; Fibroblasts; Gelsolin; Humans; Intermediate Filament Proteins; Keratins; Lamin Type B; Lamins; Mice; Mice, Mutant Strains; Mitochondria; Molecular Sequence Data; Nuclear Proteins; Plectin; Receptors, Tumor Necrosis Factor; Substrate Specificity; Tumor Cells, Cultured

Expression of cytokeratins 7 (CK7) and 20 (CK20) may help distinguish the site of origin for metastatic carcinomas. Little is known regarding their expression in biliary tract and pancreatic carcinomas. Our aim was to study the expression of CK7 and CK20 in these tumors.. Fifty-three carcinomas of the extrahepatic bile ducts (n = 8), ampulla of Vater (n = 7), gallbladder (n = 11), and pancreas (n = 27), were retrieved from the surgical pathology files of the University of Massachusetts Medical Center. Formalin-fixed, paraffin-embedded sections were immunostained with mouse monoclonal antibodies to CK7 and CK20 using an avidin-biotin immunoperoxidase technique with microwave antigen retrieval. The percentage of cells positive for each antibody was assessed on a scale of 0 to 3 (0, <10%; 1+, 10% to 50%; 2+, 51% to 90%; 3+, >90%).. The majority of carcinomas in all groups were positive for CK7 (CK7+) and negative for CK20 (CK20-). Of the CK7+ tumors, the majority of tumors in each group were 3+ positive.. (1) Carcinomas of the extrahepatic biliary tract and pancreas are strongly positive for CK7 and negative for CK20 and can be included in the differential diagnosis of other carcinomas with this profile in metastatic sites. (2) The CK7/CK20 immunostaining profile will not identify the site of origin for tumors with extensive growth in the porta hepatis region.

Topics: Adult; Aged; Aged, 80 and over; Bile Duct Neoplasms; Bile Ducts, Extrahepatic; Carcinoma; Diagnosis, Differential; Female; Gallbladder Neoplasms; Humans; Intermediate Filament Proteins; Keratin-20; Keratin-7; Keratins; Liver Neoplasms; Lymphatic Metastasis; Male; Middle Aged; Pancreatic Neoplasms

The morphologic distinction of ependymomas with epithelial cytology from metastatic carcinoma may pose a significant problem in differential diagnosis. The known presence of keratin in glioma cells further complicates the issue. Using the labeled streptavidin-biotin method with automated staining, we studied epithelial and glial marker expression in 52 ependymomas of varying type and grade, including 20 epithelial-appearing, 14 glial-appearing, eight mixed pattern, and 10 myxopapillary tumors; 38 were low grade and 14 anaplastic. All tumors were immunoreactive for glial fibrillary acidic protein (GFAP), and S-100 protein. Diffuse staining for GFAP was noted in glial-appearing ependymomas featuring perivascular pseudorosettes. Diffuse immunostaining for S-100 protein was seen in cellular lesions exhibiting epithelial-like features. Staining was more diffuse for GFAP than S-100 protein in anaplastic ependymomas. Keratin (AE1/AE3) reactivity was seen in 98% of cases, the pattern being similar to that of GFAP. The frequency of staining for other keratins varied: wide-spectrum keratin (35%), cytokeratin (CK)7 (20%), CAM 5.2 (19%), CK903 (14%), and CK20 (8%); as a rule, it was scant and limited to occasional cells and processes. epithelial membrane antigen (EMA) staining was seen in 36% of all cases and in 67% of epithelial-appearing tumors wherein it often high-lighted microlumina. Aside from AE1/AE3 staining and very infrequent wide-spectrum keratin and EMA reactivity, expression of epithelial markers was not seen in anaplastic ependymomas. No carcinoembryonic antigen (CEA) positivity was noted in any case. Collagen IV reactivity was limited to tumor cell-stroma interfaces. Although variable, S-100 protein and GFAP staining is seen in all ependymomas, particularly in true and perivascular pseudorosettes. Widespread reactivity for keratin AE1/AE3 corresponds closely to the pattern of GFAP staining. Significant staining for other keratins or for CEA is inconsistent with a diagnosis of ependymoma. EMA reactivity is largely limited to luminal staining of rosettes and tubules.

Topics: Biomarkers, Tumor; Carcinoma; Collagen; Diagnosis, Differential; Ependymoma; Glial Fibrillary Acidic Protein; Humans; Immunohistochemistry; Immunophenotyping; Keratins; Mucin-1; S100 Proteins

Topics: Axilla; Biopsy; Breast; Breast Neoplasms; Carcinoma; Epithelial Cells; Female; Humans; Immunohistochemistry; Keratins; Lymph Nodes; Lymphatic Metastasis; Melanoma; Neoplasm Seeding; Skin Neoplasms

Seventy-five skin tumours were studied to investigate the value of immunohistochemistry in differentiating basal cell, squamous cell and basosquamous carcinomas of the skin.. Archived paraffin-embedded tissue samples of basal cell carcinomas (n = 39), squamous cell carcinomas (n = 23) and basosquamous carcinomas (n = 13) were stained immunohistochemically using a panel of antibodies. All of the basal cell carcinomas stained positively for Ber EP4, in contrast to the group of squamous cell carcinomas, that showed no staining. Basosquamous carcinomas all showed at least some areas of Ber EP4 positivity. None of the basal cell carcinomas, but most of the squamous cell carcinomas (22 of 23) expressed epithelial membrane antigen (EMA). Only one of the basosquamous carcinomas expressed EMA positivity focally. CAM 5.2, carcinoembryonic antigen (CEA) and 34betaE12 antibodies lacked specificity in relation to the different tumour types.. Distinction of basal and squamous cell carcinomas of the skin can be readily achieved with routine immunohistochemistry using Ber EP4 and EMA. Identification of basosquamous carcinoma is also facilitated with this method.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Antigens, Surface; Biomarkers; Biomarkers, Tumor; Carcinoembryonic Antigen; Carcinoma; Carcinoma, Basal Cell; Carcinoma, Basosquamous; Carcinoma, Squamous Cell; Diagnosis, Differential; Female; Humans; Immunohistochemistry; Keratins; Male; Middle Aged; Mucin-1; Skin Neoplasms

To undertake a comparative evaluation of three antimesothelial markers (thrombomodulin, cytokeratin 5/6 and calretinin) with broad spectrum cytokeratin (AE1/AE3) in differentiating between sarcomatoid mesothelioma and a spectrum of spindle cell neoplasms.. Thirty-one malignant sarcomatoid mesotheliomas were studied. Calretinin expression was focally identified in 12 (39%) tumours and thrombomodulin and cytokeratin 5/6 immunoreactivity was seen in nine (29%) cases. In comparison there was strong diffuse cytoplasmic reactivity with the broad spectrum cytokeratin (AE1/AE3) in 24 of 31 (77%) tumours. Thirty mixed spindle cells neoplasms were studied. No calretinin expression was identified in any case. Thrombomodulin immunoreactivity was identified in four (16%) cases (two angiosarcomas, two high-grade sarcomas, not otherwise specified). Cytokeratin 5/6 expression was seen in one high-grade pulmonary sarcoma originally termed malignant fibrous histiocytoma. None of the antimesothelial markers was expressed in the four spindle cell carcinomas studied. In contrast, broad spectrum cytokeratin was diffusely expressed in all four spindle cell carcinomas (three pulmonary, one renal), both synovial sarcomas, both malignant mixed Müllerian tumours, one of three pulmonary leiomyosarcomas and two of nine sarcomas, not otherwise specified.. Immunohistochemistry has a more limited role in the diagnosis and distinction of sarcomatoid mesothelioma from other spindle cell neoplasms. The combination of a broad spectrum cytokeratin with calretinin combines both high sensitivity (77% for AE1/AE3) with high specificity (100% for calretinin) for sarcomatoid mesothelioma and can be diagnostically useful. The mesothelial markers, thrombomodulin and cytokeratin 5/6, are not useful alone in the diagnosis of sarcomatoid mesothelioma as each shows insufficient antibody sensitivity, although together they complement calretinin.

Topics: Biomarkers, Tumor; Calbindin 2; Carcinoma; Carcinoma, Renal Cell; Carcinoma, Squamous Cell; Diagnosis, Differential; Humans; Immunohistochemistry; Keratins; Kidney Neoplasms; Lung Neoplasms; Mesothelioma; S100 Calcium Binding Protein G; Sarcoma; Thrombomodulin

The aims of this study were to ascertain the incidence of intercalated duct hyperplasia in association with cases of epithelial-myoepithelial carcinoma (EMC), and to explore a possible relationship between them and hybrid carcinomas of salivary glands.. Seven cases of EMC with sufficient surrounding non-tumour parotid were examined. Three cases contained foci of intercalated duct hyperplasia adjacent to the tumour. One of the cases was a hybrid tumour composed of EMC and mucoepidermoid carcinoma. The hyperplastic intercalated ducts formed multiple foci within the salivary parenchyma and were composed of bland, uniform ducts. Cytological atypia was not identified.. Intercalated duct hyperplasia may be a precursor lesion to EMC. Furthermore, it may also explain why EMC is frequently associated with other salivary gland carcinomas, so-called hybrid tumours, as well as sharing histological features with adenoid cystic carcinoma. Recognition of the latter is of particular importance because adenoid cystic carcinoma carries a poor prognosis.

Topics: Actins; Biomarkers; Carcinoma; Humans; Hyperplasia; Immunohistochemistry; Keratins; Muscles; Neoplasms, Multiple Primary; S100 Proteins; Salivary Ducts; Salivary Gland Neoplasms

Sentinel lymph node (SLN) biopsy has been shown to predict axillary metastases accurately in early stage breast cancer. Some patients with locally advanced breast cancer receive preoperative (neoadjuvant) chemotherapy, which may alter lymphatic drainage and lymph node structure. In this study, we examined the feasibility and accuracy of SLN mapping in these patients and whether serial sectioning and keratin immunohistochemical (IHC) staining would improve the identification of metastases in lymph nodes with chemotherapy-induced changes. Thirty-eight patients with stage II or III breast cancer treated with neoadjuvant chemotherapy were included. In all patients, SLN biopsy was attempted, and immediately afterward, axillary lymph node dissection was performed. If the result of the SLN biopsy was negative on initial hematoxylin and eosin-stained sections, all axillary nodes were examined with three additional hematoxylin and eosin sections and one keratin IHC stain. SLNs were identified in 31 (82%) of 38 patients. The SLN accurately predicted axillary status in 28 (90%) of 31 patients (three false negatives). On examination of the original hematoxylin and eosin-stained sections, 20 patients were found to have tumor-free SLNs. With the additional sections, 4 (20%) of these 20 patients were found to have occult lymph node metastases. These metastatic foci were seen on the hematoxylin and eosin staining and keratin IHC staining. Our findings indicate that lymph node mapping in patients with breast cancer treated with neoadjuvant chemotherapy can identify the SLN, and SLN biopsy in this group accurately predicts axillary nodal status in most patients. Furthermore, serial sectioning and IHC staining aid in the identification of occult micrometastases in lymph nodes with chemotherapy-induced changes.

Topics: Adenocarcinoma, Mucinous; Adult; Aged; Axilla; Biopsy, Needle; Breast Neoplasms; Carcinoma; Carcinoma, Ductal, Breast; Carcinoma, Lobular; Female; Humans; Immunohistochemistry; Keratins; Lymph Node Excision; Lymph Nodes; Lymphatic Metastasis; Microtomy; Middle Aged; Neoadjuvant Therapy; Neoplasm Staging; Retrospective Studies

Thyroid transcription factor-1 (TTF-1), a member of the NKx2 family of homeodomain transcription factors, is a mediator of thyroid-specific transcription of the thyroglobulin (TG) gene. The combined immunohistochemical profile of TTF-1, TG, cytokeratin 7 (CK7), and cytokeratin 20 (CK20) in neoplasms of the thyroid gland and their metastases to other sites has not been defined previously. Formalin-fixed tissue of 43 thyroid tumors, including 31 carcinomas and 12 adenomas, and 16 metastasic lesions were immunostained using monoclonal antibodies to TTF-1, TG, CK7, and CK20. Immunoreactivity of the primary tumors (adenomas and carcinomas) for TTF-1 was seen in 32 cases (74%), TG 32 (74%), and CK7 34 (79%), whereas none (0%) showed positivity for CK20. The distribution of reactivity in the 31 carcinomas for TTF-1, TG, and CK7, respectively was papillary (8/8), (8/8), and (8/8); poorly differentiated (6/7), (4/7), and (6/7); oncocytic (Hürthle) cell (2/6), (6/6), and (4/6); follicular (4/4), (3/4), and (3/4); medullary (1/2), (0/2), and (1/2). One of four anaplastic carcinomas was focally immunoreactive showing positivity for TTF-1 only. Of the six follicular adenomas, five were positive for TTF-1, six for TG, and six for CK7. Among the six oncocytic cell adenomas, five were reactive for TTF-1, five for TG, and all six for CK7. Twelve (75%) of the 16 metastatic tumors were positive for TTF-1, 10 (63%) for TG, 15 (94%) for CK7, and none (0%) for CK20. In summary, TTF-1 and TG are demonstrable by immunohistochemistry in the majority of thyroid neoplasms. Compared with TG, an antibody to TTF-I is a similarly sensitive marker for thyroid tumors. Moreover, TTF-1 is a more sensitive marker for poorly differentiated carcinomas and metastasis. In most cases, its nuclear pattern of immunoreactivity facilitates interpretation. Thyroid tumors are CK7+/CK20-. The panel of antibodies for TG, TTF-1, CK7, and CK20 is useful when the thyroid origin of a metastatic tumor is a consideration.

Topics: Adenoma; Carcinoma; Humans; Immunohistochemistry; Keratins; Nuclear Proteins; Thyroglobulin; Thyroid Neoplasms; Thyroid Nuclear Factor 1; Transcription Factors

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 histogenesis of thyroid gland angiomatoid tumors, probably as a primary angiosarcoma, has been a controversy for many years. These tumors may be variants of undifferentiated (anaplastic) carcinomas. We report a thyroid gland angiomatoid carcinoma in a 61-year-old African American male. The tumor had a heterogeneous pattern with both sarcomatous and epithelioid areas. Tumor cells lined some vascular-like spaces and others had intracytoplasmic lumens containing red blood cells. The tumor cells were found to express multiple endothelial (factor VIII-related antigen, CD31, CD34, and Ulex europaeus I lectin) and epithelial (cytokeratin and epithelial membrane antigen) markers as well as thyroglobulin by immunohistochemistry. This rare presentation demonstrates the heterogeneous nature of thyroid gland angiomatoid carcinoma with both epithelial and endothelial differentiation.

Topics: Antigens, CD34; Carcinoma; Cell Differentiation; Hemangiosarcoma; Humans; Immunohistochemistry; Keratins; Lectins; Male; Middle Aged; Mucin-1; Plant Lectins; Platelet Endothelial Cell Adhesion Molecule-1; Thyroglobulin; Thyroid Neoplasms; von Willebrand Factor

Cytokeratin 7 (CK 7) and cytokeratin 20 (CK 20) are low molecular weight cytokeratins. Their anatomic distribution is generally restricted to epithelia and their neoplasms. We surveyed 435 epithelial neoplasms from various organ systems by immunohistochemistry using CK 7 and CK 20 monoclonal antibodies. Expression of CK 7 was seen in the majority of cases of carcinoma, with the exception of those carcinomas arising from the colon, prostate, kidney, and thymus; carcinoid tumors of the lung and gastrointestinal tract origin; and Merkel cell tumor of the skin. The majority of cases of squamous cell carcinoma of various origins were negative for CK 7, except cervical squamous cell carcinoma, in which 87% of cases were positive. Approximately two thirds of cases of malignant mesothelioma were CK 7-positive. CK 20 positivity was seen in virtually all cases of colorectal carcinomas and Merkel cell tumors. CK 20-positive staining was also observed in cases of pancreatic carcinomas (62%), gastric carcinoma (50%), cholangiocarcinomas (43%), and transitional cell carcinomas (29%). The expression of CK 20 was virtually absent in carcinomas from other organ systems and in malignant mesothelioma. CK 7- and CK 20-negative epithelial neoplasms included adrenal cortical carcinoma, germ cell tumor, prostate carcinoma, renal cell carcinoma, and hepatocellular carcinoma.

Topics: Biomarkers, Tumor; Carcinoma; Diagnosis, Differential; Female; Humans; Immunoenzyme Techniques; Intermediate Filament Proteins; Keratin-20; Keratin-7; Keratins; Male; Neoplasms

Thyroid anaplastic (undifferentiated) carcinomas (TACs) comprise a morphologically heterogeneous group of tumors, which can arise in the background of differentiated papillary or follicular carcinoma. The thyroid epithelial differentiation varies in these tumors and has not been completely characterized. In this study, we immunohistochemically analyzed different variants TACs from 35 patients by using antibodies specific to 9 different keratin polypeptides, epithelial membrane antigen, thyroid transcription factor I (TTF-1), and thyroglobulin. These tumors were histologically divided into 3 categories: squamoid-cohesive (SC, 13 tumors), spindle cell sarcomatous (SS, 8 cases) and intermediate group, including tumors with giant cells and solid epithelioid components (GC, 18 tumors); 4 tumors had 2 components. The patients ages ranged from 40 to 89 years, with a mean age in all groups of 70 years. TTF-1 was present in only 2 of 9 of the SC tumors, and absent in all other TACs, but was present in entrapped differentiated components. Thyroglobulin was absent in all but 1 case. A complex keratin (K) pattern of stratified epithelia was typically seen in the SC tumors with extensive K7, K8, K17, K18, and K19, and variable K13 and K14 expression; EMA was also present. K16 was limited to squamous pearls in 1 tumor, and K10 was absent. The GC carcinomas typically had K8 and K18, whereas the expression of K7 was variable and that of K14, K17, and K19 sporadic; EMA was variably present in half of the cases. The keratins in spindle cell sarcomatous tumors were usually limited to K7, K8, and K18, often in limited numbers of cells. EMA was present in 1 case only. These results indicate a complex pattern of keratins in squamoid and giant cell TACs, similar to papillary carcinoma and suggesting the possibility of relationship. There was a progressive loss of epithelial differentiation and keratins in sarcomatoid TACs. Loss of TTF-1 is a nearly uniform feature of TAC and disallows the use of this marker to pinpoint a thyroid origin of these tumors.

Topics: Adenocarcinoma, Follicular; Aged; Aged, 80 and over; Carcinoma; Carcinoma, Papillary; Female; Fluorescent Antibody Technique, Direct; Humans; Keratins; Male; Middle Aged; Nuclear Proteins; Thyroglobulin; Thyroid Neoplasms; Thyroid Nuclear Factor 1; Transcription Factors

Despite the use of radical locoregional therapeutic methods and although conventional methods of diagnosis give no indication of metastases at the time of operation, distant metastases develop in approximately 50% of carcinoma patients within 5 years. While local relapses after the R0 resection of solid tumors are mainly a matter of concern for the surgeon, distant metastases can be traced back to the systemic dissemination of tumor cells at the time of operation.. A prospective study is presented in which 145 patients suffering from colon carcinoma were analyzed for the prognostic relevance of isolated disseminated tumor cells detected in the bone marrow (IDT BM). The patients were operated on between 1993 and 1997 and subsequently observed until 1999.. The monoclonal antibody A45-B/B3 was used with the immunocytochemical standard method for detecting IDT BM. For the purpose of cell cultivation, the cells were marked with the HEA-125 antibody and separated by means of magnetic cell sorting (MACS).. In this investigation the presence of isolated disseminated tumor cells, as indicated by the A45-B/B3 antibody, proved to be an independent prognostic factor for survival time. The risk of an earlier death increased in node-negative and metastases-free patients with the detection of IDT BM by a factor of 12.60. The detection of IDT BM also represented an independent prognostic factor for the time until advancement of the tumor. The risk of an earlier relapse increased with the detection of disseminated tumor cells in the bone marrow containing the A45-B/B3 antibody by a factor of 18.02. A generally acknowledged standardization of the method is desirable. Due to the importance of the independent prognostic IDT BM factor, this method of ascertaining the pathological stage should be established at institutions of higher learning.

Topics: Aged; Antibodies, Monoclonal; Biomarkers, Tumor; Bone Marrow; Carcinoma; Colonic Neoplasms; Female; Follow-Up Studies; Humans; Immunohistochemistry; Keratins; Male; Middle Aged; Neoplasm Seeding; Prognosis; Prospective Studies; Survival Rate

A 47-year-old woman developed metastatic melanoma to the right ovary 14 years after the enucleation of the right eye for a choroidal spindle cell melanoma. An immunohistochemical study was performed on paraffin sections of both primary and metastatic melanoma specimens to identify markers of both aggressive phenotype and metastatic potential with particular attention to the anomalous expression of cytokeratin intermediate filament proteins. Neoplastic cells of both primary and metastatic tumors immunostained positively for S-100, HMB45, MART-1, and vimentin antibodies, but they were negative for cytokeratins 1-19, 8, 18, and 8,18; <10% of neoplastic cells in both the primary and the metastatic melanomas immunostained for Ki-67 proliferating antigen using MIB-1 antibody. We speculate that the indolent behavior of this ovarian metastasis is reflected by the absence of coexpression of cytokeratins 8 and 18 with vimentin. This case supports the practical value of using this panel of antibodies to evaluate the aggressive potential of uveal melanomas.

Topics: Antigens, Neoplasm; Carcinoma; Choroid Neoplasms; Female; Humans; Immunohistochemistry; Immunophenotyping; Intermediate Filament Proteins; Keratins; Ki-67 Antigen; MART-1 Antigen; Melanoma; Melanoma-Specific Antigens; Middle Aged; Neoplasm Proteins; Ovarian Neoplasms; S100 Proteins; Time Factors; Vimentin

The existence of angiosarcoma (AS) of the thyroid has been a matter of debate for many years, because some authors believe that most if not all ASs are in fact "angiomatoid" anaplastic carcinomas (ACs). Immunohistochemistry alone was not successful in solving the problem, since cytokeratin expression is a known occurrence in AS. Therefore, we wanted to compare nine cases of AS with ten cases of AC, assessing whether thyroglobulin (TG) mRNA was still transcribed in undifferentiated tumors and could be helpful to distinguish AC from AS. The cases were analyzed for TG mRNA expression by means of radioactive in situ hybridization. The silver grains were counted using an automated device, and their amount was compared with that of stroma, background, and peritumoral thyroid. A weak signal was present in all AC but not in AS (mean counts 35.7 and 9.6 arbitrary units, respectively: P<0.01). In two cases of AC, residual areas of poorly differentiated insular carcinoma had a strong signal (similar to that of peritumoral thyroid). These findings further confirm that AC and AS of the thyroid are unrelated malignant tumors.

Topics: Adult; Aged; Aged, 80 and over; Antigens, CD34; Carcinoma; Diagnosis, Differential; Endothelium, Vascular; Factor VIII; Female; Gene Expression; Hemangiosarcoma; Humans; Immunohistochemistry; In Situ Hybridization; Keratins; Male; Middle Aged; Platelet Endothelial Cell Adhesion Molecule-1; RNA, Messenger; Thyroglobulin; Thyroid Neoplasms; Vimentin

The authors describe an extremely rare case of epithelial-myoepithelial carcinoma of bronchial mucous glands involving lower lobe of the right lung, which was detected on a routine radiological examination in a 34-year-old woman, and then surgically resected.

Topics: Actins; Adult; Bronchial Neoplasms; Carcinoma; Cytoplasm; Female; Humans; Immunohistochemistry; Keratins; Lymph Nodes; S100 Proteins

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

Histopathological identification of invasive breast carcinoma in its earliest phases is fraught with pitfalls. Preinvasive malignant lesions complicated by radial scar, sclerosing adenosis, and lobular cancerization, among other lesions, may simulate invasive carcinoma. Fibrosis, inflammatory reaction, and other stromal changes around in situ carcinoma may mask microinvasive foci on routine stains. Conventional immunohistochemistry to demonstrate basement membrane or myoepithelial cell layer may not, by itself, be unequivocally diagnostic of invasion. We performed a novel double immunoenzyme labeling technique using an avidin-biotin complex peroxidase-diaminobenzidine system for smooth-muscle actin followed by an alkaline phosphatase anti-alkaline phosphatase-new fuchsin system for cytokeratin antigen on formalin-fixed, paraffin-embedded histology sections to evaluate 32 such problematic cases. The initial histologic impression with hematoxylin and eosin staining alone was as follows-first group: microinvasive carcinoma-10; second group: carcinoma in situ--"stromal invasion cannot be ruled out"--15; third group: frankly infiltrating carcinoma of various grades and morphologic types-6. The last group served as positive control for invasion. One fibroadenoma with fine-needle-aspiration-induced artifact simulating stromal invasion was also included. The double immunoenzyme labeling technique imparted a dark brown color to the myoepithelial cells and a vivid red color to the epithelial cells, making individual or loosely cohesive groups of malignant epithelial cells infiltrating the stroma easily detectable, whereas their in situ counterparts were contained within dark brown myoepithelial boundaries. The TNM 1997 definition of pT1mic, i.e., extension of malignant cells in the stroma with no focus measuring >0.1 cm, was followed to classify microinvasion. In the first group, microinvasion was confirmed in six cases but was not demonstrable in four. In the second group, definite invasion was identified in five cases, ruled out in nine, and in one case the suspicion of early invasion could not be entirely ruled out even after double immunoenzyme labeling. Thus, it was possible to render a definite opinion regarding presence or absence of invasion in 24 of 25 (96%) cases diagnosed as or suspected to be microinvasive. The precise and simultaneous elucidation of topography between malignant cells and myoepithelial cells on a single permanent section makes this tech

Topics: Actins; Breast Neoplasms; Carcinoma; Carcinoma in Situ; Carcinoma, Ductal, Breast; Carcinoma, Lobular; Female; Fibroadenoma; Fibrocystic Breast Disease; Humans; Immunoenzyme Techniques; Keratins; Neoplasm Invasiveness; Sclerosis

In urothelial low-grade carcinomas of the bladder stage pT1, prognosis in general is good. In a subset of these tumors infiltrating beyond the lamina muscularis mucosae, prognosis clearly worsens. Unfortunately, evaluation of the lamina muscularis mucosae often is very difficult or even impossible because of its incomplete extension. In an immunohistochemical study on 131 pTa and pT1 urothelial tumors without provable lamina muscularis mucosae, we evaluated the proliferative activity with the monoclonal antibody MIB-1 and the expression pattern of cytokeratins of high molecular weight with the monoclonal antibody 34betaE12. The highest proliferative indices were found in tumors with a diffuse expression pattern of MIB-1 and 34betaE12. A preliminary analysis of follow-up data showed that 70.6% of the pT1 GIb-GIa tumors that recurred showed a diffuse expression pattern for both markers. Whether these patients are candidates for a doser follow-up or even for a more radical therapy has to be subject to further follow-up studies.

Topics: Antigens, Nuclear; Carcinoma; Cell Division; DNA-Binding Proteins; Humans; Immunohistochemistry; Keratins; Ki-67 Antigen; Neoplasm Invasiveness; Neoplasm Recurrence, Local; Nuclear Proteins; Prognosis; Urinary Bladder Neoplasms

The authors present an unusual case of an epithelial-myoepithelial carcinoma of the liver in a 67-year-old man who was admitted for resection of a gastric adenocarcinoma. At operation, a 3 x 3 cm mass in the right liver lobe was also removed. This mass consisted of duct-like structures with dual differentiation. The inner layer was composed of an epithelial lining, and the outer layer consisted of clear cells, all unrelated to the moderately well-differentiated gastric adenocarcinoma. The clear cells were positive for S-100 and alpha-smooth muscle actin, suggesting myoepithelial origin. The mass was considered to be low-grade epithelial-myoepithelial carcinoma. However, the patient had a history of an oral nodule present since childhood, resected 10 years previously. These slides were reviewed and revealed a mixture of clear cells and basal cells with squamous differentiation. In addition, there were duct-like structures with the two-layer pattern found in the liver tumor. This tumor had numerous mitotic figures and showed perineural invasion, suggesting a high grade of malignancy. These findings led to an interpretation of the oral tumor as also being epithelial-myoepithelial carcinoma, which had remained as "benign" for more than 50 years and subsequently underwent malignant transformation. During this long period, liver metastases may have occurred and remained low-grade. Alternatively, the liver and oral tumors may have arisen separately in the foregut during embryologic development, remaining low-grade until malignant transformation occurred.

Topics: Actins; Aged; Carcinoma; Humans; Immunoenzyme Techniques; Keratins; Liver Neoplasms; Male; Mouth Neoplasms; Palate; S100 Proteins

Salivary duct carcinoma is rare. We describe a 56-year-old man who developed salivary duct carcinoma in the mandible 10 years after removal of the right second and third molars. The tumour originated in the retromolar gland or the ectopic minor salivary gland in the mandible. The panoramic radiograph showed a radiolucent, poorly circumscribed area about 40 x 30 mm in size and distal to the lower right first molar. This tooth, together with all neoplastic tissue, was removed, and histopathological examination showed it to be a salivary duct carcinoma in the mandible. On immunohistochemical staining, keratin antibodies stained the ductal structure, 1A4 antibody stained myoepithelial cells, but S-100 protein and vimentin were not seen. The patient was well and with no sign with recurrence 6 years postoperatively.

Topics: Actins; Carcinoma; Choristoma; Follow-Up Studies; Humans; Immunohistochemistry; Keratins; Male; Mandibular Diseases; Middle Aged; Molar; Radiography, Panoramic; S100 Proteins; Salivary Ducts; Salivary Gland Neoplasms; Vimentin

Forty-seven feline and 60 canine epithelial tumors were studied to test the coordinate expression of cytokeratin 7 (CK 7) and cytokeratin 20 (CK 20) using commercially available monoclonal antibodies and an avidin-biotin immunoperoxidase staining technique. Previously, the distribution of both cytokeratins was examined in normal tissues from 4 cats and 4 dogs. The pattern of distribution of CK 7 in normal tissues was similar, with minor differences, to that described in humans, whereas the reactivity pattern of CK 20 in cats and dogs was wider than that in humans. The subset of tumors strongly expressing CK 7 and CK 20 included pancreatic adenocarcinomas (100%), transitional cell carcinomas (75%), and endometrial carcinomas (67%) in the cat. None of the canine tumors had this immunophenotype. Feline (50%) and canine (56%) mammary gland carcinomas and canine cholangiocarcinomas (67%) were the only tumors presenting the CK 7 +/CK 20- immunophenotype, whereas the CK 7-/CK 20+ immunophenotype included thyroid carcinomas (100%), intestinal adenocarcinomas (60%), bronchioloalveolar carcinomas (50%), and renal carcinomas (50%) in the cat and intestinal adenocarcinomas (56%), gastric adenocarcinomas (50%), and ovarian carcinomas (50%) in the dog. The CK 7-/CK 20- immunophenotype included the rest of the analyzed tumors. The immunohistochemical evaluation of coordinate expression of both CK 7 and CK 20 in feline and canine carcinomas using monoclonal antibodies provides important information that can help to discriminate among carcinomas from different primary sites and could be particularly helpful in the determination of the primary site of origin of carcinomas presenting as metastatic disease.

Topics: Animals; Antibodies, Monoclonal; Carcinoma; Cat Diseases; Cats; Dog Diseases; Dogs; Female; Gene Expression Regulation, Neoplastic; Immunohistochemistry; Intermediate Filament Proteins; Intestine, Large; Keratin-20; Keratin-7; Keratins; Liver; Male; Mammary Glands, Animal; Ovary; Pancreatic Neoplasms; Pituitary Gland; Reference Values; Stomach; Tongue; Urinary Bladder

The presence of disseminated carcinoma cells in bone marrow and peripheral blood has prognostic importance in patients with carcinomas. Much evidence indicates that dissemination of tumor cells may depend on activation of a variety of degradative enzymes. A strong positive correlation has been shown between the expression of tumor cell proteases and tumor invasion. Therefore, phenotypic characterization of disseminated carcinoma cells for expression of protease activators might define the invasive potential of the cells. We present an immunocytochemically enhanced staining method that allows phenotyping of disseminated carcinoma cells in bone marrow and peripheral blood smears. In the first step, the cells were incubated with antibodies against urokinase plasminogen activator receptor (u-PAR) and subsequently with secondary antibodies conjugated to peroxidase-labeled dextran polymers. A brown color reaction was developed with diaminobenzidine as chromogen. In the second step, the cells were incubated with alkaline phosphatase-conjugated murine monoclonal antibodies against a common cytokeratin epitope and a red color reaction was developed with new fuchsin as substrate. This method allows simultaneous and unambiguous immunolabeling of intracellular cytokeratin and of u-PAR intracellularly and on the surface of carcinoma cells. This novel approach can be used for detection and phenotyping of carcinoma cells in blood smears for u-PAR or, presumably, for any other heterogeneously expressed antigen on the surface of the detected cells.

Topics: Carcinoma; Dextrans; Humans; Immunoenzyme Techniques; Keratins; Plasminogen Activators; Polymers; Receptors, Cell Surface; Receptors, Urokinase Plasminogen Activator; Tumor Cells, Cultured

In order to standardize dual-fluorescence DNA flow cytometry using cytokeratin (CK) antibodies, normal colonic mucosa and tumor tissue were sampled from 308 colorectal surgical specimens. Fresh colon specimens were processed directly and stored frozen until dissociation. The samples were divided into aliquots for manual dissociation with tweezers and scalpel, and parallel dissociation with an automated disaggregation device (Medimachine, DAKO Diagnostika GmbH, Hamburg, Germany). An indirect immunofluorescence method with anti-cytokeratin antibodies and propidiumiodide was applied and measured on a single-laser flow cytometer (FACScan, Becton Dickinson [BDI], Heidelberg, Germany). Evaluation with CellFit (BDI) or MultiPlus (Phoenix Flow Systems, San Diego, CA) showed that dual-parameter fluorescence propidiumiodide (DNA staining) and fluorescein-isothiocyanate (cytokeratin labeling) provides a reasonable staining method for DNA analysis of epithelial cells. No significant differences in coefficient of variation in CK-gated versus ungated cells could be observed. Normal colon mucosa served as a reliable internal, diploid DNA control. Medimachine dissociation led to a significantly higher gain of cytokeratin-positive cells compared to percentage of cytokeratin-positive cells after manual tissue disaggregation. Cytokeratin gating led to a clear-cut separation of S-phase fractions within the respective ploidy groups, irrespective of manual or automated dissociation. The S-phase fraction increased significantly from normal tissue to diploid and nondiploid tumors. In general, automated tissue preparation with the Medimachine allows simple cell-isolation for dual DNA/CK-flow cytometric measurement, improving the gain of CK-positive cells, and facilitating a standardized DNA analysis.

Topics: Carcinoma; Colonic Neoplasms; DNA, Neoplasm; Flow Cytometry; Humans; Keratins; Prognosis; Staining and Labeling

Lymph node metastasis is an important prognostic factor for rectal carcinoma, but only a few attempts at defining the relationship between lymph node micrometastases and prognosis have been made. The purpose of this study was to examine the correlation between the presence of micrometastases and prognosis in patients with rectal carcinoma. Six hundred forty-four lymph nodes were dissected from 42 patients with Dukes' B rectal carcinoma and stained immunohistochemically using a monoclonal antibody, CAM5.2, that binds cytokeratin. Clinicopathological factors, rate of recurrence, and prognosis were compared among patients with and without micrometastases. Micrometastases were detected in 19 lymph nodes (19 of 644 = 2.9%) from 9 patients (9 of 42 = 21.4%). The presence of micrometastases was not related to clinicopathological factors. There were significant differences in recurrence rates (5 of 9 versus 5 of 33, P = 0.02), relapse-free survival rates (P = 0.04), and 10-year survival rates (P = 0.03) between patients with and without micrometastases. Immunohistochemistry successfully identified micrometastatic foci in lymph nodes missed with conventional staining methods. The existence of micrometastases influenced the prognosis in patients with Dukes' B rectal carcinoma.

Topics: Antibodies, Monoclonal; Carcinoma; Disease-Free Survival; Female; Humans; Immunohistochemistry; Keratins; Lymphatic Metastasis; Male; Middle Aged; Predictive Value of Tests; Prognosis; Rectal Neoplasms; Recurrence; Survival Rate

The human pancarcinoma-associated epithelial glycoprotein-2 (EGP-2), also known as 17-1A or Ep-CAM, is a 38-kDa transmembrane antigen, commonly used for targeted immunotherapy of carcinomas. Although strongly expressed by most carcinomas, EGP-2 is also expressed in most simple epithelia. To evaluate treatment-associated effects and side-effects on tumor and normal tissue respectively, we generated an EGP-2-expressing transgenic Wistar rat. To express the cDNA of the EGP-2 in an epithelium-specific manner, the 5' and 3' distal flanking regions of the human keratin 18 (K18) gene were used. EGP-2 protein expression was observed in the liver and pancreas, whereas EGP-2 mRNA could also be detected in lung, intestine, stomach and kidney tissues. In this rat, EGP-2-positive tumors can be induced by injecting a rat-derived carcinoma cell line transfected with the GA733-2 cDNA encoding EGP-2. Transgenic rats were used to study specific in vivo localization of an i.v. anti-EGP-2 monoclonal antibody, MOC31, applied i.v. Immunohistochemical analyses showed the specific localization of MOC31 in s.c. induced EGP-2-positive tumors, as well as in the liver. In contrast, in EGP-2-transgenic rats, MOC31 did not bind to EGP-2-negative tumors, the pancreas, or other normal tissues in vivo. In conclusion, an EGP-2-transgenic rat model has been generated that serves as a model to evaluate the efficacy and safety of a variety of anti-EGP-2-based immunotherapeutic modalities.

Topics: Animals; Animals, Genetically Modified; Antibodies, Monoclonal; Antigens, Neoplasm; Carcinoma; Cell Adhesion Molecules; DNA, Complementary; Epithelial Cell Adhesion Molecule; Epithelial Cells; Female; Humans; Immunization, Passive; Immunoenzyme Techniques; Keratins; Male; Neoplasm Transplantation; Organ Specificity; Rats; Rats, Wistar; Recombinant Fusion Proteins; RNA, Messenger; Transfection; Tumor Cells, Cultured; Viscera

Thirty percent of lymph node negative patients with operable breast carcinoma experience disease recurrence within 10 years. Retrospective serial sectioning of axillary lymph nodes has revealed undetected metastases in 9-30% of these patients. These occult metastases have been shown to have an adverse effect on survival. Serial sectioning (SS) is impractical for all axillary lymph nodes harvested from Levels I and II, but it is feasible if applied only to sentinel lymph nodes.. Sentinel lymph nodes from 52 patients with invasive breast carcinoma were cut at 2 mm intervals, fixed in 10% formalin, and embedded in paraffin. Sections were taken from the blocks, stained with hematoxylin and eosin (H & E), and compared with cytokeratin-stained sections taken at 0.25 mm intervals throughout the entire blocks.. Tumor metastases were found in 6 patients (12%) when the sentinel lymph nodes were sectioned at 2 mm intervals and stained with H & E, compared with 30 patients (58%) when the same lymph nodes were serially sectioned at 0.25 mm intervals and stained with cytokeratin. Of 24 patients whose metastases were detected by SS and cytokeratin staining, 12 had isolated tumor cells and 12 had colonies of several thousand malignant cells.. Routine histologic examination of axillary lymph nodes, including sentinel lymph nodes, in cases of breast carcinoma significantly underestimates lymph node metastases. This deficiency may be overcome by SS of the entire lymph nodes and staining with a specific monoclonal antibody. The percentage of patients found to have colonies of cells that were missed by routine sectioning corresponds closely to the percentage of "lymph node negative" patients who would be expected to relapse. The true clinical significance of these occult metastases will be determined by long term follow-up. [See editorial on pages 905-7, this issue.]

Topics: Adult; Aged; Antibodies, Monoclonal; Axilla; Biopsy; Breast Neoplasms; Carcinoma; Female; Humans; Keratins; Lymph Nodes; Lymphatic Metastasis; Mastectomy, Segmental; Middle Aged; Neoplasm Staging

Secretory carcinoma is an uncommon variant of breast cancer, characterized by the presence of intracellular and extracellular eosinophilic secretion. Here, we report the cytologic, histologic, and immunohistochemical findings of a secretory carcinoma diagnosed in the left inguinal mammary gland of a 3-year-old female German Shepherd Dog. The fine-needle aspiration cytology showed numerous large branching sheets of neoplastic cells and isolated cells with cytoplasmic vacuoles. Histologically, the tumor was composed of cells with clear cytoplasm and prominent vacuoles that pushed the nuclei to the periphery, resembling signet ring cells. These cells were arranged in solid or tubular structures with lumenal spaces filled with eosinophilic secretion. Immunohistochemical reactions to cytokeratin (CAM 5.2) and alpha-lactalbumin were strongly positive in all neoplastic cells, and staining for vimentin and S100 protein was negative. The cytomorphologic and immunohistochemical features of this tumor are similar to those seen in tumors in women, hence enabling the diagnosis of a rare case of primary secretory carcinoma of the canine mammary gland.

Topics: Animals; Antibodies, Monoclonal; Biopsy, Needle; Carcinoma; Dog Diseases; Dogs; Fatal Outcome; Female; Immunohistochemistry; Keratins; Lactalbumin; Mammary Glands, Animal; Mammary Neoplasms, Animal; Neoplasm Recurrence, Local; S100 Proteins; Vimentin

We have previously shown that necrotic tumors retain their immunoreactivity for a range of cytokeratin antibodies. Some thyroid tumors undergo extensive necrosis after fine-needle aspiration (FNA) procedures. We evaluated the sensitivity of antibodies on necrotic thyroid tumors by examining a series of thyroid tumors consisting of 10 Hurthle cell neoplasms, 8 carcinomas, and 2 follicular adenomas (12 with post-FNA necrosis). These were stained with antibodies to AE1/3, PANCK, thyroglobulin and S100. Four of the cases of papillary carcinoma were also stained with antibodies to CK19. As a control for the specificity of thyroglobulin immunoreactivity in necrotic tissue, we also stained 11 nonthyroid tumors with extensive necrosis (7 carcinomas, 1 lymphoma, 2 melanomas, 1 sarcoma) for thyroglobulin. Six of 8 thyroid carcinomas were positive for AE1/3 and PANCK; AE1/3 reactivity was retained in necrotic areas of 4 of 6. AE 1/3 was positive in necrotic portions of 5 of 10 Hurthle cell lesions, whereas PANCKwas negative in all but 1. Thyroglobulin reactivity was present in 18 of 20 cases, and was preserved in necrotic portions of 5 of 6 carcinomas, as well as 8 of 10 Hurthle cell neoplasms. S100 cytoplasmic reactivity was present in 4 Hurthle cell neoplasms and 1 papillary carcinoma; this staining was lost in necrotic areas. No staining by thyroglobulin was observed in the viable or necrotic areas of nonthyroid neoplasms. The preservation of cytokeratin reactivity, measured by AE1/3, in thyroid neoplasms is a diagnostically useful feature in spontaneous and post-FNA infarction. PANCK is not a well-preserved marker in necrotic thyroid tissue. This difference may be due to detection of keratin 19 by AE1/3. Thyroglobulin is preserved in some necrotic thyroid carcinomas and in Hurthle cell lesions. Preservation of thyroglobulin reactivity in necrotic tissue is specific in that no staining was observed in nonthyroid neoplasms. These results suggest that thyroglobulin is useful in demonstrating thyroid lineage of both primary and metastatic necrotic tumor masses.

Topics: Adenoma; Adenoma, Oxyphilic; Carcinoma; Humans; Immunohistochemistry; Keratins; Necrosis; S100 Proteins; Thyroglobulin; Thyroid Neoplasms

Among 474 cases of gastric carcinoma studied in gastrectomy specimens from 1990 to 1996, only one (0.21%) showed positivity for vimentin. It was located on a gastric stump and, endoscopically, the tumor was classified as early gastric carcinoma type IIb + IIc. Histologically, tumor cells were extensively round to polygonal and had eosinophilic, or clear cytoplasm; the nuclei were large with conspicuous nucleoli. In some areas, the cytoplasm showed vimentin and(or cytokeratin coexpression by double immunostaining. Our results and the patient's rapid deterioration (death occurred six months after surgery) suggest that this type of tumor, although diagnosed as early carcinoma, behaved like an advanced malignancy.

Topics: Biomarkers, Tumor; Carcinoma; Cell Separation; DNA, Neoplasm; Fatal Outcome; Flow Cytometry; Gastrectomy; Gastric Stump; Humans; Inclusion Bodies; Keratins; Male; Middle Aged; Organelles; Ploidies; Rhabdoid Tumor; Stomach Neoplasms; Vimentin

Radiation therapy results in significant morphological changes in prostatic carcinoma, including decreased cancer size, acinar shrinkage and distortion, cytoplasmic vacuolization, and nuclear pyknosis. Benign acini usually display enlarged, atypical cells with hyperchromatic nuclei. These changes confound the evaluation of limited postradiation samples. The glycoprotein A-80 is known to be upregulated in prostatic intraepithelial neoplasia (PIN) and prostatic carcinoma. In this study, we assessed the expression of A-80 in radiation-treated prostatic carcinoma. Paraffin sections from 64 postradiation prostatic carcinomas obtained at salvage prostatectomy were immunostained with a monoclonal antibody to A-80; selected sections were doubly immunostained with antibodies to A-80 and various cytokeratin polypeptides. All cases showed readily detectable and often intense staining in the cytoplasm of cancer cells and in intraluminal material of malignant acini. The extent and intensity of the reactions were independent of cancer size and grade. Strong reactions were seen in preserved and distorted acini, clear cell areas, single cancer cells, and in colloid pools with few or no recognizable cancer cells. PIN was present in 34 cases (53%), of which 27 (79%) stained strongly for A-80; atrophic and hyperplastic acini generally did not stain, irrespective of the degree of cellular atypia. The A-80 glycoprotein appears remarkably durable and is readily demonstrable in postradiation prostatic carcinoma despite profound architectural and cytologic changes. This characteristic may prove useful in evaluating small samples for confirmation of diagnosis and determination of extent of residual or recurrent prostatic carcinoma after radiation therapy.

Topics: Aged; Antibodies, Monoclonal; Carcinoma; Glycoproteins; Humans; Immunoenzyme Techniques; Keratins; Male; Middle Aged; Prostatectomy; Prostatic Neoplasms; Salvage Therapy

Recently, there has been significant effort in developing techniques designed to detect disseminated tumor cells in the peripheral blood (PB). These techniques include immunocytochemical staining of cytocentrifuge slides, flow cytometry, and RT-PCR. Several authors reported various results concerning the sensitivity of the detection limit when applying these methods. The aim of this study was to assess the value of two methods in the detection of ovarian carcinoma cells in the PB. For tumor cell detection we compared RT-PCR to immunomagnetic enrichment followed by flow cytometric analysis. In a model system, single cell suspensions of ovarian cancer cell lines were mixed with full blood samples from healthy donors in order to determine the sensitivity limit of the two methods and to analyze the reproducibility of each. In a multiparameter flow cytometric analysis, tumor cells were defined as cytokeratin 7/8 positive and CD45 negative. RNA was screened for MUC1 mRNA by RT-PCR. MUC1 mRNA expression turned out not to be a specific marker of disseminated ovarian cancer cells, because a weak expression was also found in samples of healthy persons. Using immunomagnetic enrichment followed by flow cytometry, one carcinoma cell per 1 x 10(6) leukocytes was detectable. However, a minimum of 10 ml blood had to be analyzed in order to clearly distinguish real positive tumor cells from false-positive signals.

Topics: Biomarkers, Tumor; Carcinoma; Evaluation Studies as Topic; Female; Flow Cytometry; Humans; Keratins; Leukocyte Common Antigens; Mucin-1; Ovarian Neoplasms; Phycoerythrin; Reverse Transcriptase Polymerase Chain Reaction

Thirty-five chordomas and more than 100 other tumors that have to be considered in the differential diagnosis, were immunohistochemically analyzed using a panel of antibodies including those to subsets of keratins (K), HBME-1, a monoclonal antibody recognizing an unknown antigen on mesothelial cells, and neuroendocrine markers. The patterns of immunoreactivities in chordoma were compared with those in renal cell carcinoma, colorectal mucinous adenocarcinoma, pituitary adenoma, skeletal chondrosarcoma, and extraskeletal myxoid chondrosarcoma (ESMC). Chordomas were consistently positive for keratin cocktail AE1/AE3, and for the individual keratins K8 and K19, and nearly always positive for K5, but they showed negative or only sporadic reactivity for K7 and K20. The keratin K8 and K19 reactivity was retained in those chordomas showing solid sheets of epithelioid, spindle cells, or cartilaginous metaplasia, and in one of two cases showing overtly sarcomatous transformation. In comparison, keratins were never present in skeletal chondrosarcoma, although K8 and to a lesser extent K19 were seen in occasional cases of ESMC with chordoid features. HBME-1 reacted strongly with chordoma and skeletal chondrosarcoma but was almost never positive in renal or colorectal carcinoma. These carcinomas lacked K5-reactivity, in contrast to chordoma. Chordomas were also consistently positive for neuron-specific enolase and occasionally focally for synaptophysin, but never for chromogranin. In contrast, pituitary adenomas regularly expressed the full spectrum of neuroendocrine markers and differed from chordoma by having a narrower repertoire of keratins, often showing negative or focal keratin 8- or AE1/AE3 reactivity and being almost always K19-negative. These findings indicate that chordoma can be immunohistochemically separated from tumors that can resemble it. Immunohistochemistry is especially useful in the diagnosis of small biopsy specimens that offer limited material for morphological observation.

Topics: Adenocarcinoma, Mucinous; Adenoma; Antibodies, Monoclonal; Antigens, Neoplasm; Biomarkers, Tumor; Bone Neoplasms; Carcinoma; Chondrosarcoma; Chordoma; Colonic Neoplasms; Diagnosis, Differential; Humans; Immunohistochemistry; Keratins; Kidney Neoplasms; Pituitary Neoplasms

Karyotypic analysis was performed on 102 prostate cancer specimens which were obtained through radical prostatectomy, transurethral resection, or regional lymph node dissection. Short term tissue culture was applied in all cases. Of the media and growth factors evaluated, F12/DMEM, supplemented with 2% fetal calf serum, insulin, epidermal growth factor, hydrocortisone, and cholera toxin produced the largest increase of in vitro proliferation. Such in vitro cultured cells were all phenotypically acinar epithelial cells, the supposed targets for neoplastic transformation. Stromal cell growth appeared to be completely suppressed. Of the three culture techniques investigated, the method developed in Lund, Sweden, was the most successful: 11/15 cultures yielded metaphases and, in three of these, clonal aberrations were identified. All 39 karyotypes obtained essentially had a 46,XY karyotype with clonal aberrations (eight cases) and/or nonclonal aberrations (30 cases). Clonal structural aberrations involved 2p, 3q, 11p, 17p, and 21q. The clonal numerical aberrations found were: + 8, + dmin, and -Y. The most frequently observed nonclonal aberrations were 8p deletions (five cases) and loss of 6, 7, 8, 15, 17, 18, 21, and/or Y (> or = five cases). In summary, clonal aberrations were observed in 20% of the evaluable PC cell cultures, and nonclonal aberrations in 77%. So, although diploid cells without clonal abnormalities still had a growth advantage, under optimal conditions PC cells were able to proliferate in primary in vitro culture.

Topics: Carcinoma; Cell Division; Cells, Cultured; Culture Techniques; Evaluation Studies as Topic; Humans; Immunohistochemistry; Karyotyping; Keratins; Male; Prostate-Specific Antigen; Prostatic Neoplasms

Disseminated epithelial tumor cells have been detected in the bone marrow and blood of cancer patients by means of immunocytochemical or immunofluorescent staining of cytocentrifuge slides, multiparameter flow cytometry, and reverse transcriptase-polymerase chain reaction. However, it is hardly possible using such methods to detect tumor cells at a frequency below 10(-6). To increase the sensitivity of these detection techniques we have developed a new technology for the enrichment of disseminated epithelial tumor cells from hematopoietic cell samples by high-gradient magnetic cell sorting (MACS). Cells are permeabilized and fixed and carcinoma cells are magnetically labeled specifically with an anti-cytokeratin 8 monoclonal antibody (mAb) directly conjugated to superparamagnetic microbeads. Magnetically labeled cells are enriched on high-gradient magnetic columns. Tumor cells are detected in the enriched cell fraction by flow cytometry, fluorescence microscopy, or immunocytochemisty. In this study we demonstrated the method using a model system in which five to 5,000 cells from a breast cancer cell line were seeded into blood cell samples from a healthy donor containing 1.2 x 10(8) leukocytes. Tumor cells were 10,477+/-4242 (n=25)-fold magnetically enriched, and 57.7%+/-16.9% (n=33) of the initially seeded tumor cells were recovered. Applying the method to 20-40 mL blood samples from patients with advanced carcinomas of the breast, prostate, colon, rectum, or lung, we were able to detect between one and 6.8 x 10(4) cytokeratin-expressing tumor cells in 21 of 34 patients. This corresponds to frequencies of tumor cells between 6.8 x 10(-9) and 1.1 x 10(-3) among nucleated cells in the original sample. Enriched tumor cells were further analyzed for expression of tissue-specific and prognostic markers such as breast mucin glycoproteins, erbB2, and CD44v6 for additional characterization and to confirm their tumor origin. The technique described could become a valuable tool for the quantification and molecular characterization of metastatic carcinoma cells in hematopoietic tissue, and may ultimately prove useful in the diagnosis, prognosis, and monitoring of patients with carcinoma.

Topics: Adult; Aged; Breast Neoplasms; Carcinoma; Cell Separation; Colorectal Neoplasms; Epithelial Cells; Female; Humans; Hyaluronan Receptors; Immunohistochemistry; Immunologic Techniques; Keratins; Lung Neoplasms; Magnetics; Male; Middle Aged; Mucins; Neoplasm Metastasis; Prostatic Neoplasms; Receptor, ErbB-2; Tumor Cells, Cultured

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

Nodular or tumoral melanosis consists of nodular or sheetlike deposits of melanophages in the dermis. When nodular melanosis is present, a completely regressed malignant melanoma is a major diagnostic consideration. We present a case of nodular melanosis due to regression of a pigmented basal cell carcinoma with pilar differentiation. In addition to this case, we present five additional cases of epithelial neoplasms with melanin deposition in the stroma. In each case, the source of the melanin was non-neoplastic dendritic melanocytes intermingled among the tumor cells. Therefore, if nodular melanosis is found, pigmented epithelial neoplasms should also be considered in the differential diagnosis.

Topics: Aged; Antibodies, Monoclonal; Antigens, Neoplasm; Biomarkers, Tumor; Carcinoma; Carcinoma, Basal Cell; Humans; Immunohistochemistry; Iron; Keratins; Male; Melanins; Melanoma-Specific Antigens; Melanosis; Middle Aged; Neoplasm Proteins; S100 Proteins; Skin Neoplasms; Vimentin

An autopsied case of an 80-year-old man with spindle cell carcinoma of the gingiva is reported. The tumor was polypoid and mostly composed of a sarcomatous proliferation of spindle cells with a small focus of squamous cell carcinoma at the stalk portion. The carcinoma metastasized to a cervical lymph node, lungs and pleura with extension to the diaphragm. In the metastatic lymph node, the squamous cell component was more prominent than the spindle cell one, while only anaplastic pleomorphic carcinoma cells were found in the lungs. The spindle or anaplastic cells were immunohistochemically positive for vimentin and carcinoembryonic antigen (CEA) but not for other epithelial antigens. We have concluded that the sarcomatoid component arose from the oral squamous cell carcinoma by a metaplastic process. This is the first case report of an oral spindle cell carcinoma examined by autopsy.

Topics: Aged; Aged, 80 and over; Anaplasia; Autopsy; Carcinoembryonic Antigen; Carcinoma; Carcinoma, Squamous Cell; Diaphragm; Gingival Neoplasms; Humans; Keratins; Lung Neoplasms; Lymphatic Metastasis; Male; Metaplasia; Mucin-1; Neoplasms, Multiple Primary; Pleural Neoplasms; Vimentin

We report six cases of hyperplastic mesothelial cells located in the sinuses of lymph nodes. All patients but one had a concurrent serosal fluid collection (two pericardial, two pleural, one abdominal) at the time of the lymph node biopsy. All effusions cleared with treatment of the underlying disorder, which included lymphoproliferative processes, congestive heart failure, and inflammatory diseases (Dressler syndrome, vasculitis, and glomerulonephritis). Four cases were associated with vascular prominence of the involved nodal sinuses, a feature that may reflect the cause of the underlying effusion or support the transient persistence of benign mesothelial cells in lymph nodes. Two cases were characterized by distention of the nodal sinuses by sheets of mitotically active mesothelial cells. The differential diagnosis includes metastatic carcinoma, keratin-positive dendritic cells native to lymph nodes, and metastatic malignant mesothelioma. Because the latter shares both clinical and morphological features with cases of benign mesothelial cells in lymph nodes, we believe that this distinction may not always be possible in a given biopsy specimen and therefore that careful clinical follow-up is required in such cases.

Topics: Actins; Adolescent; Adult; Biomarkers, Tumor; Carcinoma; Dendritic Cells; Diagnosis, Differential; Epithelium; Female; Glomerulonephritis; Heart Failure; Humans; Hyperplasia; Immunohistochemistry; Keratins; Lymph Nodes; Lymphoproliferative Disorders; Male; Mesothelioma; Middle Aged; Platelet Endothelial Cell Adhesion Molecule-1; Vasculitis

To determine the value of immunocytochemistry in differentiation of malignant pleural mesothelioma from carcinoma in a pleural biopsy using commercially available monoclonal antibodies.. A panel of monoclonal antibodies against keratins, epithelial membrane antigen (EMA), epithelial antigen Ber-EP4, carcinoembryonic antigen (CEA), tumour-associated glycoprotein (B72.3), Leu-M1, CD30 (Ber-H2), vimentin and desmin, was applied to 40 cases of malignant pleural mesothelioma and 23 cases of carcinoma metastatic to the pleura (16 pulmonary and seven extrapulmonary). Positivities for Ber-EP4, CEA, B72.3 and Leu-M1 were found to have the highest nosologic sensitivities (87.0%, 65.2%, 52.5% and 43.5%, respectively) and specificities (97.5%, 97.5%, 100% and 95%, respectively) for carcinoma. Positive staining for vimentin had the highest sensitivity (87.5%) with 95.7% specificity for mesothelioma. Positive staining for desmin was found in 45% of mesotheliomas and 0% of carcinomas. Diagnostic sensitivity and diagnostic specificity (P-values) were calculated for these markers. In respect to the diagnostic power defined by the clinically relevant predictive values of positive and negative tests, we found that a two-marker panel of antibodies including vimentin and Ber-EP4 is most useful for the histopathological distinction between carcinoma (pulmonary or extrapulmonary) and malignant pleural mesothelioma.. A combination of Ber-EP4 and vimentin provides the most sensitive and specific pair of markers for distinguishing between malignant pleural mesothelioma and carcinoma metastatic to the pleura. The prevalence of the tested tumours should be taken into account when evaluating the clinical value of ancillary techniques in pathology.

Topics: Antibodies, Monoclonal; Biomarkers, Tumor; Carcinoma; Diagnosis, Differential; Humans; Immunohistochemistry; Keratins; Mesothelioma; Pleural Neoplasms; Predictive Value of Tests; Sensitivity and Specificity; Vimentin

Penile metastases from prostate cancer are rare and are usually a manifestation of wide-spread cancer dissemination. Isolated urethral metastases form a small fraction of these cases, have a longer survival rate and may represent spread by implantation following instrumentation. We report a case of prostatic carcinoma presenting with an isolated metastasis to the penile urethra after catheterisation and transurethral prostatectomy. The primary tumor had a prominent intraductal component whose architectural features were mimicked in the metastasis. The possible mechanisms of spread and the diverse appearances of cancer associated with an intraductal component are discussed.

Topics: Aged; Carcinoma; Humans; Immunohistochemistry; Keratins; Male; Prostate-Specific Antigen; Prostatic Neoplasms; Urethral Neoplasms

A case of sebaceous carcinoma arising in the left submandibular gland of a 66-year-old man is reported. The clinical and pathological examinations revealed a carcinoma, which was to salivary gland in origin, with regional lymph nodal metastases. Pathological findings showed features of high-grade sebaceous carcinoma with spindle myoepitheliomatous differentiation. Neither squamous cell nor duct epithelial-like cell differentiation was noted. Immunohistochemically, tumor cells were positive for cytokeratin, S-100 protein and vimentin. Lipid was demonstrated in the cytoplasm of the tumor cells. Ultrastructurally, tumor cells contained numerous intracytoplasmic lipid droplets. Myoepitheliomatous differentiation is rare in sebaceous carcinoma of the salivary gland. Presented is the second reported case of sebaceous carcinoma arising in the submandibular gland.

Topics: Aged; Biomarkers, Tumor; Carcinoma; Humans; Immunoenzyme Techniques; Keratins; Male; Microscopy, Electron; S100 Proteins; Sebaceous Gland Neoplasms; Submandibular Gland Neoplasms

Neoplasms of the choroid plexus are very rare in the rat, and few cases have been described. We report on a spontaneously occurring choroid plexus carcinoma arising from the fourth ventricle in a 2-year-old female albino rat. The infiltrative growth was observed in the adjacent brain parenchyma, in the wall of the vessels of the circle of Willis, in the perivascular space of VIRCHOW and ROBIN and in the leptomeninges. Immunohistochemical investigations demonstrated positive staining for cytokeratin (Lu-5) indicating that choroid plexus tumors in the rat express epithelial differentiation. The diagnosis was made on the basis of microscopical and immunohistochemical findings.

Topics: Animals; Carcinoma; Cerebral Ventricles; Choroid Plexus Neoplasms; Female; Immunohistochemistry; Keratins; Rats; Rats, Sprague-Dawley

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

Six hundred and ninety-three Chinese patients with non-metastatic nasopharyngeal carcinoma (NPC) were treated at one institution under a uniform protocol between 1984 and 1989. The tumour histology of these patients was subjected to a standardized review and classified into two distinct groups of World Health Organization (WHO) type I (keratinizing squamous cell carcinoma) (n = 13) or WHO types II and III (non-keratinizing carcinoma and undifferentiated carcinoma) (n = 662). The differentiation between the two groups was uncertain in 18 patients. The patient characteristics and clinical outcome after a uniform treatment policy of the two groups were not statistically significantly different. The low incidence of WHO type I NPC may account for the lack of prognostic significance of this histological subtype in Chinese populations.

Topics: Actuarial Analysis; Biopsy; Carcinoma; Carcinoma in Situ; Carcinoma, Squamous Cell; Confidence Intervals; Disease-Free Survival; Female; Humans; Incidence; Iridium Radioisotopes; Keratins; Male; Middle Aged; Nasopharyngeal Neoplasms; Neoplasm Recurrence, Local; Odds Ratio; Prognosis; Proportional Hazards Models; Radiopharmaceuticals; Radiotherapy Dosage; Survival Rate; Treatment Outcome; World Health Organization

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

Cytokeratins are constituents of the intermediate filaments of epithelial cells which are expressed in various combinations depending on the epithelial type and the degree of differentiation. The recently identified cytokeratin-20 (CK-20) was found with immunohistochemical methods to be expressed in gastrointestinal epithelium, uroepithelial cells, and Merkel cells. Clues were also found for low expression of CK-20 in endometrial carcinoma cells. The aim of this study was to examine whether CK-20 expression can be measured in endometrial carcinoma with the more sensitive reverse transcriptase-polymerase chain reaction (RT-PCR) methods and therefore used as a potential diagnostic tumor biomarker for endometrial carcinoma.. In the present study we have used RT-PCR methods to determine expression of CK-20 in endometrial epithelial cells. Endometrial specimens were collected from 18 patients with endometrial carcinoma and 22 patients that underwent hysterectomy due to benign diseases. The specimens were prepared for both RT-PCR and immunohistochemical analysis. RNA, of the various cell pellets, was extracted and RT-PCR was performed with CK-20 and CK-19 primers (CK-19 was used as a marker for normal epithelial cells). Immunohistochemistry was carried out with the avidin-biotin-peroxidase complex method on formalin-fixed paraffin sections using CK-20 antibody.. CK-20 amplification band (370 bp) was obtained with mRNA extracted from endometrial carcinoma cells of 17 of the patients with endometrial carcinoma (sensitivity, 94.4%). CK-20 was negative in 21 patients with benign endometrial disease (specificity, 91.3%). No positive results were obtained with the immunohistochemical methods.. These results indicate that RT-PCR of CK-20, because of its high sensitivity, is a potential biomarker for detecting endometrial carcinoma.

Topics: Adult; Aged; Aged, 80 and over; Biomarkers, Tumor; Carcinoma; DNA Primers; Endometrial Neoplasms; Female; Gene Expression Regulation, Neoplastic; Humans; Immunoenzyme Techniques; Keratins; Middle Aged; Polymerase Chain Reaction; RNA-Directed DNA Polymerase; Sensitivity and Specificity

Metaplastic carcinomas of the breast are defined by mesenchymal and/or squamous cell components associated with ductal carcinoma and may raise diagnostic problems in FNA cytology. We reviewed FNA smears of a series of nine cases; seven were compared with histological sections and two with cell-block sections. The cytological pattern was diagnostic of carcinoma in six cases; in two cases a diagnosis of sarcoma/phyllodes tumour was considered, as cells were predominantly spindle-shaped. One case had a pleomorphic adenoma type pattern. The cytological findings suggesting a diagnosis of metaplastic carcinoma include a liquid aspirate, a proteinaceous or chondromyxoid background and a poorly differentiated tumour with multinucleated giant cells, neoplastic or histiocytic. A definite diagnosis requires the presence of both carcinomatous and metaplastic (squamous/mesenchymal) components.

Topics: Adult; Aged; Biopsy, Needle; Breast Neoplasms; Carcinoma; Carcinoma, Adenosquamous; Carcinoma, Ductal, Breast; Carcinosarcoma; Diagnosis, Differential; Female; Giant Cells; Humans; Immunohistochemistry; Keratins; Metaplasia; Middle Aged; Phyllodes Tumor; Vimentin

Immunohistochemistry occasionally is used to determine the lineage of entirely necrotic tumors. However, the sensitivity and specificity of antibodies on necrotic tissue are unknown. To determine the usefulness of immunohistochemistry with necrotic lesions, a series of 24 known tumors consisting of 14 carcinomas, 2 lymphomas, 2 melanomas, and 6 sarcomas (all with extensive necrosis) was examined for reactivity with 6 cytokeratin antibodies, S100, and LCA. Carcinomas stained positively with at least 1 cytokeratin antibody in 78% of the cases. The cytokeratin antibodies with the highest sensitivity were AE1, AE1/3, S903, and PANCK. These antibodies also retained specificity for epithelial differentiation; no reactivity was observed in the 10 necrotic nonepithelial tumors. LCA retained its reactivity with necrotic lymphoma, but S100 reacted with only one third of the necrotic lesions. Unexpectedly, reactivity for LCA and S100 occurred in some necrotic carcinomas. Keratin markers can be used on necrotic tissue to determine epithelial differentiation, but the results obtained with S100 and LCA on necrotic tissue should be interpreted with caution.

Topics: Antibodies; Antibody Specificity; Carcinoma; Diagnosis, Differential; Humans; Immunohistochemistry; Keratins; Leukocyte Common Antigens; Lymphoma; Melanoma; Necrosis; Neoplasm Metastasis; Neoplasms; S100 Proteins; Sarcoma

Sensitive detection of circulating epithelial cancer cells might have important therapeutic and prognostic implications in patients with breast cancer (BC) receiving high-dose chemotherapy and PBSC support. We have compared the specificity and sensitivity of the recently developed 'one tube' reverse transcriptase PCR (RT-PCR) assay with the more widely used nested RT-PCR method for detection of cytokeratin 19 (CK19)-positive cells. The analysis of 30 control samples provides evidence that one tube RT-PCR is highly specific in contrast to the nested method which showed 23% false positive results. The sensitivity of both techniques to detect tumour contamination was 10(-6). PBSC harvests from 45 BC patients were tested with both RT-PCR methods and the results were compared with immunocytochemistry (ICC). The five samples found positive by ICC were also positive by one tube RT-PCR; in addition, 11 more samples were positive by one tube RT-PCR analysis. The greater number of PBSC found positive by one tube RT-PCR might be due to the larger number of cells analysed. We conclude that one tube RT-PCR is sensitive and reveals no false positive results. This method is less time consuming than the nested one, technically simpler and should be considered for tumour cell detection.

Topics: Biomarkers, Tumor; Breast Neoplasms; Carcinoma; False Positive Reactions; Female; Humans; Keratins; Polymerase Chain Reaction; Sensitivity and Specificity; Tumor Cells, Cultured

Thymic carcinoma is an uncommon tumor. Most cases appear to arise de novo, but in rare instances they can arise in thymomas. We report the clinicopathologic features and immunohistochemical profile of five cases of thymic carcinoma accompanied by a component of thymoma. Immunohistochemical studies were performed with the avidin-biotin-peroxidase complex method using monoclonal antibodies to p53(DO7), CD99(O13), epithelial membrane antigen, CD5(NCL-CD5-4C7), vimentin (V9), and cytokeratins 7, 8, 18, and 19. The patients consisted of three men and two women with a median age of 57 years. One patient had myasthenia gravis, and the other four presented with chest symptoms. One patient had concurrent adenocarcinoma of the lung with metastasis. Four of the patients died within 15 months. The thymomas consisted of two large polygonal cell thymomas, two squamoid thymomas, and one spindle cell thymoma. The malignant components included two undifferentiated carcinomas, one spindle cell carcinoma, one squamous cell carcinoma, and one clear cell carcinoma with squamous differentiation. There was no correlation between the histologic types of the thymoma and the thymic carcinoma. In three cases, excluding the two squamoid thymomas, the thymic carcinomas occurred in the necrotic areas of the thymoma. They showed upregulated expression of epithelial membrane antigen and cytokeratins 7, 8, 18, and 19, similar to the so-called "interface phenomenon" described in the invasion front of other types of carcinoma. Increased p53 protein expression was observed in all five carcinomas, and there was loss of CD99+ immature T lymphocytes. Among the thymic carcinomas, only the squamous component of the clear-cell carcinoma stained for CD5, a marker commonly expressed in thymic carcinomas. Paradoxically, a squamoid thymoma, but not its associated spindle cell carcinoma, expressed CD5, suggesting the acquisition of an "aggressive" phenotype by the squamoid thymoma, but with loss of the marker on malignant transformation. One undifferentiated carcinoma acquired vimentin immunoreactivity, whereas four other carcinomas and all five thymomas were negative. In conclusion, thymic carcinoma can arise in any histologic type of thymoma, including spindle cell thymoma, which is generally regarded as a benign neoplasm. The prognosis appears to be poor. Tumor necrosis in a thymoma should alert the pathologist to search for malignant change. The malignant change is commonly associated with increas

Topics: Adult; Aged; Biomarkers, Tumor; Carcinoma; CD5 Antigens; Female; Humans; Immunoenzyme Techniques; Keratins; Male; Middle Aged; Mucin-1; Neoplasms, Second Primary; Thymoma; Thymus Neoplasms; Tumor Suppressor Protein p53

We reviewed the clinical records of 34 patients with laryngeal (25) and hypopharyngeal (9) spindle cell carcinomas who were treated at our institution between 1960 and 1990. All the spindle cell carcinomas were studied using paraffin section immunostains, and we performed ploidy analysis of the sarcomatoid component in 31 patients. Of the 31 patients who underwent their initial treatment at our institution, 25 were men and 6 were women (median age at presentation, 64.6 years). A T1 glottic tumor, usually seen as an exophytic firm mass, was the most common type of tumor observed (16 cases). The spindle cells were nondiploid in 86% of the carcinomas, with positive keratin immunostains in 74%. The median follow-up time was 3.7 years. Recurrence of the tumor after partial or total laryngectomy or pharyngectomy occurred in 10 patients. Eight patients died of their disease. The Kaplan-Meier estimate of surviving at least 3 years after initial treatment was 56.8%. Keratin positivity adversely affected the overall survival rate (p < 0.02). The survival rate of patients with hypopharyngeal tumors was worse than that of patients with laryngeal lesions (p < 0.001). The presence of keratin positivity and nondiploid DNA content in the spindle cell population supports the neoplastic epithelial origin of these tumors (sarcomatoid carcinoma). The overall tumor behavior and surgical therapy appeared to be comparable with those of squamous cell carcinomas at a similar stage.

Topics: Adult; Aged; Carcinoma; DNA, Neoplasm; Female; Humans; Hypopharyngeal Neoplasms; Immunohistochemistry; Keratins; Laryngeal Neoplasms; Male; Middle Aged; Neoplasm Recurrence, Local; Ploidies; Prognosis; Survival Analysis

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

The expression of cytokeratin (CK) mRNA for CK5, -8, -14, -16, and -19 was investigated in normal prostate, prostatic intraepithelial neoplasia (PIN) lesions, and invasive carcinoma using in situ hybridization. Protein localization was carried out in adjacent sections using immunohistochemistry and correlated with mRNA expression. Snap-frozen human prostate samples including 22 examples of normal glands, 20 cases of PIN lesions, and 12 cases of invasive carcinoma were examined. CK5 and -14 mRNA and protein were prominently expressed only in the basal cells of normal glands and PIN lesions. CK14 mRNA was absent in the luminal cells of the most of the PIN lesions but was seen at a low level in some PIN lesions. CK14 protein was not detected in any PIN lesion, suggesting that, if the cell that makes up the PIN lesions is derived from a basal cell, CK14 translation is depressed although a low level of CK14 mRNA may persist. CK8 mRNA and protein were constitutively expressed in all epithelia of normal and abnormal prostate tissues. CK19 mRNA and protein were persistently expressed in both basal and luminal cells of the tubular portion of normal glands as well as PIN lesions, but were expressed heterogeneously in both basal and luminal cells of normal alveoli. CK16 mRNA was expressed in a similar pattern as CK19, but CK16 protein was not detected either in normal or in abnormal prostate tissues. In conclusion, the expression of CK19 in PIN lesions is similar to its tubular expression and would support an origin of PIN lesions from this structure rather than the alveolar portion of the glands. The similar cytokeratin expression between PIN lesions and invasive carcinoma further supports the concept that PIN is a precursor lesion of invasive carcinoma.

Topics: Carcinoma; Humans; In Situ Hybridization; Keratins; Male; Neoplasm Invasiveness; Prostate; Prostatic Intraepithelial Neoplasia; Prostatic Neoplasms; Reference Values; RNA, Messenger

A series of 33 tumor cases (13 fine-needle aspirates and 20 effusion specimens) were evaluated for the expression of two cytokeratin (CK) subtypes; CK 20, expressed primarily in tumors of the GI tract, mucinous ovarian tumors and transitional cell carcinomas, and CK 7, found chiefly in non-GI tract adenocarcinomas, including breast and lung. CK 20 expression was demonstrated immunocytochemically in seven of seven metastatic colon and two of three metastatic transitional cell carcinomas tested. CK 20 was absent in all metastatic carcinomas of breast, ovary, lung, and uterus examined (23 cases). Anti-CK 7 stains were negative in four of six metastatic colonic carcinomas, with equivocal results in the remaining two cases. Metastatic lung, breast, and ovarian carcinomas were strongly positive for CK 7. This study demonstrates that the combined use of anti-CK 20 and anti-CK 7 antibodies is highly sensitive and specific for metastatic colonic adenocarcinoma in cytologic material and thus could play an important role in distinguishing this entity from other common primary carcinomas.

Topics: Antibodies, Monoclonal; Biomarkers, Tumor; Biopsy, Needle; Carcinoma; Diagnosis, Differential; Female; Humans; Immunoenzyme Techniques; Intermediate Filament Proteins; Keratin-20; Keratins; Neoplasms

Undifferentiated nasopharyngeal carcinomas are universally associated with Epstein-Barr virus (EBV). This association has been exclusively established in lymphoepithelioma-like carcinomas in some locations. The relationship between EBV and lymphoepithelioma-like carcinomas in the larynx is unknown. In none of the few laryngeal lymphoepithelioma-like carcinomas reported have EBV investigations been carried out. We present here two supraglottic laryngeal lymphoepithelioma-like carcinomas in which EBV antigens were not demonstrable using immunohistochemical and molecular methods. Our results suggest that EBV may not be involved in laryngeal lymphoepithelioma-like carcinoma at least in Western patients.

Topics: B-Lymphocytes; Carcinoma; Epiglottis; Herpesvirus 4, Human; Humans; Immunohistochemistry; In Situ Hybridization; Keratins; Laryngeal Neoplasms; Male; Middle Aged; Plasma Cells; Polymerase Chain Reaction; Retrospective Studies; RNA, Viral; T-Lymphocytes; Tumor Suppressor Protein p53

Spindle cell carcinoma is a rare breast tumor. We present herein three cases of spindle cell carcinoma of the breast and review its characteristics from the literature. Spindle cell carcinoma frequently forms a large and well-circumscribed tumor with gross cyst formation. Histologically, its dominant component is of sheets of spindle shaped cells, and it includes such contiguous carcinoma components as squamous differentiation or invasive ductal carcinoma. Estrogen receptor expression and lymph node metastasis tend to be low. Despite the sarcomatous features, spindle cells are likely to be derived from epithelial cells of mammary glands. Immunohistochemical and ultrastructural examination demonstrated the expression of keratin and the desmosome-like junctional structure in the spindle cell components. Relatively favorable prognosis is expected in spindle cell carcinoma of the breast compared to common breast carcinoma.

Topics: Aged; Breast Neoplasms; Carcinoma; Female; Humans; Immunohistochemistry; Keratins; Middle Aged; Prognosis; Ultrasonography, Mammary

Congenital epithelial tumours of the salivary glands are very rare. The Salivary Gland Registry maintained in the Department of Pathology. University of Hamburg, contains only three cases among a total of 6,646 salivary gland tumours from the years 1965-1994. The three cases were classified as congenital basal cell adenoma, two of the parotid gland and one of the submandibular gland. Histologically, the three adenomas were similar in structure to the adult counterpart of basal cell adenoma with solid, trabecular or tubular (duct-like) patterns. In some cystic spaces of the duct-like structures PAS- and Astra blue-positive substances were secreted. On immunocytochemistry, the luminal duct-like cells showed membranous expression of cytokeratins 3, 5, 6, 7, 13 and 19. In the isomorphic basaloid cells of the solid and trabecular cell nests few cells expressed cytokeratin. On the outside of the solid cell nests there were smaller elongated myoepithelial-like cells, which expressed cytokeratin 14 and vimentin. Cytokeratins 1, 2, 4 and 18 were not expressed. The pattern of expression reflects the different stages of maturity of the tumour cells and is related to the development of the salivary glands until the end of the 3rd embryonal month with an arrest of further cell differentiation. No acinic cells, invasive growth, recurrence or metastases were observed. The differential diagnosis includes other congenital salivary gland tumours, such as hybrid basal cell adenoma-adenoid cystic carcinoma, sialoblastoma or embryoma, carcinoma, hamartoma and teratoma.

Topics: Adenoma; Carcinoma; Diagnosis, Differential; Female; Hamartoma; Humans; Immunohistochemistry; Infant, Newborn; Keratins; Male; Microscopy, Electron; Parotid Neoplasms; Periodic Acid-Schiff Reaction; Submandibular Gland Neoplasms; Teratoma; Vimentin

Topics: Aged; Biomarkers; Biopsy; Carcinoma; Carcinoma, Giant Cell; Colonic Neoplasms; Diagnosis, Differential; Female; Humans; Keratins

Tissue slices (500 to 1000 microns thick) of archival formalin-fixed, paraffin-embedded breast tissue were immunostained by a cytokeratin antibody (MNF116) using a streptavidin-biotin complex procedure. The technique requires prolonged exposure of tissue slices to the reagents. Use of the detergent Triton X-100 facilitated penetration of high molecular weight reagents through the tissue slices. Fifty of 58 slices 500 microns thick (86%) showed good to excellent immunostaining, and 13 of 20 slices 1000 microns thick (65%) showed similar staining. Omission of the primary antibody eliminated any immunostaining. Comparison with corresponding Haematoxylin staining of the thick slices (the conventional procedure for such breast tissue slices) showed that thick-slice cytokeratin immunostaining markedly improved visualization of the epithelial structure in normal lobules and invasive carcinomas. Although the immunohistochemical technique takes 33 days for completion, the quality of the epithelial images outweighs this disadvantage.

Topics: Antibodies; Bacterial Proteins; Biotin; Breast; Breast Neoplasms; Carcinoma; Female; Hematoxylin; Humans; Immunohistochemistry; Keratins; Octoxynol; Paraffin Embedding; Streptavidin; Tissue Fixation

Spindle cell carcinoma (SpCC) is uncommon, with a predilection for the upper aerodigestive tract. Its histogenesis has not been resolved, although most authors support the sarcomatoid carcinoma concept. Ploidy analysis and proliferation indices have not been reported for laryngeal SpCCs. The authors examined the pathological and clinical features of 26 patients (25 men, 1 woman; mean age, 64 years) with laryngeal SpCC treated at the Mayo Clinic from 1960 to 1990. Twenty-three tumors were examined with digital image analysis for DNA content of the spindle cell population (13 tumors had a sufficient squamous component to be analyzed separately). The glottis was involved most frequently (19 patients); 21 tumors were grossly polypoid. Twenty-three tumors were biphasic, and three were monophasic. Overall, 17 tumors (65%) showed keratin positivity in the spindle cell component. Polyclonal antikeratin (15 positive cases), 34betaE12 (15 positive), and AE1/AE3 (12 positive) were the most sensitive markers. Spindle cells were diploid in 5 tumors (22%) and nondiploid in 18 (78%); conventional squamous cell carcinoma was diploid in 4 cases and nondiploid in 9. DNA ploidy results were concordant between the two populations in 11 of 13 tumors (85%). Mean percent MIB-1 staining was 31% in the sarcomatoid component and 45% in the squamous component. In our primary treatment group of 22 patients (median follow-up, 6.4 years), 4 (18%) had local recurrence, 3 (14%) had distant metastasis, and 4 (18%) died of disease. Presence of a nondiploid spindle cell population in 78% of cases of laryngeal SpCC is interpreted as evidence of a neoplastic rather than reactive process. Keratin positivity in nearly two thirds of tumors supports the theory of epithelial origin of these tumors (sarcomatoid carcinoma).

Topics: Adult; Aged; Aneuploidy; Biomarkers; Carcinoma; Cell Division; DNA, Neoplasm; Female; Humans; Immunohistochemistry; Keratins; Laryngeal Neoplasms; Male; Middle Aged; Smoking

Cytokeratin 7 (CK-7) has been shown to be uncommonly expressed in colonic epithelial tumors, as opposed to ovarian epithelial tumors, which are always CK-7 positive. The authors investigated the expression of CK-7 in 17 appendiceal cystadenomas and carcinomas, 20 mucinous borderline tumors of the ovary, 10 cases of simultaneous mucinous tumors of the appendix and ovary, three so-called high-stage mucinous borderline tumors of the ovary, and three cases of pseudomyxoma peritonei (PP) of unknown origin. Nine appendiceal cystadenomas were CK-7 negative; two of these were associated with PP, and the peritoneal lesions were negative as well. Three cystadenomas were CK-7 positive. Three appendiceal carcinomas were CK-7 negative, and in one case the metastases were also negative. Two carcinomas were CK-7 positive. All 20 ovarian borderline tumors were CK-7 positive. Six cases of simultaneous mucinous tumors of the ovary and appendix were CK-7 negative, as were their peritoneal mucinous deposits. Four cases showed a positive reaction in both appendiceal and ovarian sites. Two of three so-called high-stage ovarian borderline tumors were CK-7 negative. All three cases of PP of unknown origin were CK-7 negative. In conclusion, appendiceal cystadenomas are often CK-7 negative, whereas ovarian mucinous borderline tumors are always CK-7 positive. The concordant staining pattern for CK-7 of simultaneous mucinous tumors involving the appendix and ovary (60% of which were CK-7 negative) supports an appendiceal origin for these tumors. Our results also support an appendiceal (or colonic) source for any CK-7-negative mucinous tumor involving the ovary or the peritoneum. Furthermore, our findings are in agreement with the assumption that mucinous borderline-like tumors in the ovary associated with PP are not ovarian in origin but are often, if not always, metastatic from an appendiceal (or other) mucinous tumor.

Topics: Adult; Aged; Aged, 80 and over; Appendiceal Neoplasms; Carcinoma; Cystadenocarcinoma; Female; Humans; Keratins; Male; Middle Aged; Ovarian Neoplasms; Peritoneal Neoplasms; Pseudomyxoma Peritonei

Nasopharyngeal carcinoma is a subset of head and neck squamous cell cancers with unique endemic distribution and aetiological co-factors. Epstein-Barr virus has been revealed to be an important aetiological factor for most nasopharyngeal carcinomas. Nevertheless, additional genetic alterations may be involved in their development and progression. The aim of this study was to determine the likely chromosomal locations of tumour-suppressor genes related to Epstein-Barr virus-associated nasopharyngeal carcinoma. Fifty-six microsatellite polymorphic markers located on every autosomal arm were used to estimate the incidence of loss of heterozygosity in 27 Epstein-Barr virus-associated nasopharyngeal carcinomas. High frequencies of allelic loss were observed on chromosome 3p (75.0%) and 9p (87.0%). Chromosome 9q, 11q, 13q and 14q displayed loss in over 50%, while chromosome 3q, 6p, 16q, 19q and 22q exhibited loss in 35-50%. Furthermore, several other chromosomal arms demonstrated allelic loss in 20-35%. Additionally, 1 of the 27 cases showed microsatellite instability at multiple loci. These findings provide evidence of multiple genetic alterations during cancer development and clues for further studies of tumour-suppressor genes in Epstein-Barr virus-associated nasopharyngeal carcinoma.

Topics: Carcinoma; Cell Adhesion Molecules; Chromosome Mapping; DCC Receptor; DNA, Neoplasm; DNA, Viral; Herpesviridae Infections; Herpesvirus 4, Human; Heterozygote; Humans; Keratins; Microsatellite Repeats; Nasopharyngeal Neoplasms; Receptors, Cell Surface; Sequence Deletion; Tumor Suppressor Proteins; Tumor Virus Infections

We report a case of syringoid eccrine carcinoma, a rare syringomatous tumor of the skin, occurring in a 70-year-old woman. Histological and immunohistochemical criteria are given to differentiate this neoplasm from other primary carcinomas of the skin as well as from skin metastases of internal malignancies.

Topics: Aged; Apolipoproteins; Apolipoproteins D; Biomarkers, Tumor; Carcinoembryonic Antigen; Carcinoma; Carrier Proteins; Cell Nucleus; Chromatin; Coloring Agents; Cytoplasm; Eccrine Glands; Female; Glycoproteins; Humans; Immunoenzyme Techniques; Keratins; Membrane Transport Proteins; Neoplasm Proteins; Periodic Acid-Schiff Reaction; S100 Proteins; Skin Neoplasms; Sweat Gland Neoplasms; Syringoma; Vimentin

In view of the different terminology for salivary gland tumours with giant cells, eleven cases were analysed by histopathology and immunocytochemistry. Four cases (three pleomorphic adenomas, one carcinosarcoma in a pleomorphic adenoma) were classified as having a foreign-body giant cell reaction, and five cases (two mucoepidermoid carcinomas, one acinic cell carcinoma, two carcinomas in pleomorphic adenomas) as having a sarcomatoid osteoclast-like giant cell reaction. In two further cases a giant cell tumour and a giant cell granuloma were associated with carcinomas in pleomorphic adenomas. All giant cells showed characteristic expression of CD68 as a typical marker for histiocytes and macrophages with their origin in mononuclear haematopoetic stem cells. There was no evidence for an epithelial origin of the giant cells because all those examined had a negative reaction to cytokeratin. Foreign-body cells were characterized by cytoplasmic vacuoles and irregularly dispersed nuclei. They showed a focally circumscribed reaction mostly outside the connective tissue pseudocapsule of the tumours. The sarcomatoid osteoclast-like giant cell reactions in carcinomas were distinctly intermingled with the carcinomatous patterns. In contrast, the associated osteoclast-like giant cell tumour was distinctly separate from the salivary gland tumour tissue and was composed of numerous larger osteoclast-like giant cells with a greater number of nuclei (more than 20); these giant cells were uniformly distributed throughout the tumour tissue. The giant cell granuloma was also separate from the carcinoma and was composed of nests of smaller, more irregularly distributed giant cells.

Topics: Adenoma, Pleomorphic; Antigens, CD; Antigens, Differentiation, Myelomonocytic; Biomarkers; Carcinoma; Carcinoma, Acinar Cell; Carcinoma, Mucoepidermoid; Carcinosarcoma; Cell Lineage; Cell Nucleus; Connective Tissue; Epithelial Cells; Foreign-Body Reaction; Giant Cell Tumors; Giant Cells; Giant Cells, Foreign-Body; Granuloma, Giant Cell; Hematopoietic Stem Cells; Histiocytes; Humans; Immunohistochemistry; Keratins; Macrophages; Neoplasms, Multiple Primary; Osteoclasts; Salivary Gland Neoplasms; Sarcoma; Vacuoles

The distributional patterns of MUC 1 (the mucin whose cDNA was first cloned) and Keratin 14 (K14) in the invasive regions of malignant eyelid tumors were immunohistochemically examined by comparing with other histochemical markers. The MUC 1-positive tumor cells were detected in several serial, small, invasive tumor masses in the deep subepithelial region of the low differentiated carcinoma. They were also continuously detected in the border region between accumulated lymphocytes including T cells and tumor masses of the sebaceous carcinoma. On the other hand, K14-positive tumor cells were detected in the marginal regions of large tumor masses or those with smooth edges, some of which overlapped the distribution of MUC 1-positive cells in the tissues of undifferentiated carcinoma, squamous cell carcinoma, and sebaceous carcinoma. In general, MUC 1 may be expressed in the invasive tumor cells, whereas K14 may be expressed in the marginal cells of the stable, proliferating tumor masses.

Topics: Adenocarcinoma, Sebaceous; Aged; Aged, 80 and over; Carcinoma; Carcinoma, Squamous Cell; Eyelid Neoplasms; Female; Humans; Immunohistochemistry; Keratin-14; Keratins; Male; Middle Aged; Mucin-1; Mucins; Neoplasm Invasiveness

Carcinomas metastatic to the ovary are often difficult to distinguish from primary ovarian carcinomas. Adenocarcinoma of the colon may simulate both primary endometrioid and mucinous ovarian tumors. The histologic finding of "dirty" necrosis in association with a "garland" or cribriform pattern has been suggested as a useful feature in distinguishing metastatic colonic carcinomas from primary endometrioid ovarian carcinomas. This study was performed to determine the use of "dirty" necrosis in distinguishing primary ovarian carcinoma from metastatic colonic carcinoma by studying 71 of the former and 10 of the latter. At least focal dirty necrosis was found in 68% of primary ovarian epithelial cancers, including 92% of the endometrioid subtype, and in 100% of the metastatic colonic carcinomas. A subgroup of cases was evaluated immunohistochemically using cytokeratin (CK) 7, CK 20 and carcinoembryonic antigen (CEA). The phenotype of CK 7 +/CK 20-/CEA-was present in 92% of primary ovarian carcinomas studied, whereas, 90% of metastatic colonic carcinomas were CK 7-/CK 20 +/CEA+. The finding of dirty necrosis is not specific for metastatic colonic cancer, and differential cytokeratin immunostaining is a useful adjunct in this differential diagnosis.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Biomarkers, Tumor; Carcinoembryonic Antigen; Carcinoma; Colonic Neoplasms; Female; Humans; Immunohistochemistry; Intermediate Filament Proteins; Keratin-20; Keratins; Middle Aged; Necrosis; Ovarian Neoplasms

There is controversy about the prognostic significance of occult lymph node metastases detected by immunohistochemistry with the anti-cytokeratin antibody CAM 5.2. The aim of this study was to characterize occult lymph node metastases in colorectal carcinomas that might be associated with a higher risk of recurrence. Three hundred fifty-eight lymph nodes from 10 recurrent and 9 nonrecurrent cases of colorectal carcinoma were examined. All these patients had been reported originally as having no lymph node metastases by routine hematoxylin and eosin staining. Three 10-micron sections or ten 3-micron sections (30-micron total thickness) from each lymph node were stained with CAM 5.2 and examined for the presence of occult lymph node metastases. Occult metastases were detected in 67 of 175 lymph nodes from the recurrent cases, and in 23 of 183 lymph nodes from the nonrecurrent cases. The frequency of positive nodes was significantly higher in the recurrent cases. The recurrent cases had metastases in nodes more distant from the main tumor than did the nonrecurrent cases. Detection of occult lymph node metastases with cytokeratin immunohistochemistry may make it possible to identify patients with a higher risk of recurrence after the removal of a primary colorectal tumor.

Topics: Adult; Aged; Aged, 80 and over; Carcinoma; Colorectal Neoplasms; Female; Humans; Immunohistochemistry; Keratins; Liver Neoplasms; Lung Neoplasms; Lymph Nodes; Lymphatic Metastasis; Male; Middle Aged; Neoplasm Recurrence, Local; Platelet Endothelial Cell Adhesion Molecule-1; Prognosis

Presented is a case report of a urinary bladder carcinoma that had an unusual morphology and phenotype. A 65-year-old Japanese man complained of gross hematuria. Cytological examination of the urine before a partial cystectomy revealed small, round atypical cells with a high nuclear/cytoplasmic ratio, scant cytoplasm, and hyperchromatic nuclei with coarse and granular chromatin in a bloody background. Several tumor cells had relatively large and vesicular nuclei with prominent eosinophilic nucleoli and obscure perinucleolar halos. A small number of large atypical urothelial cells were also recognized. The tumor recurred locally 3 months after the operation. The urine cytology during recurrence showed the same features without the atypical urothelial cells. These cytological findings suggested a case of small cell undifferentiated carcinoma (SCUC) combined with transitional cell carcinoma (TCC). An histology of the resected specimen before the recurrence revealed that the SCUC was consistent with a variant type of SCUC proposed for the lung and showed transition with TCC in situ. M-VAC chemotherapy after a total cystectomy was less effective. The patient died 6 months after diagnosis. A variant subtype of SCUC of the urinary bladder associated with TCC in situ has not been previously reported. Although this histological type is very rare, its earlier cytological detection is needed for appropriate therapy.

Topics: Aged; Biomarkers, Tumor; Carcinoma; Carcinoma in Situ; Carcinoma, Transitional Cell; Cytodiagnosis; Fatal Outcome; Humans; Immunohistochemistry; Keratins; Lewis X Antigen; Male; Microscopy, Electron; Neoplasm Recurrence, Local; Urinary Bladder Neoplasms

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

The monitoring of serum concentrations of Cyfra 21-1, tumor polypeptide antigen (TPA), and tissue polypeptide specific antigen (TPS) has been demonstrated to be useful in the clinical treatment of patients with lung cancer. This study was planned to evaluate the clinical usefulness of the assay of these tumor markers on bronchial washing (BW) fluid and to compare it with serum assay in patients with neoplastic and nonneoplastic disease.. Serum and BW fluid levels of Cyfra 21-1, TPA, and TPS were measured in 40 subjects (10 control subjects, 11 with chronic bronchitis, 10 with squamous cell lung cancer, and 9 with nonsquamous cell lung cancer) undergoing diagnostic bronchoscopy. BW was performed using 25 mL of pyrogen-free saline solution instilled through the working channel of the bronchoscope, and successively aspirated. The quantity of the fluid recovered was measured and used for the assay of albumin, Cyfra 21-1, TPA, and TPS.. Mean BW concentrations of Cyfra 21-1, TPA, and TPS concentrations were significantly higher than serum concentrations (p < 0.01). Serum Cyfra 21-1, TPA, and TPS concentrations were significantly lower in controls and in those with chronic bronchitis than in patients with epidermoid and nonepidermoid carcinoma (p < 0.01). No difference in serum concentrations of the three markers was observed between controls and patients with chronic bronchitis. On the contrary, BW Cyfra 21-1 and TPA concentrations were significantly higher in those with chronic bronchitis and in cancer patients than in controls (p < 0.01), whereas they did not differ between patients with chronic bronchitis and cancer patients. No significant difference in BW TPS concentration was observed among the four groups. Sensitivity and specificity of the BW markers in diagnosing lung cancer were as follows: 68.4% and 61.9% for Cyfra 21-1; 68.4% and 66.6% for TPA; and 57.9% and 66.6% for TPS.. BW fluid concentrations of Cyfra 21-1 and TPA are increased in patients with chronic bronchitis and in patients with lung cancer. Being unable to distinguish malignant from nonmalignant inflammatory conditions, the measurement of airway concentrations of such markers has a too-low specificity to be considered useful in diagnosing malignant abnormalities of the lung.

Topics: Adult; Aged; Albumins; Antigens; Antigens, Neoplasm; Biomarkers, Tumor; Bronchitis; Bronchoalveolar Lavage Fluid; Bronchoscopy; Carcinoma; Carcinoma, Squamous Cell; Chronic Disease; Female; Humans; Keratins; Lung Neoplasms; Male; Middle Aged; Peptides; Sensitivity and Specificity; Tissue Polypeptide Antigen

Keratin filaments in simple epithelial cells are heteropolymers of keratin 8 (K8) and keratin 18 (K18), which can be stained by the monoclonal antibody (MAb) LE61. This antibody has been widely used to study keratin expression in normal and neoplastic tissues. In this study we have found that MAb LE61 does not react with individual keratin polypeptides either derived from natural sources or expressed as recombinant proteins in Escherichia coli. However, when K8 or K18 bound to nitrocellulose were incubated with complementary keratin they became reactive with this antibody. A mixture of K8 and K18 in solution also reacted strongly with the MAb LE61 in ELISA. These observations suggest that the antibody recognizes a discontinuous epitope on the keratin complex. The antibody also reacted with complexes of K8 and K18 with other keratins. To locate the epitope of this antibody we have expressed K8 and K18 fragments, deleted from the amino- and carboxyl-termini, as fusion proteins with glutathione S-transferase. These fragments were able to form a heterotypic complex with the complementary keratin. Binding of the MAb LE61 to these complexes mapped the two halves of the epitope on K8, between residues 353 and 367, and on K18, between residues 357 and 385. The two halves of the epitope appear to be in close association in the heterotypic complex since deletions from the amino-terminus did not influence the antibody binding. The highly conserved nature of this epitope in both type I and type II keratins could explain the MAb LE61 reactivity with complexes of K8 or K18 with other keratins.

Topics: Amino Acid Sequence; Antibodies, Monoclonal; Antibody Specificity; Base Sequence; Carcinoma; Enzyme-Linked Immunosorbent Assay; Epitope Mapping; Epitopes; HT29 Cells; Humans; Keratinocytes; Keratins; Molecular Sequence Data; Protein Conformation; Recombinant Fusion Proteins; Tumor Cells, Cultured

A fatal collecting duct carcinoma, presenting with pleural metastases, arose from the right kidney in an 8-year-old child. A distal nephron origin of the tumor is supported by positive tumor staining with Ulex europaeus and Arachis hypogaea, and a lack of staining with Tetragonolobus lotus. The ultrastructural features of short stubby microvilli, smooth basal cell membranes, and lateral membrane infoldings also support a distal nephron origin (inner most inner medullary collecting duct). This rare childhood renal neoplasm behaved similarly to that reported in adults with metastatic disease at presentation and a short fatal clinical course.

Topics: Carcinoma; Child; Fatal Outcome; Humans; Keratins; Kidney Neoplasms; Kidney Tubules; Kidney Tubules, Collecting; Male; Pleural Neoplasms

Myoepitheliomas of the salivary glands remain a controversial entity. To contribute to the knowledge of this entity, 16 myoepithelial tumors of the salivary glands were studied: 12 benign myoepitheliomas (BME) and 4 malignant myoepitheliomas (MME). The clinical and the histologic findings of each case were studied Immunohistochemistry and flow-cytometry analysis were performed from the paraffin-embedded material in 15 cases. An electron-microscopy study was performed in 8 cases. The myoepithelial tumors affected patients of both sexes equally. The mean age of the patients with BME was 54 years, and the mean age of patients with MME was 62 years. Eight cases of BME originated in the parotid gland and 4 cases originated in the minor salivary glands. All the MME developed from a benign preexistent tumor: two developed from a pleomorphic adenoma in the parotid gland, and the other two MME developed in the minor salivary gland from a BME. The myoepithelial tumors were composed of epithelioid, plasmacytoid, spindle, or clear cell types, and they showed a solid or a myxoid pattern of growth. Immunohistochemical studies revealed marked and diffuse positivity to cytokeratins, vimentin, and S-100 protein in all cases. Glial fibrillary acidic protein was positive in 8 cases (53%), and muscle-specific actin and smooth-muscle actin were positive in only 3 cases (20%); they were all cases of BME. Desmin was negative in all tumors. Ultrastructural studies showed the presence of basal membrane, tight junctions, intermediate filaments, and microvilli as well as actin-like filaments lacking focal densities in all cases. But actin-like filaments with focal densities were not identified. Flow cytometry determined that all BME were diploid with a mean proliferative index of 7.73%. Two of the MME were diploid and the other two MME were aneuploid. The mean proliferative index of MME was 11.93%. In conclusion, BME and MME originated in major and minor salivary glands can display different histologic patterns and cellular features. Some immunohistochemical and ultrastructural characteristics have been found in all these neoplasms, which supports the idea that myoepitheliomas are composed by neoplastic modified myoepithelial cells, not fully differentiated. These techniques can be useful for the diagnosis of these tumors.

Topics: Adult; Aged; Aged, 80 and over; Carcinoma; Desmin; DNA, Neoplasm; Female; Flow Cytometry; Glial Fibrillary Acidic Protein; Humans; Immunohistochemistry; Keratins; Male; Maxillary Neoplasms; Microscopy, Electron; Middle Aged; Myoepithelioma; Parotid Neoplasms; Ploidies; S100 Proteins; Salivary Gland Neoplasms; Salivary Glands; Salivary Glands, Minor; Vimentin

TGFbeta1 has been implicated in cell cycle control and carcinogenesis. To address the exact function of TGFbeta1 in skin carcinogenesis in vivo, mice with TGFbeta1 expression targeted to keratinocytes were subjected to long-term chemical carcinogenesis treatment. TGFbeta1 showed biphasic action during multistage skin carcinogenesis, acting early as a tumor suppressor but later enhancing the malignant phenotype. The transgenics were more resistant to induction of benign skin tumors than controls, but the malignant conversion rate was vastly increased. There was also a higher incidence of spindle cell carcinomas, which expressed high levels of endogenous TGFbeta3, suggesting that TGFbeta1 elicits an epithelial-mesenchymal transition in vivo and that TGFbeta3 might be involved in maintenance of the spindle cell phenotype. The action of TGFbeta1 in enhancing malignant progression may mimic its proposed function in modulating epithelial cell plasticity during embryonic development.

Topics: Animals; Carcinoma; Carcinoma, Squamous Cell; Cells, Cultured; Female; Immunologic Techniques; Integrins; Keratins; Mice; Mice, Transgenic; Papilloma; Skin Neoplasms; Transforming Growth Factor beta

It is not known how tightly regulation of cytokeratin (CK) protein expression is correlated with transcriptional activity in breast cancer. The level of control of CK expression in the normal mammary gland and in breast cancer has been assessed by combining in situ hybridization with riboprobes, and with immunohistochemistry using monospecific antibodies. In normal mammary gland, luminal cells showed abundant hybridization with complementary RNA (cRNA) probes for CK7, CK8, CK18, and CK19. Proteins of these CKs were correspondingly distributed except for that of CK19, which showed a heterogeneous staining. In primary carcinomas, both messenger RNAs (mRNAs) and proteins of CK8 and CK18 were generally expressed to a degree similar to that of normal epithelia, but a lower level of mRNA and protein of CK18 was observed in metastatic carcinomas. Reduced expression of CK7 and CK14 was observed in all carcinomas, and the correlation between mRNA and protein for these two cytokeratins was unbalanced, whereas the expression of CK19 mRNA and the proportion of its protein-positive cells were increased. The results suggest that these major CKs in normal mammary gland epithelia are regulated at the transcriptional level except for CK19, which is partially under the posttranscriptional control. The alterations observed in breast cancer are not only reflected by the reduced or increased expression of individual cytokeratins, but characterized by partial loss of the normal regulation of cytokeratin expression.

Topics: Adult; Breast; Breast Neoplasms; Carcinoma; Female; Fibroadenoma; Humans; Immunohistochemistry; In Situ Hybridization; Keratins; Reference Values; RNA, Messenger

Salivary duct carcinoma (SDC) has been established as a morphologically distinct and highly aggressive (HG) malignancy of the major salivary glands. However, a low grade (LG) or intermediate grade salivary duct neoplasm has not been described.. We report the clinicopathologic findings of 10 cases believed to represent the (LG) counterpart of SDC. Immunoperoxidase stains were performed on five cases, and electron microscopy on three.. All of the tumors occurred in adult patients with no sex predilection, and presented as slow growing parotid gland lesions. Four cases involved the superficial lobe, one the deep lobe, and one arose within an intraparotid lymph node. The exact location of the tumor within the parotid gland was not stated in four cases. The size of the tumors ranged from 0.7 to 4 cm in greatest dimension, with most measuring between 1 and 2 cm. The gross appearance was focally to predominantly cystic. Microscopically, the tumors were characterized by intraductal proliferative lesions exhibiting three main patterns: (1) cystic ducts with micropapillary, tufted, and plaque-like intraluminal projections; (2) ducts distended by a solid or pseudocribriform (fenestrated) cellular proliferation, with varied cystic dilatation; and (3) ducts exhibiting architectural atypia. The three patterns coexisted and merged in most tumors, in varying proportions. All tumors shared bland to LG cytologic features, with the exception of one that had focal high-grade cytologic ductal atypia. Despite gross circumscription, there was microscopic multifocality, and in one case, stromal invasion. By immunohistochemistry, the neoplastic cells expressed the conventional ductal and glandular epithelial cell markers in addition to strong positivity for S-100 with coexpression for CK-903. Electron microscopy confirmed the ductal phenotype of the tumors and supported an in situ process evidenced by the presence of native myoepithelial cells. Nine patients underwent total parotidectomy and one superficial parotidectomy. One patient received radiation therapy following total parotidectomy. Follow-up for 6 cases ranged from 2 to 12 years and revealed no evidence of disease.. LG-SDC represents the LG end of the spectrum of salivary duct malignant neoplasms and exhibits differentiation towards an intercalated duct-like cell phenotype. Its relationship to HG-SDC should be further explored.

Topics: Adult; Aged; Carcinoma; Cell Membrane; Cytoplasm; Female; Humans; Immunoenzyme Techniques; Keratins; Male; Microvilli; Middle Aged; Organelles; Parotid Neoplasms; S100 Proteins; Salivary Ducts

In this study, we demonstrated the clonal origin of trisomy for chromosome 7 in epithelial cells of colon neoplasia. By using the double-target fluorescence in situ hybridization (FISH) technique in frozen tissue sections that were also immunostained for keratin and vimentin, ratio analysis of FISH signals for chromosomes 7 and 17 could be performed in epithelial (cytokeratin-positive) or stromal (vimentin-positive) areas. The data demonstrated that trisomy for chromosome 7 is found exclusively in the epithelial compartments and not in the stroma of colon adenocarcinoma. We then demonstrated the occurrence of trisomy for chromosome 7 in the different types of epithelial neoplastic cells, i.e., columnar and goblet cells, which were isolated from frozen tissue sections by mechanical disaggregation of colon tissue and mild lysis of the cells while protease activity was inhibited. In these cell suspensions, the columnar cells were detected with an antibody to villin, and the goblet cells were stained for mucin, whereas all cells were subsequently subjected to FISH for chromosome 7. For analysis of neuroendocrine cells, which are present in a very low frequency in colon neoplasia, frozen tissue sections that were immunostained for Chromogranin A could be used. Individual neuroendocrine cells could be distinguished in these thin frozen tissue sections. The presence of trisomy for chromosome 7 in all three different epithelial cell types strengthens our suggestion that this chromosomal aberration is found in the epithelial stem cell compartment of colon neoplasia.

Topics: Adenoma; Carcinoma; Cell Line; Chromosome Aberrations; Chromosomes, Human, Pair 7; Clone Cells; Colonic Neoplasms; Epithelium; Humans; In Situ Hybridization, Fluorescence; Keratins; Trisomy; Vimentin

Amplification of keratin 19 mRNA (K19) by reverse transcriptase-polymerase chain reaction (RT-PCR) has been shown to be a sensitive method to detect occult breast cancer metastases in lymph nodes.. Axillary lymph nodes were obtained from 126 patients with breast cancer, and metastases in these lymph nodes were studied by both histologic examination and K19 RT-PCR. The patients were categorized into 3 groups according to the results of these 2 examinations, i.e., patients with 1) both histologically and K19 RT-PCR negative lymph nodes (metastases negative group [n = 91]); 2) histologically negative but K19 RT-PCR positive lymph nodes (occult metastases positive group [ n = 15]); and 3) histologically positive lymph nodes (metastases positive group [n = 20]).. Various histologic parameters such as tumor size, histologic type, histologic grade, lymphatic invasion, vascular invasion, and estrogen receptor status were compared among these three groups. There were no significant differences among any of these histologic parameters between the metastases positive and occult metastases positive groups. Conversely, tumor size of the metastases positive (2.5 +/- 0.2 cm) and occult metastases positive (2.5 +/- 0.2 cm) groups was significantly (P < 0.05) greater than that of the metastases negative group (1.9 +/- 0.1 cm), and positivity of lymphatic vessel invasion in the former 2 groups (70% and 53%, respectively) was also significantly (P < 0.01) greater than that in the latter group (18%).. These results demonstrate that histologic characteristics of breast cancers with occult metastases are similar to those of breast cancers with histologically detectable metastases.

Topics: Actins; Adult; Aged; Aged, 80 and over; Blood Vessels; Breast Neoplasms; Carcinoma; Female; Gene Amplification; Humans; Keratins; Lymph Node Excision; Lymph Nodes; Lymphatic Metastasis; Mastectomy, Modified Radical; Mastectomy, Segmental; Middle Aged; Neoplasm Invasiveness; Neoplasms, Unknown Primary; Polymerase Chain Reaction; Receptors, Estrogen; RNA, Messenger; Transcription, Genetic

Topics: Biopsy, Needle; Carcinoma; Fatal Outcome; Female; Humans; Immunohistochemistry; Keratins; Lung Neoplasms; Lymphatic Metastasis; Middle Aged; Thyroglobulin; Thyroid Neoplasms

We have developed a reverse transcriptase-polymerase chain reaction (RT-PCR) assay to identify breast carcinoma cells in bone marrow aspirates with high sensitivity and specificity. This assay relies on the detection of cytokeratin 19 (K19) RNA by nested primer PCR followed by annealing to a (32P)-labeled internal sequence probe and autoradiography. In reconstitution experiments, this assay is capable of detecting 10 fg of admixed mammary tumor RNA in 1 microgram of normal marrow RNA (a dilution of 1:10(7)). Thirty of 30 primary breast tumor specimens, 19 of 19 cytologically positive bone marrow aspirate specimens, and three of 11 aspirate negative/biopsy positive specimens showed detectable K19 transcript. This assay shows high specificity, with 50 of 52 negative control aspirates showing no detectable amplification product. False-positive amplification was noted in two of 18 aspirates obtained from patients with active chronic myelogenous leukemia. Of stage II and III postsurgical breast carcinoma patients with histologically negative bone marrows and no radiographic bone disease, 14 of 30 were K19 positive by PCR. RT-PCR analysis of K19 transcript is a highly sensitive and specific method of detecting and monitoring low-level metastatic disease in patients with primary carcinoma of the breast. The presence of K19 RNA in histologically negative bone marrows suggests that this assay may prove a powerful monitor for patients undergoing curative therapy as well as a novel prognostic indicator.

Topics: Breast Neoplasms; Carcinoma; DNA Primers; Female; Humans; Keratins; Neoplasm, Residual; Polymerase Chain Reaction; RNA-Directed DNA Polymerase; Sensitivity and Specificity; Tumor Cells, Cultured

Epidermotropic metastases from internal malignancies are exceedingly rare. We report two examples of epidermotropic metastatic breast carcinoma with striking intraepidermal involvement. The first case mimicked melanoma because the neoplastic cells contained melanin and were disposed both as single units and as nests at the dermoepidermal junction and throughout the epidermis. In the second case, the neoplastic cells were seen as isolated neoplastic cells with large, pale cytoplasm scattered throughout the epidermis, closely resembling extramammary Paget's disease. Immunohistochemical studies in both cases demonstrated the epithelial nature of intraepidermal neoplastic cells, which showed an immunophenotype identical to the neoplastic cells present in the dermis: positive staining with anti-cytokeratins, CEA, EMA, and GCDFP-15 and negative with anti-S-100 protein and HMB-45. These findings ruled out the possibility of a collision lesion, or simultaneous occurrence of melanoma and metastatic breast carcinoma. Pagetoid intraepidermal spread of metastatic breast carcinoma, as in our two cases, is exceptional. We also discuss the histogenetic similarities between our findings and those of mammary and extramammary Paget's disease, as well as the differential diagnosis of other cutaneous disorders characterized by pagetoid intraepidermal spread of neoplastic cells.

Topics: Aged; Antigens, Neoplasm; Breast Neoplasms; Carcinoma; Carcinoma, Ductal, Breast; Diagnosis, Differential; Epidermis; Female; Humans; Immunohistochemistry; Keratins; Melanins; Melanoma; Melanoma-Specific Antigens; Middle Aged; Neoplasm Proteins; Paget Disease, Extramammary; Paget's Disease, Mammary; S100 Proteins; Skin Neoplasms

Three cases of sarcomatoid carcinoma of the small intestine are presented. One of them was found accidentally in the duodenum of a patient with a well differentiated adenocarcinoma and a malignant lymphoma that were limited to the stomach. The other two cases arose from the ileum. All of the tumors were whitish, soft and ulcerated with focal hemorrhage and necrosis and showed expansive growth. Each tumor consisted of a mixture of polygonal and spindle shaped anaplastic neoplastic cells arranged in sheet, short fascicular or haphazard fashion, with no finding suggesting epithelial differentiation. Special stains demonstrated intracellular mucin in only a small number of tumor cells in two cases, but not in the other case. Immunohistochemically, the tumor cells of two cases at both primary and metastatic sites showed a positive immunoreaction for cytokeratin and epithelial membrane antigen. In the other case, only a few tumor cells at the metastatic site, but not at the primary site, showed cytokeratin positivity. Various numbers of tumor cells positive for vimentin, alpha-1-antitrypsin (AAT), alpha-1-antichymotrypsin (ACT) and KP-1 were detected in each case. Ultrastructurally, some populations of tumor cells possessed various amounts of tonofilaments with a few intercellular connections between adjacent tumor cells. These cases should be classified as sarcomatoid carcinoma of the small intestine, despite partial or complete loss of epithelial features, and distinguished from the various sarcomas.

Topics: Aged; Carcinoma; Diagnosis, Differential; Female; Humans; Immunohistochemistry; Intestinal Neoplasms; Intestine, Small; Keratins; Male; Mucin-1

A case of epithelial-myoepithelial carcinoma (EMC) of the palate in a 72-year-old Japanese man is described. The patient had noticed swelling of the palate commencing about 20 years previously. Histologically, the tumor consisted of a proliferation of double-layered duct-like structures with two distinctive cell types. The inner layer was composed of eosinophilic epithelial cells, while the outer layer was composed of clear cells. Immunohistochemical analysis revealed that reaction products for total keratin were predominantly found in the cytoplasm of the inner epithelial cells, while those for S-100 protein and smooth muscle actin were observed only in the outer cells. Immunoreactive products for secretory component and lysozyme were found in some of the luminal contents and the inner cells of the tumor nests. These findings indicated this tumor to be an EMC of the palate, which had shown no aggressiveness over a twenty-year period prior to surgical excision.

Topics: Actins; Aged; Carcinoma; Cell Division; Cytoplasm; Epithelium; Humans; Immunohistochemistry; Keratins; Male; Muramidase; Palatal Neoplasms; S100 Proteins; Secretory Component

Malignant progression of tumour cells is caused by the accumulation of genetic defects, which when combined will generate a large phenotypic diversity. Simultaneous quantitation of a large number of gene products in tumour cells is desirable, but difficult to achieve. We have here quantitated the levels of a number of abundant polypeptides in human breast carcinoma cells using two-dimensional gel electrophoresis (2-DE; PDQUEST). For this purpose, tumour cells were prepared from the tissue of 17 breast carcinomas. Fibroadenoma tissue was used as reference for benign cells. An increase of the spot density of the PCNA polypeptide was observed in rapidly proliferating tumour cells, confirming the validity of the procedures used. In the set of 24 polypeptide spots with known identity, decreases in cytokeratin and tropomyosin levels were observed. The levels of all cytokeratin forms resolved (CK7, CK8, CK15 and CK18) were significantly lower in carcinomas than in fibroadenomas. The levels of tropomyosin 2 and 3 were lower in carcinomas than in fibroadenomas. In contrast, the levels of some members of the stress protein family (pHSP60, HSP90 and calreticulin) were higher in carcinomas. Furthermore, changes in the expression of lactate dehydrogenase and GT-pi, but not in nm23, were observed. We conclude that simultaneous analysis of multiple polypeptides in human carcinomas can be achieved by 2-DE and may be useful in prognostic studies, and that malignant progression of breast carcinomas results in the decreased expression of cytokeratin polypeptides. This phenomenon must be considered in studies where cytokeratins are used as markers to identify the epithelial cell compartment in breast carcinomas.

Topics: Breast Neoplasms; Carcinoma; Cell Cycle Proteins; Cytoskeletal Proteins; Down-Regulation; Electrophoresis, Gel, Two-Dimensional; Female; Fibroadenoma; Glutathione Transferase; Heat-Shock Proteins; Humans; Keratins; Monomeric GTP-Binding Proteins; Neoplasm Proteins; NM23 Nucleoside Diphosphate Kinases; Nucleoside-Diphosphate Kinase; Transcription Factors

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 occurrence of approximately 5% of common epithelial malignant tumors of the ovary can be traced to inheritance of risk. One prophylactic strategy to decrease the probability of development of disease in individuals within families where this mendelian-dominant pattern of occurrence is apparent is to remove the ovaries of individuals at risk for ovarian cancer. The procedure, when done for this purpose, is recommended soon after completion of childbearing.. Our goal was to compare the histologic features of the ovaries of women at increased risk for ovarian cancer to those at no known increased risk for the disease.. Ovaries removed for prophylaxis from 20 women considered to be at increased risk for developing ovarian cancer were examined histologically. During the course of this work, it seemed apparent that these ovaries contained numerous atypical features compared with the expected appearance of normal ovaries. Hence, we expanded the study to include a control group whose ovaries were removed for reasons unrelated to cancer. The study, therefore, was not blinded. The increased risk in the cancer-prone individuals was determined by family history, specifically the presence of at least one first-degree relative and one second-degree relative with ovarian and/or breast cancer and positive linkage or mutational analysis of BRCA1 in some. The difference in mean ages of patients in the control and high-risk groups was not statistically significant. The difference among both groups with respect to the number of atypical features as well as the intensity of those features was ascertained by computing probabilities using Fisher's exact test (two-sided) for rows x columns contingency tables.. Two unanticipated microscopic or near-microscopic malignant neoplasms and other benign and borderline tumors were discovered in the ovaries of the high-risk individuals. Of substantial interest was the finding that among the ovaries of high-risk women, 85% presented two or more and 75% presented three or more of the following histologic features: surface epithelial pseudostratification; surface papillomatosis; deep cortical invaginations of the surface epithelium, frequently with multiple papillary projections within small cystic spaces (microscopic papillary cystadenomas); epithelial inclusion cysts, frequently with epithelial hyperplasia and papillary formations; cortical stromal hyperplasia and hyperthecosis; increased follicular activity; corpus luteum hyperplasia; or hilar cell hyperplasia. Two or more or three or more such changes were observed in a lesser percentage (30% or 10%, respectively) of ovaries obtained from the control individuals, with a statistically significant difference (P = .001 or P = .00007, respectively), particularly considering that a detailed determination of a family history of cancer in the control group was not possible.. The frequency of these changes in the high-risk ovaries compared with control ovaries suggests a characteristic histologic preneoplastic phenotype defined by an increased frequency and intensity of the above-described histologic features in the high-risk ovaries. Limited access to numerous small (stage I) ovarian cancers or cancer-prone ovaries by any one pathologist may explain the failure to identify the phenotype in the past.. We suggest that the ovaries removed from ovarian cancer-prone individuals as a preventative measure should be thoroughly examined histologically to identify or rule out microscopic or near-microscopic invasive neoplasms.

Topics: Adult; Carcinoma; Case-Control Studies; Female; Genetic Linkage; Humans; Keratins; Middle Aged; Neoplasm Invasiveness; Ovarian Neoplasms; Ovariectomy; Ovary; Phenotype; Polymorphism, Single-Stranded Conformational; Precancerous Conditions; Receptors, Estrogen; Risk

The histopathological findings of two cases of primary lymphoepithelioma-like carcinoma (LELC) of the skin occurring in two elderly Chinese individuals are presented. Microscopically, they were well circumscribed and were composed of irregular nests of malignant epithelial cells in a background of reactive lymphoid cells including mature plasma cells. A focus of epithelial dysplasia was noted in the adjacent epidermis in one case, suggesting that the LELC might have originated from the overlying epidermis. The epithelial nature of the tumors was confirmed by cytokeratin staining. In situ hybridization for Epstein-Barr virus-encoded RNA (EBER) showed that the tumor cells were uniformly negative, although positive signals were detected in scattered background lymphocytes in case 1. Our results confirm the previous observation that LELC of skin is not related to Epstein-Barr virus, even in Chinese subjects. Nevertheless, such negative findings may prove to be of diagnostic value in excluding the alternative more common diagnosis of metastatic nasopharyngeal carcinoma, which is uniformly positive for EBER.

Topics: Aged; Aged, 80 and over; Carcinoma; Carcinoma, Squamous Cell; China; Epidermis; Epithelium; Female; Herpesvirus 4, Human; Humans; In Situ Hybridization; Keratins; Lymphocytes; Lymphoid Tissue; Male; Nasopharyngeal Neoplasms; Plasma Cells; RNA, Viral; Skin Neoplasms

Using 8 different monoclonal antibodies, immunohistology was performed on 36 follicular adenomas and on 28 follicular, 34 papillary, 27 medullary and 29 anaplastic carcinomas of the thyroid. The panel of antibodies was directed against broad-spectrum cytokeratins (pan-CK, antibody lu-5), against basic and acid high-molecular-weight CK of types #1, 5, 10 and 14, against basic (#5 and 6) and acid high-molecular-weight CK (#13) and against basic (#7 and #8) and acid low-molecular-weight CK (#19 and #20). With the exception of a large number of anaplastic carcinomas, nearly all other tumours exhibited strong immunoreactivity with antibodies against pan-CK, CK 8 and CK 19. CK 20 expression was exclusively shown for 2 medullary carcinomas. Reactivity for high-molecular-weight CK could only, each time focally, be demonstrated for 14 papillary and 2 follicular carcinomas and for 2 anaplastic carcinomas with partial squamous differentiation. Thirteen anaplastic carcinomas were not decorated by any of the CK antibodies applied. CK 7 staining exceeding the staining of individual cells was observed in 26 papillary cancers. In contrast, such a finding could only be obtained with each one follicular adenoma, medullary carcinoma and anaplastic carcinoma and with 5 follicular carcinomas. These results confirm earlier studies in that CK 20 expression among thyroid tumours is restricted to the neuroendocrine medullary carcinomas and that in a larger percentage of anaplastic thyroid carcinomas an epithelial phenotype can not be demonstrated even upon using broad-spectrum CK antibodies. New is the finding that there exist considerable differences between papillary carcinomas and all other non-papillary thyroid tumours regarding CK 7 expression. This result might be of differential diagnostic value for the distinction of follicular and papillary thyroid neoplasias which sometimes have an overlapping histological pattern.

Topics: Adenocarcinoma, Follicular; Adenoma; Antibodies, Monoclonal; Biomarkers, Tumor; Carcinoma; Carcinoma, Medullary; Carcinoma, Papillary; Diagnosis, Differential; Humans; Keratins; Thyroid Gland; Thyroid Neoplasms

We describe an epithelial neoplasm arising from the fourth ventricle of a goat and extending into the subjacent cerebellum along the spaces of Virchow-Robin. The neoplastic cells are consistent with squamous epithelium based upon light microscopic morphology and cytokeratin immunoreactivity. The lack of overt keratin formation and the lack of an exophytic component distinguishes this neoplasm from intracranial epidermoid cysts, resulting in the classification of this caprine tumor as an epithelioma.

Topics: Animals; Carcinoma; Cerebellar Neoplasms; Cerebral Ventricle Neoplasms; Female; Goat Diseases; Goats; Immunohistochemistry; Keratins; Neoplasm Invasiveness

Fourteen endometrioid carcinomas of the ovary with a prominent component of spindle-shaped epithelial cells are reported. Eleven were initially misdiagnosed as sexcord stromal tumors, malignant mesodermal mixed tumors, tumors of probable wolffian origin, or metastatic carcinomas. All of the tumors, however, had one or more features establishing them as endometrioid carcinomas, including (a) glands typical of endometrioid adenocarcinoma, (b) foci of squamous differentiation, and (c) an adenofibromatous component. Six cases were examined immunohistochemically, and the epithelial nature of the spindle cells was supported by immunostaining for keratin and epithelial membrane antigen. The patients ranged in age from 42 to 89 years (mean, 61). Four cases were stage I, five stage II, and three stage III. Follow-up information was available in seven cases. Five patients were free of disease at 8, 11, 32, 56, and 103 months, and two patients were alive with disease at 10 and 20 months. The age of the patients, clinical presentation, tumor stage, and gross appearance were similar to those of typical endometrioid carcinomas. It is important that this tumor be distinguished from other ovarian neoplasms with a spindle-cell component because of differences in treatment and prognosis.

Topics: Adult; Aged; Aged, 80 and over; Antigens, Neoplasm; Carcinoma; Diagnosis, Differential; Diagnostic Errors; Endometrial Neoplasms; Female; Humans; Immunoenzyme Techniques; Keratins; Middle Aged; Mucin-1; Ovarian 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

Previous studies on the cell-cell adhesion molecules P- and E-cadherin have shown that P-cadherin is not expressed in breast cancer. In contrast, the expression of E-cadherin is a normal event in these tumors, but a reduction in the levels of this molecule in neoplastic cells is associated with the histological type, high histological grade, greater tumor size, and metastasis. The expression pattern of P- and E-cadherin were immunohistochemically studied in tissue sections from normal breast tissue, benign breast lesions, and 57 infiltrating breast carcinomas. Cadherin expression was analyzed in parallel with pathological features and the immunohistochemical expression of estrogen and progesterone receptors in breast carcinomas. P-cadherin was detected in the myoepithelial cells and E-cadherin in luminal epithelial cells from normal breast and benign breast lesions. P-cadherin expression was detected in 9 of 45 cases (20%) of infiltrating ductal carcinomas of no special type; none of the special histological types that were analyzed (7 infiltrating lobular carcinomas, 3 colloid carcinomas, and 2 infiltrating papillary carcinomas) expressed P-cadherin. In infiltrating ductal carcinomas, P-cadherin expression correlated significantly with a reduction in E-cadherin expression, histological grade (all cases were grade III tumors), and hormone receptor content (8 of 9 cases were estrogen and progesterone receptor negative). Although E-cadherin was not found in the 7 infiltrating lobular carcinomas, it was present in the remaining histological types and was preserved in 15 infiltrating ductal and 3 colloid and 2 papillary carcinomas and was reduced in 30 infiltrating ductal carcinomas. In addition, a reduction in E-cadherin expression was significantly associated with high histological grade and a lack of steroid hormone receptors in infiltrating ductal carcinomas. No apparent relationship was found between P- and E-cadherin expression and tumor size and axillary lymph node metastasis. The distinct patterns of P- and E-cadherin expression observed in this study strongly suggest a differential role for these cadherins in human breast carcinogenesis.

Topics: Actins; Adult; Breast; Breast Neoplasms; Cadherins; Carcinoma; Carcinoma, Ductal, Breast; Female; Humans; Keratins; Middle Aged; Muscles; Receptors, Cell Surface; Reference Values; S100 Proteins

To clarify the keratin staining patterns of invasive carcinoma of the oesophagus, 22 cases of formalin-fixed paraffin-embedded surgical specimens were examined immunohistochemically with the labelled streptavidin biotin method using a panel of six different monoclonal anti-keratin antibodies. The antibody reacted adequately when antigen was retrieved in a microwave oven, and the relationship between morphological characteristics and keratin reaction patterns was analyzed in carcinomas and compared with adjacent histologically normal epithelium. In the normal oesophageal epithelium, AE3 and CK8.12 labelled all layer of cells, KS-1A3, E3 and KL1 labelled suprabasal cells, and LL002 selectively labelled the basal cells. In squamous cell carcinomas, AE3, CK8.12, KL1 and LL002 labelled almost all the tumour cells regardless of their differentiation, E3 only labelled keratinized cells, while marked decrease or loss of KS-1A3 staining was seen in all cases examined. Therefore, the characteristic profile of squamous cell carcinoma was a strong and diffuse expression of keratin 14 and 16, strong but localized expression of keratin 17, and loss of keratin 13 expression. Undifferentiated carcinoma totally lacked all keratin reactivity. The findings suggested that the neoplastic epithelial cells showed different keratin reactivity and distribution compared to normal oesophageal epithelium. In addition, histologically normal epithelium, dysplasia and carcinoma-in-situ adjacent to or overlying carcinoma expressed keratin 14.

Topics: Antibodies, Monoclonal; Carcinoma; Carcinoma, Squamous Cell; Esophageal Neoplasms; Esophagus; Humans; Immunoenzyme Techniques; Keratins

We have tried to find a reliable panel of markers that would allow distinction between mesotheliomas and carcinomas metastatic to the pleura. In a prospective study, we evaluated 54 pleural effusions: In 27 of the patients, a diagnosis of histologically proven metastatic carcinoma was subsequently established, 7 patients had biopsy-proven malignant mesotheliomas and 20 had benign, reactive effusions whose benign etiologies were established by more than 2 years clinical follow-up. The MAb (monoclonal antibody) IOB3 proved to be diagnostic for carcinomas in all 27 cases (100%), whereas CEA (carcinoembryonic antigen) expression was found in only 22 out of 27 (81%). None of the malignant mesotheliomas, nor benign reactive mesothelial cells reacted with these two markers. All carcinomas, as well as one malignant mesothelioma, reacted with the MAb HEA125. Antibodies against 12 single cytokeratins, vimentin, and EMA (epithelial membrane antigen) were not helpful in the differentiation between malignant mesotheliomas and malignant carcinomatous pleural effusions. We conclude that adding the antibody IOB3 to the CEA assay should allow a reliable differentiation between these two entities.

Topics: Adult; Aged; Antibodies, Monoclonal; Antigens, CD; Biomarkers, Tumor; Carcinoembryonic Antigen; Carcinoma; CD24 Antigen; Diagnosis, Differential; Female; Humans; Immunoenzyme Techniques; Keratins; Male; Membrane Glycoproteins; Mesothelioma; Middle Aged; Pleura; Pleural Effusion, Malignant; Pleural Neoplasms; Predictive Value of Tests; Vimentin

Topics: Adult; Antigens, Neoplasm; Carcinoma; Conjunctival Neoplasms; Cryosurgery; Female; Humans; Keratins; Membrane Glycoproteins; Mucin-1; Mucins

All neoplasms require angiogenesis and resulting neovascularity for growth. The authors and others have confirmed the staging and prognostic significance of quantitative microvascularity density (MVD) in human prostate carcinoma (CAP). In the present investigation, the authors sought to identify the specific site of neovascularity within the neoplasm and adjacent benign tissue.. Histologically benign and malignant tissues from 14 random radical prostatectomy specimens were studied. The tumor edge was defined precisely by immunohistochemistry, suggesting a high molecular weight cytokeratin that stains only the basal cells of benign histology. Microvascularity density quantification was performed using von Willebrand factor antigen immunohistochemistry as previously defined. Five parallel arcs were defined along which vessel density was calculated including arcs within, on the edge, and removed from the neoplasm.. In 13 of 14 cases, the highest vessel density was found within the tumor. Significant differences were observed between the edge of the tumor and 2.5 mm within the benign periphery, between the benign and malignant tissue at the border, and between CAP at the edge and CAP 2.0 mm within the neoplasm. These findings suggest a stepwise increase in MVD toward the center of the neoplasm.. These data confirm the authors' previous observation that prostate cancer has approximately a two-fold increase in MVD compared with the benign tissue. Moreover, high vascularization of the center explains the rare finding of necrosis in CAP. These data suggest that angiogenic promoters may have their highest activity in the center of the neoplasm.

Topics: Carcinoma; Humans; Keratins; Male; Microcirculation; Necrosis; Neoplasm Staging; Neovascularization, Pathologic; Prognosis; Prostate; Prostatic Neoplasms; von Willebrand Factor

To study the expression of a range of cytokeratins by malignant myoepithelioma of the breast.. Immunophenotyping was carried out using a panel of antibodies on paraffin wax embedded and frozen material using immunohistochemistry and double-labelled immunofluorescence. Electron microscopy was also performed.. The tumour cells were positive for CAM 5.2, actin, vimentin, and cytokeratin 14 and negative for cytokeratins 18 and 19. Electron microscopy showed well formed desmosomes and hemidesmosomes together with pinocytic vesicles, plentiful rough endoplasmic reticulum and 6 nM microfilaments with focal densities.. The pattern of cytokeratin expression provides further evidence that tumours with a specific myoepithelial phenotype occur rarely in the breast.

Topics: Actins; Aged; Biomarkers, Tumor; Breast Neoplasms; Carcinoma; Cell Adhesion Molecules; Female; Humans; Immunohistochemistry; Immunophenotyping; Keratins; Microscopy, Electron; Vimentin

Retinoids are powerful regulators of epidermal cell growth and differentiation and are widely used in the prevention and treatment of skin disorders and cancers in humans. Since many of the effects of retinoids on cell growth and differentiation are mediated by nuclear retinoid receptors (RARs and RXRs), we were interested in determining RAR and RXR gene expression during mouse skin tumor progression. The two-stage system of mouse skin carcinogenesis was used to generate papillomas and carcinomas, and the different stages of malignant progression (papillomas, differentiated squamous cell carcinomas, undifferentiated squamous cell carcinomas, and spindle cell carcinomas) were characterized in each tumor by specific keratin expression prior to receptor characterization. Using in situ hybridization analysis, we show that the two major RAR isoforms (alpha 1 and gamma 1), which account for most of RARs in the skin, were expressed in both the basal and suprabasal layers in mouse epidermis. In contrast, RXR alpha transcripts were compartmentalized to the basal cell layers and concentrated in hair follicles. During skin tumor progression, RAR (alpha 1 and gamma 1) transcripts were down-modulated in malignant tumor cells, whereas RXR (alpha and beta) transcript expression was expanded in papillomas and carcinomas as the number of undifferentiated cells also increased. RXR gamma was not detected in the skin or at any stage during skin tumor progression. Spindle cell tumors lacked markers of the keratinocyte phenotype and lost RAR expression, yet retained expression of RXR alpha and beta. The increased abundance of transcripts for RXRs and decreased presence of RARs in skin tumor progression may favor other nuclear signal transduction pathways requiring RXR for heterodimer formation and contribute to phenotypic progression of cancer cells.

Topics: 9,10-Dimethyl-1,2-benzanthracene; Animals; Carcinoma; Cell Compartmentation; Epidermis; In Situ Hybridization; Keratins; Mice; Papilloma; Receptors, Retinoic Acid; Retinoid X Receptors; Skin Neoplasms; Tetradecanoylphorbol Acetate; Transcription Factors

Topics: Aged; Carcinoembryonic Antigen; Carcinoma; Cystadenocarcinoma, Mucinous; Female; Humans; Immunoenzyme Techniques; Immunohistochemistry; Keratins; Microscopy, Electron; Neoplasms, Multiple Primary; Pancreatic Neoplasms; Vimentin

Transgenic mice that expressed v-fos exclusively in the epidermis by means of a human keratin K1-based targeting vector (HK1.fos) developed preneoplastic epidermal hyperplasia and hyperkeratosis after long latency and an associated wound promotion stimulus. To assess the requirements for papilloma formation and malignant conversion and determine the sensitivity to a chemical promotion stimulus, HK1.fos mice were promoted with 12-O-tetradecanoylphorbol-13-acetate (TPA). HK1.fos mice were sensitive to TPA promotion but developed papillomas only after long latency (20-30 weeks of promotion) and in relatively few numbers per animal, suggesting the necessity of an additional genetic event prior to overt lesion formation. Consistent with this idea, at 60 weeks, on cessation of TPA promotion, these HK1.fos TPA-papillomas were found to be autonomous, TPA-independent tumors which persisted, grew larger, and converted to malignancy. Analysis of HK1.fos tumor RNA and DNA identified endogenous c-rasHa mutations at codons 12 and 61 in papillomas and carcinomas; however, no p53 tumor suppressor gene mutations were detected. These data indicate that epidermal expression of v-fos induces sensitivity to TPA promotion, but since additional genetic events, such as endogenous c-rasHa activation, appear to be required in tumorigenesis, v-fos may predominantly play a role in the mechanism of promotion to achieve papilloma autonomy and TPA independence. Furthermore, spontaneous malignant conversion in this model does not appear to involve mutations in the p53 tumor suppressor gene.

Topics: Animals; Base Sequence; Biomarkers; Carcinoma; Cell Differentiation; Cell Transformation, Neoplastic; DNA, Neoplasm; Epidermis; Gene Expression Regulation, Neoplastic; Genes, fos; Genes, p53; Genes, ras; Hyperplasia; Keratins; Keratosis; Mice; Mice, Transgenic; Molecular Sequence Data; Mutation; Oncogene Proteins v-fos; Papilloma; ras Proteins; RNA, Neoplasm; Tetradecanoylphorbol Acetate

Pleomorphic carcinoma of the pancreas is a rare, histologically characterized pancreatic tumor with a rapid and fatal course. We report a case of a resected pleomorphic carcinoma located in the body of the pancreas in a 61-yr-old male. Histological analysis of the resected specimen revealed the coexistence of pleomorphic carcinoma with adenocarcinoma, but the recurrent tumors at autopsy 20 mo later were only of the adenocarcinomatous type. Cells in the adenocarcinomatous component showed a diffuse reactivity for CA19-9, CEA, and cytokeratin, and a focal reactivity for vimentin. In contrast, vimentin was diffusely expressed in pleomorphic lesion. Adenocarcinoma at autopsy expressed CA19-9, CEA, and cytokeratin, but not vimentin. These findings suggest that the recurrent adenocarcinoma may have developed as a consequence of sequential change in the nature of the tumor.

Topics: CA-19-9 Antigen; Carcinoembryonic Antigen; Carcinoma; Humans; Immunohistochemistry; Keratins; Male; Middle Aged; Pancreatic Neoplasms

The immunohistochemical expression of the oncofetal proteins alpha-fetoprotein (AFP) and carcinoembryonic antigen (CEA), and the intermediate filament proteins keratin and vimentin was analysed in 18 canine liver carcinomas. All the tumours other than hepatocellular carcinomas, with the exception of one poorly differentiated carcinoma, were AFP negative, and only cholangiocarcinomas and mixed (hepatocellular and cholangiocellular) carcinomas were CEA positive. All the histological types of tumours expressed high and low molecular weight keratins, and keratin and vimentin were both expressed in three tumours (one moderately differentiated hepatocellular carcinoma, one mixed carcinoma and one poorly differentiated carcinoma). The findings demonstrate the use of immunohistochemical staining methods for analysing the expression of some tumour markers in routinely processed tissue samples of canine liver carcinomas, and suggest that some of the tumour markers are correlated with histological types of tumour.

Topics: alpha-Fetoproteins; Animals; Antibody Specificity; Carcinoembryonic Antigen; Carcinoma; Carcinoma, Hepatocellular; Cholangiocarcinoma; Dog Diseases; Dogs; Humans; Immunohistochemistry; Keratins; Liver Neoplasms; Sensitivity and Specificity; Vimentin

Topics: Carcinoembryonic Antigen; Carcinoma; Carcinoma, Squamous Cell; Chemotherapy, Adjuvant; Follow-Up Studies; Humans; Hypopharyngeal Neoplasms; Keratins; Laryngeal Neoplasms; Liver Neoplasms; Lung Neoplasms; Lymphatic Metastasis; Male; Middle Aged; Neoplasms, Multiple Primary; Neoplasms, Second Primary; Paget Disease, Extramammary; Penile Neoplasms; Skin Neoplasms

In breast carcinomas, S-phase fraction calculated after flow cytometric selection of epithelial cells improves the prediction of distant recurrence. However, the presence of DNA aneuploid cells registered as non-epithelial cells and the intertumoural variation of cytokeratin positivity may cause selective loss of tumour cells in flow cytometric analysis. In the present study, the expression of cytokeratins 8 and 18 was examined by both immunohistochemistry and flow cytometry. The proportion of cytokeratin-positive cells was decreased by 25% when estimated by flow cytometry compared with immunohistochemistry; however, the correlation between these two methods was significant (P < 0.01). Fewer cells were cytokeratin-positive in DNA hypodiploid tumours compared with DNA diploid and DNA aneuploid tumours (P = 0.006). Also, rapidly proliferating tumours tended to have a smaller proportion of cytokeratin-positive tumour cells. Our results indicate that loss of cytokeratins in breast cancer cells is related to both cellular factors and the preparation procedure.

Topics: Breast Neoplasms; Carcinoma; DNA, Neoplasm; Flow Cytometry; Humans; Immunohistochemistry; Keratins; Reproducibility of Results

We report a case of epithelial-myoepithelial carcinoma of the parotid gland arised in a 72 years-old woman, in which the diagnosis was suspected on fine-needle aspiration and confirmed on surgical specimen. Immunohistochemical evidence for the dual differentiation (glandular and myoepithelial) of the tumour was obtained both on surgical specimen and cytological inclusion. Morphological features and proliferating index (MIB1) analysis suggest that this case is an intermediate grade malignant neoplasm. Main differential diagnosis of the epithelial-myoepithelial carcinoma with predominantly clear cell tumours of the salivary glands were discussed.

Topics: Adenocarcinoma, Clear Cell; Aged; Biomarkers, Tumor; Carcinoma; Coloring Agents; Diagnosis, Differential; Female; Humans; Keratins; Mitotic Index; Mucin-1; Neoplasm Proteins; Nerve Tissue Proteins; Parotid Neoplasms

Sarcomatoid carcinoma is a rare tumor in the urinary bladder and accounts for approximately 0.3% of all bladder malignancies. In this study, the clinicopathologic findings of 18 cases are described. Distribution of sex and age and clinical symptoms are not distinctive from transitional cell carcinoma. The tumor behaves as a high-grade malignancy with advanced initial stage and unfavorable outcome. Surgery is the therapy of choice. Histological differentiation from true sarcoma may be difficult. Recognition rests on the co-existence of an overt carcinomatous component or demonstration of the epithelial nature by immunohistochemistry or electron microscopy.

Topics: Aged; Aged, 80 and over; Carcinoma; Female; Follow-Up Studies; Humans; Immunohistochemistry; Keratins; Male; Membrane Glycoproteins; Microscopy, Electron; Middle Aged; Mucin-1; Urinary Bladder Neoplasms; Vimentin

We examined bone marrow aspirates from 100 metastasis-free primary breast cancer patients. In 38/100 patients (38%), tumour cells were detected in the marrow using an immunocytochemical technique with a cocktail of two monoclonal antibodies: anti-EMA and anti-cytokeratin. Median follow-up was 34 months: 15/38 (39%) tumour cell-positive patients have since relapsed, but only 9/62 (15%) tumour cell-negative patients. The median interval between tumour cell detection and relapse was 11.4 months. No statistically significant correlation existed between tumour cell presence and 'established' prognostic factors. However, relapse-free survival was significantly shorter in tumour cell-positive patients. Multivariate analysis showed tumour cell presence as a strong, significant prognostic factor for relapse-free as well as overall survival. We conclude that screening for tumour cells in bone marrow of primary breast cancer patients identifies high-risk patients for early relapse. In particular, patients with node-negative tumours who have tumour cells in their bone marrow may require subsequent systemic therapy.

Topics: Adult; Aged; Antibodies, Monoclonal; Antineoplastic Combined Chemotherapy Protocols; Biomarkers, Tumor; Bone Marrow; Breast Neoplasms; Carcinoma; Carcinoma, Ductal, Breast; Carcinoma, Lobular; Chemotherapy, Adjuvant; Cyclophosphamide; Female; Fluorouracil; Follow-Up Studies; Humans; Immunohistochemistry; Keratins; Lymphatic Metastasis; Methotrexate; Middle Aged; Postmenopause; Premenopause; Prognosis; Receptors, Estrogen; Receptors, Progesterone; Recurrence; Survival Analysis; Tamoxifen; Time Factors

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

The monoclonal antibody OV-TL 12/30, which detects keratin 7, was tested for its usefulness in cytologic diagnosis by reincubating previously Papanicolaou-stained slides. For this purpose malignant effusions of 73 patients with histologically confirmed cancers of the colon, ovary, mesothelium, breast, lung, esophagus, pancreas, urinary bladder, stomach, kidney, and prostate were used. All malignant cells from ovarian adenocarcinomas were positive, whereas malignant cells from colonic adenocarcinomas and malignant mesotheliomas were negative. Adenocarcinomas of gastric, renal, pancreatic, esophageal, and mammary origin demonstrated variable staining. Transitional cell carcinomas were positive, whereas squamous and small cell lung carcinomas were negative. Because OV-TL 12/30 does not react with normal and atypical mesothelial cells in these preparations, this reagent is a valuable tool in distinguishing benign mesothelial cells and adenocarcinoma cells. The authors' results demonstrate that this antibody is an excellent tool in the differential diagnosis of malignant cells in effusions and can be used in routinely stained cytologic specimens to determine primary tumor localization. In addition to its ability to distinguish between ovarian and colonic adenocarcinomas, its negativity in mesotheliomas may prove helpful in several diagnostic considerations.

Topics: Antibodies, Monoclonal; Carcinoma; Diagnosis, Differential; Female; Humans; Immunohistochemistry; Keratins; Male; Neoplasms; Papanicolaou Test; Vaginal Smears

Undifferentiated carcinoma of the nasopharynx has a well-known association with Epstein-Barr virus (EBV), but only an inconsistent relationship has been identified in undifferentiated carcinomas occurring at other sites. We investigated 22 formalin-fixed, paraffin-embedded cases of sinonasal undifferentiated carcinomas (SNUCs) occurring in Western and Asian patients. A highly sensitive in situ hybridization method was performed using an antisense oligonucleotide probe to the EBER1 gene of EBV. We identified EBV RNA in seven of 11 SNUCs from Asian patients, but in none of the Western SNUC patients (0/11). The EBER1 signal was present in all or virtually all of the tumor cell nuclei in the seven EBV-RNA-positive Asian SNUCs. The latent membrane protein-1 (LMP1) of EBV was not identified in any of the five positive cases tested. Our results suggest that genetic predisposition or environmental/geographical cofactors play an important role in determining the strength of the association of SNUC with EBV.

Topics: Adult; Aged; Aged, 80 and over; Asian People; Carcinoma; Female; Herpesvirus 4, Human; Hong Kong; Humans; Immunohistochemistry; In Situ Hybridization; Keratins; Male; Membrane Glycoproteins; Middle Aged; Mucin-1; Nasal Cavity; Nose Neoplasms; Paranasal Sinus Neoplasms; Phosphopyruvate Hydratase; RNA, Viral; United States; White People

Monoclonal antibodies to human stratifying keratin (StK), simple keratin (SK), broad spectrum keratin (BSK) and vimentin were applied to 47 canine mammary tumours (three benign hyperplasia, 26 benign mammary tumours, one malignant mixed tumour, two malignant complex tumours, seven lobular carcinomas, three papillary carcinomas and five squamous cell carcinomas). In benign hyperplasia the SK antibody reacted with acinar and duct epithelial cells; the StK and BSK antibodies reacted strongly with duct epithelial cells in the canine mammary tumours expressed mainly keratins of stratified epithelia rather than those of simple epithelia. Myoepithelial cells in complex and mixed tumours can express StK and vimentin. The finding might be helpful in the assessment of complex tumours where stromal reactions may be confused with myoepithelial neoplastic proliferation. Stromal mesenchymal tissues, including precartilage in complex tumours, and clearly differentiated myoepithelial cells always stained positively for vimentin. Occasional carcinoma cells stained positively for vimentin.

Topics: Animals; Antibodies, Monoclonal; Carcinoma; Carcinoma, Lobular; Carcinoma, Papillary; Carcinoma, Squamous Cell; Dog Diseases; Dogs; Female; Hyperplasia; Immunohistochemistry; Keratins; Mammary Glands, Animal; Mammary Neoplasms, Animal; Vimentin

Topics: Actins; Aged; Breast Neoplasms; Carcinoma; Female; Humans; Immunohistochemistry; Keratins; Myoepithelioma; Neoplasm Proteins; S100 Proteins

Metastases of internal tumors to the oral cavity are unusual and involve in most cases maxilla and mandible. Metastases to the gingival soft tissue are extremely rare.. To report a case of gingival metastasis from undifferentiated carcinoma of the lung.. The lesion was removed and hematoxylin and eosin sections were performed. Immunohistochemical investigations were performed with a standard three-step immunoperoxidase technique on formalin-fixed, paraffin-embedded tissue sections using anti-CEA, anti-S-100, HMB45, and anti-LCA antibodies.. Based on clinicopathologic findings, a diagnosis of metastasis from undifferentiated carcinoma of the lung was established. Further investigations revealed a primary undifferentiated carcinoma of the lung.. Metastasis from internal neoplasms should be considered among other differential diagnoses in the evaluation of gingival tumors. In the present case, onset of oral lesion preceded detection of the primary lung tumor. Complete screening of the patient should therefore follow a diagnosis of gingival neoplasm of unknown origin.

Topics: Aged; Carcinoembryonic Antigen; Carcinoma; Cell Nucleus; Cytoplasm; Gingival Neoplasms; Humans; Keratins; Leukocyte Common Antigens; Lung Neoplasms; Male; S100 Proteins

Sarcomatoid carcinoma is a rare variant of malignant tumor arising from the urinary tract. This tumor had been termed carcinosarcoma because of its carcinomatous and sarcomatous components. There is still some confusion in the terminology between true carcinosarcoma and sarcomatoid carcinoma; however, the latter is now regarded as primarily a malignant epithelial tumor with pseudosarcomatous transformation. Four cases of sarcomatoid carcinoma arising from the urinary tract are reported. The patients were a 77 year old female, and three males aged 62, 69 and 80 years. All but the eldest patient complained of gross hematuria. Surgical removal was performed in the younger three cases, and an autopsy was done in the remaining case. All the tumors were macroscopically polypoid. Histopathologic examination revealed fasciculated spindle-cell tumors with myxoid stroma or malignant fibrous histiocytoma-like spindle cell tumors. The epithelial nature was proven in these sarcomatous cells by immunohistochemical and/or electron-microscopic examinations. Only a small amount of squamous cell carcinoma components was also evident in the latter three cases. Although the younger three patients were alive at 44, 23 and 39 months' follow-up, respectively, constant careful monitoring is recommended.

Topics: Aged; Aged, 80 and over; Carcinoma; Female; Humans; Immunoenzyme Techniques; Keratins; Male; Middle Aged; Urologic Neoplasms

The presence of keratin 19 (K19) was searched for by immunostaining in 16 medullary carcinomas, comprising 12 typical and four atypical cases, in 29 undifferentiated high-grade carcinomas (NOS-HG) with conspicuous lymphoid response and in 12 well differentiated low-grade carcinomas (NOS-LG). The medullary carcinomas were all negative whereas 23 of the high-grade and all 12 low-grade carcinomas expressed K19. Staining for K19 could be of value in the differential diagnosis of these tumours. Furthermore, these findings, with other observations, raise the possibility that medullary carcinoma cells could be linked to precursor cells of the terminal duct lobular units because both populations share several characteristics.

Topics: Breast Neoplasms; Carcinoma; Carcinoma, Medullary; Cytoplasm; Female; Humans; Immunoenzyme Techniques; Keratins; Paraffin Embedding

Monoclonal antibodies (mAbs) specific for cytokeratins are potent probes for the identification of disseminated individual epithelial tumour cells in mesenchymal organs such as bone marrow. We have used a monoclonal antibody (mAB) against cytokeratin 18 (CK18) for the detection of individual metastatic tumour cells in bone marrow aspirates from 84 patients with carcinoma of the prostate. CK18+ cells were detected in a sensitivity of 1 per 8 x 10(5) marrow cells using the alkaline phosphatase anti-alkaline phosphatase (APAAP) system for staining. We were able to detect CK18+ tumour cells in the marrow of 33% of patients with stage N0M0 prostate cancers. The incidence of CK18+ cells showed a significant correlation with established risk factors, such as local tumour extent, distant metastases and tumour differentiation. For further characterization of such cells in patients with prostate cancer, we developed an immunocytochemical procedure for simultaneous labelling of cytokeratin component no. 18 (CK18) and prostate-specific antigen (PSA). In a first step, cells were incubated with a murine mAb against PSA, followed by gold-conjugated goat anti-mouse antibodies. In a second step, a biotinylated mAb to CK18 was applied as primary antibody and subsequently incubated with complexes of streptavidin-conjugated alkaline phosphatase, which were developed with Newfuchsin substrate. The binding of gold-labelled antibodies was visualized by silver enhancement. CK18+ cells co-expressing PSA were found in bone marrow aspirates from 5 out of 14 patients with carcinomas of the prostate. 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 hyperplasia (BPH).(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Bone Marrow Diseases; Bone Neoplasms; Carcinoma; Cells, Cultured; Humans; Immunohistochemistry; Keratins; Male; Phenotype; Prostate-Specific Antigen; Prostatic Neoplasms; Staining and Labeling

Aim of the present study was to investigate the efficacy of 4 different proteolytic treatments (Ficin, Protease type XIV, Microwave irradiation in Citrate buffer and Microwave irradiation in Lead Tiocyanate), compared to the incubation with buffer only, for the detection of cytokeratins in 10 cases of carcinomas from different organs. The same anti-cytokeratin antibody was applied to two sets of tissue sections, after proteolytic treatment, and the reaction was developed by using a different method (ABC or APAAP) for each set of slides. The semiquantitative evaluation of the specimens demonstrated that the higher number of immunoreactive tumor cells was present after Microwave irradiation in Lead Tiocyanate and, to quite a lesser extent, in Citrate buffer. Ficin and Protease type XIV appeared less effective and in some circumstances, the enzymatic digestion of tumor cells seemed to negatively affect the quality of immunostain. When buffer only was used the percentage of immunoreactive tumor cells was considered to be unreliable for diagnostic purposes. The results of the study seem to suggest that proteolytic pretreatment is essential to avoid false negative results when cytokeratin immunostain is essential in histopathology and that Microwave irradiation in Citrate buffer is eligible as the best procedure.

Topics: Carcinoma; Epitopes; False Negative Reactions; Humans; Immunoenzyme Techniques; Keratins; Microwaves; Peptide Hydrolases

The expression of bcl-2 and p53 was investigated by immunocytochemistry in combination with that of conventional structural and differentiation antigens on the archival material of 22 cases of undifferentiated carcinoma (UC) and 19 of poorly differentiated carcinoma (PDC) of the thyroid gland. The restriction of bcl-2 expression to PDC in comparison to UC was 84.2% versus 13.6% of cases, respectively, in contrast to an almost equal percentage of p53 expression in the two histologic types, that is, 52.6% and 54.5% of cases of PDC and UC, respectively. However, the pattern of distribution of p53-immunoreactive cells was definitely different, being restricted to areas showing active infiltrating growth in PDC and involving almost all tumor cells in UC. Furthermore, in the subset of cases of UC showing the residual presence of a differentiated component, a distinctive mutual exclusion of bcl-2 and p53 immunoreactivity was observed in the two components. The results suggest that the evaluation of bcl-2 expression may be usefully applied to the differentiation of PDC from UC, whereas all morphologic findings related to p53 expression are in keeping with a significant role of the deregulation of this gene in the mechanism of dedifferentiation and progression of the disease.

Topics: Adult; Aged; Antibodies; Antibodies, Monoclonal; Carcinoma; Female; Humans; Immunohistochemistry; Keratins; Male; Middle Aged; Molecular Weight; Neoplasm Staging; Proto-Oncogene Proteins; Proto-Oncogene Proteins c-bcl-2; Survival Rate; Thyroglobulin; Thyroid Neoplasms; Tumor Suppressor Protein p53; Vimentin

The aim of the study is to estimate the new tumor marker CYFRA 21-1 in non-small cell lung cancer (NSCLC) patients and comparison of this results with SCC-Ag. The investigation was carried out on 115 NSCLC patients (55 with squamous cell, 35 with adenocarcinoma, 25 with large cell) qualified for surgical treatment and in 48 nonmalignant lung diseases patients. CYFRA 21-1 was determined by the means of IRMA method (CIS bio international--GIF-SUR-Yvette, France) and SCC-Ag--MEIA method (IMx system Abbott). Elevated levels of CYFRA 21-1 were obtained in 48.7% and SCC-Ag in 39.1%. Elevated levels of examined markers most frequently occurred in squamous cell type (SCC). It was found out that CYFRA 21-1 dependent on: a) SCC stage (I-40%, II-61.1%, III-85.2%), b) tumor size (T1-38.4%, T2-73.1%, T3-87.5%), c) mediastinal lymph nodes metastases (No and N1-53.8% and N2-86.9%). Similar correlations were not observed in SCC-Ag examination. Simultaneous determination of CYFRA 21-1 and SCC-Ag showed minimal sensitivity increase from 48.7% to 52.1% in NSCLC and from 69.1% to 70.1% in SCC and decrease of specificity from 95.8% to 85.4%. To sum up, determination of CYFRA 21-1 in NSCLC patients (especially in SCC patients) is useful in diagnosis and clinical stage determination.

Topics: Adult; Aged; Antigens, Neoplasm; Biomarkers, Tumor; Carcinoma; Carcinoma, Non-Small-Cell Lung; Humans; Keratins; Lung Neoplasms; Middle Aged; Neoplasm Staging; Peptide Fragments; Sensitivity and Specificity; Serpins

The expression pattern of cytokeratin filaments in epithelia has been shown to be dependent on their type and grade of differentiation. The type of expression of cytokeratin in a cell may also be altered during carcinogenesis or other pathological conditions. The present study examined the alterations in expression of various cytokeratin types during different stages of tumour progression in the oral mucosa. Six monoclonal anti-cytokeratin antibodies were used for the study. Conspicuous staining differences with these antibodies were evident between normal keratinizing and non-keratinizing mucosa. These differences can be correlated to the differentiation pattern of the normal mucosa types. Antibodies specific to cytokeratin types 10/11, 19 and 14 showed significant correlation with stage of tumour progression. In addition cytokeratin type 18 also showed prominent differences in expression between different stages of tumour progression. These alterations in cytokeratin expression suggest that the terminal differentiation pathway of keratinocytes is disturbed during oral carcinogenesis. The results of the present study also emphasize the potential of using cytokeratin filaments as markers in the biological staging of oral premalignant and malignant lesions.

Topics: Antibodies, Monoclonal; Carcinoma; Carcinoma, Squamous Cell; Carcinoma, Verrucous; Humans; Immunohistochemistry; Keratins; Leukoplakia, Oral; Mouth Mucosa; Mouth 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

Pseudosarcomatous fibromyxoid tumor of the genitourinary tract is a rare pathologic entity of hitherto unknown etiology that, because of the cellular pleomorphism and the infiltrative nature of the lesion, may be mistakenly diagnosed as sarcomatoid carcinoma or sarcoma. We retrospectively studied nine pseudosarcomatous fibromyxoid tumors involving the bladder and prostate to define characteristic parameters that may allow for accurate diagnosis. The study patients included four men and five women with a mean age of 48.7 years. Histologic analysis revealed myxoid lesions with a proliferation of spindle fibroblastic cells in a background of granulation tissue-type vascularity and inflammatory cells. Mitoses were infrequent and no atypical forms were found. Immunostaining was positive for vimentin and smooth muscle actin, and negative for S-100 protein, desmin, myoglobin, and keratin. Ultrastructurally, the lesion displayed fibroblastic and myofibroblastic cell features. Flow cytometric DNA content analysis revealed uniform DNA diploidy and a low S-phase fraction. All patients were alive and well with no evidence of disease after a mean follow-up of 4.8 years. In contrast, the sarcomatoid carcinomas and sarcomas of the urinary bladder and prostate that were used as controls occurred in older patients and had more frequent mitoses with atypical forms, tumor-type necrosis, and different immunostaining profiles; they were preponderantly aneuploid or diploid with high S-phase fraction. Awareness of the clinicopathologic and biologic characteristics of these lesions is necessary to ensure their accurate diagnosis and to prevent unnecessary radical therapy.

Topics: Actins; Adult; Carcinoma; Desmin; Diagnosis, Differential; DNA, Neoplasm; Female; Fibroma; Flow Cytometry; Humans; Immunohistochemistry; Keratins; Male; Microscopy, Electron; Middle Aged; Myoglobin; Ploidies; Prostatic Neoplasms; Retrospective Studies; S Phase; S100 Proteins; Sarcoma; Urinary Bladder Neoplasms; Vimentin

Biliary glycoprotein (BGP) is the human homologue of a cell adhesion molecule (CAM) of the rat designated Cell-CAM. The BGP gene is a member of the carcinoembryonic antigen gene family, which belongs to the immunoglobulin superfamily. BGP is expressed in cells of epithelial and myeloid origin. In granulocytes, BGP is a main antigen of the CD66 cluster of differentiation antigens that mediate the binding to endothelial E-selectin. Since BGP is a major human CAM, the expression of BGP was studied in 21 colorectal carcinoma tissue specimens and in the respective adjacent normal mucosae. As an internal control for epithelial mRNA, the expression of cytokeratin 18 was evaluated in parallel. In addition, the expression of carcinoembryonic antigen and nonspecific crossreacting antigen, which are highly homologous to BGP, was investigated. Two BGP mRNAs of 3.9 and 1.5 kilobases were detected in the normal colonic mucosa samples. The median of the tumor-to-normal ratios of mRNA expression was 0.2 for both BGP mRNAs. In contrast, the median was 1.2 for cytokeratin, 1.0 for carcinoembryonic antigen, and 1.4 for nonspecific crossreacting antigen. Relative to cytokeratin 18 expression, the expression of BGP was reduced to < or = 0.1 in half of the tumors and to < or = 0.4 in > 80% of the tumors. These findings indicate that the loss or reduced expression of the adhesion molecule BGP is a major event in colorectal carcinogenesis.

Topics: Antigens, CD; Antigens, Neoplasm; Carcinoembryonic Antigen; Carcinoma; Cell Adhesion Molecules; Colorectal Neoplasms; Gene Expression Regulation, Neoplastic; Glycoproteins; Humans; Intestinal Mucosa; Keratins; Lymphatic Metastasis; Membrane Glycoproteins; RNA, Messenger; RNA, Neoplasm

Breast carcinoma arose in or in conjunction with microglandular adenosis (MGA) in 14 of 60 (23%) patients with MGA listed in the authors' files. This article describes the clinicopathologic and immunohistochemical features and prognosis of these carcinomas. The median patient age was 47 years (range, 26-68 years). All patients had a mass. Six (43%) had a family history of breast carcinoma. Lymph node metastases were found in 3 of 11 axillary dissections. Ten patients treated by mastectomy were recurrence-free, with a median follow-up of 57 months (range, 3-108 months). Two of three patients treated by excisional surgery were recurrence-free 12 and 105 months later. The third woman had bone metastases at 51 months and was alive 98 months after treatment. Carcinoma arose in the MGA in 13 patients. In these patients, in situ carcinoma was found in expanded MGA glands composed of cells with vesicular poorly differentiated nuclei. One patient with benign MGA had carcinoma develop in the opposite breast that was not associated with MGA. When it arose in MGA, basement membranes were present in benign MGA and in situ carcinoma but tended to be disrupted in invasive foci that appeared to be formed by coalescent MGA glands. Strong immunoreactivity for cytokeratin, S-100, and cathepsin D was detected in carcinomas. Two carcinomas had nuclear progesterone receptors, and one of these had estrogen receptors. One carcinoma had positive findings for HER-2neu, and four had immunoreactivity for p53 protein. The following conclusions were drawn from these observations: (1) carcinomas arising in MGA have a distinctive histopathologic pattern; (2) the carcinomas are composed of epithelial cells (cytokeratin positive, actin negative) that are strongly immunoreactive for S-100 protein and cathepsin D; and (3) with a median follow-up of nearly 5 years, patients with these carcinomas had a relatively favorable prognosis, despite histopathologic and immunohistochemical features usually associated with a poor prognosis.

Topics: Adult; Aged; Breast Neoplasms; Carcinoma; Combined Modality Therapy; Family; Female; Fibrocystic Breast Disease; Follow-Up Studies; Humans; Keratins; Lymphatic Metastasis; Middle Aged; Treatment Outcome

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 normal pattern of keratin expression in epidermis is altered in carcinomas as well as in nonmalignant diseases such as psoriasis and wound healing. Under these circumstances, the transcription of differentiation-specific keratins K1 and K10 is suppressed, whereas the activation- and hyperproliferation-associated keratins K6 and K16 are induced. Very little is known regarding transcriptional regulators involved in this switch. To investigate the nuclear factors that participate in regulation of expression of the K6 gene, we have characterized the binding sites for nuclear proteins on the promoter DNA of the K6 gene by gel retardation assays and site-specific deletion mutagenesis. We found four nuclear protein binding sites in the K6 gene promoter. Two are near the TATA box, but their ability to bind HeLa or keratinocyte nuclear extracts is independent of the TATA box-binding protein complex. The third binding site is a large palindrome. The sequences of these three sites do not correspond to any described target sequences for characterized transcriptional factors. The fourth is an AP-1 site, the target sequence for the proto-oncoproteins fos and jun. All four sites are independent of the previously characterized epidermal growth factor-responsive element, EGF-RE. These findings suggest that there may be two parallel pathways of induction of K6 transcription. One proceeds through the EGF-RE, which may be involved in nonmalignant hyperproliferation processes; the other, through the AP-1 site and the fos-jun proto-oncoproteins, may be related to induction in malignant processes.

Topics: Animals; Base Sequence; Binding Sites; Carcinoma; Cattle; DNA, Neoplasm; Gene Expression Regulation, Neoplastic; HeLa Cells; Humans; Keratinocytes; Keratins; Molecular Sequence Data; Polymerase Chain Reaction; Proto-Oncogene Proteins c-jun; Repetitive Sequences, Nucleic Acid; TATA Box; Transfection

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

Immunohistochemical analysis was carried out to examine the characteristics of nasopharyngeal carcinoma (NPC) using 38 biopsy cases obtained from southern China. These cases were divided into 3 groups according to their predominant pattern associated with cell and tissue differentiation which is based on World Health Organization (WHO) classification as follows: 6 cases of squamous cell carcinoma (16%), 25 cases of differentiated non-keratinizing carcinoma (66%), 7 cases of undifferentiated carcinoma (18%). All tumor tissues reacted with MB-1, but they did not react with L26 (CD20), 4KB5 (CD45R), MT-1, and leukocyte common antigen (LCA). Keratin and epithelial membrane antigen (EMA) as epithelial markers focally stained NPC tissues in all cases. Carcinoembryonic antigen (CEA)-positive staining was detected in 7 (28%) of the 25 cases of differentiated non-keratinizing carcinoma and in 3 (43%) of the 7 cases of undifferentiated carcinoma; thus, of 38 cases, 10 (26%) were CEA-positive. On the other hand, squamous cell carcinoma cases did not react with CEA. These NPC tissues did not react with S-100 protein, alpha-1-antichymotrypsin (ACT), lysozyme, vimentin, and desmin. Therefore, it is concluded that some cases of NPC are difficult to distinguish from malignant lymphoma. In certain cases, NPC may be distinguished from malignant lymphoma, using immunohistochemical methods for the detection of MB-1, keratin, EMA, and LCA. Specifically, this evidence suggests that MB-1 may be useful as a tumor marker of NPC. Moreover, the CEA reaction to NPC may be related to the cell differentiation.

Topics: Antigens, CD; Antigens, CD20; Antigens, Differentiation, B-Lymphocyte; Antigens, Neoplasm; B-Lymphocytes; Biopsy; Carcinoembryonic Antigen; Carcinoma; Carcinoma, Squamous Cell; Humans; Immunoenzyme Techniques; Immunohistochemistry; Keratins; Leukocyte Common Antigens; Membrane Glycoproteins; Mucin-1; Nasopharyngeal Neoplasms

By employing cytochemistry, immunocytochemistry, selective double extraction, whole mount electron microscopy and electrophoretic scanning quantitative analysis, the intermediate filaments (IF) of in vitro cultured nasopharyngeal carcinoma cell lines CNE-1 (highly differentiated) and CNE-2Z (poorly differentiated) have been studied. The results demonstrated that although the keratin-type IF were organized in a network pattern in both kinds of cells, significant differences could be observed between the two kinds of cells regarding IF organization, subtypes and quantity of keratin. The poorly differentiated cell line CNE-2Z exhibited a far more irregular and confused IF organization structure, and the content of keratin was lower while the variety of keratin subtypes was increased.

Topics: Carcinoma; Humans; Intermediate Filaments; Keratins; Nasopharyngeal Neoplasms; 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

We have studied in this report the expression of keratins in mouse epidermal keratinocytes transformed in culture by a chemical carcinogen (PDV) and in cell lines (PDVCM1, PDVCM2, PDVCV1, and PDVC57) derived by tumor transplantation of PDV cells in syngeneic C57Bl/6 mice. PDV, PDVCM1, PDVCM2, and PDVCV1 cell lines are weakly to moderately tumorigenic, giving rise to squamous cell carcinomas, although not at all injection points, whereas PDVC57 cells are more malignant, inducing highly anaplastic carcinomas at 100% of injection sites. All the cell lines synthesize anomalously simple epithelial keratins, substantial amounts of K8, and minor quantities of K18 and K19, but the level of expression is increased in PDVC57. We have found that in PDVC57 cells upregulation of K8 is linked to down-regulation of the normal keratins produced by epidermal keratinocytes in culture (i.e., K5, K6, K14, and K17). On the other hand, K8 does not generally colocalize with K13, a keratin also aberrantly expressed by epidermal cell cultures when induced to differentiate by high Ca2+ medium. K13, normally synthesized in internal stratified epithelia, is anomalously induced in mouse epidermal tumors and has been used as an early marker of carcinoma progression. In tumors induced by the cell lines upon injection in mice, K8 is found in the less differentiated regions as opposite to K13, restricted to the differentiating areas of the tumors. In PDV, PDVCM1, PDVCM2, and PDVCV1 carcinomas the overall expression of K13 is higher than that of K8. However, this relation is inverted in tumors induced by PDVC57 cells, in a good correlation with the tumoral phenotypes produced by the cell lines. Our results suggest that upregulation of the simple epithelial keratin K8, as found in transformed epidermal cell lines and tumors, is a late marker of malignant progression and is associated with the loss of the differentiated phenotype.

Topics: 9,10-Dimethyl-1,2-benzanthracene; Animals; Carcinoma; Carcinoma, Squamous Cell; Cell Line, Transformed; Cell Transformation, Neoplastic; Genes, ras; Keratinocytes; Keratins; Mice; Mice, Inbred C57BL; Neoplasm Transplantation; Skin Neoplasms; Up-Regulation

Apocrine carcinomas of the skin are rare and incompletely studied neoplasms.. An immunohistochemical and ultrastructural study is reported of specimens from six patients with apocrine skin carcinoma in various body sites. Three tumors were in the axilla; one, the eyelid; one, the ear; and one, the scalp. There were three local recurrences and three regional lymph node metastases, but no patient died of cancer (follow-up, 2-10 years).. The most reliable histopathologic criteria for identifying apocrine skin carcinoma appear to be decapitation secretion, periodic acid-Schiff-positive diastase-resistant material in the cells or lumen, and immunoreactivity with gross cystic disease fluid protein 15. All specimens expressed common epithelial antigens (cytokeratins, carcinoembryonic antigen, and epithelial membrane antigen) and histiocytic-secretive antigens (Leu-M1, lysozyme, LN5, alpha-1-antitrypsin, and alpha-1-antichymotrypsin). S-100 protein was found in the three nonaxillary tumors. Ultrastructurally, the primary tumors, and especially the secondary lesions, were dedifferentiated compared with normal apocrine glands.. Apocrine differentiation in skin tumors does not indicate an exclusive origin from the apocrine sweat glands; these neoplasms usually have an indolent clinical course.

Topics: Adult; Aged; Aged, 80 and over; Apocrine Glands; Carcinoma; Female; Humans; Immunohistochemistry; Keratins; Male; Middle Aged; Sweat Gland Neoplasms

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 immunoreactivity of OV-TL 12/30, a monoclonal antibody to keratin 7 was investigated on paraffin-embedded human lung cancer tissues of 61 patients. A modified AEC-immunoperoxidase method with pepsin pre-digestion was used. In normal lung tissue keratin 7 was found in bronchial and bronchiolar epithelium, pneumocytes and compound glands. Squamous metaplasia of the bronchial tree was negative. All 24 squamous cell carcinomas were negative irrespective of grade of differentiation. All differentiation grades of 20 adenocarcinomas including bronchioalveolar carcinomas were positive. Since six large cell anaplastic carcinomas did not react with keratin 7 antibody these tumours are considered to be of squamous cell rather than adenocarcinomatous origin. Small cell anaplastic carcinomas were negative in 10 of 11 cases. Our study demonstrates that this keratin 7 antibody is useful in differentiating between squamous cell carcinoma and adenocarcinoma of the lung and it may be particularly useful in making the correct diagnosis in small lung biopsy specimens.

Topics: Antibodies, Monoclonal; Carcinoma; Humans; Immunoenzyme Techniques; Keratins; Lung; Lung Neoplasms

Fifty-eight formalin-fixed paraffin-embedded canine mammary tumors, 19 malignant and 39 benign, were used in this study. Tumors were obtained from dogs submitted for surgical resection of lesions at private veterinary practices in Brussels or from the surgery unit of the Faculty of Veterinary Medicine, University of Liège. Immunohistochemical evaluation was performed, using monoclonal antibodies directed against keratins 8-18 and 19, vimentin, desmin, and alpha-actin and polyclonal antibodies directed against high-molecular-weight keratins and S-100 protein. The main cell types, epithelial, myoepithelial, and connective, were identified, and myoepithelial cells represented the major component of most tumors, both benign and malignant. Myoepithelial cells had five patterns: resting and proliferative suprabasal cells, spindle and star-shaped interstitial cells, and cartilage. Reactivity to keratin 19, vimentin, alpha-actin, and S-100 protein suggested a progressive transformation from resting cells to cartilage. Epithelial cell reactivities were limited to keratins; only keratinized cells were positive for polyclonal keratins. Myofibroblasts were positive for both vimentin and alpha-actin, and connective tissue cells were positive for vimentin. Myoepithelial cells appeared to be the major component of carcinomas, justifying reevaluation and simplification of histomorphologic classifications, with a "pleomorphic carcinoma" group including all carcinomas except squamous, mucinous, and comedo carcinomas. Immunohistochemical evaluation, in addition to routine hematoxylin and eosin histopathologic evaluation is recommended for precise classification of canine mammary tumors.

Topics: Actins; Adenoma; Animals; Carcinoma; Dog Diseases; Dogs; Female; Immunohistochemistry; Keratins; Mammary Neoplasms, Animal; Vimentin

The mid portion of the lateral thyroid lobes from 64 fetuses was systematically analysed for the presence of ultimobranchial body nests. The nests showed a prevalence of 1/24 (4.2 per cent) or 13/40 (32.5 per cent) depending on whether a single- or a multi-step sectioning method was employed, respectively, and showed anatomical, morphological, and histochemical features similar to those of ultimobranchial postnatal thyroid solid cell nests. Histochemical studies revealed the presence of mucosubstances in 73 per cent of the cases, calcitonin-immunoreactive cells in 36 per cent, and both carcinoembryonic antigen and high-molecular-weight cytokeratin-immunoreactive epidermoid cells in 85.7 per cent, respectively. These findings indicate that these markers, which are also expressed by solid cell nests of the thyroid, are of value for the detection and tracing of ultimobranchial tissue to earlier stages of development. The findings of this study support the hypothesis that mucoepidermoid carcinomas of the thyroid are of ultimobranchial tissue origin.

Topics: Animals; Calcitonin; Carcinoembryonic Antigen; Carcinoma; Female; Gestational Age; Humans; Immunohistochemistry; Keratins; Male; Thyroid Gland; Thyroid Neoplasms; Ultimobranchial Body

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

Nasopharyngeal carcinoma (NPC) has a relatively high incidence in Chinese living in Taiwan, Hong Kong, Singapore, and South China. To better understand this cancer, we have established several new NPC cell lines.. We collected biopsy specimens from suspected NPC patients and divided each specimen into two parts: the first part was fixed for routine histopathologic examination, and the other part was put into culture medium for primary culture. Once the cell lines were established, they were extensively characterized.. Seven NPC cell lines were established, and all have been passaged more than 100 times. Two lines were derived from keratinizing carcinomas and five from undifferentiated carcinomas. Electron microscopic examination revealed that both dark and light tumor cells contained intermediate filaments with clear desmosome formation. The average doubling time ranged from 10.7 to 16.3 hours. Karyotypic analysis showed multiple chromosome abnormalities with the average chromosome number between 84 and 95. Colony forming efficiency in soft agar was 18-42%. All cell lines could induce solid tumor mass formation when transplanted into nude mice, and the histopathological findings showed two keratinizing and five nonkeratinizing carcinomas. All cell lines contained less acidic keratin polypeptides than basic keratin polypeptides. Strong expression of vimentin in each single cell of all cell lines was also observed. The oncosuppressor retinoblastoma gene in each cell line showed no remarkable abnormality, but retinoblastoma protein was abnormally expressed in some interphase cells. The oncogenes, erbB and c-fgr, were both normally expressed. While the c-myc oncogene in all cell lines was overexpressed when compared with the Burkitt's lymphoma Raji Cell line, the c-myc DNA sequence in each cell line showed neither amplification nor rearrangement.. The newly established seven NPC cell lines have been well characterized, and all showed overexpression of c-myc oncogene. The oncosuppressor retinoblastoma gene revealed no remarkable rearrangement, but its protein product was abnormal in certain interphase cells of each cell line.

Topics: Adult; Aged; Antigens, Viral; Carcinoma; DNA-Binding Proteins; Epstein-Barr Virus Nuclear Antigens; Female; Genes, Retinoblastoma; Humans; Karyotyping; Keratins; Male; Microscopy, Electron; Middle Aged; Nasopharyngeal Neoplasms; Proto-Oncogene Proteins c-myc; Tumor Cells, Cultured; Tumor Stem Cell Assay; Vimentin

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

Squamous carcinomas of both human and rodent origin can undergo a transition to a more invasive, metastatic phenotype involving reorganization of the cytoskeleton, loss of cell adhesion molecules such as E-cadherin and acquisition of a fibroblastoid or spindle cell morphology. We have developed a series of cell lines from mouse skin tumors which represent different stages of carcinogenesis, including benign papillomas, and clonally related squamous and spindle carcinomas derived from the same primary tumor. Some spindle cells continue to express keratins, but with a poorly organized keratin filament network, whereas in others no keratin expression is detectable. All of the spindle cells lack expression of the cell adhesion molecule E-cadherin and the desmosomal component desmoplakin. Loss of these cell surface proteins therefore appears to precede the destabilization of the keratin network. At the genetic level, it is not known whether such changes involve activation of dominantly acting oncogenes or loss of a suppressor function which controls epithelial differentiation. To examine this question, we have carried out a series of fusion experiments between a highly malignant mouse skin spindle cell carcinoma and cell lines derived from premalignant or malignant mouse skin tumors, including both squamous and spindle carcinoma variants. The results show that the spindle cell phenotype as determined by cell morphology and lack of expression of keratin, E-cadherin, and desmoplakin proteins, is recessive in all hybrids with squamous cells. The hybrids expressed all of these differentiation markers, and showed suppression of tumorigenicity to a variable level dependent upon the tumorigenic properties of the less malignant fusion partner. Our results suggest that acquisition of the spindle cell phenotype involves functional loss of a gene(s) which controls epithelial differentiation.

Topics: Animals; Antigens, Differentiation; Cadherins; Carcinoma; Carcinoma, Squamous Cell; Cell Transformation, Neoplastic; Cytoskeletal Proteins; Cytoskeleton; Desmoplakins; Epidermis; Fluorescent Antibody Technique; Gene Expression Regulation; Genes, Recessive; Genes, Suppressor; Hybrid Cells; Immunohistochemistry; Keratins; Mice; Phenotype; Skin Neoplasms; Tumor Cells, Cultured

The clinical, morphological and immunohistochemical features of 27 patients with anaplastic large cell lymphoma (ALCL) of CD30-positive type, with cutaneous lesions as the sole initial clinical manifestation, were analyzed. The neoplasm presented as solitary or multiple, usually ulcerated skin lesions, affecting predominantly elderly patients (median age: 67 years) with a male preponderance (male to female ratio of 6:1). In most patients, there was an excellent response to chemotherapy. The cardinal histological features included diffuse dermal and subcutaneous infiltration by large, anaplastic tumor cells, all or nearly all of which showed diffuse, strong membrane staining and frequently a paranuclear, dot-like reaction with the CD30 marker (Ber-H2). Epidermal ulceration, pseudo-epitheliomatous hyperplasia and dermal vascular proliferation were also observed.

Topics: Adult; Aged; Aged, 80 and over; Antigens, CD; Antigens, Neoplasm; Carcinoma; Female; Humans; Immunohistochemistry; Keratins; Ki-1 Antigen; Lymphoma, Large B-Cell, Diffuse; Male; Membrane Glycoproteins; Middle Aged; Mucin-1; S100 Proteins; Skin Neoplasms

Expression of keratins (cytokeratins, CK) known to be suitable markers for different types of epithelial differentiation was analyzed in specimens of feline mammary tissue. A panel of specific anti-CK monoclonal antibodies (MAb) was used to determine CK distribution pattern in normal feline tissues (n = 3), and in benign (n = 18) and malignant (n = 20) feline mammary tumors. In selected tumors, the CK distribution pattern was also determined by biochemical methods. A MAb specific for alpha-smooth muscle actin was used to discriminate between myoepithelial cells and luminal epithelial cells. In normal mammary gland tissues, 6 MAb reacted exclusively, either with myoepithelial cells or with luminal epithelial cells. Luminal epithelial cells reacted with MAb specific for CK typical of simple epithelia, whereas myoepithelial cells reacted with MAb specific for CK in basal cells of stratified epithelia. A similar distribution of CK was detected in specimens from benign tumors, except that CK4 was not detected in normal mammary gland tissues and was detected in some ducts in specimens with adenosis. Almost all tumor cells in specimens from malignant tumors reacted with MAb specific for CK typical of simple epithelia. Concomitant expression of CK typical of stratified epithelia was detected in small or large subpopulations of tumor cells in 70% of carcinomas. Cytokeratins typical of basal cell layers and typical for suprabasal layers of inner stratified epithelia were detected. Cytokeratins typical of stratified epithelia were always found in areas of squamous metaplasia, but also were found in adenocarcinomal cells surrounding these areas.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adenofibroma; Animals; Antibodies, Monoclonal; Biomarkers, Tumor; Carcinoma; Cat Diseases; Cats; Electrophoresis, Gel, Two-Dimensional; Keratins; Mammary Glands, Animal; Mammary Neoplasms, Animal; Metaplasia; Precancerous Conditions

The expression of involucrin, a structural component of the envelope of mature squamous epithelium, was studied in 166 paraffin-embedded breast carcinomas. In 41 cases (24.7%) involucrin-positive, light microscopically non squamous tumour cells were detected. The number of involucrin-positive tumour cells varied considerably from case to case. For further characterization, involucrin-positive cases were studied using monoclonal antibodies to various cytokeratins (PKK1, EAB 903, EAB 904) and, in selected cases, double immunostaining with antibodies to cytokeratins and involucrin were performed. Coexpression of involucrin and cytokeratins demonstrated by PKK1 was seen in all tumour cells, whereas coexpression of involucrin and cytokeratins detected by EAB 904 was only seen in single and scattered cells in a few cases. Cytokeratins detected by EAB 903 were not coexpressed with involucrin in our cases. Our results indicate heterogeneity of cytokeratins in breast carcinomas and suggest a dissociation in the regulation of involucrin and cytokeratin expression.

Topics: Breast Neoplasms; Carcinoma; Female; Humans; Immunohistochemistry; Keratins; Male; Protein Precursors

Extramammary Paget disease appears in anogenital, axillary, or other areas. In this study, the authors addressed the question of whether the histogenesis of 35 cases of Paget disease arising at different sites was the same.. Specimens of 35 cases of extramammary Paget disease (16 genital; 9 invasive carcinomas of genital; 6 axillary; 1 periumbilical; and 3 perianal), 4 cases of mammary Paget disease, 4 cases of breast carcinomas, and 6 cases of anal carcinomas of perianal spread from primary rectal adenocarcinomas were retrieved and stained by the avidin-biotin-complex method, using various kinds of monoclonal antikeratin antibodies.. There was no significant difference in cytokeratin expression among these cases of extramammary Paget disease. Simple epithelial keratins were expressed in Paget cells in extramammary Paget disease, but no expression of differentiation-specific or noncornifying stratified squamous epithelial keratins was observed, regardless of the degree of invasion. Paget cells in extramammary Paget disease revealed a similar cytokeratin expression to that in secretory cells of normal apocrine or eccrine glands. In addition, there was no significant difference in cytokeratin expression in tumor cells among extramammary and mammary Paget disease, breast carcinomas, and anal carcinomas.. Cases of Paget disease arising at different locations could not be distinguished from each other based on cytokeratin expression. In addition, antikeratin antibodies against simple epithelial keratins were demonstrated to be more useful for the identification of Paget cells in the paraffin sections than were conventional antibodies, such as an antibody against carcinoembryonic antigen (CEA).

Topics: Antibodies, Monoclonal; Breast Neoplasms; Carcinoembryonic Antigen; Carcinoma; Eccrine Glands; Gene Expression Regulation, Neoplastic; Humans; Keratins; Neoplasm Invasiveness; Paget Disease, Extramammary; Paget's Disease, Mammary; Protein Precursors; Urogenital Neoplasms

Fifty-three breast lesions, which had been fixed in formalin and embedded in paraffin, were immunohistochemically analyzed with monoclonal antibodies to cytokeratin subtypes 1, 5, 10, 14 (34BE12), muscle-specific actins (HHF35) and antiserum to S100 protein, all of which have been used as markers for myoepithelial cells. With these antibodies, a continuous myoepithelial cell layer could generally be seen around the benign ducts and acini. In in situ carcinomas, such a layer could still be observed, though it was usually discontinuous and sometimes absent. In infiltrating carcinomas, no myoepithelial cell layer could be observed. In intraductal hyperplasias, scattered HHF35, 34BE12 and S100-positive cells could be seen amongst the proliferating intraductal cells. In in situ and infiltrating carcinomas, however, such cells could also be observed. This was seen especially with antibodies 34BE12 and S100, and to a lesser extent also with HHF35. Morphologically these cells seemed to belong to the malignant cell population. Although myoepithelial cell preservation is an important morphological parameter in the histological evaluation of breast lesions, the results suggest that the myoepithelial cell markers 34BE12, HHF35 and S100 cannot be used in the differential diagnosis between benign and malignant breast lesions in a straightforward manner. This is because in situ carcinomas have a more or less preserved myoepithelial cell layer, and because many infiltrating and in situ carcinomas contain a subpopulation of neoplastic cells expressing these markers, possibly signifying myoepithelial cell differentiation.

Topics: Actins; Breast Diseases; Breast Neoplasms; Carcinoma; Female; Humans; Immunohistochemistry; Keratins; Papilloma; S100 Proteins

Topics: Antibodies, Monoclonal; Biomarkers, Tumor; Breast Neoplasms; Carcinoma; Female; Humans; Keratins; Lymph Nodes; Lymphatic Metastasis; Neoplasm Staging; Neoplastic Cells, Circulating

The authors have recently identified a new cytokeratin (CK) polypeptide, CK 20, whose expression is almost entirely confined to the gastric and intestinal epithelium, urothelium, and Merkel cells. Seven monoclonal antibodies (MAbs) specific for CK 20 were raised and characterized by applying immunoblotting and immunocytochemical screening. All of them reacted on frozen tissue sections. A further MAb, IT-Ks20.8, recognized CK 20 in sections of formalin-fixed, paraffin-embedded tissue samples. A total of 711 cases of primary and metastatic cancer, mostly carcinomas, were analyzed immunohistochemically for CK-20 expression, using CK-20 specific guinea-pig antibodies and MAbs. The expression spectrum of CK 20 in carcinomas resembled that seen in the corresponding normal epithelia of origin. CK-20 positivity was seen in the vast majority of adenocarcinomas of the colon (89/93 cases), mucinous ovarian tumors, transitional-cell and Merkel-cell carcinomas and frequently also in adenocarcinomas of the stomach, bile system, and pancreas. Most squamous cell carcinomas in general and most adenocarcinomas from other sites (breast, lung, endometrium), nonmucinous tumors of the ovary, and small-cell lung carcinomas were essentially or completely negative. The authors propose to use CK 20 as a diagnostic marker valuable in distinguishing different types of carcinomas, notably when presenting as metastases.

Topics: Animals; Antibodies, Monoclonal; Biomarkers, Tumor; Carcinoma; Cytoskeleton; Dogs; Electrophoresis, Polyacrylamide Gel; Humans; Immunoblotting; Immunoenzyme Techniques; Keratins; Microscopy, Fluorescence; Microscopy, Immunoelectron; Rats; Reference Values; Swine

The immunostaining patterns of adrenocortical tumors are not clearly defined, primarily due to their inconsistent expression of cytokeratins (CK). To address this issue and to investigate whether adrenocortical tumors can be immunohistochemically differentiated from histologically similar tumors arising from the kidney and liver, we studied four normal adrenal glands, two adrenocortical adenomas (ACAs), 31 adrenocortical carcinomas (ACCs), 37 renal cell carcinomas (RCCs), and 33 hepatocellular carcinomas (HCCs) with anti-CK antibodies AE1, CAM 5.2, UCD/PR10.11, 35BH11, PKK1, and Ks19.1, as well as antibodies to vimentin (VIM), epithelial membrane antigen (EMA), and HMFG-2. Normal adrenal cortical cells showed variable staining with all anti-CK antibodies on fixed and frozen sections. In contrast, only one of two fixed ACAs stained with a single anti-CK, although both neoplasms reacted with multiple anti-CK antibodies on frozen sections. Similarly, 20 of 31 fixed ACCs contained VIM, but only one tumor stained for CK; frozen sections of this and another, previously negative tumor, however, stained with most of the anti-CK antibodies tested. One-dimensional Western immunoblot analysis confirmed the presence of CKs 18 and 19 in two examples of normal adrenal cortex, one ACA, and the ACC immunohistochemically positive on fixed and frozen sections, with CK 19 identified in the ACC that was positive on frozen section alone. All fixed HCCs and most RCCs stained with multiple anti-CK antibodies (33 and 34 cases, respectively), with a proportion of tumors positive for VIM (six and 22 cases, respectively), EMA (seven and 30 cases, respectively), and HMFG-2 (15 and 28 cases, respectively). The results suggest that CK expression is diminished in most adrenocortical tumors to levels too low to be recognized following the deleterious effects of fixation. While the immunohistochemical absence of CK, EMA, and HMFG-2 in fixed sections in the majority of ACCs is distinctive, sufficient phenotypic overlap exists such that differentiation between RCC and HCC may not be possible in an individual case.

Topics: Adrenal Cortex Neoplasms; Carcinoma; Carcinoma, Hepatocellular; Carcinoma, Renal Cell; Diagnosis, Differential; Electrophoresis, Polyacrylamide Gel; Humans; Immunoblotting; Immunoenzyme Techniques; Keratins; Kidney Neoplasms; Liver Neoplasms

Cytokeratin (CK) immunoreactivity in malignant fibrous histiocytoma (MFH) and other selected cases of spindle cell tumors were assessed using two cytokeratin monoclonal antibodies, AE1/AE3 and CAM 5.2. Frozen tissue was used to minimize the effects of fixation on keratin antigenicity; in addition, one block of fixed, paraffin-embedded tissue was tested for comparison. CK immunoreactivity was noted in nine frozen tissue samples (7/20 [35%] MFH, 1/3 schwannomas, 1/3 leiomyosarcomas). In the majority of cases, only rare individual positive cells were seen. Of 19 MFH cases in paraffin-embedded tissue, CK immunoreactivity was noted in three (16%). All 32 cases examined showed vimentin immunoreactivity. MFH must be added to the growing list of mesenchymal tumors exhibiting sporadic CK immunoreactivity. Such reactivity is less frequent in paraffin-embedded tissues. This finding has important implications for tumor diagnosis, particularly in the differential diagnosis of pseudosarcomatous carcinoma. Caution is recommended in the interpretation of CK immunoreactivity, particularly as it relates to speculations regarding histogenesis.

Topics: Adult; Aged; Aged, 80 and over; Antibodies, Monoclonal; Carcinoma; Cryopreservation; Female; Histiocytoma, Benign Fibrous; Humans; Immunohistochemistry; Keratins; Male; Middle Aged; Paraffin; Vimentin

Studies concerning flow cytometric assessed DNA content reveal problems in interpretating DNA histograms of tumor specimens. The main problems are histograms with a broad coefficient of variation in the G0/G1 fraction; a high G2M fraction and samples with a low percentage of tumor cells. Therefore, in the present study, 382 fresh tumor specimens of carcinomas were analysed routinely, double labeled with, on the one hand, propidium-iodide for assessing DNA content and, on the other, a monoclonal keratin-antibody for marking epithelial and tumor cells. Of the 311 tumor samples, using single parameter analysis 165 (54%) were classified as DNA aneuploid and 146 (46%) as DNA "euploid." By double parameter analysis, 224 (72%) samples were keratin positive and 87 (27%) keratin negative and, of the 224 keratin positive tumors, 175 (78%) were DNA aneuploid and 49 (22%) DNA euploid. The DNA histograms of single and double parameter analysis were compared and it was concluded that in 24 cases (11%) keratin labeling was necessary to recognize DNA aneuploidy. In another 23 (10%) cases, keratin labeling was helpful in assessing DNA aneuploidy. Finally when the results of the 311 samples were combined, 215 (68%) were scored as DNA aneuploid and 99 (32%) DNA euploid. Thus the overall gain in assessing DNA aneuploidy using the double labeling technique is 14%. In conclusion, it is shown that keratin labeling on fresh tumor cell suspensions of epithelial tumors is of additional value in establishing DNA content. Because single parameter DNA assessment is adequate in approximately 60% of the tested samples, the double labeling technique can be performed routinely, or after initial single parameter DNA assessment. Histograms having a broad CV and/or a high G2M are good candidates for the double labeling technique. Using this technique, DNA-content assessment becomes more reliable.

Topics: Antibodies; Carcinoma; DNA, Neoplasm; Epithelium; Flow Cytometry; Humans; Keratins; Ploidies; Propidium

To examine the importance of immunocytochemically detectable occult axillary lymph node metastases in patients with lobular carcinoma of breast, tumor registry data from 54 cases indexed as lobular carcinoma during the period 1973-82 were reviewed. Recurrences and/or deaths due to cancer were essentially confined to the group of patients with a component of invasive lobular carcinoma (ILC), therefore this subset was selected for further study. Seven of 20 cases had lymph node metastases diagnosed histologically at the time of mastectomy. Follow-up of these patients showed four dead of disease (DOD) at one, three, three, and seven years; one alive with disease (AWD) at one year; and two with no evidence of disease (NED) at four and five years. Eleven of 20 were node negative. Follow-up of this group showed nine NED and two DOD at two and four years. Two of 20 had unknown node status. Formalin-fixed, paraffin embedded lymph node blocks were available in 12 of 20 cases with a component of ILC. Of these, 4/12 cases had histologically positive nodes while 8/12 were originally diagnosed as negative. A cytokeratin monoclonal antibody cocktail (MAK-6, CAM 5.2 and AE1/AE3) was applied to all 12 cases. Cytokeratin immunoreactivity (CK-IR) was found in all four cases that were histologically positive. Five of eight histologically negative nodes lacked CK-IR, however the other three cases showed CK-IR in micrometastases. Review of newly prepared hematoxylin-eosin sections from the paraffin blocks failed to demonstrate metastases.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Aged; Aged, 80 and over; Antibodies, Monoclonal; Axilla; Breast Neoplasms; Carcinoma; Female; Humans; Keratins; Lymph Nodes; Lymphatic Metastasis; Mastectomy; Middle Aged; Prognosis; Retrospective Studies

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

Primary tumors of the peritoneum are rare. Histological differentiation between papillary mesotheliomas, primary ovarian tumors, borderline tumors of the ovary with peritoneal deposits and primary peritoneal carcinoma may be difficult. The expression of vimentin, keratin, pankeratin, CEA, CA125, CA19-9, S100, B72.3 and BerEP4 was therefore investigated in twelve women with primary malignant peritoneal tumors, twelve women with pleural mesothelioma, eight women with serous ovarian carcinoma and four men with peritoneal mesothelioma. The marker pattern we used was no help in differentiating between metastatic ovarian carcinoma and primary peritoneal carcinomatosis. A combination of the markers S100, B72.3 and BerEP4 helped the distinction between mesotheliomas and the other malignancies. If two or all three markers are detectable, primary peritoneal carcinomatosis or metastatic ovarian carcinoma is the possible diagnosis. If none of the three markers are found, a diagnosis of mesothelioma is highly probable.

Topics: Biomarkers, Tumor; Carcinoma; Diagnosis, Differential; Female; Humans; Immunohistochemistry; Keratins; Male; Mesothelioma; Ovarian Neoplasms; Peritoneal Neoplasms

Topics: Carcinoma; Diagnosis, Differential; Female; Glycogen; Humans; Immunohistochemistry; Keratins; Mandibular Neoplasms; Middle Aged; Salivary Gland Neoplasms; Salivary Glands, Minor

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

One of the problems in histopathology of ovarian tumors is differential diagnosis between the poorly differentiated carcinomas and granulosa cell tumors of the sarcomatoid type. Hence we evaluated the expression of various cytokeratins (CK 1-19; CK 10, 13, 14, 15, 19; CK 8, 18, 19; CK HMW 1, 5, 10, 11; CK 8; CK 1-19 Stähli; CK AE1/AE3) immunohistochemically in 53 ovarian malignancies (11 of them poorly differentiated carcinomas and 12 granulosa cell tumors). CK HMW was not detected in granulosa cell tumors, and in only half of the carcinomas. AE1/AE3 was expressed by more than 90% of ovarian carcinomas but by one granulosa cell tumor only. The other keratins we investigated showed higher expression rates in granulosa cell tumors and/or lower expression rates in ovarian carcinomas. We think that cytokeratin immunohistochemistry is of value in differentiating between granulosa cell tumors and ovarian carcinomas.

Topics: Antibodies, Monoclonal; Biomarkers, Tumor; Carcinoma; Diagnosis, Differential; Female; Granulosa Cell Tumor; Humans; Immunoenzyme Techniques; Keratins; Ovarian Neoplasms; Ovary

Immunoreactivities in 25 cases of prostatic adenocarcinoma and 10 normal/hyperplastic prostates were investigated in methacarn-fixed, paraffin-embedded serial sections using a panel of nine anti-keratin monoclonal antibodies (mAbs); 34 beta E12, CK8.12, 312C8-1, CK4.62, RPN1165, RPN1162, 35 beta H11, CK5, M20, and one of anti-actin mAb, HHF35. In normal/hyperplastic prostates, RPN1162, 35 beta H11, CK5 and M20 stained luminal cells without staining basal cells, and 34 beta E12, CK8.12 and 312C8-1 stained basal cells but not luminal cells. Other mAbs, CK4.62 and RPN1165, stained basal cells as well as luminal cells. All of the mAbs labelling luminal cells stained cancer cells with variable frequencies in a manner unrelated to the grade of tumour differentiation. Of the prostate cancer cases 92% were scored positive with M20, 84% with 35 beta H11, 80% with CK5, 68% with CK4.62, 60% with RPN1165 and 4% with RPN1162. However, basal cell-specific keratins labelled with 34 beta E12, CK8.12 and 312C8-1 were totally negative in the cancer cells. HHF35 showed no labelling in normal, hyperplastic or neoplastic epithelial cells of the prostate. Our findings indicate that the major part of the cells of prostatic adenocarcinomas have keratin phenotypes similar to luminal cells but not basal cells, and that no myoepithelial differentiation can be detected in epithelial cell of the prostate. Thus, mAbs for keratins facilitate the identification of epithelial cell phenotypes in normal, benign and malignant conditions of the prostate.

Topics: Adolescent; Adult; Aged; Carcinoma; Child; Child, Preschool; Humans; Infant; Keratins; Male; Middle Aged; Prostate; Prostatic Neoplasms

We have examined the microscopic appearance, immunohistochemical staining properties, and clinical behavior of 28 cases of acinar cell carcinoma of the pancreas. Two of the tumors occurred in children. The adult patients ranged in age from 40 to 81 years (mean, 62 years). Males greatly outnumbered females, and most of the patients were white. Presenting symptoms were nonspecific, and jaundice was infrequent. The frequently reported complications from increased serum lipase levels (i.e., arthralgias and subcutaneous fat necrosis) were present in only 16% of the patients. Grossly, the tumors were relatively circumscribed and fleshy, averaging 10.8 cm, with occasionally extensive hemorrhage and necrosis. Microscopically, the tumors were very cellular and characteristically lacked a desmoplastic stroma. Acinar, solid, trabecular, and glandular patterns of growth were identified; individual tumors were usually mixed. Nuclei were round to oval, with minimal pleomorphism and single prominent nucleoli. Mitotic activity was variable. In general the cytoplasm was moderately abundant, eosinophilic, and granular, but many of the solid tumors had cells with scanty cytoplasm. Characteristic periodic acid-Schiff-positive, diastase-resistant cytoplasmic granules were demonstrated in greater than 90% of the cases, and the butyrate esterase histochemical stain for lipase activity was positive in 73%. Immunohistochemically, there was positivity for trypsin in 100% of the cases, for lipase in 77%, for chymotrypsin in 38%, and for amylase in 31%. A minor endocrine component was recognized with antibodies against chromogranin or islet cell hormones in 42% of the tumors. Ultrastructurally, exocrine secretory features were present, with polarized cells showing microvillilined lumina, abundant rough endoplasmic reticulum, and 125-1,000-nm zymogen-like granules. In addition, many cases showed pleomorphic electron-dense granules measuring up to 3,500 nm and containing fibrillary internal structures. Follow-up information was available in 88% of the cases. Half of the patients had metastatic disease at presentation and an additional 23% subsequently developed metastases, which were usually restricted to the regional lymph nodes and liver. The mean survival for all cases was 18 months, with 1- and 3-year survivals of 57 and 26%, respectively. Patients presenting before age 60 years survived nearly twice as long as older patients did. Stage also influenced prognosis, whereas the histo

Topics: Adult; Aged; Aged, 80 and over; alpha-Amylases; Carcinoma; Cell Division; Cell Nucleus; Child; Chymotrypsin; Cytoplasmic Granules; Diagnosis, Differential; Female; Glucagon; Humans; Immunohistochemistry; Insulin; Keratins; Lipase; Male; Microscopy, Electron; Middle Aged; Mitotic Index; Pancreatic Neoplasms; Prognosis; Trypsin

Rat keratin K5 and vimentin complementary DNAs have been isolated, identified, and used to study keratin and vimentin expression as markers for cell differentiation. Isologous rat neoplastic epithelial cell lines used were based on a clonal benign epithelial line (A5P/B10) and a clonal anaplastic malignant derivative line (T952/F7). Stable cytoplasmic mRNA was detected for keratin but not vimentin in the benign cells. The anaplastic derivative cells expressed vimentin but showed a 1000-fold reduction in the keratin message, which nuclear run-on assays identified as being due to posttranscriptional down-regulation. An identical pattern of posttranscriptional down-regulation was found in independent malignant somatic cell hybrids of the benign and anaplastic cells. trans-acting regulatory mechanisms implicated in posttranscriptional (pretranslational) keratin down-regulation in these anaplastic malignant cells may play a role in the apparent loss of differentiation evident in tumor progression.

Topics: Animals; Base Sequence; Carcinoma; Cycloheximide; Down-Regulation; Flow Cytometry; Keratins; Molecular Sequence Data; Phenotype; Rats; RNA Processing, Post-Transcriptional; RNA, Messenger; RNA, Neoplasm; Species Specificity; Tumor Cells, Cultured; Up-Regulation; Vimentin

Spindle cell squamous carcinoma (SCSC) and atypical fibroxanthoma (AFX) are both spindle cell neoplasms (SCN) that usually arise in areas of solar or ionizing radiation of elderly patients. Both lesions have a similar biologic behavior. In addition, the morphologic and ultrastructural similarities found in AFX and the spindle cell component of SCSC, have led some investigators to conclude that these tumors have a similar cell of origin. We studied 15 SCNs with no evidence of epithelial origin and no morphologic epithelial component, that showed immunohistochemical and ultrastructural evidence that would support metaplastic changes of a squamous cell carcinoma to a neoplasm with mesenchymal characteristics.

Topics: Aged; Aged, 80 and over; Carcinoma; Carcinoma, Squamous Cell; Female; Humans; Immunohistochemistry; Keratins; Male; Microscopy, Electron; Middle Aged; Skin Neoplasms; Vimentin

Monoclonal anticarcinoembryonic antigen (antiCEA), human milk factor globulin (HMFG2), and antikeratin antibodies were assessed for their value in the differential diagnosis of pleural mesothelioma (53 cases) and carcinoma of the lung (60 cases) in material from necropsies. In 40 of the cases pleural biopsies were also studied in the same manner. AntiCEA was found to be the best discriminating antibody for most types of mesothelioma; HMFG2 was slightly less valuable but a useful additional tool. Antikeratin was the least useful. For both antiCEA and HMFG2 antibodies, however, the proportion of carcinomas staining was smaller than in previous studies and this, combined with the positive staining of some mesotheliomas, reduces the value of the reactions in the individual case. Medical panels adjudicating compensation claims should not use these reactions as the sole criteria in deciding the origin of the tumours in these cases.

Topics: Antigens, Neoplasm; Autoantibodies; Biomarkers, Tumor; Carcinoembryonic Antigen; Carcinoma; Diagnosis, Differential; Humans; Keratins; Lung Neoplasms; Membrane Glycoproteins; Mesothelioma; Mucin-1; Occupational Diseases; Pleural Neoplasms

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

In normal breast tissue and in noninvasive breast carcinomas, various keratin-14 antibodies were reactive predominantly with the basal/myoepithelial cell layer, although mainly in terminal and larger ducts luminal cells sometimes also were stained. A similar reaction pattern was found with an antibody directed against keratin 17, although this antibody was more often found negative than keratin 14 in the pre-existing myoepithelial cells in intraductal carcinomas. Furthermore antibodies reactive with hyperproliferation-related keratins 6 and 16 were used. One of these (LL025) was completely negative in normal breast tissue and noninvasive breast carcinomas. However 10% of the invasive carcinomas were diffusely or focally positive with this latter antibody, while in 18 of 115 cases of invasive breast carcinomas studied, a basal cell phenotype was detected. A relatively high concordance was found between the carcinomas immunostaining with the basal cell and the hyperproliferation-related keratins, but not between these markers and the proliferation marker Ki-67. This supports the conclusion that basal cells in breast cancer may show extensive proliferation, and that absence of Ki-67 staining does not mean that (tumor) cells are not proliferating.

Topics: Antibodies, Monoclonal; Biomarkers, Tumor; Breast; Breast Neoplasms; Carcinoma; Carcinoma in Situ; Carcinoma, Intraductal, Noninfiltrating; Cell Division; Female; Humans; Keratins; Neoplasm Invasiveness; Reference Values

Because the data on the antigenic phenotype of mucoepidermoid carcinoma (MEC) are incomplete and somewhat disparate, 45 MECs were evaluated immunohistochemically for low- and high-molecular-weight keratins, vimentin, glial fibrillary acidic protein, smooth muscle actin, and S-100 protein. Tumors stained uniformly for keratins and, on occasion, focally for vimentin. Tumors were nonreactive with antibodies to glial fibrillary acidic protein and, with few exceptions, to muscle-specific actins and S-100 protein. Clear cell and papillary histologic variants were seen as potential diagnostic pitfalls. If used with hematoxylin-and-eosin-stained sections, limited potential is seen for this antibody panel in surgical pathology. Myoepithelial cell-associated antigens are expressed to a very limited extent in MECs.

Topics: Actins; Adolescent; Adult; Aged; Aged, 80 and over; Carcinoma; Child, Preschool; Female; Glial Fibrillary Acidic Protein; Humans; Immunohistochemistry; Keratins; Male; Middle Aged; S100 Proteins; Salivary Gland Neoplasms; Salivary Glands, Minor; Vimentin

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

The clinical, microscopical, immunocytochemical and ultrastructural features of five cases of benign mesenchymal proliferative lesions of the urinary bladder, mimicking sarcoma, are presented. Four of the five patients are alive and disease-free following diagnosis, an interval ranging from 9 months to 9 years, mean 4 years. A fifth patient, who had a pseudosarcomatous stromal response adjacent to a urinary transitional cell carcinoma, now has invasive transitional cell carcinoma. The lesions revealed a striking microscopical, immunocytochemical and ultrastructural similarity to nodular fasciitis, suggesting the lesions represented a bizarre mesenchymal proliferative response to inflammation.

Topics: Adult; Carcinoma; Desmin; Female; Humans; Immunohistochemistry; Keratins; Lectins; Male; Microscopy, Electron; Middle Aged; Plant Lectins; Urinary Bladder Neoplasms; Vimentin

Immunostaining for glial fibrillary acidic protein (GFAP) identifies a minor subpopulation of immunoreactive myoepithelial cells in the normal resting human breast. The GFAP-immunoreactive cells also express a panel of myoepithelial cell markers, including cytokeratin 14 (CK 14), vimentin, smooth-muscle-specific actin isoforms, nerve growth factor receptor (NGFR) and common acute lymphoblastic leukaemia antigen (CALLA). The percentage of GFAP-immunoreactive myoepithelial cells is greatly increased in various neoplastic and non-neoplastic diseases of the breast, being highest in adenomyoepitheliomas. Furthermore, in all the instances of fibroadenoma, phyllodes tumour, epitheliosis and gynaecomastia, a variable number of epithelial cells also acquires immunoreactivity for GFAP, vimentin, CK 14, NGFR and, to a lesser extent, for CALLA. Conversely, GFAP immunoreactivity has never been encountered in the malignant cells of the different types of breast carcinoma. These findings suggest that the expression of GFAP might be a (possibly transient) feature of proliferating epithelial and myoepithelial cells in breast diseases other than carcinomas.

Topics: Actins; Adenofibroma; Antibodies; Antigens, Differentiation; Antigens, Neoplasm; Breast; Breast Diseases; Breast Neoplasms; Carcinoma; Female; Glial Fibrillary Acidic Protein; Gynecomastia; Humans; Immunohistochemistry; Keratins; Male; Neprilysin; Receptors, Cell Surface; Receptors, Nerve Growth Factor; Vimentin

'Universal fuser' clones of a human papillomavirus type 16 positive cervical carcinoma cell line (SiHa) were established to study the effect of a non-tumorigenic fusion partner on the regulation of a stably integrated chloramphenicol acetyltransferase (CAT) gene controlled by the HPV18 upstream regulatory region under non-selective conditions. The CAT expressing cells were fused with both non-tumorigenic, spontaneously immortalized human keratinocytes (HaCaT) and non-modified SiHa cells. The resulting hybrids were characterized by restriction enzyme fragment length polymorphism analysis and flow cytometry. While the non-selectable, HPV18-driven indicator gene is constitutively expressed in SiHa cells, the CAT activity is extinguished in SiHa x HaCaT cells, but still present in SiHa x SiHa hybrids. Examination of the cytokeratin expression pattern reveals that the keratinocyte phenotype seems not only to be dominant in terms of the extinction of the HPV18 regulatory region but also by the conservation of most of the differentiation markers of the non-tumorigenic fusion partner. Cycloheximide treatment and intracellular competition experiments using the transient COS7 fusion-amplification technique are accompanied by the reactivation of the marker gene in previously CAT- SiHa x HaCaT hybrids. These data strongly suggest that trans-acting negative regulatory factors derived from the non-malignant human keratinocytes are responsible for the extinction phenomenon.

Topics: Animals; Blotting, Northern; Carcinoma; Cell Fusion; Chlorocebus aethiops; Electrophoresis, Gel, Two-Dimensional; Female; Gene Expression Regulation, Viral; Humans; In Vitro Techniques; Keratinocytes; Keratins; Papillomaviridae; Polymorphism, Restriction Fragment Length; Regulatory Sequences, Nucleic Acid; Repressor Proteins; RNA, Messenger; Transcription, Genetic; Transfection; Uterine Cervical Neoplasms

Hybrids have been developed from two cell lines originally derived from human mammary epithelial cells. MTSV1-7 (hygro), developed from cultured milk epithelial cells, shows a cuboidal morphology, expresses high levels of keratins (but no vimentin), and forms ball-like three-dimensional structures in collagen gels. 5.3.1E (neo), derived from a cell cultured from tissue taken from a primary breast cancer, shows an elongated morphology, expresses high levels of vimentin and low levels of keratins, and does not form structures on collagen gels. An examination of the hybrids formed by fusion of MTSV1-7 cells and 5.3.1E cells showed that while all could form three-dimensional structures in collagen gels, the type of structures formed resembled either ductal or alveolar-ball-like structures depending on the individual hybrid. Nine hybrids were examined and a clear correlation was observed between cell shape as seen on plastic, intermediate filament expression, and the form of the structures as seen in collagen gels. All the hybrids resembling the parent MTSV1-7 cells by showing a cuboidal morphology and high level of keratin expression formed ball-like structures; on the other hand, hybrids resembling 5.3.1E by showing an elongated morphology and a high level of vimentin expression formed duct-like structures in collagen gels. The results show that the ability to form structures in collagen gels was inherited in a dominant fashion from the MTSV1-7 parent. They also suggest that the profile of intermediate filament expression in the hybrids may influence both cell shape on plastic and the morphology of the three-dimensional structures formed in collagen gels.

Topics: Blotting, Southern; Blotting, Western; Breast; Breast Neoplasms; Carcinoma; Cell Differentiation; Cell Line; DNA; Epithelial Cells; Female; Fluorescent Antibody Technique; Humans; Hybrid Cells; Intermediate Filaments; Keratins; Phenotype; Vimentin

The clinical and pathologic features of 31 breast lesions composed of a prominent proliferation of myoepithelial cells either admixed with epithelial cells or in pure form were studied. The lesions were divided into three categories: myoepitheliosis, adenomyoepithelioma, and malignant myoepithelioma (myoepithelial carcinoma); the latter is the only lesion composed purely of myoepithelial cells. Three multifocal, microscopic lesions located in the peripheral duct system were designated as myoepitheliosis. Twenty-seven solitary, grossly palpable, predominantly centrally located lesions qualified as adenomyoepithelioma. These were further subdivided into spindle-cell, tubular, and lobulated variants. Two lesions in the latter group had a carcinoma arising within them. Only one case, which was characterized by a solitary mass composed of an infiltrative spindle cell proliferation, qualified as malignant myoepithelioma (myoepithelial carcinoma). Two patients with adenomyoepithelioma developed recurrences; one tumor was of the tubular type, the other of the lobulated type. Both of these tumors had irregular margins. One of these patients had two recurrences and is currently well 8.5 years after the initial excision. The second patient developed a recurrence 8 months after initial excision; the recurrence presented as multiple nodules. One of the patients with myoepithelial carcinoma arising in an adenomyoepithelioma also developed a recurrence within 2.3 years. Her initial tumor was located in the axillary tail of the breast, and she had axillary node metastasis at the time of presentation. All remaining patients with follow-up are well without evidence of recurrence up to 17.3 years after the initial diagnosis (average follow-up, 6.1 years); one patient died of unrelated causes.

Topics: Actins; Adult; Aged; Aged, 80 and over; Breast; Breast Neoplasms; Carcinoma; Female; Follow-Up Studies; Glial Fibrillary Acidic Protein; Humans; Immunohistochemistry; Keratins; Microscopy, Electron; Middle Aged; Myoepithelioma; S100 Proteins

Three commonly used keratin monoclonal antibodies (MAB)--AE1:AE3, CAM 5.2, and MAK-6--were compared with routinely used cytokeratin antibody. The expression of these antibodies was analyzed in several tissues obtained from clinically normal dogs and in a variety of neoplasms from dogs. Using appropriate enzymatic digestion, paraffin-embedded tissues processed in routine manner retained their typical keratin expression. Differentiated and poorly differentiated epithelial neoplasms, lymphomas, and melanomas were studied by use of the avidin-biotin-peroxidase technique. All 4 of the aforementioned antibodies had similar staining profiles. Of 3 anaplastic carcinomas, 2 had positive reaction to all 4 antibodies. All lymphomas, plasma cell tumors, and amelanotic melanomas had negative reaction to MAK-6, CAM 5.2, AE1:AE3, and cytokeratin MAB. Three basal cell epitheliomas had positive reaction to all 4 antibodies, whereas 1 basal cell tumor with a solid pattern had negative staining reaction. Two carcinoids had negative reaction to all markers and 1 of 2 malignant chemodectomas and 1 transitional cell carcinoma had staining reaction to only AE1:AE3 MAB. Comparing the 4 antibodies, use of AE1:AE3 MAB produced the strongest staining intensity followed by cytokeratin, MAK-6, and CAM 5.2 MAB. All 4 antibodies had low background staining. In conclusion, AE1:AE3 and MAK-6 MAB are as useful as cytokeratin MAB for identification of poorly differentiated epithelial neoplasms in dogs and cats.

Topics: Animals; Antibodies, Monoclonal; Carcinoma; Dog Diseases; Dogs; Immunohistochemistry; Intestine, Small; Keratins; Lung Neoplasms; Neoplasms; Predictive Value of Tests; Urinary Bladder

We report two cases of neuroendocrine carcinomas of the breast displaying unusual histological features: numerous spindle cells and argyrophilic signet-ring cells. Both patients were older than 70 years, and both presented with a bloody nipple discharge. The tumor in both cases was predominantly intraductal. The tumor cells showed little pleomorphism or cytological atypia; because of the presence of spindle cells, benign diagnoses, such as ductal epithelial hyperplasia and intraductal papilloma, were considered for the in situ component. Recognition of the palisading arrangement of the peripheral cells, intracytoplasmic lumina, mitotic figures, and mucin permitted the diagnosis of intraductal carcinoma. Invasive nests composed of identical cells confirmed the diagnosis of malignancy in both cases. Our cases, along with those previously reported, suggest that neuroendocrine carcinoma with mucin production is a distinct breast tumor that usually occurs in older patients who experience bloody nipple discharge. The prognosis may be more favorable than that of the usual type of breast carcinoma. Common histological features include predominantly intraductal growth, an absence of desmoplasia, and low-grade atypia. Awareness of morphological variants of this tumor, such as those reported here, is necessary to avoid erroneous diagnoses.

Topics: Aged; Breast Neoplasms; Carcinoembryonic Antigen; Carcinoma; Female; Humans; Immunohistochemistry; Keratins; Membrane Glycoproteins; Microscopy, Electron; Mucin-1; Mucins; Phosphopyruvate Hydratase; Silver; Staining and Labeling

Comparative immunomorphological study of keratinous proteins was performed in 17 basaliomas, 4 metatypical (MT) and 1 squamous cell carcinomas by means of a spectrum of antibodies to the individual keratins. It is found that cells of MT carcinoma are distinguished from basalioma cells by the absence of keratins N8 and 17 and this may be used for the differential diagnosis of these two tumours. The spectrum of keratins expressed by basalioma cells coincides with that of early stages of hair follicles. Keratin N17 is locally induced in parabasal layers of the morphologically intact epidermis adjacent to the tumour.

Topics: Aged; Carcinoma; Carcinoma, Basal Cell; Carcinoma, Squamous Cell; Diagnosis, Differential; Humans; Keratins; Middle Aged; Neoplasm Proteins; Skin 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

The immunohistochemical reactivities of 69 cases of breast carcinoma were examined on methacarn-fixed, paraffin-embedded sections using eight different monoclonal antibodies which recognize one or a few keratin polypeptides. In the normal breast, the monoclonal antibodies RPN1162, RPN1165 and AE1 stained almost all the luminal cells but not the basal (myoepithelial) cells. The monoclonal antibodies 35BH11, M20, CK5 and CK8.12 stained only a subset of the luminal cells. In contrast, 312C8-1 stained basal cells but not luminal cells. All the tumour specimens reacted with AE1, while over 80% of them also reacted with 35BH11 (57/69), CK5 (57/69) and RPN1165 (55/69); 30% reacted with CK8.12 (21/69) and 16% with RPN1162 (11/69). Basal cell-specific keratin, as defined by 312C8-1, was detected in only 1% of cases (1/69). Monoclonal antibodies to different keratin polypeptides may be of use in the characterization and subdivision of breast cancer.

Topics: Antibodies, Monoclonal; Breast; Breast Neoplasms; Carcinoma; Female; Humans; Immunoenzyme Techniques; Keratins

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

A case is presented of a rhabdomyosarcoma of the oesophagus with a description of the cytology, light microscopy, and immunocytochemical findings and a discussion of spindle cell tumours occurring at this site. Cytologically, large bizarre shaped pleomorphic cells were seen in which desmin was demonstrated in order to confirm the diagnosis after destaining a Papanicolaou stained slide and restaining it with antibody to desmin.

Topics: Carcinoma; Carcinosarcoma; Desmin; Diagnosis, Differential; Esophageal Neoplasms; Humans; Immunohistochemistry; Keratins; Male; Middle Aged; Rhabdomyosarcoma; Sarcoma; Staining and Labeling; Vimentin

Nasopharyngeal carcinoma (NPC) can provoke a local granulomatous reaction which may cause diagnostic difficulty. To further elucidate this possible diagnostic pitfall, 47 cases who were initially diagnosed as tuberculosis or granulomatous inflammation were reexamined; 7 cases (15%) were found to have NPC. In a routine histological stain, residual malignant tumor cells could be identified in 2 cases. In the remaining 5 cases, malignant tumor cells could only be accurately identified after careful examination. Immunohistochemical staining for keratin easily demonstrated the residual tumor cells engulfed in a granulomatous lesion in all 7 cases. This finding suggests that an immunohistochemical stain for keratin is useful and should be performed for any nasopharyngeal biopsy showing granulomatous lesion with suspicion of malignancy, particularly in countries where NPC is prevalent. The overall 5-year survival rate among these NPC patients was 83%, a most favorable outcome, which suggests that a granulomatous reaction may reflect a favorable local host, and a cell-mediated immune response.

Topics: Adult; Carcinoma; Female; Follow-Up Studies; Granuloma; Humans; Immunohistochemistry; Keratins; Male; Middle Aged; Nasopharyngeal Neoplasms; Prognosis

Six cases of spindle cell squamous carcinoma (SCSC) of the oral cavity were studied clinicopathologically, immunohistochemically and ultrastructurally to summarize the clinicopathological features of this rare neoplasm and to discuss the debatable histogenesis of the sarcomatoid component and the differential diagnosis of SCSC. The mean age of the patients was 72 years and the female to male ratio was 1:2. Four of them had a history of irradiation for pre-existing squamous cell carcinoma. One patient died of SCSC. While clinical and histological prognostic factors of SCSC could not be determined, it was shown that radical surgery resulted in good prognosis. The epithelial nature of the sarcomatoid component of SCSC was clearly revealed by a combination of immunohistochemical staining for keratins and electron microscopic demonstration of tonofilament-like filaments and/or desmosome-like structures. Together with electron microscopic evaluation of the tumour cells, immunohistochemical characterization of tumour cells using antibodies to keratin, vimentin, glial fibrillary acidic protein and S-100 protein is very helpful in differentiating SCSC from true spindle cell sarcoma, melanoma and malignant myoepithelioma. In the immunohistochemical differential diagnosis of SCSC, it is important to remember that SCSC should not be ruled out of the differential diagnosis by a positive reaction for vimentin in sarcomatoid tumour cells. Absence of staining for keratin in the sarcomatoid tumour cells does not always exclude SCSC, because some SCSCs show immunoreactivity of keratin in their sarcomatoid components only with some anti-keratin antibodies. Different kinds of anti-keratin antibodies should be applied in the differential diagnosis of SCSC.

Topics: Aged; Aged, 80 and over; Carcinoma; Carcinoma, Squamous Cell; Diagnosis, Differential; Female; Humans; Immunohistochemistry; Keratins; Male; Microscopy, Electron; Middle Aged; Mouth Neoplasms; Vimentin

We report an undifferentiated sweat gland carcinoma of the vulva in an 80-year-old woman. The tumor, which was located in the right labium majus, resembled an epithelioid sarcoma histologically; it had a granulomatous appearance with multiple tumor nodules containing epithelioid tumor cells. The tumor also contained rhabdoid cells; a large cluster of them showed histological features indistinguishable from those of a malignant rhabdoid tumor. Immunohistochemically, the tumor cells reacted not only for epithelial markers such as cytokeratins, EMA, and CEA, which are known to be expressed by epithelioid sarcoma, but also for CA125 and with monoclonal antibodies recognizing sweat gland structures--namely, EKH5 and EKH6. For comparison, two epithelioid sarcomas and two extrarenal malignant rhabdoid tumors were also studied. Of these tumors, only one extrarenal rhabdoid tumor reacted with EKH5, and none reacted for CA125. Electron-microscopic examination of the present tumor showed the presence of discontinuous basal laminae and tonofibril-like structures as well as primitive cell junctions and interdigitating filopodia. From these findings, we conclude that the tumor was an undifferentiated sweat gland carcinoma mimicking an epithelioid sarcoma. Findings in this case support the idea of the diverse histogenesis of extrarenal malignant rhabdoid tumors and indicate that electron microscopy is important for differentiating epithelioid sarcoma from skin adnexal carcinoma.

Topics: Aged; Aged, 80 and over; Antibodies, Monoclonal; Antigens, Tumor-Associated, Carbohydrate; Carcinoembryonic Antigen; Carcinoma; Cell Transformation, Neoplastic; Diagnosis, Differential; Female; Humans; Immunohistochemistry; Keratins; Membrane Glycoproteins; Microscopy, Electron; Mucin-1; Sarcoma; Skin Neoplasms; Sweat Gland Neoplasms; Sweat Glands; Vulvar Neoplasms

Multiparametric, two-color DNA and cell cycle analyses were performed on 112 consecutive mechanically dissociated, ethanol-fixed breast carcinomas using a dual-label method with monoclonal antibodies (CAM 5.2) to cytokeratin (CK) and leukocyte common antigen (LCA) with propidium iodide (PI) staining. There was marked intertumoral variation of CK-positive (range, 3-87%; mean, 40%) and LCA-positive (range, 1-28%; mean, 6.5%) events in DNA histograms. Approximately 70% of DNA aneuploid cells were CK positive. CAM 5.2-stained (avidin-biotin technique) Cytospin preparations correlated with flow cytometric (FCM) detection of CK-positive cells in 15/21 (71%) cases. In each discrepant case, FCM detected greater numbers of CK-positive cells. Cytospin controls of tumor suspensions revealed that cytoplasmic loss was the major cause of decreased CK staining. Synthesis phase fraction (SPF) calculation from CK-gated histograms resulted in kinetic indices (mean ungated, 12.3%, vs. mean CK-gated, 16.8%; P less than .01) with improved statistical correlations with tumor grade and estrogen receptor (ER) status. Differences between ungated vs. CK-gated SPF were greatest in cases having less than 20% CK-positive events (P less than .05). Cases with lower CK staining events generally had higher SPF and were more often high grade (below median CK staining, 61% high grade, vs. above median CK staining, 31% high grade) and ER-negative (below median CK staining, 55% ER negative, vs. above median CK staining, 12% ER negative).(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Antigens, Differentiation; Breast Neoplasms; Carcinoma; DNA, Neoplasm; Evaluation Studies as Topic; Female; Flow Cytometry; Fluorescent Antibody Technique; Humans; Keratins; Receptors, Estrogen

The undifferentiated carcinoma cell line (HMG) was established from a nude mouse tumor which had been produced by transplantation of a intraperitoneal tumor of 27-year-old woman. The HMG cell line has the following biological properties. 1. The HMG cells are round to oval in shape and grow as floating cell aggregates like a rouleau or a cluster of grapes. 2. 100 passages have been carried out over a year, and the population doubling time is about 17 hrs. 3. In the original tumor, keratin and vimentin were expressed simultaneously, in HMG cells, however, only localization of vimentin was confirmed. 4. By chromosomal analysis, over 90% of the cells revealed 46, XX, with no karyological abnormalities, at passage 82. 5. When heterotransplanted into the subcutis of a nude mouse, HMG cells produced a undifferentiated carcinoma resembling the original tumor.

Topics: Adult; Animals; Biomarkers, Tumor; Carcinoma; Cell Division; Culture Media, Serum-Free; Female; Humans; Karyotyping; Keratins; Mice; Neoplasm Transplantation; Ovarian Neoplasms; Tumor Cells, Cultured; Vimentin

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

In the present investigation we show data from our studies of anaplastic human thyroid carcinoma cell lines. The cell lines employed in the study were HTh 7, HTh 74, C 643 and SW 1736, all derived from tumours diagnosed as anaplastic thyroid carcinomas. Northern blot analysis with four different thyroid specific cDNA probes showed a varying pattern of expression. Thyroglobulin mRNA was found in three of the carcinoma cell lines, although the signal was very weak compared to the expression in tissue from a toxic goitre, used as positive control. Interestingly, two of the cell lines expressed the receptor for thyrotropin, but none of them contained thyroperoxidase mRNA. Three of the cell lines expressed mRNA for receptors platelet-derived growth factor, PDGFR-alpha and/or PDGFR-beta type. Messenger RNA of a thyroid specific transcription factor, TTF-1, known to regulate the normal function of thyrocytes, was found in the toxic goitre but not in the anaplastic thyroid carcinoma cell lines. Lack of expression of TTF-1 might the immediate cause of the anaplastic phenotype, considering the possibility that TTF-1 functions as a master regulatory gene in thyroid cell differentiation.

Topics: Blotting, Northern; Carcinoma; DNA Probes; Fluorescent Antibody Technique; Gene Expression; Humans; Keratins; Nuclear Proteins; Receptors, Platelet-Derived Growth Factor; Receptors, Thyrotropin; RNA, Messenger; RNA, Neoplasm; Thyroglobulin; Thyroid Neoplasms; Thyroid Nuclear Factor 1; Transcription Factors; Tumor Cells, Cultured

Serous surface carcinoma (SSC) of the peritoneum is defined as a primary tumor histologically indistinguishable from serous carcinoma of the ovary, diffusely involving the peritoneal surface but sparing or only superficially invading the ovaries. In this study of 22 cases of SSC, it was found that the main clinical manifestations of SSC were abdominal pain and enlargement. In most cases, SSC evenly involved the entire mesothelial surface but rarely was predominant in or even limited to the pelvis. It frequently invaded the submesothelium, but deep invasion into abdominal and pelvic organs or local metastasis was rare, and distant metastasis was not seen at presentation. Microscopically, SSC was a high-grade tumor frequently showing high mitotic rate, psammomas bodies, and necrosis. The tumor was usually contiguous with hyperplastic mesothelium on either ovarian surface or other locations. Tumor cells in all cases except one showed cytoplasmic or surface neutral or acidic mucin or both. Tumor cells stained positive for keratin (100% of cases), epithelial membrane antigen (100%), Leu-M1 (45%), B72.3 (85%), vimentin (35%), and carcinoembryonic antigen (25%). Electron microscopic studies of six cases showed epithelial differentiation in each. Seven patients (32%) were alive with no clinical disease at 3 to 31 months, one patient (4%) was alive with extensive local disease at 24 months, 11 patients (50%) died almost exclusively of local recurrence at 1 to 70 months, and three patients (14%) died of operative complications. It is concluded that SSC arises from peritoneal mesothelium but has epithelial phenotype. It can be morphologically differentiated from other conditions with similar laparotomy findings, such as malignant mesothelioma, benign papillary mesothelioma, cystic mesothelioma, and benign or borderline peritoneal serous tumors. The prognosis of SSC is poor, and most patients die of uncontrollable local disease.

Topics: Adult; Aged; Biomarkers, Tumor; Carcinoma; Female; Humans; Keratins; Lymphatic Metastasis; Membrane Glycoproteins; Middle Aged; Mucin-1; Ovarian Neoplasms; Peritoneal Neoplasms

Since its initial description, microcystic adnexal carcinoma (MAC) of the skin has been controversial. In particular, it features keratin production of the type seen in some pilar neoplasms , and has been thought to pursue partial follicular differentiation. Diagnostically, MAC may be difficult to separate from desmoplastic trichoepithelioma (DTE) in superficial biopsy specimens. We studied 12 MACs, 22 malignant eccrine acrospiromas, 7 sudoriferous syringometaplasias, 6 syringomas, 5 DTEs, and 40 other benign pilar neoplasms immunohistochemically. Paraffin sections and antibodies to "hard" (pilar) keratins. epithelial membrane antigen (EMA), carcinoembryonic antigen (CEA), Leu-M1, and S100 protein were employed. The MACs exhibited reactivity for hard keratin subclasses AE 13 and AE 14, EMA, CEA, and Leu-M1. Desmoplastic trichoepitheliomas expressed positivity for AE 14, EMA, and Leu-M1 focally, but lacked the other specified markers. Syringomas and malignant acrospiromas displayed EMA, CEA, and AE 14 reactivity, and 5 syringometaplastic lesions were AE 14-reactive. Benign pilar tumors aside from DTEs were reactive only for AE 13, AE 14, or both. These data indicate that MAC exhibits an immunophenotype that is a "hybrid" of those seen in pure sweat glandular and follicular neoplasms, and suggest that it may indeed show combined pilar and sudoriferous differentiation. Based on these results, it also appears that immunohistochemical analysis may be useful in the diagnostic separation of MAC and DTE.

Topics: Adenoma, Sweat Gland; Adult; Antigens, CD; Antigens, Differentiation, Myelomonocytic; Antigens, Neoplasm; Biomarkers, Tumor; Carcinoembryonic Antigen; Carcinoma; Female; Humans; Immunohistochemistry; Keratins; Lewis X Antigen; Male; Membrane Glycoproteins; Middle Aged; Mitosis; Mucin-1; Skin; Skin Neoplasms

We present a new method for detection of micrometastases to axillary lymph nodes and estrogen receptor determination. Cellular suspensions from primary infiltrating ductal breast carcinoma or level I axillary lymph nodes of patients who underwent mastectomies were obtained, by loosely grinding fresh tumors or lymph nodes through a grid and then transferring the matrix to a slide using cytocentrifugation. Tumor samples were analyzed for estrogen receptor status using an immunocytochemical kit and compared with the dextran-coated charcoal method. Thirty-eight of 48 correlated (20 were estrogen positive, and 18 were estrogen negative). Seven of 46 were estrogen positive while results from the dextran-coated charcoal method were estrogen negative. One of 46 was estrogen negative, while the results from the dextran-coated charcoal method were estrogen positive. Lymph node slide preparations were stained to detect tumor cells using antikeratin monoclonal antibodies. Three of 8 node-negative patients were found to have micrometastases. Four of 15 node-positive patients had additional nodes with tumor. Our method combines the advantages of serial sectioning and immunohistochemical staining.

Topics: Antibodies, Monoclonal; Axilla; Breast Neoplasms; Carcinoma; Carcinoma, Intraductal, Noninfiltrating; Female; Humans; Keratins; Lymph Nodes; Lymphatic Metastasis; Mastectomy; Receptors, Estrogen; Staining and Labeling

We present a patient with microcystic adnexal carcinoma. The lesion was an indurated plaque on the skin of the right upper lip of a 58-year-old woman which was slowly growing during 27 years. Carcinoembryonic antigen was immunoreactive in the luminal contents of the tumor ducts and in the cytoplasm of cells surrounding ducts. S-100 protein was positive in the cytoplasm of a few cells at the lower dermis. These observations suggested that this tumor was related to sweat glands. Furthermore, electron microscopy revealed that tumor cells had features of eccrine ductal cells. These observations confirm that this tumor appeared at least capable of eccrine duct differentiation.

Topics: Carcinoembryonic Antigen; Carcinoma; Female; Humans; Immunohistochemistry; Keratins; Lip Neoplasms; Microscopy, Electron; Middle Aged; Time Factors

Using intact ethanol-fixed cytokeratin monoclonal (CAM 5.2) and propidium iodide dual-stained cells, we have performed two-color multiparametric flow cytometric (FCM) DNA analysis and S-phase fraction (SPF) determination on 165 mechanically dissociated breast carcinomas. Sixty-seven patients were axillary node positive, 33 patients node negative; 59 had biopsy only and in 8, FCM was performed on tissue from metastatic lesions. Overall, 62% of the tumors contained aneuploid cell populations. Abnormal cellular DNA content (aneuploidy) was significantly correlated with high nuclear grade (p less than 0.001), lack of estrogen receptors (p less than 0.001), presence of vascular invasion (p less than 0.04), high histologic grade (p less than 0.04), and tumor size (p less than 0.03) but not with patient age (p greater than 0.07) or axillary node status (p greater than 0.50). SPF values derived from ungated histograms had a positively skewed frequency distribution (range 2 to 30%, N = 152) with an overall median of 11% (diploid, 8.9%; aneuploid, 15.7%). Higher SPF values were significantly correlated with aneuploidy (p less than 0.001), presence of necrosis (p less than 0.001), lack of estrogen receptor (p less than 0.0001), high nuclear grade (p less than 0.001), vascular invasion (p less than 0.003), tumor size (p less than 0.006), and high histologic grade (p less than .004) but not the presence of lymph node metastases (p greater than 0.56). Mean SPF values were significantly higher when calculated from cytokeratin gated DNA histograms (14.1% versus 11.5%, p less than 0.001), probably due to exclusion of contaminating stromal/inflammatory cells; and significantly lower when calculated from debris subtracted histograms (7.8% versus 11.4%). Cytokeratin gated and debris subtracted SPF values both had a greater degree of correlation than ungated values with clinicopathologic factors of known prognostic significance.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Breast Neoplasms; Carcinoma; Cell Cycle; DNA; Flow Cytometry; Humans; Interphase; Keratins; Ploidies

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

Immunohistochemical study of cervical carcinoma used EE21-06d monoclonal antibodies which identify five cytokeratin polypeptides inherent in the squamous epithelium. PAP-method and reaction of immunofluorescence were employed. Initial stages of squamous cell carcinoma invasion were characterized by bleaching or complete cell discoloring of most tumor cells. However, in deeply invading tumors, the share of intensively stained cells was markedly increased. The results point to expression of different cytokeratins or cell clones replacement with tumor progression. The peculiarities of cytokeratin distribution may serve to determine the degree of invasion and differentiation of tumor cells.

Topics: Adult; Antibodies, Monoclonal; Carcinoma; Carcinoma, Squamous Cell; Cervix Uteri; Female; Fluorescent Antibody Technique; Humans; Immunoenzyme Techniques; Keratins; Middle Aged; Uterine Cervical Neoplasms

Topics: Carcinoma; Female; Humans; Keratins; Uterine Cervical Neoplasms

A monoclonal antibody (mAb) directed against the cytokeratin (CK) polypeptide no. 18 specifically expressed in cells derived from simple epithelia was used to detect epithelial tumor cells in bone marrow aspirates. Of 156 patients with colorectal carcinoma, 42 presented with cells at the time of primary surgery. The incidence of positive findings varied considerably with the size and the localization of the primary tumor, the involvement of regional lymph nodes, and the presence of clinically manifest metastases. Applying a sensitive double-staining procedure, we could demonstrate that epithelial cells in bone marrow showed a heterogeneic expression of receptors for epidermal growth factor (EGF-R) and transferrin (Tf-R) as well as of the proliferation-associated Ki67 antigen. Also human leukocyte antigen (HLA) class I antigens differed widely in their expression on the CK-positive cells. Clinical follow-up studies on 85 patients showed a significantly higher relapse rate in patients presenting with CK-positive cells in their bone marrow at the time of primary surgery. Twenty-three patients were monitored for the presence or absence of CK-positive cells in bone marrow over time. The majority of monitored patients (18 of 23) exhibited a constant pattern of immunocytochemical findings during the time of observation. Thus, the technique may be useful in identifying high-risk patients as well as in monitoring adjuvant therapeutic trials.

Topics: Antibodies, Monoclonal; Antigens, Surface; Bone Marrow; Carcinoma; Colorectal Neoplasms; ErbB Receptors; Histocompatibility Antigens Class I; Humans; Immunohistochemistry; Keratins; Ki-67 Antigen; Phenotype; Prognosis; Receptors, Transferrin; Recurrence; Risk Factors; Survival Rate

Topics: Antibodies, Monoclonal; Breast Neoplasms; Carcinoma; Humans; Keratins; Lymphatic Metastasis

Topics: Carcinoma; Carcinoma, Squamous Cell; Humans; Keratins; Molecular Weight

A series of adrenal cortical adenomas (ACA) and carcinomas (ACC), as well as normal adrenal cortex have been studied by a panel of 11 antibodies to characterize antigenic changes that may distinguish these morphologically similar entities. Normal adrenal cortex and ACA express low-molecular weight cytokeratin intermediate filaments. However, none of the six primary or seven metastatic ACCs were found to express detectable levels of cytokeratins. In contrast, vimentin was seen in all ACCs studied and was heterogeneously expressed by ACAs. However, its expression was usually confined to stromal elements of the normal adrenal cortex. We conclude that adrenal cortical cells undergo characteristic changes in intermediate filament expression during the process of neoplastic conversion and malignant transformation. Undetectable expression of cytokeratins and strong expression of vimentin is associated with malignant adrenal cortical lesions. In addition, we examined the antigenic phenotype of a series of primary renal cell carcinomas (RCC). Renal cell carcinomas express cytokeratins, while ACCs do not. The majority of primary RCCs express Lewis blood group isoantigens (most commonly Lewis X), while ACAs and ACCs do not. The panel of antibodies described here may help to distinguish morphologically similar lesions of like histogenesis (ACAs vs. ACCs) and lesions of different histogenesis (adrenal vs. renal) on the basis of their composite antigenic phenotypes.

Topics: Adenoma; Adrenal Cortex; Adrenal Gland Neoplasms; Antigens; Carcinoma; Cell Transformation, Neoplastic; Humans; Immunohistochemistry; Isoantigens; Keratins; Kidney Cortex; Kidney Neoplasms; Vimentin

Four new cases of ectopic hamartomatous thymoma are presented. The tumor occurred either superficially or deep in the area of the sternoclavicular joint and consisted of solid islands of squamous epithelium which blended with spindled cells. Cysts lined by squamous epithelium, small glands, and fat also occurred in variable amounts. Both the spindled and epithelial regions of the tumor expressed keratin and muscle actin, but neither desmin nor S100 protein. The tumor probably originates from thymic anlage associated with the third pharyngeal pouch (thymus III), although origin from other structures such as thymus IV and the cervical sinus of His are discussed. Our experience indicates that the large size and extreme cellularity of the spindled portion of some tumors may result in the mistaken diagnosis of sarcoma.

Topics: Actins; Adult; Aged; Carcinoma; Desmin; Diagnosis, Differential; Hamartoma; Humans; Immunohistochemistry; Keratins; Male; Middle Aged; S100 Proteins; Sarcoma, Synovial; Thymoma; Thymus Neoplasms

Topics: Animals; Carcinoma; Dog Diseases; Dogs; Female; Immunoenzyme Techniques; Keratins; S100 Proteins; Salivary Gland Neoplasms; Salivary Glands; Salivary Glands, Minor; Tongue Neoplasms

These two cases of bladder tumours with an unusual histological appearance were observed at Hôpital Saint-Louis in 1988. They contained two cellular components: the usual epithelial type and a spindle cell type. Immunohistochemistry performed in order to identify the various cell contingents established the diagnoses of carcinosarcoma and spindle cell carcinoma and emphasised the differences and similarities between these two entities, which we believe can be differentiated.

Topics: Aged; Aged, 80 and over; Carcinoma; Carcinosarcoma; Desmin; Female; Humans; Immunohistochemistry; Keratins; Male; Myoglobin; Urinary Bladder Neoplasms; Vimentin

A case of spindle cell carcinoma of the breast in association with myoepithelial cell hyperplasia is presented. Immunocytochemistry demonstrated labelling of tumour cells for cytokeratin, vimentin and S-100 protein. Electronmicroscopy showed desmosomes and bundles of tonofilaments as well as fine filaments in the cytoplasm. The findings in the present case point to the metaplastic spindle cell nature of squamous carcinoma of the breast. The possible role of myoepithelial cells in the origin of the spindle cell component is discussed.

Topics: Breast Neoplasms; Carcinoma; Female; Humans; Immunohistochemistry; Keratins; Middle Aged; S100 Proteins; Vimentin

One hundred twenty-one cases of anaplastic carcinoma of the thyroid treated at M.D. Anderson Cancer Center, Houston, were reviewed. Anaplastic carcinoma is a rapidly growing neoplasm with a dismal prognosis. The mean survival of our patients was 7.2 +/- 10 months. A significant percentage of our patients (35%) had areas of well-differentiated thyroid carcinoma elsewhere, supporting the hypothesis that anaplastic thyroid carcinoma arises from preexisting well-differentiated thyroid carcinoma. Twenty-four of 30 tumors analyzed (84%) stained for keratin, 28 (93.3%) stained for vimentin, and ten (33%) stained for epithelial membrane antigen. Younger patients lived longer than older patients, and patients whose disease was earlier-stage at presentation responded better than patients with metastases at presentation. Radical surgery alone did not significantly increase survival duration over less radical surgery. The role of multimodality therapy needs further evaluation.

Topics: Adult; Aged; Aged, 80 and over; Antigens, Neoplasm; Carcinoembryonic Antigen; Carcinoma; Female; Humans; Immunoenzyme Techniques; Keratins; Male; Membrane Glycoproteins; Middle Aged; Mucin-1; Retrospective Studies; Survival Analysis; Thyroglobulin; Thyroid Neoplasms; Vimentin

Six cases of conjunctival spindle cell carcinoma, a rare variant of squamous cell carcinoma, were studied. The median age of the three men and three women was 63.5 years. The tumors appeared as a single nodule in some patients or diffusely involved the conjunctiva in others. Two of the four individuals with intraocular extension presented with phthisis bulbi. Polyclonal antikeratin antibody was helpful and gave the most consistent results when compared with monoclonal antikeratin antibodies, AE1/3 and PKK1. The electron microscopic study of four lesions also established the epithelial nature of the tumor cells. Intracytoplasmic tonofilaments and a few desmosomes were present. Histopathologically, this variant of squamous cell carcinoma is difficult to distinguish from other spindle cell tumors, and this study demonstrates the value of immunohistochemistry and electron microscopy in supporting the correct diagnosis.

Topics: Adult; Aged; Aged, 80 and over; Antibodies, Monoclonal; Carcinoma; Conjunctival Neoplasms; Desmin; Female; Humans; Immunoenzyme Techniques; Keratins; Male; Middle Aged; S100 Proteins

Normal and well differentiated neoplastic canine tissues were immunohistochemically stained for keratin, vimentin and desmin intermediate filament proteins using commercially available monoclonal antibodies. Keratin was detected in 56 of 57 carcinomas, vimentin in 59 of 62 sarcomas and desmin in three of four muscle cell tumors. Most normal and neoplastic tissues expressed only one type of intermediate filament; exceptions were one hemangiosarcoma and one pulmonary carcinoma in which there was coexpression of vimentin and keratin proteins. Since immunohistochemical detection of intermediate filaments has tissue-specific distribution in the majority of well differentiated canine neoplasms, these stains may be useful in the differential diagnosis of anaplastic canine tumors. However, the monoclonal antibodies to cytokeratin which were tested in this study failed to detect intermediate filaments in liver, pancreas and salivary glands which suggests that these antibodies may also be unable to detect epithelial tumors derived from these tissues. In addition, in nine neoplasms, the normal tissues adjacent to neoplastic cells failed to stain for the intermediate filament normally expressed. When this occurs, evaluation of intermediate filament expression is invalid for the determination of tissue of origin of the neoplastic cells.

Topics: Animals; Antibodies, Monoclonal; Carcinoma; Desmin; Dog Diseases; Dogs; Immunohistochemistry; Intermediate Filament Proteins; Keratins; Sarcoma; Vimentin

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

The results of our study may be summarized as follows: 1. Medullary carcinomas of the thyroid are derived from the C cells of the gland and are characterized by strong histologic and cytologic pleomorphism with inconstant stromal amyloid deposits. 2. The decisive morphodiagnostic criterion is immunohistochemical evidence of calcitonin coinciding with negative TG reactivity. 3. In addition to obligatory calcitonin expression, MCs may show variable synthesis of several polypeptids and biogenic (?) amines. 4. The varying immunoreactivity patterns are not related to the clinical behavior of the respective tumors. 5. Leu-M-1 antigen, a monocyte-granulocyte marker known to express in Reed-Sternberg cells and in certain nonhemopoietic neoplasms, can also be demonstrated in MCs. Leu-M-1 immunoreactivity was found to correlate significantly with an unfavorable course. Thus, the introduction of immunostaining for Leu-M-1 in cases of thyroid carcinoma may provide significant prognostic information for these patients.

Topics: Antigens, Differentiation, Myelomonocytic; Carcinoembryonic Antigen; Carcinoma; Humans; Immunohistochemistry; Keratins; Thyroid Neoplasms

The authors studied by immunohistochemistry the intermediate filament (IF) protein profile of 66 frozen samples of breast tissue, including normal parenchyma, all variants of fibrocystic disease (FCD), fibroadenomas, cystosarcoma phylloides, and ductal and lobular carcinomas. Monoclonal antibodies (MAbs) to cytokeratins included MAb KA 1, which binds to polypeptide 5 in a complex with polypeptide 14 and recognizes preferentially myoepithelial cells; MAb KA4, which binds to polypeptides 14, 15, 16 and 19; individual MAbs to polypeptides 7, 13, and 16, 17, 18, and 19, and the MAb mixture AE1/AE3. The authors also applied three MAbs to vimentin (Vim), and three MAbs to glial filament protein (GFP). Selected samples were studied by double-label immunofluorescence microscopy and by staining sequential sections with some of the said MAbs, an MAb to alpha-smooth muscle actin, and well-characterized polyclonal antibodies for the possible coexpression of diverse types of cytoskeletal proteins. Gel electrophoresis and immunoblot analysis also were performed. All samples reacted for cytokeratins with MAbs AE1/AE3, although the reaction did not involve all cells. Monoclonal antibody KA4 stained preferentially the luminal-secretory cells in the normal breast and in FCD, whereas it stained the vast majority of cells in all carcinomas. Monoclonal antibody KA1 stained preferentially the basal-myoepithelial cells of the normal breast and FCD while staining tumor cell subpopulations in 4 of 31 carcinomas. Vimentin-positive cells were found in 8 of 12 normal breasts and in 12 of 20 FCD; in most cases, Vim-reactive cells appeared to be myoepithelial, but occasional luminal cells were also stained. Variable subpopulations of Vim-positive cells were noted in 9 of 20 ductal and in 1 of 7 lobular carcinomas. Glial filament protein-reactive cells were found in normal breast lobules and ducts and in 15 of 20 cases of FCD; with rare exceptions, GFP-reactivity was restricted to basally located, myoepithelial-appearing cells. Occasional GFP-reactive cells were found in 3 of 31 carcinomas. Evaluation of sequential sections and double-label immunofluorescence microscopy showed the coexpression of certain cytokeratins (possibly including polypeptides 14 and 17) with vimentin and alpha-smooth muscle actin together with GFP in some myoepithelial cells. The presence of GFP in myoepithelial cells was confirmed by gel electrophoresis and immunoblotting. Our results indicate that coexpression

Topics: Adenofibroma; Antibodies, Monoclonal; Breast; Breast Neoplasms; Carcinoma; Carcinoma, Intraductal, Noninfiltrating; Female; Fibrocystic Breast Disease; Fluorescent Antibody Technique; Glial Fibrillary Acidic Protein; Humans; Immunoenzyme Techniques; Keratins; Phyllodes Tumor; Reference Values; Vimentin

We report a 58-year-old woman with proliferating trichilemmal cyst (PTC), from which a spindle cell carcinoma arose. The tumor on her scalp had been removed at another hospital. Histological examination had revealed almost typical features of PTC. However, the case showed a partial transformation to spindle cell carcinoma, and transition zones between squamous epithelium and spindle cells were present. Three months after histologic examination, the patient came to us for the treatment of recurrent tumor. Despite surgical resection, the patient died as a result of distant metastases. Histologically, the recurrent tumor was composed of only spindle-shaped tumor cells. We describe the first example of this uncommon condition.

Topics: Carcinoma; Diagnosis, Differential; Epidermal Cyst; Female; Humans; Immunohistochemistry; Keratins; Lung Neoplasms; Middle Aged; Skin Diseases; Skin Neoplasms

Mammary adenocarcinoma was diagnosed in a 3-year-old Landrace sow with prolonged infertility, anorexia and progressive emaciation after parturition. Gross examination confirmed a large tumour in the left anterior mammary gland with metastatic nodules on the pleura and in the parenchyma of lung. Microscopically, the tumour consisted mainly of solid adenomatous proliferations with numerous mitotic figures. Irregular glandular structures, solid nests of polygonal tumour cells without polarity and nests consisting of glandular, cribriform and solid portions were evident in dense fibrous stroma. Immunostaining revealed keratin in the tumour cells.

Topics: Animals; Carcinoma; Female; Immunohistochemistry; Keratins; Lung Neoplasms; Mammary Neoplasms, Animal; Swine; Swine Diseases

We examined pulmonary carcinomas with prominent sarcoma-like lesions both clinicopathologically and immunohistochemically. Grossly, two tumors had predominantly endobronchial growths, four bulky parenchymal growths, and two endobronchial, parenchymally mixed growths. In these eight patients, six tumors were completely resected, one patient was given irradiation only, and one patient died in the early postoperative period. On the basis of specific differentiation of the sarcoma-like lesions, the tumors were separated into three groups: two with "true" sarcoma differentiated into soft tissues such as striated muscle or osteoid tissue; three with a fibromatous sarcoma resembling atypical pseudosarcomatous stroma; and three with spindle cell carcinoma with evidence of epithelial differentiation. The prognosis was poor, and tumors with specific differentiation into rhabdomyosarcoma, chondrosarcoma, or spindle cell carcinoma progressed more rapidly than did those with a fibromatous sarcoma. Because the fibromatous sarcoma-like lesions were found to relate to a longer survival time for the patients, we wish to emphasize that a distinction of sarcomatous components should be made with regard to assessing the prognosis of pulmonary carcinoma with sarcoma-like lesions.

Topics: Aged; Carcinoembryonic Antigen; Carcinoma; Carcinosarcoma; Female; Humans; Immunohistochemistry; Keratins; Lung Neoplasms; Male; Membrane Glycoproteins; Middle Aged; Mucin-1; Secretory Component; Vimentin

Monoclonal antibodies to keratins No. 8 and 17 specific for lining epithelium and myoepithelium of the mammary gland, respectively, as well as to basement membrane laminin, entactin, collagen type IV and heparan sulfate proteoglycan were used to the immunohistochemical analysis of 77 benign and malignant human breast lesions and that of 38 cases in which an intraoperative biopsy diagnosis was difficult. Morphologically similar benign and malignant proliferations were distinguished by keratin expression. In benign lesions both keratins were present, while in malignant ones only keratin No. 8 was expressed. Basement membranes associated with a myoepithelial layer were intact in benign lesions and in situ structures, but they were absent around the vast majority of invasive tumor foci. Basement membrane loss was important in differential diagnosis of benign sclerosing adenosis and cystadenopapilloma from invasive tubular and papillary carcinoma, respectively. Diagnosis of microinvasion in ductal and lobular carcinoma was much easier when combination of antibodies to keratins and basement membrane proteins was used.

Topics: Antibodies, Monoclonal; Basement Membrane; Biopsy; Breast; Breast Neoplasms; Carcinoma; Diagnosis, Differential; Female; Fluorescent Antibody Technique; Humans; Immunohistochemistry; Intermediate Filament Proteins; Keratins; Membrane Proteins

Histological review and immunohistochemical studies of 8 cases of medullary carcinoma were carried out by using ABC technique. The results showed 8 calcitonin positive cases, 3 Somatostatin positive cases, 7 NSE positive cases, 5 CEA positive cases and 8 keratin positive cases. In addition, histogenesis, histological characteristics and the evaluation of immunohistochemistry in diagnosis of thyroid medullary carcinoma are discussed.

Topics: Apudoma; Biomarkers, Tumor; Calcitonin; Carcinoma; Humans; Immunohistochemistry; Keratins; Thyroid Neoplasms

We report two cases of osteoclast-like giant cell tumour of urinary bladder associated with papillary transitional cell tumours. Both cases were morphologically identical to giant cell tumour of bone. The giant cells stained strongly for acid phosphatase which was resistant to tartrate digestion, a staining reaction typical of osteoclasts. In view of the ability of urinary bladder to induce metaplastic and neoplastic bone, we believe that these tumours may represent extraosseous giant cell tumours of bone.

Topics: Acid Phosphatase; Aged; Bone Neoplasms; Carcinoma; Carcinoma, Transitional Cell; Diagnosis, Differential; Giant Cell Tumors; Humans; Immunohistochemistry; Keratins; Male; Membrane Glycoproteins; Mucin-1; Muramidase; Osteoclasts; S100 Proteins; Urinary Bladder Neoplasms; Vimentin

Immunohistochemical staining of cell lines derived from human liver tumours showed that five cell lines derived from hepatocellular carcinoma (HCC) and hepatoblastoma were stained positively with monoclonal keratin antibodies, CK-5 (Ker-18-specific) and KL-1 (broad specificity), but not with CK-7 (Ker-7-specific). On the other hand, four carcinoma cell lines derived from the biliary system were stained positively with not only CK-5 and KL-1, but also CK-7.

Topics: Albumins; Alkaline Phosphatase; alpha-Fetoproteins; Antibodies, Monoclonal; Bile Duct Neoplasms; Biomarkers, Tumor; Carcinoma; Carcinoma, Hepatocellular; Gallbladder Neoplasms; Humans; Keratins; Liver Neoplasms; Neoplasm Proteins; Tumor Cells, Cultured

13 cases of salivary glands and 30 of salivary gland tumors were studied by ABC method with 6 monoclonal antibodies to intermediate filaments and one to microfilament. The results showed that the distribution of intermediate filaments in salivary glands had their regularity. According to the reaction to the antibodies, these tumors could be divided into 3 groups and 3 subgroups. The findings also suggested that in the salivary gland tissue the epithelial cells which mainly contained the 54 Kd keratin and the epithelial cells which mainly contained 57/66 Kd keratin were the origin of the salivary gland tumors. The actin-positive myoepithelial cells might play a role in some tumor formation.

Topics: Actins; Adenoma, Pleomorphic; Antibodies, Monoclonal; Carcinoma; Carcinoma, Adenoid Cystic; Humans; Immunohistochemistry; Intermediate Filaments; Keratins; Parotid Gland; Salivary Gland Neoplasms; Salivary Glands

Normal human foreskin keratinocytes cotransfected with the neomycin resistance gene and recombinant human papillomavirus (HPV) DNAs (types 16, 18, 31, and 33) that have a high or moderate association with cervical malignancy acquired immortality and contained integrated and transcriptionally active viral genomes. Only transcripts from the intact E6 and E7 genes were detected in at least one cell line, suggesting that one or both of these genes are responsible for immortalization. Recombinant HPV DNAs with low or no oncogenic potential for cervical cancer (HPV1a, -5, -6b, and -11) induced small G418-resistant colonies that senesced as did the nontransfected cells. These colonies contained only episomal virus DNA; therefore, integration of HPV sequences is important for immortalization of keratinocytes. This study suggests that the virus-encoded immortalization function contributes to the pathogenesis of cervical carcinoma.

Topics: Carcinoma; Cell Transformation, Viral; Cells, Cultured; DNA, Viral; Electrophoresis, Agar Gel; Epidermal Cells; Epidermis; Female; Humans; Keratins; Papillomaviridae; Plasmids; RNA, Messenger; RNA, Viral; Transfection; Uterine Cervical Neoplasms

Sixteen choroid plexus (CP) tumors in 12 male and four female adult dogs were analyzed microscopically. Tumors were in the lateral (six), third (six), and fourth (four) ventricles. The average age of the dogs was 6 years. Tumors were classified by the following criteria: 1) choroid plexus papilloma (CPP), which resembled normal choroid plexus and had low mitotic activity; 2) choroid plexus papilloma (CPP), which resembled normal choroid plexus and had low mitotic activity; 2) choroid plexus papilloma with atypical features (atypical CPP), which had increased cellular density, nuclear atypia, two to four mitoses per 40x microscopic field, necrosis, and infiltration of the brain parenchyma and/or leptomeninges; and 3) choroid plexus carcinoma (CPC), which had marked nuclear atypia, poorly formed papillae, greater than four mitoses per 40x microscopic field, abnormal mitotic figures, and/or extraneural metastasis. The 16 tumors were classified either as CPP or atypical CPP (none as CPC). Statistically significant associations between brain infiltration and necrosis and atypical CPP were identified. Immunohistochemical studies in 11 tumors demonstrated staining for keratin in three tumors, two of which also reacted with carcinoembryonic antigen (CEA). There was no immunoreactivity with glial fibrillary acidic protein or epithelial membrane antigen. Choroid plexus from one of three control dogs stained focally for cytokeratin only. It is concluded that normal choroid plexus and CP tumors in the dog express epithelial, but not glial differentiation.

Topics: Animals; Carcinoembryonic Antigen; Carcinoma; Cerebral Ventricle Neoplasms; Choroid Plexus; Dog Diseases; Dogs; Ependymoma; Female; Immunoenzyme Techniques; Immunohistochemistry; Keratins; Male

Archival paraffin sections from normal salivary gland tissue and salivary gland neoplasms were stained by immunoperoxidase technique with a well characterized cytokeratin antibody (PKK1). In normal parotid tissue, myoepithelial cells and peripheral cells of larger ducts were selectively stained. In pleomorphic adenomas, most cells were stained, the staining being somewhat stronger towards the duct lumina. In basal cell adenomas, only cells adjacent to the duct lumina were stained where a differentiation of cells into peripheral and ductal was seen. In adenolymphomas basal cells were stained, and in oncocytomas small elongated cells reacted with the PKK1 antibody. Only a few duct cells in an acinic cell carcinoma were reactive and in mucoepidermoid carcinoma, peripheral epidermoid cells were strongly stained. In adenoid cystic carcinoma, mostly duct cells were stained whereas the peripheral ones remained unstained. Although the intermediate filament protein expression is very stable during tumorigenesis, the staining with the presently used monoclonal antibody in salivary gland neoplasms differed markedly from what could be expected according to current views on the participation of this cell type. This supports our view that cells in tumors should be characterized on the basis of their staining, i.e. state of differentiation and not on their presumed histogenesis.

Topics: Adenoma; Antibodies, Monoclonal; Carcinoma; Humans; Immunoenzyme Techniques; Keratins; Salivary Gland Neoplasms

A 51-year-old man with microcystic adnexal carcinoma of the face is reported. In addition to extensive soft tissue invasion by the cancer, there was direct bone invasion into the marrow of the mandible as well as perineural spread along the mental and inferior alveolar nerves. This represents the first case of microcystic adnexal carcinoma with documented bone invasion. Recognition of the aggressive nature of this cancer with potential for invasion into the skull is important for proper evaluation and treatment.

Topics: Bone Marrow; Carcinoma; Cysts; Cytoplasm; Facial Neoplasms; Humans; Keratins; Lip Neoplasms; Male; Mandibular Neoplasms; Middle Aged; Neoplasm Invasiveness; Neoplasm Recurrence, Local

Using immunohistochemistry, the distribution patterns of basement membrane components type VII collagen (monoclonal antibody LH7.2), type IV collagen, and laminin were investigated in normal and malignant human breast tissue and compared with that of keratin 14 (monoclonal antibody LL002), which is expressed only by the basal (myoepithelial) cells in the secretory epithelia of the mammary gland. In normal breast tissue as well as in intraductal carcinomas, a more or less continuous basement membrane was observed at the epithelial stromal interface. Unlike laminin and type IV collagen, type VII collagen was not detected in the basement membrane of blood vessels. The keratin 14 antibody stained the basal cell layer of normal ducts and ducts with in situ cancer. In 85% of the invasive carcinomas no basement membrane or basal cells were detected. In 13 cases, however, laminin, type IV collagen, and/or type VII collagen were detected around tumor nests and individual tumor cells. Five of these tumors also showed a positive reaction with the keratin 14 antibody. In five cases keratin 14 expression was found without detectable basement membrane components. It is concluded that 18 of 103 invasive ductal breast carcinomas examined in this study exhibit a basal cell phenotype as determined from the expression of keratin and the deposition of basement membrane components.

Topics: Basement Membrane; Biomarkers; Breast Neoplasms; Carcinoma; Carcinoma in Situ; Carcinoma, Intraductal, Noninfiltrating; Humans; Immunohistochemistry; Keratins; Neoplasm Invasiveness; Reference Values; Tissue Distribution

A case of undifferentiated malignant tumor of the stomach is reported. The immunohistochemistry of biopsy specimens pointed to a diagnosis of carcinoma, the tumor cells being cytokeratin positive and leukocyte common antigen (LCA) negative. After resection, however, histopathologic results showed that the tumor was a large cell lymphoma with plasmablastic differentiation. A new immunohistologic study confirmed, on the one hand, the diagnosis of lymphoma with its monotypic character IgA kappa and, on the other, positivity with three different cytokeratins of the lymphoma cells and their negativity with LCA. The aberrant immunophenotyping of this lymphoma is exceptional and must not undermine the recognized usefulness of LCA and cytokeratin, which both are basic antibody markers of immunohistochemistry in undifferentiated malignant neoplasms.

Topics: Antigens, Differentiation; Biomarkers, Tumor; Carcinoma; Diagnostic Errors; Female; Histocompatibility Antigens; Humans; Immunoenzyme Techniques; Keratins; Leukocyte Common Antigens; Lymphoma; Middle Aged; Stomach Neoplasms

A carcinoma of the renal pelvis characterized histologically by a spindle cell sarcomatoid morphological growth pattern was studied by electron microscopy and immunohistochemical techniques. Ultrastructural examination revealed abundant perinuclear cytoplasmic tonofilament bundles in association with prominent rough endoplasmic reticulum. Immunohistochemical study demonstrated coexpression of keratin and vimentin, two intermediate filaments thought to be specific for epithelial and nonepithelial cells, respectively. It is proposed that the spindle transformation of the epithelial cells in such cases may be explained on the basis of the development by the tumor cells of nonepithelial characteristics, such as the expression of vimentin intermediate filaments, that may be responsible for the adoption of the morphological growth pattern characteristic of neoplasms following mesenchyme-derived lines of differentiation.

Topics: Aged; Aged, 80 and over; Carcinoma; Humans; Intermediate Filaments; Keratins; Kidney Neoplasms; Kidney Pelvis; Male; Vimentin

A 28-year-old man with a large abdominal mass was found to have a tumor involving the peritoneum that had no other apparent primary origin. By light microscopy, the histologic pattern of the tumor was that of a small-cell epithelial neoplasm. Electron-microscopic examination demonstrated desmosomes and paranuclear aggregates of intermediate filaments. Immunohistochemical studies revealed reactivity for keratin, desmin, and vimentin. The globoid staining observed for the last two markers correlated with the paranuclear concentration of intermediate filaments observed by electron microscopy. We believe this case represents an unusual small-cell epithelial tumor, expressing mesenchymal-type intermediate filaments, that should be distinguished from other small-cell neoplasms.

Topics: Abdominal Neoplasms; Adult; Antibodies, Monoclonal; Carcinoma; Desmin; Humans; Intermediate Filament Proteins; Keratins; Male; Peritoneum; Vimentin

Undifferentiated cervical carcinomas vary considerably in their intercellular organization and patterns of invasion. In spite of its clinical significance, the basis for such variation is poorly understood. We investigated the cellular properties that may be responsible for this diversity, using as a model two human cervical carcinoma cell lines that were derived from the same tumor specimen and the same clone. It was shown previously that, in spite of their common origin, each line forms a histologically distinct type of undifferentiated carcinoma when heterotransplanted in vivo: cells of line C-4I grow as compact expanding masses with central necrosis, while tumors of line C-4II infiltrate host tissues as small, well-vascularized, dispersed cell groups. The characteristic behavior of each line was retained in culture, where C-4I cells formed highly multilayered cohesive colonies, while C-4II cells formed diffuse, monolayered colonies and shed into the culture medium. These observations as well as ultrastructural data suggested that each line may be arrested at a different stage of stratified squamous differentiation. In the present study, this hypothesis was tested by examining specific differentiation markers. An analysis of the cultures by immunofluorescence microscopy and immunoblotting revealed that keratin was more abundant in the compact C-4I line than in the dispersed C-4II line. C-4I cells expressed keratins 5, 6, 8, 16, 18, and 19, while C-4II expressed only keratins 8, 16, 18, and 19. In the multilayered C-4I colonies, involucrin-positive cells occurred in the apical cell layers only. In C-4II, involucrin-positive cells occurred in monolayers and domes, and they were most consistently located apically in crowded cultures. Laminin was secreted by both lines, but only C-4II cells deposited a fibronectin matrix. The results suggest that C-4I cells resemble normal cervical cells at the spinous stage of stratified squamous differentiation, while C-4II cells resemble basal/suprabasal cells. The different growth patterns of the tumors, formed by the lines in vivo, therefore likely reflect functional and behavioral differences that normally exist between spinous and basal cervical epithelial cells. The results suggest that differentiation-related functional properties may lead to histological diversity among cervical carcinomas that are categorized as undifferentiated by histopathological criteria.

Topics: Carcinoma; Cell Differentiation; Female; Fibronectins; Humans; Keratins; Laminin; Neoplasm Proteins; Protein Precursors; Tumor Cells, Cultured; Uterine Cervical 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

Primary cultures are introduced as a method for an immunocytochemical and functional characterization of epithelial cells (ECs) from human thymic epithelial tumors. Neoplastic ECs were obtained after enzymatic digestion of the tumor tissue with dispase. The ECs were kept in culture for up to 1.5 months. Over this period a progressive decline in their proliferation rate was observed. In all five cases studied, ECs showed a co-expression of keratin and vimentin intermediate filaments in vitro as well as strong expression of major histocompatibility complex (MHC)-class I antigens and a progressive loss of MHC-class II antigens. Acetylcholine receptor (AchR)-epitopes were detected immunohistochemically by using monoclonal antibodies (mAbs) to the cytoplasmic site of the alpha-chain if the AchR. Epitopes were found in three of five thymomas in vivo and to a varying degree in all five cases in vitro.

Topics: Antibodies, Monoclonal; Carcinoma; Cell Adhesion; Humans; Immunoenzyme Techniques; Immunohistochemistry; Keratins; Phenotype; Thymoma; Thymus Neoplasms; Tumor Cells, Cultured

Twelve anaplastic thyroid carcinomas were investigated with a panel of antibodies. The squamoid and giant cell anaplastic carcinomas showed coexpression of cytokeratin and vimentin in 66% of the cases. Reactivity for A-1-AT and A-1-ACT antiserum appeared when the spindle cell component became prevalent. The antidesmoplakin antibody can be employed on cryostat sections in differential diagnosis between sarcoma and carcinoma of the thyroid.

Topics: Adult; Aged; alpha 1-Antichymotrypsin; alpha 1-Antitrypsin; Carcinoma; Carcinoma, Squamous Cell; Cytoskeletal Proteins; Desmoplakins; Diagnosis, Differential; Female; Humans; Immunoenzyme Techniques; Keratins; Male; Membrane Glycoproteins; Middle Aged; Thyroid Gland; Thyroid Neoplasms; Vimentin

Two cases of in situ and invasive histiocytoid breast carcinoma are described. The invasive components of both tumours showed architectural and cytological similarities to lobular carcinoma. The in situ components showed areas of classical lobular carcinoma in situ, areas of lobular carcinoma with apocrine features and areas with transitional features. It is concluded that histiocytoid carcinoma represents an apocrine variant of lobular carcinoma. Differentiation of this tumour from chronic sclerosing inflammation may be difficult in both primary and secondary lesions.

Topics: Aged; Breast Neoplasms; Carcinoma; Female; Humans; Keratins

The first case of a sarcomatoid carcinoma of the adrenal gland is reported. The patient, a 68-year old woman, developed a recurrence two months after presentation and died of the disease 7 months later with multiple metastases. The differential diagnosis of this entity is discussed and its aggressive behaviour is emphasized.

Topics: Adrenal Gland Neoplasms; Aged; Carcinoma; Female; Humans; Immunochemistry; Keratins; Sarcoma; Tomography, X-Ray Computed; Vimentin

The clinical and pathologic features of 100 examples of spindle cell carcinoma (SpCC) of the breast are reported. Eighty-three neoplasms contained overt carcinoma; 72 had infiltrating ductal or intraductal carcinoma and in 11 the carcinomatous component was purely squamous. Seventeen neoplasms lacked overt carcinoma, but were identified as SpCC by immunoreactivity for keratin and the typical bland spindle cell proliferation forming a variable complex of fibrocollagenous stroma with feathered, myxoid, angioid, and storiform patterns. Areas of epithelium merging imperceptibly with the spindle cell component were commonly observed. Sixty neoplasms were studied by immunohistochemistry for the presence of keratin, epithelial membrane antigen (EMA), vimentin, S-100, and actin. The spindle cell component in 98% of SpCC was immunoreactive for keratin. Most were also immunoreactive for vimentin and actin, and in approximately one half, S-100 immunoreactivity was noted. These findings, in conjunction with histopathologic features, and ultrastructural observations from three cases, support myoepithelium as an integral component of SpCC. The cumulative 5-year survival rate for SpCC was 64%, better than survival rates usually reported for metaplastic carcinomas. Of 47 patients with axillary dissection, only 6% had metastases to axillary lymph nodes. Development of metastasis was an ominous sign as 29 of the 30 patients who developed metastases died from tumor. Local recurrence was not as ominous as only 29% who had only local recurrence subsequently died from tumor. The difference in size between tumors that recurred (mean, 5.0 cm) and those that did not (mean 3.7 cm), and the presence or absence of complete microscopic circumscription, were both significant prognostic factors.

Topics: Adult; Aged; Aged, 80 and over; Breast Neoplasms; Carcinoma; Female; Humans; Immunohistochemistry; Keratins; Middle Aged; Neoplasm Recurrence, Local; Vimentin

Microcystic adnexal carcinoma (MAC) is a recently described rare adnexal neoplasm showing benign histologic features but a locally aggressive behavior. It has most commonly been reported to occur on the face but it has also been noted in the axilla and buttock. We describe a 41-year-old white male with a 5-year history of MAC on the scalp and treatment by Mohs micrographic surgery. To our knowledge, this is the first case of MAC reported to occur on the scalp.

Topics: Adult; Carcinoma; Cysts; Epidermis; Humans; Keratins; Male; Scalp; Sclerosis; Skin Neoplasms

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

We used an avidin-biotin complex immunoperoxidase technique with various monoclonal antibodies to determine Langerhans cell densities, class II antigen expression on keratinocytes, and phenotypes of other infiltrating cells in several malignant and benign epithelial tumors of the skin. Our observations indicate (1) there are few Langerhans cells in nests of basal cell carcinoma and squamous cell carcinoma; (2) there are increased Langerhans cell densities in seborrheic keratoses, verrucous epidermal nevus, and Bowen's disease; (3) there is an expression of class II molecules on the keratinocytes and cancer cells of basal cell carcinoma, squamous cell carcinoma, Bowen's disease, seborrheic keratosis, and verrucous epidermal nevus; and (4) there is a netlike staining of the keratinocyte surface with OKM5 in the epidermal lesion of seborrheic keratosis, verrucous epidermal nevus, and Bowen's disease, as well as in the epidermis adjacent to the basal cell carcinoma and squamous cell carcinoma nests.

Topics: Adolescent; Adult; Aged; Antibodies, Monoclonal; Bowen's Disease; Carcinoma; Carcinoma, Basal Cell; Carcinoma, Squamous Cell; Epidermal Cells; Female; Histocompatibility Antigens Class II; Humans; Keratins; Keratosis; Langerhans Cells; Male; Middle Aged; Skin Neoplasms

Five cases of monophasic and 7 cases of biphasic spindle-cell carcinomas were analyzed immunohistochemically for the presence of vimentin and keratin type intermediate filaments in the pleomorphic spindle cells. Vimentin reactivity proved to be a consistent feature but keratin reactivity was more variable, this latter filament being lost in two cases initially presenting as pure squamous cell carcinomas showing dedifferentiation towards a pure monophasic spindle-cell tumour when recurring. The converse was also noted: acquisition of keratin in a monophasic spindle-cell tumour that recurred as squamous cell carcinoma. These results were considered to support the concept that spindle-cell tumours of the upper aerodigestive tract are a peculiar type of carcinoma and not a product of a pluripotent stem cell exhibiting bidirectional differentiation. Diagnostic implications are as follows: keratin positivity in a spindle-cell tumour substantiates its carcinomatous nature but its absence does not rule out a diagnosis of spindle-cell carcinoma.

Topics: Aged; Aged, 80 and over; Carcinoma; Carcinoma, Squamous Cell; Female; Humans; Immunoenzyme Techniques; Immunohistochemistry; Keratins; Laryngeal Neoplasms; Male; Middle Aged; Mouth Neoplasms; Neoplasm Recurrence, Local; Vimentin

Eleven benign and five malignant choroid plexus papillomas in children and adults were studied immunohistologically with a panel of antibodies against glial fibrillary acidic protein, S-100 protein, vimentin, desmin, epithelial membrane antigen and two different cytokeratins (LP34 and CAM 5.2). Glial fibrillary acidic protein was focally present in epithelial tumour cells, in cells within solid areas and in clusters of cells within the stroma. S-100 protein was diffusely present in tumour cells with focal accentuation. Vimentin was present in all cases, the epithelial tumour cells demonstrating strong and diffuse positivity with perinuclear accentuation; malignant tumours, however, showed stronger positivity than benign ones. Desmin was negative in all tumours. Epithelial membrane antigen and cytokeratin (LP34) were demonstrated in four of five malignant tumours but were absent in the benign ones; CAM 5.2 reacted with four of five malignant tumours and also reacted with eight of the 11 benign ones. The significance of these findings is discussed in respect of the ontogeny of these tumours.

Topics: Adolescent; Adult; Antigens, Neoplasm; Carcinoma; Cerebral Ventricle Neoplasms; Child; Child, Preschool; Choroid Plexus; Diagnosis, Differential; Female; Glial Fibrillary Acidic Protein; Humans; Immunohistochemistry; Infant; Infant, Newborn; Keratins; Male; Membrane Glycoproteins; Middle Aged; Mucin-1; Papilloma; S100 Proteins; Vimentin

The purpose of the present investigation was to study the histogenesis of the mucoepidermoid carcinoma of the salivary glands. Eleven cases of mucoepidermoid carcinoma of the minor salivary glands and five of the major glands were extensively studied employing immunohistochemical and fluorescent microscopic techniques. Both the intermediate cells and the duct cells showed a rather similar pattern of reactivity for vimentin, actin and EMA. Also, the intermediate cells and the myoepithelial cells showed a similar reaction pattern for keratin and UGA-1. The intermediate, myoepithelial and duct cells shared a similar reaction pattern for desmin, myosin, CEA, and S-100 protein. However, the rest of the tumor markers studied (AFP, PNA and WGA) were found to be non contributary. We also found that the intermediate and to some extent the epidermoid tumor cells showed a positive reaction with Azophloxine GA, which is a selective stain for myoepithelial cells in the normal glands. Based on these findings, the duct cells, the myoepithelial cell in the normal glands and the intermediate cells of the mucoepidermoid carcinoma share certain similar characteristics. The intermediate cells may actually be a mixed population, some having characteristics of the myopithelial cells and others of duct cells. These findings are relevant to the possible role of the intermediate cell in the histogenesis of the mucoepidermoid carcinoma.

Topics: Actins; Antigens, Neoplasm; Antigens, Surface; Azo Compounds; Biomarkers, Tumor; Carcinoembryonic Antigen; Carcinoma; Coloring Agents; Humans; Immunoenzyme Techniques; Immunohistochemistry; Keratins; Microscopy, Fluorescence; Naphthalenesulfonates; S100 Proteins; Salivary Gland Neoplasms; Salivary Glands, Minor; Staining and Labeling; Vimentin

Two types of high grade dysplasia were associated with invasive carcinomas. The first, deeply localized, had a pagetoid appearance and a particular phenotype: the dysplastic cells had keratins of low molecular weight rarely present in the esophagus; keratins of stratified epithelia were absent. This dysplasia was probably the origin of undifferentiated invasive carcinoma with which it was often associated. The second type, transepithelial, extended through the entire thickness of the epithelium. The abnormal cells presented some differentiation and stained positive for keratins of stratified epithelia. This dysplasia was often associated with differentiated squamous cell carcinoma. An intermediate-type dysplasia shared some characteristics with both main types. Several types of dysplasia and several areas of differently differentiated carcinoma were often associated in the same case. The evolutional potential of the different dysplasias is not known.

Topics: Carcinoma; Epithelial Cells; Epithelium; Esophageal Neoplasms; Esophagus; Humans; Immunohistochemistry; Keratins; Neoplasm Invasiveness; Phenotype

Topics: Antibodies, Monoclonal; Biomarkers, Tumor; Breast; Breast Neoplasms; Carcinoma; Carcinoma in Situ; Carcinoma, Intraductal, Noninfiltrating; Humans; Keratins; Lymph Nodes; Lymphatic Metastasis; Neoplasm Invasiveness

Eighteen cases of primary thymic carcinoma were reviewed from the viewpoint of glandular differentiation. Squamous differentiation was evident in 14 cases (83%). Immunohistochemical study revealed secretory component (SC)-positive carcinoma cells in 12 cases (67%), most of which were also associated with squamous differentiation. Three of these 12 cases contained areas with a definite glandular or microcystic structure with occasional epithelial mucin, and were diagnosed as adenosquamous carcinoma. Review of patients' medical records revealed that thymic carcinomas with a glandular element were more often resectable at surgery, and had a much better prognosis than those without a glandular element. However, further study on larger number of cases is necessary to confirm this relationship. Because SC-positive epithelial cells do exist in the non-neoplastic thymus, the presence of a glandular component suggests another direction of morphological and/or functional differentiation of thymic carcinoma cells in addition to the well-known squamous differentiation.

Topics: Biomarkers, Tumor; Carcinoma; Carcinoma, Squamous Cell; Cell Differentiation; Cell Transformation, Neoplastic; Humans; Immunohistochemistry; Keratins; Prognosis; Thymus Gland; Thymus Neoplasms

Spindle cell carcinomas were identified using polyacrylamide gel electrophoresis and immunoblotting of proteins extracted from paraffin-embedded tissue sections. Immunohistochemistry using rabbit monospecific antisera against the mouse 55 kd keratin polypeptide also identified these tumors. A group of 53 SENCAR mice initiated with 7,12-dimethylbenz[a]anthracene (DMBA) and promoted with 12-O-tetradecanoylphorbol-13-acetate (TPA) yielded, after one year, four spindle cell carcinomas (0.07/mouse), whereas another group of 31 mice treated with a three-stage carcinogenesis protocol (initiation with DMBA and promotion for 10 weeks with TPA followed by 10 weeks of benzoyl peroxide) gave rise to six spindle cell carcinomas (0.19/mouse). The number of keratin-positive tumor cells and the intensity of the immunostain varied markedly, but all tumors expressed the 55 kd polypeptide. Although other carcinogens, mainly UV radiation, have been able to induce spindle cell tumors, the present data indicate that chemical carcinogenesis protocols are able to induce the formation of this highly malignant variant of skin carcinoma.

Topics: 9,10-Dimethyl-1,2-benzanthracene; Animals; Blotting, Western; Carcinoma; Drug Administration Schedule; Immunoenzyme Techniques; Keratins; Mice; Skin Neoplasms; Tetradecanoylphorbol Acetate

Ten cases of choroid plexus tumors (3 papillomas and 7 carcinomas) were tested for the presence of glial fibrillary acidic protein (GFAP) and cytokeratin. None of the papillomas and one of the carcinomas were positive with GFAP antisera. Cytokeratin-positive cells were present in 2 of 7 carcinomas and in all papillomas. There seems to be a positive correlation between the degree of the tumor differentiation and the expression of intermediate filaments.

Topics: Carcinoma; Cerebral Ventricle Neoplasms; Choroid Plexus; Glial Fibrillary Acidic Protein; Humans; Immunohistochemistry; Keratins; Papilloma

We report a case of gastric carcinoma with an unusual histologic appearance and type of cellular differentiation. The tumor was resected from an 85-yr-old man who presented with epigastric pain and monoclonal gammopathy. The tumor was antral in location and transmurally infiltrated the stomach wall. Histologically, the tumor closely resembled a lymphoma with diffuse poorly cohesive sheets of tumor cells interspersed with histiocytes. Immunohistochemical study, however, clearly demonstrated the epithelial nature of this tumor. Electron microscopy also revealed evidence of epithelial differentiation and features of parietal cell differentiation. In this report, we describe the light and electron microscopic findings, immunohistochemical staining properties, and DNA flow cytometric findings of this tumor and briefly review the literature on parietal cell carcinomas.

Topics: Aged; Aged, 80 and over; Carcinoma; Diagnosis, Differential; Follow-Up Studies; Humans; Keratins; Lymphoma; Male; Parietal Cells, Gastric; Stomach Neoplasms

The cytokeratins 8, 18, and 19, expressed in many normal and malignant epithelial cells, were purified from human gastrointestinal tumors and used as immunogen for hybridoma generation. The reactivity pattern of five of the generated ten monoclonal antibodies (MAb) was characterized biochemically and immunohistochemically. All of the generated MAb were reactive with the central rod portion of the cytokeratins, as determined after partial enzymatic degradation, and displayed characteristic reactivity patterns. MAb TS 4 exhibits pan-epithelial immunohistochemical reactivity staining of all epithelial structures, including all layers of epidermis and non-keratinizing squamous epithelium and myoepithelial cells. The determinant involved is present on several different cytokeratins, i.e., nos. 1, 5, 7, 8, and 15, as determined by immunoblotting experiments from different tissues and cell lines. MAb TS 1, TS 3, and TS 7 reveal pluri-epithelial reactivity pattern immunohistochemically, similar to TS 4, but they are unreactive with whole epidermis and with superficial cell layers of non-keratinizing squamous cells. MAb TS 1 was found to be highly specific and reactive only with cytokeratin 8. Furthermore, the TS 1 MAb alone can precipitate the antigen, indicating reactivity with repetitive epitopes on cytokeratin 8. MAb TS 3 and 7 bind to cytokeratins 7 and 8. Finally, MAb TS 8 was found to be immunohistologically the most restricted, in general lacking reactivity to hepatocytes, pancreatic and salivary gland acinar cells, proximal renal tubules, and luminal cells of the epididymis. TS 8 was mainly reactive with cytokeratin 19 and showed weak binding to cytokeratin 8 and 14.

Topics: Antibodies, Monoclonal; Antibody Specificity; Binding, Competitive; Blotting, Western; Carcinoma; Cell Line; Cytoskeleton; Epithelium; Epitopes; Fixatives; Formaldehyde; Humans; Immunohistochemistry; Intermediate Filaments; Keratins; Paraffin; Placenta; Tissue Distribution

The histological features of mucoepidermoid mammary carcinomas (MMCs) are presented, and criteria for distinguishing these tumours from squamous epithelial metaplasia in other mammary carcinomas are considered. Immunohistochemical and gel-electrophoretic analyses of the intermediate-filament proteins in one MMC case revealed a complex pattern of cytokeratin polypeptide expression. The simple-epithelium-type cytokeratins 7, 8, 18, and 19 were detected mainly in nonsquamous (including mucinous) cells, while the stratified-epithelium-type cytokeratins 5, 6, 14, 16, and 17 were present in squamous cells. However, in both the nonsquamous and squamous regions of the tumour, cytokeratins of the "reverse" type were detected in individual cells. This pattern of single-cell heterogeneity with respect to cytokeratin polypeptide expression suggests that the mixed phenotype of this tumour is not caused by the clonal divergence of tumour cell types. Rather, histogenetically, a pluripotent stem cell with the ability to differentiate into squamous (epidermoid) or mucinous cells might be the starting-point of such a tumour and such differentiation processes may continue to occur during tumour growth. The present case also revealed that mucoepidermoid tumours are not necessarily of low malignancy; there are highly malignant forms with rapid metastasis.

Topics: Adult; Aged; Aged, 80 and over; Breast Neoplasms; Carcinoma; Female; Glial Fibrillary Acidic Protein; Humans; Immunohistochemistry; Intermediate Filaments; Keratins; Middle Aged; Vimentin

It has been suggested that cytokeratin 13 is a useful marker of malignancy. We examined normal squamous cell epithelia, hyperplasia, dysplasias of various grades, intraepithelial neoplasia and invasive squamous cell carcinomas of the pyriform fossa using K13 and KL1. Positive staining for K13 was seen in all normal or hyperplastic benign epithelia, was inconstant in dysplasia, and intraepithelial neoplasia and carcinoma was negative. KL1 expression is constant and non significant. These results suggest that tumour cells are unable to synthesize keratin 13 a finding which may be valuable in surgical pathology.

Topics: Biomarkers, Tumor; Carcinoma; Carcinoma, Squamous Cell; Epithelium; Gene Expression; Head and Neck Neoplasms; Humans; Hyperplasia; Immunohistochemistry; Keratins; Larynx; Pharynx

An infiltrating epithelial and spindle cell neoplasm developed in the breast of a 63-year-old female. An excisional biopsy was performed. Recurrence with rapid growth due to cyst development eventually resulted in more radical surgery. Interim fine needle aspirations had established its partially cystic nature. The unique microscopic appearance prompted the application of immunohistochemistry and electron microscopy. The tumour cells were found to exhibit characteristics denoting squamous and myoepithelial differentiation. Histopathological features of malignancy were absent. Our findings demonstrate the differentiation potential of breast epithelium. They are in concordance with the results of previous studies which delineate the histochemical and ultrastructural features of myoepithelial and establish the relationship of these cells to squamous metaplasia.

Topics: Actins; Breast Neoplasms; Carcinoma; Cell Transformation, Neoplastic; Female; Humans; Immunohistochemistry; Keratins; Membrane Glycoproteins; Microscopy, Electron; Middle Aged; Mucin-1; Myoepithelioma; Vimentin

Primary carcinoid tumours of the middle ear are extremely rare, only nine cases having been reported. However, their true incidence is probably greater, since they are very difficult or impossible to distinguish from adenomas and adenocarcinomas with conventional histological stains. We describe the clinical, histological, immunohistochemical and ultrastructural findings in a carcinoid tumour of the middle ear in a 50-year-old woman. Immunohistochemical studies on non-neoplastic middle ear mucosa undertaken to investigate the histogenesis of such tumours are also reported. Histologically, the tumour consisted of both solid areas and areas of tubular structures containing intraluminal mucus. All the tumour cells reacted with the anti-keratin antibody KL 1; some were argyrophil and reacted with antibodies against neuron-specific enolase, chromogranin A, Leu-7, serotonin, pancreatic polypeptide, glucagon and lysozyme. Electron microscopy revealed dense core granules in the tumour cells. Endocrine cells could not be detected in non-neoplastic middle ear mucosa. Pancreatic-polypeptide-like immunoreactivity was demonstrated immunohistochemically in all three other published cases of carcinoid tumour of the middle ear investigated for this peptide, and glucagon-like immunoreactivity was also exhibited by one of these. Since carcinoid tumours of the middle ear often, as in this case, exhibit some degree of glandular differentiation, immunohistochemical or electron-microscopic investigation to detect neuroendocrine differentiation is of particular importance in adenomatous middle ear neoplasms.

Topics: Carcinoma; Ear Neoplasms; Ear, Middle; Female; Humans; Immunohistochemistry; Keratins; Middle Aged; Phosphopyruvate Hydratase

Squamous differentiation of thyroid carcinoma was studied clinicopathologically and immunohistochemically in 29 autopsy cases. Tumor cell nests with squamous differentiation (CNSD), which histologically resembled squamous cell carcinoma, were found in 6 cases (20.7%). All of these 6 cases with CNSD had areas of undifferentiated carcinoma, representing 31.6% of 19 cases with undifferentiated carcinoma, and all but one case also showed coexisting papillary carcinoma. The CNSD were histologically associated with undifferentiated carcinoma in 5 cases, and with papillary carcinoma in one case; the CNSD were occasionally intermingled with these types of carcinoma, and there were findings suggesting a histological transition between the CNSD and undifferentiated carcinoma or papillary carcinoma. Immunohistochemistry revealed that all the CNSD were reactive with antibodies for keratin and vimentin, whereas thyroglobulin and desmin were not expressed. It was concluded that the CNSD examined here were most probably due to extensive squamous differentiation (squamous metaplasia) in undifferentiated carcinoma and papillary carcinoma. In addition, the present results may explain the fact that cases diagnosed solely as squamous cell carcinoma sometimes show a prognosis similar to that of undifferentiated carcinoma, and may well represent extensive squamous differentiation in such tumors rather than true squamous cell carcinoma of the thyroid.

Topics: Adult; Aged; Carcinoma; Carcinoma, Squamous Cell; Cell Differentiation; Female; Humans; Immunohistochemistry; Keratins; Male; Middle Aged; Thyroid Neoplasms; Vimentin

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

The clinicopathological features of 14 laryngeal neoplasms consisting of spindle-shaped cells are presented. Light microscopy showed a variety of morphological patterns from that of pleomorphic sarcoma and fibrosarcoma to more loose vascular patterns. Immunohistochemistry revealed that the spindle-shaped cells had a positive keratin immunoreactivity in 8 of 14 cases, and also that some cases had a dual expression of keratin and vimentin filaments. Electron microscopy showed that spindle-shaped cells had epithelial ultrastructures. The results support the hypothesis that the spindle cell carcinomas are true carcinomas with mesenchymal metaplasia and that the spindle-shaped cells are part of the neoplasm and not benign, reactive fibroblasts. These lesions occurred mainly on the true vocal cords in elderly patients. The neoplasms were nearly all polypoid, and many also ulcerated. There is no significant difference in clinical behaviour between laryngeal spindle cell carcinomas and ordinary squamous cell carcinomas of the larynx, and the same treatment policy is therefore advocated. Being polypoid and therefore able to be surgically removed with relative ease, they may even present a more favourable clinical course.

Topics: Adult; Aged; Carcinoma; Collagen; Female; Humans; Immunohistochemistry; Keratins; Laryngeal Neoplasms; Male; Microscopy, Electron; Middle Aged; Vimentin

In this study antibodies specific for different intermediate-sized proteins (cytokeratins and neurofilaments) have been tested on a series of neuroendocrine (NE) lung tumors in order to evaluate their diagnostic validity. In particular we used a panel of polyclonal anti-neurofilament 200-kilodalton subunits whose reactivity against phospho-dependent epitopes was known. At least one NF subunit was constantly present and in all cases coexpression of cytokeratins and neurofilaments was confirmed. However, in cases of carcinoid tumor (CT) the results were homogeneous, while the cases of small cell lung carcinoma (SCLC) showed a much wider range of immunostaining. Our investigation confirms the hypothesis that the phosphorylation state is a significant determinant of immunohistochemical properties of neurofilaments. This might explain the large number of negative results obtained in previous investigations on NE tumors. The phosphorylation of neurofilaments may also be considered an indication of the degree of differentiation of the tumor.

Topics: Biomarkers, Tumor; Carcinoma; Carcinoma, Small Cell; Humans; Immunohistochemistry; Intermediate Filament Proteins; Keratins; Lung Neoplasms; Phosphorylation

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

Eight primary carcinomas of the lung with a prominent spindle-cell sarcomatoid component were studied by immunocytochemical staining and electron microscopy. The eight tumors were indistinguishable by conventional light microscopy, with the exception of one unusual neoplasm that followed multiple pathways of differentiation with elements of squamous cell carcinoma, rhabdomyosarcoma, chondrosarcoma, and an undifferentiated spindle-cell population. Reticulin fiber production by individual spindle cells and a sharp demarcation of the carcinomatous and sarcomatoid domains by light microscopy were not useful differentiating features. Three of the eight tumors exhibited keratin expression in both the carcinomatous and spindle-cell components. Both immunocytochemical and electron microscopic analyses were required to detect epithelial differentiation, as in one case keratin was identified only by immunocytochemical staining and in another only by ultrastructural examination. Epithelial differentiation was undetectable in the sarcomatoid component of five tumors, and in one case immunoreactive myoglobin was identified in spindle cells; skeletal muscle differentiation was confirmed ultrastructurally. We propose that pulmonary carcinomas exhibiting evidence of epithelial differentiation in a sarcomatoid component be termed spindle-cell carcinomas and that those biphasic tumors exhibiting mesenchymal differentiation into specific tissues, such as neoplastic bone, cartilage, or striated muscle, or lacking epithelial differentiation by light microscopy, immunocytochemistry, and electron microscopy be classified as carcinosarcomas. This distinction may ultimately be unnecessary, because these two tumors may represent different points along a morphologic and biologic continuum.

Topics: Carcinoembryonic Antigen; Carcinoma; Female; Humans; Immunohistochemistry; Keratins; Lung Neoplasms; Male; Microscopy, Electron; Sarcoma

Twenty-six ependymal and 15 choroid plexus tumors were examined with monoclonal antibody against cytokeratin using the avidin-biotin-peroxidase complex (ABC) technique. Serial sections were examined with antisera to glial fibrillary acidic protein (GFAP). In five ependymal tumors (one ependymoma, two papillary ependymomas, and two primitive neuroectodermal tumors [PNET] with ependymal cells), a variable number of cytokeratin-positive cells were present. Most tumor cells (except two PNET) were positive with GFAP antisera. Many cytokeratin-positive cells were present in all choroid plexus tumors. GFAP-positive cells were present focally in six of 11 papillomas and in one of four carcinomas. Although their staining patterns and distribution were clearly different, focal coexistence of cytokeratin and GFAP was observed in six papillomas and two ependymal tumors. Thus, some ependymal tumors (especially papillary ependymomas and occasional PNET) and many choroid plexus tumors have demonstrable positivity with antibody to cytokeratin, suggesting a transitional cell type with features of both ependyma and choroid plexus.

Topics: Carcinoma; Cerebral Ventricle Neoplasms; Child; Choroid Plexus; Ependyma; Ependymoma; Glial Fibrillary Acidic Protein; Humans; Immunoenzyme Techniques; Immunohistochemistry; Keratins; Papilloma

Seven consecutive cases of primary spindle celled tumours of the breast have been studied immunohistologically using antisera to the intermediate filament proteins (IFP) vimentin, cytokeratin, and desmin, and with an antibody to epithelial membrane antigen. Representative paraffin sections were examined using a peroxidase-antiperoxidase method. In three cases, very occasional foci of epithelial differentiation were apparent by conventional microscopy, and in one case, adjacent ductal carcinoma in situ was present. The remaining three cases were composed of spindle cell elements entirely, with no evidence of epithelial differentiation morphologically. Immunoreactivity of spindle cell elements for vimentin was found in all seven cases, and for cytokeratin in six cases. One case showed immunoreactivity for vimentin, cytokeratin, and desmin, and one case only for vimentin. Epithelial membrane antigen was not identified in the spindle cell elements of any tumour, but was present in the invasive epithelial component of three cases and the in situ component of one case. We conclude that many spindle cell tumours of breast show immunohistological evidence of epithelial differentiation and can be regarded as spindle cell carcinomas. However, in some cases IFP expression may be complex and histogenesis cannot be determined. This technique can aid histological diagnosis in some cases.

Topics: Adult; Aged; Antigens; Breast Neoplasms; Carcinoma; Carcinoma in Situ; Carcinoma, Intraductal, Noninfiltrating; Desmin; Female; Humans; Intermediate Filament Proteins; Keratins; Membrane Glycoproteins; Middle Aged; Mucin-1; 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

The expression of cytokeratins (CKs) in human lung cancer was studied using chain-specific monoclonal antibodies to CKs 4, 7, 8, 10, 13, 18, and 19. When applied to adenocarcinomas (ACs) of the lung, high levels of CKs 7, 8, 18, and 19 were detected in all tumors, while CK 4 was found in high concentrations in some ACs. CK 10 and 13 were completely absent, or only present in low numbers of cells. Small cell lung cancers (SCLCs) and lung carcinoids contained CK 18 and sometimes 8 and 19, but no CK 7 in most cases. Three out of four tumors, histologically classified as SCLC, and expressing CK 7 in a variable number of cells were found by electron microscopic studies to contain regions with AC and/or squamous cell carcinoma (SQC) differentiation. The monoclonal antibody specific for CK 7 can therefore possibly help to distinguish AC differentiation within SCLC. CKs 10 and 13 were completely absent in SCLCs and lung carcinoids, while few CK 4-positive cells were found in some SCLCs and in one lung carcinoid. Within SQCs the monoclonal antibodies revealed a pronounced heterogeneity in CK expression. CKs 4, 7, 8, 10, 13, 18, and 19 could be detected, although not evenly distributed among all tumor cells. Highly differentiated SQCs expressed high levels of the CKs specific for squamoid differentiation, i.e., CKs 4, 10, and 13 in variable numbers of cells. With decreasing histologically detectable SQC differentiation these markers were gradually lost, while the number of cells containing CKs 7, 8, 18, and 19 increased. Application of this panel of monoclonal antibodies can therefore distinguish not only the main subtypes of lung cancer, but can also indicate the degree of differentiation and the degree of heterogeneity. These findings can be used as a diagnostic aid in lung tumor pathology, which may have an impact on treatment and prognosis.

Topics: Antibodies, Monoclonal; Carcinoma; Cytoskeleton; Electrophoresis, Polyacrylamide Gel; Humans; Immunoenzyme Techniques; Keratins; Lung Neoplasms

Monospecific antikeratin antisera and specific complementary DNA probes were used to analyze expression of keratin genes in newborn mouse skin and skin papillomas and carcinomas by indirect immunofluorescence, immunoblotting, and in situ hybridization. Tumors were induced by initiation with 7,12-dimethylbenz[a]anthracene and promotion with 12-O-tetradecanoylphorbol-13-acetate. Type I epidermal keratin K14 protein (Mr 55,000) is found in all living layers of the newborn skin but is most abundant in the lower strata. K1 (Mr 67,000) and K10 (Mr 59,000) proteins are predominantly suprabasal and K1 is processed in the stratum corneum. Transcripts for K14 were confined largely to the basal cell layer by in situ hybridization. Transcripts for K1 and K10 were highly expressed in suprabasal cells including the granular cell layer. In benign tumors, distribution of K14 protein is similar to that in newborn skin, while the abundance of K1 and K10 appears to be somewhat reduced although the tissue distribution remains suprabasal. Transcription of K14 is aberrant in benign tumors and transcripts persist throughout much of the suprabasal cell layers. Transcripts of K1 and K10 are normally distributed in papillomas but grain density is less intense than in newborn epidermis. Keratin expression in carcinomas is highly disturbed. K14 protein and transcripts are highly expressed in all strata in carcinomas while protein and transcripts for K1 and K10 are essentially absent. These results suggest that papilloma cells fail to respond to or generate signals to regulate K14 expression in the differentiating suprabasal cell layers and may not fully express their suprabasal cell keratins. Carcinomas fail to express suprabasal cell keratins and this is regulated at the transcriptional level. The loss of suprabasal keratin expression may provide a marker for malignant conversion in the mouse skin carcinogenesis model.

Topics: 9,10-Dimethyl-1,2-benzanthracene; Animals; Animals, Newborn; Carcinoma; Cell Transformation, Neoplastic; Female; Gene Expression Regulation; Genes; Keratins; Mice; Mice, Inbred Strains; Nucleic Acid Hybridization; Papilloma; Skin; Skin Neoplasms; Tetradecanoylphorbol Acetate; Transcription, Genetic

The authors studied 79 common epithelial ovarian tumors in order to ascertain the intermediate filament profiles in formalin-fixed and methacarn-fixed, paraffin-embedded surgical pathology materials. Ultra-structural correlations were attempted with several tumors. All categories of common benign and malignant epithelial tumors were examined. Antibodies used in the study included antikeratins (AE1/AE3, 35BH11, 34BE12), carcinoembryonic antigen (CEA), and vimentin. All ovarian epithelial tumors expressed keratin in uniform fashion, except high molecular weight keratin (34BE12) which was focal. Vimentin was coexpressed with cytokeratins in 42% of serous carcinomas, 71% of endometrioid carcinomas, and 7% of clear cell carcinomas. Vimentin decoration in serous carcinoma was very focal, whereas endometrioid decoration tended to involve larger areas, similar to uterine-based endometrial adenocarcinoma. Mucinous, Brenner, and solid (not otherwise specified) ovarian tumors were positive only for cytokeratin. Carcinoembryonic antigen luminal staining was present in 52% of serous carcinomas and 87% of mucinous carcinomas. Whereas there are distinct differences in intermediate filament expression among ovarian carcinomas, these differences do not allow for specific categorization of ovarian neoplasms because there is some overlap of intermediate filament expression. In order to differentiate ovarian carcinoma from other carcinomas and mesothelioma, other methods of study would be necessary in addition to intermediate filament profiles, such as CEA immunohistochemistry, mucin histochemistry, and ultrastructural study.

Topics: Carcinoembryonic Antigen; Carcinoma; Female; Humans; Immunohistochemistry; Intermediate Filament Proteins; Keratins; Ovarian Neoplasms; Vimentin

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

The pattern of cytokeratins expressed in normal urothelium has been compared with that of various forms of transitional cell carcinomas (TCCs; 21 cases) and cultured bladder carcinoma cell lines, using immunolocalization and gel electrophoretic techniques. In normal urothelium, all simple-epithelium-type cytokeratins (polypeptides 7, 8, 18, 19) were detected in all cell layers, whereas antibodies to cytokeratins typical for stratified epithelia reacted with certain basal cells only or, in the case of cytokeratin 13, with cells of the basal and intermediate layers. This pattern was essentially maintained in low-grade (G1, G1/2) TCCs but was remarkably modified in G2 TCCs. In G3 TCCs simple-epithelial cytokeratins were predominant whereas the amounts of component 13 were greatly reduced. Squamous metaplasia was accompanied generally by increased or new expression of some stratified-epithelial cytokeratins. The cytokeratin patterns of cell culture lines RT-112 and RT-4 resembled those of G1 and G2 TCCs, whereas cell line T-24 was comparable to G3 carcinomas. The cell line EJ showed a markedly different pattern. The results indicate that, in the cell layers of the urothelium, the synthesis of stratification-related cytokeratins such as component 13 is inversely oriented compared with that in other stratified epithelia where these proteins are suprabasally expressed, that TCCs retain certain intrinsic cytoskeletal features of urothelium, and that different TCCs can be distinguished by their cytokeratin patterns. The potential value of these observations in histopathologic and cytologic diagnoses is discussed.

Topics: Antibodies, Monoclonal; Carcinoma; Carcinoma, Transitional Cell; Cell Differentiation; Epithelium; Fluorescent Antibody Technique; Humans; Keratins; Microscopy, Fluorescence; Reference Values; Tumor Cells, Cultured; Urinary Bladder Neoplasms; Urinary Tract; Urogenital Neoplasms

Immunoreactivity for S-100 protein, typically a marker for malignant melanoma and neural-derived tumors, was observed in neoplastic cells of 57 of 68 cases (84%) of formalin-fixed, paraffin-embedded primary and/or metastatic carcinoma of the breast of various histologic types. The extent of S-100 immunoreactivity varied, with only a minor proportion of positive tumor cells noted in some cases. An awareness of this staining profile for S-100 protein, particularly in metastatic poorly differentiated neoplasms with unknown primaries, is imperative for accurate immunohistochemical interpretation. Using a panel of reagents which includes antibodies to keratin proteins and epithelial membrane antigen, the epithelial nature of S-100-positive carcinomas may be readily defined. Tumor cells in all cases of primary and metastatic carcinoma of the breast evaluated in this study exhibited strong staining for both of these tissue markers. To preclude misinterpretation of tumor type due to anomalous staining patterns for a specific antibody, eg, S-100 protein, a panel of antibodies is recommended for assessment of metastatic poorly differentiated tumors.

Topics: Breast Neoplasms; Carcinoma; Female; Humans; Keratins; Membrane Glycoproteins; Mucin-1; S100 Proteins

Using conventional murine hybridoma technology, we have produced a monoclonal antibody (MAb), 89E5, which recognizes two keratin-like polypeptides (Mr 53,000 and 45,000), which are preferentially expressed by epithelial tumors. In addition to detection of tumor cells by immunohistochemistry, MAb 89E5 was able to localize to tumor xenografts in nude mice after iodination of its F(ab')2 fragments. To develop potentially less immunogenic antibodies to antigens defined by MAb 89E5, studies were performed to produce a human counterpart to the mouse MAb. The mouse 89E5 MAb was used to purify the 89E5 polypeptides from tumor cell lines. The partially purified 89E5 antigen was then used to sensitize human splenic lymphocytes in vitro. Immortalization of the sensitized cells by cell fusion resulted in a human IgM MAb, PA1, which showed the same reactivity pattern on a panel of cell lines as did the mouse MAb 89E5. Immunofluorescent studies showed that both 89E5 and PA1 had staining patterns on epithelial cells indicative of antibodies to cytokeratin. Furthermore, PA1 immunoprecipitated two polypeptides (Mr 53,000 and 45,000) which comigrated with the 89E5 polypeptides. Competitive binding assays showed that the PA1 MAb and 89E5 MAb recognized closely associated epitopes. As with the 89E5 MAb, PA1 was reactive with tumor tissues in immunohistochemical studies. These studies indicate that the PA1 MAb is a human counterpart of the mouse 89E5 MAb. Direct comparison of human MAb and mouse MAb against the same antigen could yield valuable information on the efficacy of using human MAb in vivo.

Topics: Animals; Antibodies, Monoclonal; Antigens, Neoplasm; Carcinoma; Humans; Hybridomas; Immunohistochemistry; Keratins; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Molecular Weight

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

Eighty colon carcinomas reflecting the histologic spectrum were studied immunohistochemically; their epithelial characteristics had been established by demonstrating cytokeratin polypeptides. Paraffin sections were immunostained with monoclonal antibody (Mab) A-80 that recognizes a mucin-like glycoprotein related to exocrine differentiation. Sequential sections were immunostained with neuroendocrine (NE) differentiation antibodies: NSE, human chromogranin A, serotonin, somatostatin, substance P and VIP. Twenty-one/80 carcinomas immunoreacted exclusively with Mab A-80; these included adenocarcinomas with variably defined glands, colloid, "solid", and linitits plastica carcinomas. Eleven/80 carcinomas immunoreacted only with antibodies to NE markers. Twenty-nine/80 carcinomas of histologically variable patterns expressed both exocrine and NE antigens. A notable group of 19 adenocarcinomas immunostaining with Mab A-870 included a minority NE cell subpopulation. We tentatively conclude that given a limited battery of immunoprobes, colon carcinomas comprise 4 groups: 1) pure exocrine carcinomas, 2) pure NE carcinomas, 3) mixed exocrine and NE carcinomas, and 4) exocrine carcinomas with occasional NE cells. Thus, phenotypically mixed exocrine and NE carcinomas comprise the largest group while the second largest group exhibited exclusively features of exocrine phenotype. Preliminary clinical correlative data indicate that pure NE colon carcinomas behave more aggressively than their exocrine counterparts; moreover, colon carcinomas containing a NE subpopulation, even if small, also seem to behave worse than their counterparts without an NE subpopulation.

Topics: Antibodies, Monoclonal; Antigens, Tumor-Associated, Carbohydrate; Carcinoma; Cell Differentiation; Chromogranins; Colonic Neoplasms; Humans; Immunoenzyme Techniques; Keratins; Microscopy, Electron; Phosphopyruvate Hydratase; Serotonin; Somatostatin; Substance P

Immunohistochemical expression of 8 cases of mucoepidermoid carcinomas (G-I, 3 cases; G-II, 2 cases; and G-III, 3 cases) revealed marked heterogeneity of the proteins examined. Immunohistochemically detectable keratins (TK, KL1, and PKK1) were distributed in epidermoid cells, but were absent in mucous secreting cells. Strongly positive deposits of keratin proteins were detected in squamoid tumor cells in the G-I tumors. The tumor cells displayed positive staining for S-100 alpha, but did not stain with polyclonal S-100 antiserum or with monoclonal S-100 beta. The cells showing highest reactivity for S-100 protein were scattered in neoplastic foci and were probably Langerhans cells. Lactoferrin and lysozyme reactions were generally negative in tumor foci; but a positive reaction for lactoferrin was found in luminal tumor cells although rarely, and lysozyme staining was occasionally noted in histiocytes in the stroma. Amylase activity was usually absent in the tumor cells, with the exception of one case in which it was confined to the tumor cells. Mucoepidermoid carcinomas of various grades indicated marked heterogeneity in terms of various immunohistochemically detectable proteins.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Amylases; Carcinoma; Female; Histocytochemistry; Humans; Immunoenzyme Techniques; Keratins; Lactoferrin; Lactoglobulins; Male; Middle Aged; Muramidase; Periodic Acid-Schiff Reaction; S100 Proteins; Salivary Gland Neoplasms; Staining and Labeling

In this study, the immunoreactivity of several cytokeratin antibodies; 115 D8, a monoclonal antibody against MAM-6, an epithelial membrane antigen; and two vimentin antibodies, is examined in relation to the degree of morphologic differentiation in carcinomas of the head and neck. The results indicate that a relationship exists between the degree of morphologic differentiation and the expression of cytokeratin, MAM-6, and vimentin, as detected by polyclonal antikeratin, 115 D8 and anti-vimentin. Expression of cytokeratin and MAM-6 is reversely related to vimentin. Polyclonal anti-keratin; CAM 5.2, a monoclonal antibody against cytokeratin 8, 18 and 19; and 115 D8, used in combination, were still able to identify the epithelial nature of undifferentiated/spindle cells. Since these immunohistochemical markers precede light microscopic detectable signs of epithelial differentiation, they can be used for the identification of the epithelial nature of undifferentiated/spindle tumors of the head and neck.

Topics: Antigens, Differentiation; Carcinoma; Carcinoma, Squamous Cell; Cytoskeleton; Desmin; Diagnosis, Differential; Head and Neck Neoplasms; Humans; Keratins; Membrane Glycoproteins; Microscopy, Electron; Mucin-1; Staining and Labeling; Vimentin

Topics: Adenocarcinoma; Carcinoma; Carcinoma, Squamous Cell; Humans; Immunohistochemistry; Intermediate Filament Proteins; Keratins; Nasopharyngeal Neoplasms; Staining and Labeling; Vimentin

Topics: Carcinoembryonic Antigen; Carcinoma; Diagnosis, Differential; Humans; Immunoenzyme Techniques; Keratins; Membrane Glycoproteins; Mucin-1

Two murine monoclonal anti-cytokeratin antibodies with defined specificity were shown to distinguish between basal cells and luminal cells in human prostate tissue. Forty-one biopsies or transurethral resection specimens were characterized using these two antibodies. In cases of benign prostatic hyperplasia, focal loss of the basal cell layer was noted in areas of glandular proliferation. Ten cases of adenocarcinoma of the prostate, varying in Gleason's histological grade from 2 to 4, were also studied. In each case the carcinoma was shown to represent the luminal cell phenotype with no evidence of involvement of the basal cell phenotype. An analysis of three established metastatic prostatic carcinoma cell lines (DU-145, PC-3, and LNCaP) using two-dimensional electrophoresis showed that the cytokeratin complement of each cell line was slightly different but retained the phenotype of the luminal cell. It was concluded that during both hyperplasia and neoplastic transformation of the prostate, the luminal cell phenotype is primarily involved and that the basal cell phenotype does not appear to contribute to either intraluminal proliferation or invasive cell populations.

Topics: Antibodies, Monoclonal; Breast Neoplasms; Carcinoma; Cell Line; Humans; Keratins; Male; Phenotype; Prostate; Prostatic Neoplasms

Early passage normal human fetal kidney epithelial cells were inoculated on top of a confluent monolayer of X-ray lethally irradiated human fibroblasts to determine the colony-forming ability of these epithelial cells. The results indicate that the great majority of the epithelial cells did not have the clonogenic ability on the fibroblast cell mat, although they were capable of colony formation on plastic surface without the cell mat. A small subpopulation of these epithelial cells, however, was able to proliferate on the cell mat. These contact-insensitive fetal epithelial cells were found to be deficient in gap junction-mediated intercellular communication, to contain keratin and gamma-glutamyl transpeptidase but not fibronectin. These contact-insensitive cells appear to have greater proliferative potential than the parental cell population and to exist transiently in early passage but not in late passage culture. The ability of proliferation on cell mat was found to be shared by 22 different human carcinoma cell lines that were tested. This unique clonogenic ability of normal contact-insensitive and human carcinoma cells on the cell mat could provide a selection method for presumptive normal stem and tumor cells and for an assay for screening potential antitumor drugs and assessing the efficacy of chemotherapeutic drugs against a given tumor.

Topics: Carcinoma; Cell Communication; Cell Differentiation; Cell Division; Cell Line; Epithelial Cells; Fetus; Humans; Keratins; Kidney

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

Using an avidin-biotin immunoperoxidase technic, the authors studied 29 anaplastic thyroid tumors (ATTs) to determine the frequency of hormonal (thyroglobulin--TG; calcitonin--CT), epithelial (epithelial membrane antigen, monoclonal keratin), or sarcoma (desmin; alpha-1-antichymotrypsin--ACT; vimentin) markers. Their results indicate that 27% of ATTs stain for TG and none for CT. Fifty-five percent showed epithelial markers, 48% marked for ACT, and 47% for vimentin. Coexpression of keratin and vimentin was found in 39% of cases tested. The expression of the tested antigens did not correlate significantly with histologic pattern (epithelial vs. "sarcomatous"). Of note is the fact that 30% of the ATTs the authors tested expressed none of the markers they examined, indicating total lack of differentiation.

Topics: Adult; Aged; Aged, 80 and over; Anaplasia; Calcitonin; Carcinoma; Chymotrypsin; Epithelium; Female; Humans; Immunoenzyme Techniques; Keratins; Male; Membrane Proteins; Middle Aged; Mucin-1; Sarcoma; Thyroglobulin; Thyroid Neoplasms; Vimentin

In this study we examined 198 sarcomas, 38 carcinomas, 13 'tumours with a spindle cell component' and 22 malignant melanomas with a commercial monoclonal vimentin antibody. All histopathological material was formalin fixed and paraffin embedded. The results show this antibody to be a sensitive and specific marker of mesenchymal derivation or differentiation. It is a useful tool in separating sarcomas from most carcinomas, and in separating malignant melanomas from carcinomas. When used in combination with a cytokeratin antibody it identifies carcinosarcomas and synovial sarcomas.

Topics: Antibodies, Monoclonal; Carcinoma; Carcinosarcoma; Diagnosis, Differential; Humans; Immunoenzyme Techniques; Keratins; Melanoma; Neoplasms; Retrospective Studies; Sarcoma; Vimentin

This study compares the immunoprofiles of 25 cutaneous and mucosal melanomas with those of 400 poorly differentiated carcinomas, using a polyclonal antiserum to S100 and murine monoclonal antibodies to keratin (KER) and epithelial membrane antigen (EMA). All malignant melanomas expressed S100 but lacked reactivity for KER and EMA. Conversely, all of 49 carcinomas (12%) that displayed S100 also exhibited positivity for both epithelial markers. The latter group of tumors included 17 carcinomas of the breast, 16 eccrine sweat gland carcinomas, five high-grade salivary glandular adenocarcinomas, four lung cancers, three pancreatic ductal carcinomas, two serous ovarian carcinomas, one clear cell adenocarcinoma of the bladder, and one uterine cervical squamous carcinoma. None of 32 epithelial neoplasms that lacked both KER and EMA (19 testicular seminomas, four hepatocellular carcinomas, eight adrenocortical carcinomas, and one Merkel's cell carcinoma) contained S100 protein. These results suggest that S100 protein is relatively nonspecific as a single immunodeterminant in the diagnostic separation of melanoma and anaplastic carcinoma. The concomitant use of stains for EMA and KER, however, obviates this problem. Finally, since it is somewhat restricted in distribution, S100 reactivity in a known carcinoma may be of some use in predicting possible primary sources for a metastasis of unknown origin.

Topics: Carcinoma; Diagnosis, Differential; Histocytochemistry; Humans; Immunoenzyme Techniques; Keratins; Melanoma; Membrane Proteins; Mucin-1; Neoplasm Proteins; Predictive Value of Tests; S100 Proteins

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

The distribution of cytokeratin antigens during embryogenesis of the kidney and in 57 renal tumours has been studied using immunocytochemical techniques. A polyclonal antiserum to epidermal prekeratins and the monoclonal antibodies CAM 5.2 and PKK1 have been used to identify cytokeratins of different molecular weights. The ureteric bud-derived structures expressed large molecular weight cytokeratins. The tubular component of the kidney expressed cytokeratins detected by CAM 5.2 and PKK1. During glomerular development there was transient expression of low molecular weight cytokeratins by the visceral glomerular epithelium but in the adult kidney only the parietal epithelium expressed cytokeratins. Tubules in nephroblastomas contained low molecular weight cytokeratins but the blastema did not. Some ureteric bud-derived structures were identified in six nephroblastomas. Renal carcinomas expressed low molecular weight cytokeratins. Four collecting duct carcinomas were studied; these all expressed the large molecular weight cytokeratins found in collecting duct epithelium. These results indicate that the cytokeratin phenotype of renal tumours is unchanged from that of the normal epithelial cells.

Topics: Antibodies, Monoclonal; Carcinoma; Cytoskeletal Proteins; Fetus; Humans; Immunologic Techniques; Keratins; Kidney; Kidney Neoplasms; Wilms Tumor

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

In order to investigate the intermediate filament protein content of hormone producing lung tumor cell cultures a panel of 16 different cytokeratin antisera were tested using immunocytochemical and biochemical techniques on lung carcinoma cell cultures from different origin. These included three cell cultures derived from small cell lung carcinoma, two large cell carcinoma cell cultures, and two cell cultures derived from squamous cell carcinomas. Flow cytometric analysis of the cell cultures demonstrated that all cell lines examined were aneuploid with DNA-indices ranging from 1.7 to 3.1 rimes the DNA-content of normal human lymphocytes. In both immunofluorescence and immunoperoxidase techniques six out of seven cell cultures reacted with most of the cytokeratin antisera used in a filamentous manner, while a large cell carcinoma cell culture did not react with any of the cytokeratin antisera used. None of the cell cultures examined reacted with the antibodies to neurofilament proteins, suggesting that none of these (neuro)hormone producing cell cultures were of neural origin. All cell cultures which were growing as adherent cell cultures did express vimentin. The cell culture that grew with cells floating in aggregates did not express this intermediate filament protein while a subline which did attach, expressed vimentin. This findings strongly indicates the relation between growth pattern in vitro (floating vs. adherent) and the expression of vimentin. No reaction was found with antisera to desmin and GFAP. The presence of cytokeratins and vimentin in most cell cultures could be confirmed using one- and two-dimensional gel electrophoresis. Cytokeratins 7, 8, 18 and 19 were most commonly present.

Topics: Carcinoma; Carcinoma, Small Cell; Carcinoma, Squamous Cell; Cell Line; Cytoskeleton; Electrophoresis, Polyacrylamide Gel; Flow Cytometry; Fluorescent Antibody Technique; Histocytochemistry; Humans; Immunoenzyme Techniques; Intermediate Filament Proteins; Intermediate Filaments; Keratins; Lung Neoplasms; Neurofilament Proteins

Topics: Adenoma; Carcinoma; Cytoskeleton; Fluorescent Antibody Technique; Histocytochemistry; Humans; Immunoenzyme Techniques; Intermediate Filaments; Keratins; Salivary Gland Neoplasms; Vimentin

Immunohistochemical analysis of 21 prototypic mucosal spindle-cell carcinomas of the aerodigestive tract was performed at the Armed Forces Institute of Pathology (AFIP) to establish the usefulness of selected immunohistochemical markers in distinguishing spindle-cell carcinoma from other mucosal spindle-cell neoplasms. Immunoreactive keratin could be demonstrated in only 13/21 (62%) of cases. Coexpression of keratin and vimentin was demonstrated in 10/17 (59%) of the tumors evaluated for both of these intermediate filaments. All spindle-cell carcinomas lacked S100 protein, which is an immunoreactivity we would expect to find in spindle-cell malignant melanoma, one of the principal considerations in a differential diagnosis. Both alpha-1-antitrypsin (AAT) and alpha-1-antichymotrypsin (ACT) were demonstrated in the tumor cells in all cases. However, albumin had a similar distribution in the tumors, which suggested that passive uptake was a serious confusing factor. The results of this study indicate that AAT and ACT are unreliable markers for distinguishing spindle-cell carcinomas from malignant fibrous histiocytomas.

Topics: Aged; alpha 1-Antichymotrypsin; alpha 1-Antitrypsin; Antigens, Neoplasm; Carcinoma; Female; Head and Neck Neoplasms; Humans; Keratins; Male; Middle Aged; Muramidase; S100 Proteins; Serum Albumin; Vimentin

We studied four mixed carcinoma-neuroendocrine neoplasms from gastrointestinal tract and pancreas by routine light microscopy (LM), immunohistochemistry (IH), electron microscopy (EM), and ultrastructural cytochemistry (UC). By LM, the individual tumors showed fairly pure neuroendocrine (carcinoid) or epithelial (papillary) patterns, mixed neuroendocrine-carcinoma features and poorly-differentiated tumor in sheets and nests which did not lend itself to morphologic characterization. IH demonstrated mixed expression, within different areas of the same neoplasm, of epithelial antigens (keratins and carcinoembryonic antigen [CEA]) and neuroendocrine markers (neuron-specific enolase [NSE], bombesin and neurohormonal peptides). By EM, each tumor showed ultrastructural features of epithelial and neuroendocrine differentiation which varied substantially in terms of number of cells involved and their distribution; two of the neoplasms showed biphasic differentiation within single cells. The nature of the neurosecretory granules was verified with the uranaffin reaction (UR). This study illustrates the value of combining LM, IH, EM and UC for the identification of mixed carcinoma-neuroendocrine lesions.

Topics: Aged; Bombesin; Carcinoembryonic Antigen; Carcinoma; Female; Gastrointestinal Hormones; Gastrointestinal Neoplasms; Histocytochemistry; Humans; Immunologic Techniques; Keratins; Male; Pancreatic Neoplasms; Phosphopyruvate Hydratase

The case of a young woman is presented who had a long history of oral contraceptive use and who was found to have a focal hepatic adenoma within a large spindle cell carcinoma of the liver. The pleomorphic tumor is positive for keratin and alpha 1-antitrypsin by immunohistochemistry, has intracellular lumina by electron microscopy, a moderately high thymidine labeling index, and is negative for estrogen and progesterone receptors. A review of the literature concerning liver tumors occurring in young patients indicates that there is an underlying disturbance of the hormonal milieu in all instances reported. The prognosis is widely variable and unpredictable.. Clinical and laboratory evidence of an association of oral contraceptive (OC) use with the subsequent development of benign and malignant hepatobiliary neoplasia is growing. The authors present a case in which an adenoma within a large, multicentric anaplastic spindle cell carcinoma occurred in a woman with a long history of OC use. The patient, a 38-year-old gravida 2, para 2, was diagnosed following low-grade fevers and right upper quadrant pain. A partial hepatectomy was performed with no complications; however, a follow-up examination 2 months later revealed widespread intra-abdominal tumor recurrence histologically identical to the original tumor. Immunostaining for alpha 1 antitrypsin and keratin was strongly positive in tumor cells, indicating a biliary derivation. Electron microscopy indicated an epithelial derivation as well, including the presence of intracellular lumens, intermediary filaments, and numerous intercellular junctions. Estrogen and progesterone receptors were negative in the tumor. The tritiated thymidine labeling index was 5.05%, with an estimated potential doubling time of 11 days. This woman had no history of hepatitis, no family or personal history of neoplasms, and no known hepatotoxin exposure. The only medication used by the patient was Norlestrin, an OC containing 1 mg norethindrone and 50 mcg ethinyl estradiol that she had taken continuously for the past 8 years.

Topics: Adult; alpha 1-Antitrypsin; Biopsy, Needle; Carcinoma; Carcinoma, Hepatocellular; Contraceptives, Oral, Combined; Ethinyl Estradiol; Female; Histocytochemistry; Humans; Keratins; Liver; Liver Neoplasms; Microscopy, Electron; Norethindrone; Time Factors

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

Forty-three cases of large cell anaplastic thyroid carcinoma were examined with various antisera. Four histological patterns were identified: spindle cell, giant cell, trabecular and squamous. In 38 cases the epithelial origin was demonstrated with various epithelial markers: 11 cases stained positively for thyroglobulin, 19 for T3 and/or T4, 35 for fat globule membrane antigens, 28 for keratin, 29 for lactoferrin, and one for calcitonin. Five cases were negative for all epithelial markers but could not be characterized further since, except for vimentin, they did not have mesenchymal markers. The immunohistochemical proof of the epithelial nature of anaplastic thyroid tumours is given by staining with anti-keratin and anti-fat globule membrane antigen. In addition the detection of lactoferrin seems useful, but not that of thyroglobulin which was present in only 4% of the spindle cell tumours and in 32-56% of the other histological types. Thirty carcinomas were positive for vimentin; the co-expression of vimentin and epithelial markers seems frequent in thyroid anaplastic carcinomas.

Topics: Aged; Aged, 80 and over; Animals; Calcitonin; Carcinoma; Female; Histocytochemistry; Humans; Immunoenzyme Techniques; Keratins; Lactoferrin; Lectins; Male; Membrane Proteins; Middle Aged; Mucin-1; Peptides; Plant Lectins; Rabbits; Thyroglobulin; Thyroid Neoplasms; Thyronines; Tissue Polypeptide Antigen; Vimentin

Four clonal cell lines of two types were established from a heterotransplantable mixed mesodermal tumor of the human ovary. Biologic properties of these cell lines (designated CS-C1, CS-S1, CS-S2, and CS-S3) were examined. Cells of one line (CS-C1) had an epithelioid shape and grew in monolayers (C-type). The cells showed alkaline phosphatase activity, stained positively with antikeratin antiserum, and had an ultrastructure with carcinomatous characteristics. Cells of the other three cell lines (CS-S1, CS-S2, and CS-S3) had an irregular shape and grew in multilayers (S-type). Most of the cells did not show alkaline phosphatase activity. They stained, not with antikeratin antiserum, but in fibrillar array with antifibronectin antiserum. Their ultrastructure had sarcomatous characteristics. By low cell density cultures, S-type sublines arose from CS-C1 cell line, but no C-type sublines arose from CS-S1 cell line. These findings may support the theory of the combination tumor as the cytogenesis of mixed mesodermal tumor of the ovary; they also suggest the conversion of carcinomatous cells to sarcomatous cells.

Topics: Carcinoma; Cell Line; Female; Humans; Karyotyping; Keratins; Microscopy, Electron; Neoplasms, Germ Cell and Embryonal; Ovarian Neoplasms; Sarcoma; Tumor Cells, Cultured

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

Eight cases of esophageal carcinoma with prominent spindle cells (carcinosarcoma or pseudosarcoma) were studied using the avidin-biotin immunoperoxidase method and monoclonal antibodies to various keratins and vimentin. In all eight cases positive immunoreactivity for keratin was found in carcinomatous areas and for vimentin, in the spindle cells. It is interesting that five cases demonstrated focal immunoreactivity to keratin in the spindle cell component. Trace positivity to vimentin was seen in the carcinomatous areas in one case. These findings are consistent with the hypothesis that esophageal carcinoma with prominent spindle cells is of epithelial origin and may represent a morphologic variant of squamous cell carcinoma.

Topics: Aged; Aged, 80 and over; Antibodies, Monoclonal; Carcinoma; Carcinoma, Squamous Cell; Carcinosarcoma; Esophageal Neoplasms; Female; Fibroma; Humans; Immunoenzyme Techniques; Keratins; Male; Middle Aged; Molecular Weight; Vimentin

Primary cultures of cells from breast carcinomas were attempted in 74 cases. Growth was observed in 46 cases. Using immunochemical demonstration of keratin proteins (KER), epithelial membrane antigen (EMA) and carcinoembryonic antigen (CEA), three morphologically distinct cell populations were characterized and described. Two cell types (E- and E'-cells) were identified as epithelial by their positive staining for KER and EMA. The third type (F cells) displayed a negative staining for these two epithelial markers; they were considered as stromal cells (fibroblasts). More than 50% of the cultures consisted of pure epithelial cells. Positive CEA staining was observed only in KER- and EMA-positive cells. Out of the 30 cultures, 15 displayed positive staining for CEA. In 7 of these, 30-50% of cells displayed positive, diffuse staining for CEA. The other 8 cultures consisted of more than 50% CEA-positive cells. Strong and homogeneous positivity was restricted to the E-cells, while in the same cultures, E'-cells displayed heterogeneous and diffuse staining. Efficiency and value of this cell culture system are discussed, in comparison with other human breast tumor cell (HBTC) culture techniques. Identification of growing cells and cellular composition of primary cultures are emphasized.

Topics: Breast Neoplasms; Carcinoembryonic Antigen; Carcinoma; Cells, Cultured; Female; Humans; Immunohistochemistry; Keratins; Membrane Glycoproteins; Mucin-1

Human esophageal carcinoma cell lines (8 cell lines) differed from their normal counterpart in terms of their morphological appearance, growth properties, and the expression of certain differentiated functions, namely keratin proteins and cross-linked envelopes. In contrast to normal human esophageal keratinocytes, the carcinoma cells were pleomorphic and tended to pile up in an unorganized fashion. When grown under optimal growth conditions the carcinoma cells generally grew to a higher saturation density than their nontransformed counterpart; their generation times were variable. Transformed cells grew better under stringent growth conditions (e.g., decreased serum and no additional growth factors except hydrocortisone) than did nontransformed human esophageal keratinocytes but their growth was still restricted under these conditions. The carcinoma cells retained a requirement for a 3T3 feeder layer when grown at clonal densities (5 X 10(3) cells/60-mm dish) but could be passaged and maintained without a feeder layer if plated at higher than clonal densities (10(5) cells/60-mm dish). All cell lines grew in an anchorage-independent fashion in soft agarose although the colony forming efficiency and size of the colonies varied among the different cell lines. Not all anchorage-independent cell lines were tumorigenic. Tumorigenic potential was greatly augmented by the use of cell lines derived from soft agarose selected clones. Altered expression of keratin proteins and cross-linked envelopes was observed in the carcinoma cell lines and generally reflected those changes seen in primary esophageal carcinomas. In two cell lines (HCE-4 and HCE-6), the synthesis of the Mr 44,000 (analogous to Rheinwald's Mr 40,000 keratin) and 52,000 keratins was suppressed coincident with the appearance of the 67 Kd keratin in tumors derived from these cell lines. These keratin patterns were once again reversed in cell lines recultured from these tumors, suggesting that the expression of these specific keratins is subject to extrinsic growth regulation. Another feature of terminal differentiation in keratinocytes, cross-linked envelope formation, was found to be significantly altered (reduced) in most but not all human esophageal carcinoma cell lines.

Topics: Animals; Carcinoma; Cell Differentiation; Cell Division; Cell Line; Cell Membrane; Cells, Cultured; Epithelium; Esophageal Neoplasms; Esophagus; Humans; Keratins; Lasalocid; Mice; Mice, Nude; Molecular Weight; Neoplasms, Experimental

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 diagnosis of adrenocortical carcinoma (ACC) is often difficult, because this tumor may present with direct extension into adjacent renal parenchyma or with metastatic disease. Renal cell carcinoma and other histologically similar tumors are potentially confused with ACC by conventional light microscopy, and their separation from the latter is often impossible without the aid of additional studies. Furthermore, the distinction between adrenal cortical adenoma and ACC may also be problematic. Because of these factors, the authors studied 10 cases each of ACC, adrenocortical adenoma, and renal cell carcinoma (RCC) immunohistochemically, in an attempt to develop objective parameters which may aid in this differential diagnostic dilemma. Nontrypsinized, formalin-fixed, paraffin-embedded specimens were used in all cases, and tissue from the adrenocortical tumors was also studied for intermediate filament content after protease digestion. All 20 nontrypsinized adrenocortical neoplasms were positive for vimentin, but not for cytokeratin, epithelial membrane antigen, or blood group isoantigens. Conversely, each of 10 cases of RCC expressed epithelial membrane antigen, cytokeratin, and blood group isoantigens, but none was immunoreactive for vimentin. Two adrenocortical carcinomas and three adenomas manifested cytokeratin positivity after trypsin digestion. There were no significant differences between the immunostaining profiles of ACC and adrenocortical adenoma, which suggest that this distinction must still rely upon clinical and morphologic criteria.

Topics: Adenoma; Adrenal Cortex Neoplasms; Adult; Aged; Antigens; Blood Group Antigens; Carcinoma; Carcinoma, Renal Cell; Cell Nucleolus; Cell Nucleus; Child, Preschool; Cytoplasm; Diagnosis, Differential; Epithelium; Female; Histocytochemistry; Humans; Immunoenzyme Techniques; Infant; Isoantigens; Keratins; Kidney Neoplasms; Male; Middle Aged; Vimentin

Twenty-four cases of thymic epithelial tumors, including 18 cases of thymoma, five cases of squamous cell carcinoma, and one case of undifferentiated carcinoma, were studied immunohistochemically using monoclonal antibody Leu-7 (HNK-1) and antikeratin antibody. Seven cases of non-neoplastic thymic tissues were also studied. Leu-7 antibody stained epithelial cells in the outer cortex of the normal thymus, and antikeratin antibody stained thymic epithelial cells in both cortex and medulla of the normal thymus. Seventeen thymomas and one undifferentiated carcinoma were focally or diffusely stained with Leu-7, some showing cortical and medullary differentiation as seen in the normal thymus. On the other hand, none of the five squamous cell carcinomas were stained with Leu-7. All thymomas stained for keratin in varying degrees, and all squamous cell carcinomas were diffusely and strongly stained with antikeratin antibody. It is concluded that normal thymic epithelial cells showed zonal differentiation, and neoplastic cells were considered to retain these characteristics to some extent; i.e., thymomas had the same phenotype of epithelial cells of the cortex, especially the outer cortex of the thymus in some instances (Leu-7-positive, keratin-positive) and of both cortex and medulla (mixture of Leu-7-positive and -negative cells) with organoid arrangement in other instances, and thymic squamous cell carcinoma had the same phenotype as epithelial cells in the thymic medulla (Leu-7-negative, keratin-positive).

Topics: Antigens, Surface; Carcinoma; Carcinoma, Squamous Cell; Epithelium; Humans; Immunoenzyme Techniques; Keratins; Thymoma; Thymus Neoplasms

For six patients with partial or total laryngectomies with extensive mucosal hyperplasias, we generated DNA histograms from multiple mucosal sites using Feulgen-stained tissue sections and microspectrophotometric microscopy. Aneuploid DNA histograms were identified in the mucosa of all six specimens, indicating that neoplastic transformation had occurred. The histologic characteristics of neoplastic change included thickened or hyperplastic epithelium, surface maturation or keratinization, often a proliferation of small, immature basallike cells in the depths of the epithelium, and evidence of abnormal epithelial maturation as evidenced by focal areas of cytoplasmic keratinization in the lower portions of the mucosa. We think this histologic expression of intraepithelial neoplasia is more common than the "classic" form of carcinoma in situ with full mucosal replacement by proliferating immature basallike cells. Keratin is a common reaction in laryngeal mucosa, and its presence on the surface or in the depths of the epithelium does not militate against the diagnosis of severe intraepithelial neoplastic transformation.

Topics: Aged; Carcinoma; Carcinoma in Situ; Carcinoma, Squamous Cell; Cell Transformation, Neoplastic; DNA, Neoplasm; Epithelium; Humans; Hyperplasia; Keratins; Laryngeal Mucosa; Laryngeal Neoplasms; Male; Middle Aged

Human breast carcinomas have been one of the most difficult tumor types to culture in agar-based clonogenic assays. This fact has limited their clinical applicability. We have used statistically motivated experimental designs to systematically improve the clonal culture of enzymatically monodispersed primary human carcinoma cells in an anchorage-independent agar system. Based upon an initial comparison of two basal media, we selected one which gave the best colony growth and then sought to optimize the individual additives in the medium. Hydrocortisone, fetal bovine serum, and red blood cells all improved both plating efficiency and median size of colonies derived from breast carcinoma cells. Next, the concentrations of these three components were simultaneously idealized using response surface methodology. By these methods, it was found that the optimal concentration of hydrocortisone was 0.35 microgram/ml, fetal bovine serum was 6.5%, and red blood cells was 2.1 X 10(7) cells/ml. Using these culture conditions, we have achieved plating efficiencies of 0.39% and 0.19% for colonies with diameters greater than 50 (50 cells) or 70 (130 cells) micron, respectively.

Topics: Animals; Breast Neoplasms; Carcinoembryonic Antigen; Carcinoma; Cells, Cultured; Culture Media; Erythrocytes; Female; Hormones; Humans; Hydrocortisone; Keratins; Membrane Proteins; Mucin-1; Oxygen; Rats; Subcellular Fractions

Twenty cases of undifferentiated thyroid tumours were reviewed histologically. In seven cases the histogenesis was difficult to determine using morphological criteria. Immunohistochemical staining with a panel of antibodies to lymphoid and epithelial cells, including monoclonal antibodies directed against the leucocyte common antigen, cytokeratin, and epithelial membrane antigen confirmed that four of these cases were lymphomas and that one was a medullary carcinoma. In the remaining two cases immunohistochemistry was unhelpful. In the thirteen histologically typical tumours, the immunohistochemical profile was in keeping with their histogenesis as determined by morphological criteria. Immunohistochemical staining with a panel of selected antibodies allows the reliable diagnosis of undifferentiated thyroid neoplasms, when this cannot be reached using routine histological techniques.

Topics: Aged; Antibodies, Monoclonal; Antigens; Carcinoma; Female; Histocompatibility Antigens; Humans; Immunoenzyme Techniques; Keratins; Lymphoma; Membrane Proteins; Middle Aged; Mucin-1; Thyroid Neoplasms

Two monoclonal antibodies, KA 1 and KA 4, raised against human epidermis, were biochemically and immunologically characterized and were shown to react with specific cytokeratin polypeptides. On frozen sections of human mammary gland, these antibodies distinguish between myoepithelial and luminal epithelial cells. We present evidence that in these cells KA 1 antibody recognized cytokeratin 5 and KA 4 antibody cytokeratin 19. In normal mammary tissue, KA 4 antibody invariably reacted with the epithelial cells lining the lumina of acini, ductules, ducts, and sinus. In contrast, KA 1 antibody decorated only the myoepithelial and basal epithelial cells of acini, ducts, and sinus. In ductules, however, KA 1 also stained the luminal cells. All 73 invasive lobular and ductal carcinomas studied reacted with KA 4 antibody; five of these were also positive, apparently in the same tumor cells, with KA 1. The tumor cells of in situ carcinomas were also stained in a homogeneous pattern with KA 4 antibody; KA 1 antibody reacted only with the surrounding myoepithelium. In epithelial hyperplasias, the proliferating cells were decorated by KA 1 and KA 4 antibodies in a heterogeneous pattern. Other antibodies were used for comparison. The results are discussed with respect to epithelial differentiation and pathogenesis and to the application of such antibodies for immunohistodiagnosis of mammary lesions.

Topics: Adenoma; Antibodies, Monoclonal; Antibodies, Neoplasm; Breast Neoplasms; Carcinoma; Carcinoma in Situ; Carcinoma, Intraductal, Noninfiltrating; Epithelium; Female; Fibroma; Fluorescent Antibody Technique; Humans; Keratins; Lactation; Neoplasm Proteins; Papilloma; Pregnancy

Tumours of uncertain tissue of origin were investigated by immunohistochemistry on formalin fixed paraffin embedded sections. Two antibodies--PD7/26, an anti common leucocyte antigen, and CAM5.2, an anticytokeratin--recognised most lymphomas and carcinomas, respectively: 88% of these tumours were identified by the two antibodies alone. These antibodies permitted the separation of the cases into groups: positive with CAM5.2, positive with PD7/26, and a third comprising those negative with both. The negative group contained other tumours and a small number of carcinomas and lymphomas; many of the lymphomas were, apparently, of histiocytic origin. Comparison of CAM5.2 with other epithelial markers showed that it was the most effective. Some further classification of the tumours was carried out with a panel of organ and cell specific antibodies: mesotheliomas were recognised by their pattern of reactivity with epithelial markers. Overall, the tumour type was determined in 90% of cases. Immunohistochemistry performed as described can be a potent aid to the diagnostic histopathology of tumours.

Topics: Antibodies, Monoclonal; Breast Neoplasms; Carcinoma; Carcinoma, Squamous Cell; Histocompatibility Antigens; Humans; Keratins; Leukocyte Common Antigens; Lymphoma; Mesothelioma; Neoplasms; Sarcoma; Skin Neoplasms; Thyroid Neoplasms

Paraffin sections of formalin-fixed tumor samples from 26 patients with neuroendocrine (Merkel cell) carcinoma of the skin (NECS) were studied immunohistochemically with three monoclonal antibodies to low molecular weight keratin (MAB-K) and with antibodies to leukocyte common antigen (LCA), neurofilament (NF), neuron-specific enolase (NSE), S100 protein (S100), and chromogranin (CGN), to investigate the relative diagnostic value of these antibodies. Samples from 20 lymphomas, 10 non-oat cell undifferentiated carcinomas, 10 oat cell carcinomas, and 10 melanomas served as controls. Keratin was found in 25 of the 26 NECS and in all undifferentiated and oat cell carcinomas. A ball-like immunostaining for keratins, resembling an inclusion body was seen only in cases of NECS and some carcinoids. Neurofilament, NSE, and CGN were expressed by fewer NECS than was keratin and all NECS were negative for LCA and S100. None of the lymphomas and melanomas contained detectable keratin, NF, NSE, or CGN. Only the lymphomas stained with LCA. Only the melanomas were S100-positive. It is concluded that keratin is the most useful single discriminating marker in the separation of neuroendocrine (Merkel cell) carcinoma of the skin from lymphoma, melanoma and, when the characteristic inclusion-like pattern is seen, from metastatic oat cell carcinoma.

Topics: Adult; Aged; Antibodies, Monoclonal; Carcinoid Tumor; Carcinoma; Carcinoma, Small Cell; Diagnosis, Differential; Female; Gastrointestinal Neoplasms; Histocytochemistry; Humans; Immunochemistry; Keratins; Lung Neoplasms; Lymphoma; Male; Melanoma; Microscopy, Electron; Middle Aged; Nerve Tissue Proteins; Skin Neoplasms

The presence and distribution of tissue polypeptide antigen (TPA) were assessed in gastrointestinal carcinomas of different origin, morphology and degree of differentiation. Immunocytochemistry was employed, using the PAP technique on formalin-fixed, paraffin-embedded material and compared with the results obtained with antibodies to cytokeratins. Like cytokeratins, TPA was a reliable marker of epithelial differentiation and showed tissue distribution patterns similar to cytokeratins, as revealed by antibodies with broad-range cytokeratin immunoreactivity. In most carcinomas, TPA-specific immunostaining was less intense than in non-neoplastic tissue. No direct relationship between intensity of TPA staining and morphological degree of differentiation and proliferation was found. TPA staining was most pronounced at the periphery of the cells. In stratified epithelium, i.e. oesophageal mucosa, basally located cells exceeded superficial cells in TPA immunoreactivity in contrast to the cytokeratin antibodies which decorated the more superficially placed cell layers. TPA and cytokeratin staining patterns were similar in neoplastic and non-neoplastic gastric, intestinal mucosa, as well as in biliary tract epithelium. Antral and cardial mucoid glands of the stomach as well as gastric carcinomas of the pylorocardial type remained unstained with both types of antibodies. Similar staining with TPA and cytokeratin antibodies was also observed in pancreatic and liver tissue. In this study, hepatocytes were, although weakly, stained by TPA antibodies and an identical staining was found with benign and malignant hepatocellular neoplasms. Ductal and ductular TPA-staining was most conspicuous and so was the immunoreactivity of cholangiocellular carcinomas. A comparison between TPA and cytokeratins was also made by immunoblotting which revealed immunoreactivity of antibodies to TPA with cytokeratin polypeptides of different species (man, mouse) and organs (epidermis, liver), particularly with the cytokeratin component 8 of human liver and the related component A of mouse liver. The significance of this finding is uncertain until the pertinent epitopes have been revealed by monoclonal mapping of the components which exhibit similar molecular weights by SDS polyacrylamide gel electrophoresis.

Topics: Antigens, Neoplasm; Carcinoma; Gastrointestinal Neoplasms; Histocytochemistry; Humans; Immunochemistry; Keratins; Peptides; Tissue Distribution; Tissue Polypeptide Antigen

Epithelial membrane antigen and keratin proteins represent markers of epithelial differentiation that may be detected in routine formalin-fixed, paraffin-embedded tissues. Eighty-seven neoplasms, including 48 adenocarcinomas of various types, squamous and transitional cell carcinomas, small-cell anaplastic carcinomas, carcinoid tumors, mesotheliomas, hepatomas, melanomas (metastatic), adrenal cortical carcinomas, germ cell tumors, and extramammary Paget's disease, were assessed to determine the relative effectiveness of these antigens as tumor markers. Immunoperoxidase studies were performed using monoclonal antibodies to epithelial membrane antigen and monoclonal (combined AE1 and AE3) and polyclonal (bovine muzzle keratins) antibodies to keratin proteins. In more than half the cases (50/87%), both markers yielded comparable results. However, in 29 cases (33%), keratin proteins were clearly superior to epithelial membrane antigen as a tumor cell marker. Particular discrepancies were apparent for some gastrointestinal adenocarcinomas, squamous cell carcinomas, hepatomas (hepatocellular type), spindle cell components of mesotheliomas, and carcinoid tumors. Epithelial membrane antigen represented a better marker in eight cases (9%), mainly for small-cell anaplastic carcinomas and some renal cell and pulmonary adenocarcinomas. Adrenal cortical carcinomas, melanomas, and seminomas were nonimmunoreactive for both antigens. Epithelial membrane antigen and keratin proteins represent useful complementary markers in diagnostic surgical pathology.

Topics: Antibodies, Monoclonal; Antigens, Neoplasm; Antigens, Surface; Carcinoma; Humans; Immunoenzyme Techniques; Keratins; Lymphoma; Membrane Proteins; Mucin-1; Neoplasms

Twenty-one cases of anaplastic carcinoma of the nasal cavity and paranasal sinuses were diagnosed by conventional light microscopy and the use of monoclonal antibodies to epithelial membrane antigen and cytokeratin. Lymphomas and malignant melanomas were excluded by immunohistochemical staining for leukocyte common antigen and S100 protein respectively. The median survival time for these patients was only 1 year despite all forms of treatment. Two patients survived for a longer period and their cases had unusual pathologic features that may have influenced the prognosis.

Topics: Adult; Aged; Antibodies, Monoclonal; Antigens, Surface; Carcinoma; Carcinoma, Squamous Cell; Female; Histocompatibility Antigens; Histocytochemistry; Humans; Immunoenzyme Techniques; Keratins; Leukocyte Common Antigens; Male; Middle Aged; Nose Neoplasms; Paranasal Sinus Neoplasms; Prognosis; S100 Proteins; Staining and Labeling

The unlabeled antibody peroxidase-antiperoxidase technique was used to examine esophageal neoplasms for the tumor markers beta-human chorionic gonadotropin, human placental lactogen (HPL), alpha-fetoprotein, carcinoembryonic antigen (CEA), and nonspecific cross-reacting antigen (NCA) before and after xenotransplantation to athymic nude mice. In addition, keratin was used as an epithelial cell marker. Immunoreactive beta-human chorionic gonadotropin was detected in four of seven primary tumors and in three of seven xenografts. Two of seven primary tumors contained HPL immunoreactive cells while four of seven tumor xenografts had HPL immunoreactivity. alpha-Fetoprotein was detected in two of seven primary tumors and in one of seven xenografts. NCA and CEA were detected in six of seven primary tumors and in all tumor xenografts. Five of seven primary neoplasms and six of seven tumor xenografts were found to contain both NCA and CEA, while one tumor and its xenografts displayed only NCA immunoreactivity. All seven primary carcinomas displayed keratin immunoreactivity, but only six of the seven xenograft tumors showed keratin positive cells. When a tumor marker was detected in a primary tumor, it was usually found in at least some of the xenografts arising from that tumor. However, marker loss did occur with repeated passage of tumors in some cases. On the other hand, markers were expressed in xenografts which were not present in the corresponding primary tumor. In three instances, HPL was detected in xenografts derived from HPL negative primary carcinomas. This was also true for CEA and NCA in one case. These results show that tumor markers are expressed to varying degrees by tumors growing as xenografts in nude mice. In primary tumors, HPL is associated with poorly differentiated squamous cell carcinomas and this marker was found to appear in HPL negative tumors as the tumor cells became less differentiated while growing as xenografts in nude mice.

Topics: alpha-Fetoproteins; Animals; Antigens, Neoplasm; Carcinoembryonic Antigen; Carcinoma; Cell Adhesion Molecules; Chorionic Gonadotropin; Esophageal Neoplasms; Glycoproteins; Humans; Immunoenzyme Techniques; Keratins; Mice; Mice, Nude; Neoplasm Transplantation; Placental Lactogen

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 malignant intraepithelial proliferations--malignant melanoma level I, bowenoid epithelial dysplasia, and mammary as well as extramammary Paget's disease--may cause differential diagnostic difficulties. We have examined 12 cases of malignant melanoma level I, nine cases of bowenoid epithelial dysplasia, 17 cases of extramammary and five cases of mammary Paget's disease for S100 protein, carcinoembryonic antigen (CEA), cytokeratin, and keratin to evaluate the sensitivity and specificity of these reactions with regard to their differential diagnostic value. Antibodies against S100 reacted specifically with the tumor cells in intraepithelial malignant melanomas; antibodies against CEA reacted specifically with the tumor cells in Paget's disease; and cytokeratin and keratin antibodies reacted with the epithelial tumor cells in Paget's disease as well as in bowenoid epithelial dysplasia. However, only antibodies to CEA and keratin showed 100% sensitivity. We conclude that the investigated antibodies may be of differential diagnostic value in cases of intraepidermal neoplasias, but that a negative reaction does not exclude diagnosis of these diseases.

Topics: Bowen's Disease; Breast Neoplasms; Carcinoembryonic Antigen; Carcinoma; Diagnosis, Differential; Humans; Immunologic Techniques; Keratins; Melanoma; Paget Disease, Extramammary; Paget's Disease, Mammary; Retrospective Studies; S100 Proteins; Skin Neoplasms

The histogenetic origin of the spindle-cell component of spindle-cell carcinoma of the head and neck mucosa remains controversial. The spindle cells have been considered a variant growth pattern of squamous-cell carcinoma, a non-neoplastic mesenchymal reaction, and a malignant admixture of epithelial and mesenchymal neoplasm. To evaluate the spindle-cell component, we studied 25 tumors (18 biphasic and seven monophasic) by utilizing the following: an avidin-biotin complex immunoperoxidase technique with a variety of antikeratin antibodies (AE1, AE3, CAM 5.2, 35BH11, and polyclonal Dako) and a monoclonal antivimentin antibody, and an avidin-biotin alkaline phosphatase double-labeling technique to detect coexpression of keratin and vimentin. The immunohistologic staining pattern was compared with electron-microscopic studies. Eight of 18 biphasic neoplasms contained immunoreactive keratin in the spindle-cell component that was distributed focally in a minority of cells in 3 tumors and diffusely throughout five of the neoplasms. Four of seven ulcerated monophasic spindle-cell tumors devoid of histologic squamous-cell carcinoma also were keratin positive, confirming epithelial differentiation. The majority of the spindle cells in all the tumors contained vimentin intermediate filaments. In three immunoperoxidase keratin positive biphasic tumors examined with alkaline phosphatase double labeling, occasional spindle cells were found that coexpressed keratin and vimentin and were interspersed with cells expressing either intermediate filament. Electron microscopy was performed on the spindle-cell component of 13 tumors, nine biphasic and four monophasic. Of the biphasic tumors, four were immunoperoxidase keratin positive; three of these showed epithelial differentiation by electron microscopy. Five biphasic tumors were keratin negative, and three tumors had epithelial differentiation by electron microscopy. Four monophasic spindle-cell tumors were immunoperoxidase keratin positive, and one of these had epithelial features by electron microscopy. Two monophasic tumors were keratin negative and without ultrastructural evidence of epithelial features. By using a combination of immunohistochemical and electron-microscopic observations, we identified evidence for epithelial differentiation in the spindled cells in 11 of 18 biphasic tumors and four of seven monophasic spindle-cell tumors.

Topics: Aged; Aged, 80 and over; Antibodies, Monoclonal; Carcinoma; Carcinoma, Squamous Cell; Female; Head and Neck Neoplasms; Humans; Immunoenzyme Techniques; Keratins; Laryngeal Neoplasms; Male; Microscopy, Electron; Middle Aged; Mucous Membrane; Vimentin

Eight cases of a highly aggressive undifferentiated carcinoma of the nasal cavity and paranasal sinuses are described. The patients, who ranged in age from 30-77 years, had multiple sinonasal symptoms, and each had involvement of the nasal cavity, maxillary antrum, and ethmoid sinus. Six tumors extended into the orbital bones, and five penetrated the cranial cavity. Five patients died of disease from 1 to 41 months after diagnosis (median: 4 months), and three are alive with tumor less than 1 year following diagnosis. Microscopically, the neoplasms formed nests, trabeculae, and sheets containing medium-sized cells with small to moderate amounts of eosinophilic cytoplasm. A high mitotic rate, tumor necrosis, and prominent vascular permeation were characteristic. Seven neoplasms were immunoreactive for cytokeratin, five for epithelial membrane antigen, and four for neuron-specific enolase. Ultrastructurally, occasional small desmosomes and rare membrane-bound, dense-core granules were observed. Sinonasal undifferentiated carcinoma is a distinctive clinicopathologic entity that must be distinguished from other, less aggressive sinonasal neoplasms.

Topics: Adult; Aged; Carcinoma; Combined Modality Therapy; Ethmoid Sinus; Female; Follow-Up Studies; Humans; Keratins; Male; Maxillary Sinus Neoplasms; Membrane Proteins; Middle Aged; Mucin-1; Nasal Cavity; Neuroectodermal Tumors, Primitive, Peripheral; Nose Neoplasms; Orbital Neoplasms; Paranasal Sinus Neoplasms; Phosphopyruvate Hydratase

Two hundred and three sarcomas, 40 carcinomas, 10 carcinomas with spindle cell features, 27 malignant melanomas and one spindle cell melanoma were examined using CAM 5.2, a monoclonal antibody to cytokeratin. This antibody which was prepared against colorectal carcinoma cells and which identifies low molecular weight intermediate filament cytokeratin proteins is suitable for use in formalin fixed, paraffin embedded material. Seventeen of the 203 sarcomas showed positive staining. These included 15/21 synovial sarcomas, 1/5 epithelioid sarcomas and 1/18 malignant neural tumours. Five carcinosarcomas showed positive staining of their epithelial components but negative staining of their spindle cell components; three out of four pure spindle cell carcinomas stained positively; a metastasis from a spindle cell renal carcinoma was negative. A spindle cell thymoma also stained positively. Thirty-seven of the 40 carcinomas stained positively; the three negative carcinomas were a squamous cell carcinoma, a renal cell carcinoma and an oat cell carcinoma. All malignant melanomas were negative. These results are compared with those of other workers and the sensitivity and specificity of CAM 5.2 as an epithelial marker is assessed.

Topics: Antibodies, Monoclonal; Carcinoma; Histocytochemistry; Humans; Keratins; Melanoma; Sarcoma; Sarcoma, Synovial; Vimentin

Topics: Antigens, Neoplasm; Carcinoma; Cytoskeletal Proteins; Desmoplakins; Diagnosis, Differential; Female; Humans; Immunoenzyme Techniques; Intermediate Filaments; Keratins; Membrane Proteins; Ovarian Neoplasms; Vimentin

Topics: Antigens, Neoplasm; Carcinoma; Cytoskeletal Proteins; Desmoplakins; Epithelium; Epitopes; Fluorescent Antibody Technique; Humans; Keratins; Membrane Proteins

Two cell lines, named VX2T and VX2R, were isolated from the transplantable VX2 carcinoma, a wholly anaplastic tumor established from a carcinoma induced by the Shope cottontail rabbit papillomavirus (CRPV) (J.G. Kidd and P. Rous, J. Exp. Med. 71:813-838, 1940). The CRPV genome was found to be maintained and transcribed in both cell lines, as in the VX2 carcinoma. The VX2T cells retained the tumor-producing capacity in the rabbit and the low expression of epidermal keratinocyte differentiation of the VX2 tumor cells. The VX2R cells, although tumorigenic for nude mice, were no longer serially transplantable in the rabbit and expressed differentiated functions of keratinocytes. These data indicate that the anaplastic characteristic and the transplantability of VX2 carcinoma cells to immune competent allogenic hosts may be lost without any detectable modification of the physical state and transcription of the CRPV genome.

Topics: Animals; Carcinoma; Cell Differentiation; Cell Line; Cytoskeletal Proteins; DNA, Neoplasm; DNA, Viral; Keratins; Neoplasm Transplantation; Papillomaviridae; Rabbits; Skin Neoplasms; Tumor Virus Infections

Two distinctly different clonal cell lines were isolated from a mammary tumor induced by ingestion of 7,12-dimethylbenz[a]anthracene (CAS: 57-97-6) in a SD rat. Cells of one of the clones, RMT-1 clone E4, showed typical epithelial characters; it was concluded that they were derived from neoplastic mammary epithelial cells. The other clone, M2, exhibited characters consistent with its derivation from the normal mammary myoepithelial component. The 2 cell lines had different proliferative responses to growth factors (GF) such as cholera toxin, dexamethasone, and epidermal GF. The epithelioid E4 cells were found to produce potent growth-promoting activity in culture medium that stimulated proliferation of myoepithelial M2 cells as well as that of stromal fibroblasts. The present work provides supporting evidence that the mechanism of "paracrine stimulation" is operative in the mammary tumorigenesis of the rat.

Topics: Animals; Carcinoma; Cell Line; Culture Media; Cytoskeleton; Epidermal Growth Factor; Female; Glycoproteins; Growth Substances; Keratins; Mammary Neoplasms, Experimental; Rats; Rats, Inbred Strains

Antisera of several secretory products of the salivary gland were used to investigate the histogenesis of acinic cell tumors and mixed salivary gland tumors for comparison. Amylase, lactoferrin, secretory piece, and proline-rich protein (PRP) immunoreactivity was detected in the majority of acinic cell tumors; staining was focal, except for PRP, which was diffuse. Lysozyme immunoreactivity was rare. There was discordance for immunoreactivity with several antisera in identifiable tumor lobules of half of the neoplasms. An antikeratin serum outlined microcystic and follicular areas but rarely solid foci. These findings support the contention that acinic cell tumors derive from a tubular type stem cell. Lactoferrin and secretory piece immunoreactivity was not common in mixed tumors and was confined to scattered ductal cells and luminal contents. Rare small foci of amylase and PRP immunoreactivity were found in two mixed tumors only.

Topics: Adenoma, Pleomorphic; Adolescent; Adult; Aged; Amylases; Carcinoma; Female; Humans; Immunochemistry; Keratins; Lactoferrin; Male; Middle Aged; Muramidase; Peptides; Proline-Rich Protein Domains; Salivary Gland Neoplasms; Staining and Labeling

A monoclonal antibody, 44-3A6, was raised against the human pulmonary adenocarcinoma cell line A549. This antibody recognizes a protein antigen at the cell surface, which is preserved after formalin fixation and paraffin embedding. Immunohistochemical staining of lung tissue with this antibody revealed diffuse immunoreactivity of type II pneumocytes. Bronchial epithelial cells were also focally immunoreactive. Immunostaining of various bronchopulmonary carcinomas demonstrated characteristic patterns of reactivity. All of the 42 adenocarcinomas and 18 carcinoids were strongly immunoreactive either diffusely or focally. The immunoreaction occurred at the cell membrane and/or in the cytoplasm. None of the 39 squamous cell carcinomas, 12 bronchioloalveolar carcinomas, and 30 small cell neuroendocrine carcinomas was immunostained. Ten intermediate cell neuroendocrine carcinomas and 8 well-differentiated neuroendocrine carcinomas were relatively weakly immunoreactive, while 7 and 2 of them were negative. Six adenosquamous carcinomas were focally positive in glandular and "basaloid" areas, whereas squamous areas were negative. Twenty-one large cell carcinomas were focally immunoreactive, while 6 were negative. It appears that MCA 44-3A6 is an effective marker for certain features of "glandular" differentiation, which may be present even in tumors lacking obvious glands, and that it may be useful for the differential diagnosis of various bronchopulmonary carcinomas.

Topics: Adenocarcinoma; Antibodies, Monoclonal; Carcinoma; Diagnosis, Differential; Histocytochemistry; Humans; Keratins; Lung Neoplasms

Alterations in the pattern of epidermal differentiation and proliferation occur during mouse skin carcinogenesis. We have used cDNA clones corresponding to the major keratin subunits synthesized in differentiating epidermal cells (Mr 67,000 and 59,000) and in proliferating epidermal cells (Mr 60,000, 55,000, and 50,000) to study changes in keratin gene transcript levels in mouse epidermis exposed to tumor promoters. The same probes were used to characterize the keratin expression patterns in benign and malignant skin tumors. A single topical treatment with 12-O-tetradecanoylphorbol-13-acetate caused a rapid initial decrease in the epidermal transcript levels corresponding to the Mr 67,000 and 59,000 keratin subunits. By 48 h the transcript level for the Mr 67,000 keratin subunit was restored to control values, whereas the transcript levels for the Mr 59,000 subunit returned to control at a slower rate. In contrast, the transcript level for the Mr 55,000 subunit was increased substantially 12- 48 h after treatment, the Mr 50,000 subunit transcript increased to a lesser extent, and the Mr 60,000 subunit message was transiently decreased at 12 h but returned to the level of solvent-treated skin by 24 h. Single exposure to the incomplete tumor promoters 4-O-methyl-12-O-tetradecanoylphorbol-13-acetate, the ionophore A23187, and mezerein induced changes in keratin gene transcripts similar to those of 12-O-tetradecanoylphorbol-13-acetate. The antipromoter fluocinolone acetonide, administered with 12-O-tetradecanoylphorbol-13-acetate, partially inhibited the decrease in the Mr 59,000 and 67,000 transcripts and completely inhibited the increase in the Mr 55,000 transcript. In skin papillomas produced by initiation and promotion, keratin gene expression was similar to normal skin, with the exception of a two-fold increase in the transcript levels for the Mr 55,000 keratin subunit. However, in carcinomas, the transcript levels for the Mr 67,000 and 59,000 subunits were only 1-3% of those observed in untreated mouse epidermis. In concert with other data, the rapid and selective loss of transcripts for differentiation-related keratins after exposure to both complete and incomplete tumor promoters is most consistent with an accelerated rate of maturation in differentiating keratinocytes, resulting in the rapid production of transcript-depleted fully mature squames. The enhanced level of Mr 55,000 transcripts suggests a concomitant increase in the number of all cells or

Topics: Animals; Carcinoma; Female; Fluocinolone Acetonide; Gene Expression Regulation; Keratins; Mice; Molecular Weight; Papilloma; Phorbols; Skin; Skin Neoplasms; Tetradecanoylphorbol Acetate; Transcription, Genetic

Papillomas induced by standard initiation-promotion protocols progress to carcinomas at a low frequency. Experimental protocols were developed to elicit papillomas with a higher probability of malignant conversion. SENCAR mice initiated by 7,12-dimethylbenz[a]anthracene were promoted by treatment with 12-O-tetradecanoylphorbol-13-acetate (TPA) for 5, 10, 20 or 40 weeks. With promotion for 10 weeks or more, a peak of papilloma incidence at 16-20 weeks was followed by a 35-40% decrease within 3 months. A much lower papilloma response was seen in mice promoted for 5 weeks, but these papillomas persisted. The yield of malignant tumors was similar in all four groups, with 20-25 carcinomas per group of 30 mice. Thus, the papillomas induced by the first few TPA treatments are much more likely to progress to carcinomas than those which appear later. In a separate study, initiated Charles River CD-1 mice were promoted with TPA for either 12 or 52 weeks. Acetone solvent treatment was begun at Week 13 in the group treated 12 weeks with TPA. At Week 16, the papilloma incidence was identical in the two groups of mice. However, by Week 28, the papilloma yield in the continuous TPA group had increased and was twice that of the acetone group, in which papillomas had regressed. The first carcinoma arose 14 weeks earlier with continuous TPA, but the final number of carcinomas per group of 40 mice was 17 with TPA and 20 with acetone. Neither the increase in papillomas in TPA-treated mice nor the regression of papillomas after cessation of promotion with TPA affected the final carcinoma yield. This result suggests that TPA-dependent papillomas are very unlikely to progress to carcinomas. In a third experiment, promotion of initiated SENCAR mice with mezerein resulted in a small number of papillomas which had a much higher probability of progression to carcinomas than the large number of papillomas promoted by TPA. The ability to induce papillomas promoted by TPA. The ability to induce papillomas with a known probability of conversion to carcinomas will facilitate the identification of markers associated with malignant progression.

Topics: 9,10-Dimethyl-1,2-benzanthracene; Animals; Carcinoma; Cocarcinogenesis; Diterpenes; DNA; Female; Keratins; Mice; Mice, Inbred Strains; Papilloma; Probability; Terpenes; Tetradecanoylphorbol Acetate; Time Factors

The undifferentiated malignant neoplasm presents a significant problem in the intelligent selection of therapy. Because of advances in chemotherapy, there are cancers that are effectively palliated, and sometimes cured if appropriately treated. Characterization of tumors by immunohistochemical stains drastically reduces the incidence of "undifferentiated" diagnoses and will optimize patient management, as illustrated by two cases of large-cell lymphoma arising in skeletal muscle.

Topics: Biopsy; Carcinoembryonic Antigen; Carcinoma; Diagnosis, Differential; Histocytochemistry; Humans; Immunoglobulins; Immunologic Techniques; Keratins; Lymphoma; Male; Middle Aged; Muscle Proteins; Muscles; Muscular Diseases; Sarcoma

We have isolated a mouse monoclonal antibody that, upon immunohistochemical localization in frozen sections, displays specificity for human myoepithelial cells in the resting mammary gland, sweat glands, and salivary glands. Furthermore, this antibody was strongly and homogeneously reactive with frozen sections of 3 of 60 breast carcinoma specimens. Using immunolocalization techniques in conjunction with polyacrylamide gel electrophoresis, we have determined that the reactivity of this monoclonal antibody is directed toward a 51,000-dalton keratin polypeptide. The potential uses of this antibody in the prognosis of human mammary carcinoma and in understanding the role of the myoepithelium in development and differentiation are discussed.

Topics: Animals; Antibodies, Monoclonal; Breast; Breast Neoplasms; Carcinoma; Carcinoma, Intraductal, Noninfiltrating; Cell Differentiation; Electrophoresis, Polyacrylamide Gel; Epithelium; Humans; Keratins; Mice; Mice, Inbred BALB C; Neoplasm Proteins; Salivary Glands; Sweat Glands

We report a case of polypoid spindle cell squamous carcinoma (pseudosarcoma) occurring in the anal canal. Electron microscopic findings and the demonstration of keratin by an immunoperoxidase method, gave clear cut evidence of the epithelial nature of the sarcomatoid cells forming this tumour. To our knowledge, this is the first reported case in the literature.

Topics: Anus Neoplasms; Carcinoma; Humans; Keratins; Male; Microscopy, Electron; Middle Aged

A large number of human neoplasms were tested for their keratin expression in routinely processed tissues by a simple, three-stage immunoperoxidase method using a broadly reactive monoclonal anti-keratin antibody AE1, which recognizes a number of keratin polypeptides distributed in a wide variety of epithelia. All carcinomas, with the exception of hepatocellular, adrenocortical, and basal cell carcinomas and occasional renal cell, pulmonary small-cell, and pulmonary large-cell anaplastic carcinomas, reacted with this antibody irrespective of differentiation, in most instances displaying staining of strong or moderate intensity in the majority of tumor cells. Equivocal results were obtained in some seminomas and dysgerminomas. Malignant melanoma, large-cell lymphoma, Hodgkin's disease, malignant histiocytosis, and stromal mesenchymal elements in all tumors did not show any reactivity with AE1. Even after routine processing, the determinant detected by AE1 is conserved and restricted to epithelial neoplasms. This suggests that AE1 would be valuable in the diagnostic distinction of anaplastic carcinoma from lymphoma and melanoma in routinely processed tissues.

Topics: Antibodies, Monoclonal; Antibody Specificity; Carcinoma; Epithelium; Immunoenzyme Techniques; Keratins; Neoplasm Proteins; Neoplasms

We have examined 18 primary malignant lung tumours categorized as either carcinosarcoma, blastoma or spindle-cell carcinoma according to accepted criteria. Two monoclonal antibodies to keratins, CAM 5.2 and LP 34, were used to determine whether the non-epithelial or spindle-cell components of each tumour showed evidence of keratin expression. By this means the epithelial nature of the five tumours classified as spindle-cell carcinomas was confirmed. In all four pulmonary blastomas and in five of nine carcinosarcomas, the sarcomatous elements failed to stain for keratin but in the remaining four carcinosarcomas there was focal staining. The histogenesis of these tumours is discussed and it is suggested that the sarcomatous component of a carcinosarcoma may be derived from malignant epithelial cells by a process of mesenchymal metaplasia with a switch in intermediate filament type. It remains uncertain whether blastomas are derived from both endoderm and mesoderm, or from either one of these tissues, with one component representing complete metaplastic transformation.

Topics: Aged; Antibodies, Monoclonal; Carcinoma; Carcinosarcoma; Cell Transformation, Neoplastic; Female; Humans; Intermediate Filaments; Keratins; Lung Neoplasms; Male; Middle Aged; Neoplasms, Germ Cell and Embryonal

Neuroendocrine (Merkel cell) carcinomas of the skin have been recognized as such for several years. Given the reported wide variability in the morphology and clinical evolution of these tumors, the notion that may they comprise several variants rather than a single type has been advocated. Electron microscopy has played a key role in the early recognition of these tumors while immunohistochemical studies for various neuroendocrine markers have facilitated their subsequent diagnosis and improved our understanding as to their complexity by the demonstration of immunoreactivity for NSE (neuron specific enolase) and a number of neuropeptides. There has also been considerable interest in the study of the cytoskeletal intermediate filament complement of neuroendocrine neoplasms in general and of those of the skin in particular. Early reports indicated that neuroendocrine skin carcinomas had neurofilaments while subsequent investigations determined that they had cytokeratin. However, more recent studies have indicated that at least some neuroendocrine skin carcinomas could in fact coexpress both aforementioned classes of intermediate filament proteins. This brief report is presented to confirm the latter investigations.

Topics: Carcinoma; Humans; Immunoenzyme Techniques; Intermediate Filament Proteins; Keratins; Male; Microscopy, Electron; Middle Aged; Neurofilament Proteins; Nose Neoplasms; Skin Neoplasms

Because tissue culture studies have suggested that mesothelial cells might produce large amounts of vimentin, I stained eight mesotheliomas (two fixed in alcohol) for vimentin using the Gown and Vogel monoclonal antibody 43 beta E8. The two tumors that had alcohol fixed blocks were strongly positive for vimentin, whereas one of the tumors fixed only in formalin showed moderately strong staining and two others showed very weak focal positivity; the remaining tumors were negative. In the mesotheliomas that did stain, both epithelial and spindled elements gave a positive reaction. Three alcohol-fixed lung cancers and two blocks of alcohol-fixed pleura failed to stain for vimentin. By contrast, all mesotheliomas and carcinomas, whether alcohol or formalin fixed, as well as sections of pleura, were strongly positive when stained with anticytokeratin antibody 35 beta H11. I conclude that the combination of staining for vimentin and keratin might be a useful diagnostic finding in malignant mesothelioma, but that specially fixed material is required for reliable vimentin staining.

Topics: Antibodies, Monoclonal; Carcinoma; Humans; Immunoenzyme Techniques; Keratins; Mesothelioma; Pleural Neoplasms; Vimentin

Topics: Breast; Breast Neoplasms; Carcinoma; Carcinoma in Situ; Carcinoma, Intraductal, Noninfiltrating; Female; Fibronectins; Humans; Immunoenzyme Techniques; Keratins; Laminin; Neoplasm Proteins

A clinicopathologic study was done of 21 cutaneous, sarcoma-like lesions previously diagnosed as atypical fibroxanthoma, spindle cell carcinoma, or dermal sarcoma. These lesions were most commonly presented as a solitary, often ulcerated nodule, occurring on exposed skin of the face in the elderly or, occasionally, on roentgen-damaged or burnt skin of the head, leg, or hand. Microscopic features of the 21 lesions were, however, not alike, thereby implying that such sarcoma-like lesions had derived from heterogeneous origins. The immunohistochemical staining in a comparative study with two other cases of unequivocal spindle cell squamous carcinoma suggested that these lesions could be histogenetically divided into two different groups: (1) the major group of true atypical fibroxanthoma, consisting of 19 cases, and (2) the minor group of probable spindle cell squamous carcinoma, consisting of 2 cases. Despite a wide histologic spectrum and of heterogeneity of these lesions, there was a benign clinical course in the majority, due in part to the small size and superficial location of the lesions.

Topics: Adult; Aged; Carcinoma; Diagnosis, Differential; Female; Fibroma; Histocytochemistry; Humans; Immunoenzyme Techniques; Keratins; Male; Middle Aged; Skin Neoplasms

Twenty cases of infiltrating lobular carcinoma (12 of classical type, five of trabecular type and three of alveolar type) and one case of lobular carcinoma in situ were studied by transmission electron microscopy. The in situ component in three of the infiltrating carcinomas was also studied. The ultrastructure of the tumour cells in the alveolar variant of infiltrating lobular carcinoma was the same as seen in the tumour cells of lobular carcinoma in situ. The tumour cells in infiltrating lobular carcinoma of the classical and trabecular types had more irregular nuclei and were more organelle- and filament-rich. Immunohistochemical staining for the presence of alpha-lactalbumin was proved in 19 per cent of the cases, casein 81 per cent, CEA in 65 per cent and prekeratin in 90 per cent. The light microscopic separation of some subgroups of infiltrating lobular carcinoma may be difficult, in particular the distinction between the classical and the trabecular variants. Unfortunately, our study shows that these distinctions cannot easily be made either by electron microscopy or by light microscopic immunohistochemistry with antibodies against prekeratin, CEA, casein and alpha-lactalbumin.

Topics: Adult; Aged; Breast Neoplasms; Carcinoembryonic Antigen; Carcinoma; Carcinoma in Situ; Caseins; Cell Nucleus; Female; Humans; Intermediate Filament Proteins; Keratins; Lactalbumin; Microscopy, Electron; Middle Aged; Protein Precursors

Seventy cases of anaplastic thyroid carcinomas studied at the Universities of Florence (Italy) and Minnesota are presented. Three morphologic patterns were seen: spindle, giant cell, and squamoid, sometimes in combination. Ultrastructurally, evidence of epithelial differentiation was seen in most but not all cases studied. Immunohistochemically, a stain for cytokeratin using a monoclonal antibody was found the most useful adjunct to diagnosis. Unexpected positivity for carcinoembryonic antigen (CEA) was found in several squamoid tumors. The alleged frequent positivity of this tumor type for thyroglobulin and calcitonin was not confirmed. A third of the tumors were associated with a better differentiated component, of which, presumably, they represented a dedifferentiation. The extremely aggressive behavior of anaplastic thyroid carcinomas was confirmed amply in this series: all of the patients in whom follow-up information was available died of their tumor. Small cell tumors should not be included into the anaplastic category, since they invariably belong to other groups, i.e., malignant lymphoma, medullary carcinoma, and poorly differentiated ("insular") carcinoma.

Topics: Adult; Aged; Calcitonin; Carcinoembryonic Antigen; Carcinoma; Carcinoma, Papillary; Combined Modality Therapy; Diagnosis, Differential; Female; Histocytochemistry; Humans; Immunochemistry; Keratins; Male; Microscopy, Electron; Middle Aged; Neoplasm Metastasis; Palliative Care; Sarcoma; Staining and Labeling; Thyroglobulin; Thyroid Neoplasms

Eighteen examples of nasopharyngeal carcinoma (NPC), a tumor with potential diagnostic difficulty, were studied retrospectively. Using the WHO classification, 16 cases were undifferentiated carcinoma (UC). Immunohistochemistry for each tumor was performed on paraffin sections using two commercially available polyclonal antisera and a monoclonal antibody, AE-1. Method 1 used trypsinization, overnight incubation with the primary antibody and the avidin-biotin complex (ABC) technic. Method 2 used a 20-minute incubation with the primary antibody without trypsinization and employed the peroxidase-antiperoxidase (PAP) technic. Method 2 is the one most frequently employed by pathologists who use immunohistochemistry as a diagnostic aid. Method 1 gave clear positive results in each case with antibody AE-1 and, in most cases, with the polyclonal antisera. Electron microscopy in 10 cases demonstrated desmosomes in each case and easily demonstrable tonofilaments in five. The results of this study indicate that in the diagnosis of UC, the most common variant of NPC, squamous differentiation can be documented readily by electron microscopy and immunohistochemistry for keratin proteins. With the latter, optimization of technic is essential for reliable results.

Topics: Adult; Aged; Antibodies, Monoclonal; Carcinoma; Carcinoma, Squamous Cell; Female; Humans; Immunoenzyme Techniques; Keratins; Male; Microscopy, Electron; Middle Aged; Nasopharyngeal Neoplasms; Retrospective Studies

Twenty-one examples of neuroendocrine carcinoma of the skin were examined by the unlabeled antibody enzyme method for several neural hormones and peptides, carcinoembryonic antigen, S-100 protein, neuron-specific enolase, and three intermediate filaments: neurofilament, glial fibrillary acidic protein, and cytokeratin. Vasoactive intestinal polypeptide from two sources reacted with the neoplastic cells of four (18%) and seven (32%) of the cases, and pancreatic polypeptide reacted with scattered cells of one case. Neuron-specific enolase reactivity occurred in 50% of the cases. Neurofilament (70, 150, 200 kilodaltons) was strongly positive in 40% of the tumors whereas neurofilament (200 kilodaltons) was negative. Two monoclonal anticytokeratin antibodies of 54 kilodaltons and 44-54 kilodaltons reacted in 77% and 64% of the cases, respectively, in a distribution similar to the neurofilament. Sections reacted with antisera against cytokeratins of higher molecular weight were negative. The demonstration of vasoactive intestinal polypeptide, pancreatic polypeptide, neurofilament, and neuron-specific enolase is evidence of the neuroendocrine nature of this neoplasm.

Topics: Carcinoma; Epidermal Cells; Epidermis; Humans; Immunoenzyme Techniques; Intermediate Filament Proteins; Keratins; Neurofilament Proteins; Pancreatic Polypeptide; Phosphopyruvate Hydratase; Skin Neoplasms; Vasoactive Intestinal Peptide

Normal salivary glands and 55 salivary gland tumors were examined by immunostaining (immunoperoxidase [IMP] and immunofluorescence [IMF]) to identify myoepithelial cells (MCs) and speculate on their role in the histogenesis of the tumors. The classic (C) MCs of normal salivary glands stained by IMP with antibodies to cytokeratin and S100 protein and stained by IMF with the same antibodies and with antibodies to vimentin and actin. Modified (M) MCs of pleomorphic adenomas stained positively by IMP and IMF with all of the preceding antibodies. In many mucoepidermoid carcinomas, adenoid cystic carcinomas, and basal cell adenomas, variable numbers of CMCs and MMCs stained positively by IMP with anti-cytokeratin and anti-S100 protein antibodies. No MCs were detected in adenolymphomas or acinic cell carcinomas. We believe that MCs play a major role in the histogenesis of pleomorphic adenomas and may also be important in many mucoepidermoid carcinomas, adenoid cystic carcinomas, and basal cell adenomas.

Topics: Actins; Adenolymphoma; Adenoma; Adenoma, Pleomorphic; Carcinoma; Carcinoma, Adenoid Cystic; Epithelial Cells; Epithelium; Fluorescent Antibody Technique; Histocytochemistry; Humans; Immunoenzyme Techniques; Keratins; Membrane Proteins; Mucin-1; Muscle, Smooth; S100 Proteins; Salivary Gland Neoplasms; Salivary Glands; Vimentin

Immunohistochemical studies using antisera to keratin and secretory component (SC) and monoclonal antibody against leukocyte common antigen (LCA) were performed on 92 biopsy and autopsy specimens taken from 65 patients with nasopharyngeal carcinoma. Five biopsy specimens from malignant lymphoma of the nasopharynx and tonsil, and 20 biopsy specimens of nasopharyngeal epithelium were also included in the study. Keratin was positively stained in all squamous cell carcinomas and nonkeratinizing carcinomas, and 38 of 46 undifferentiated carcinomas (82.6%), but in no malignant lymphomas. LCA was intensely stained in all malignant lymphoma, but in no nasopharyngeal carcinomas. SC was positively stained in two of the 46 undifferentiated carcinomas (4.3%). Nasopharyngeal carcinoma is a definite malignant epithelial neoplasm and can be distinguished from malignant lymphoma by immunostaining for keratin and LCA. Some undifferentiated carcinoma may show cellular differentiation toward ciliated epithelium.

Topics: Adolescent; Adult; Aged; Antigens; Carcinoma; Carcinoma, Squamous Cell; Child; Female; Histocompatibility Antigens; Histocytochemistry; Humans; Immunoenzyme Techniques; Immunoglobulin Fragments; Keratins; Leukocyte Common Antigens; Leukocytes; Lymphoma; Male; Middle Aged; Nasopharyngeal Neoplasms; Secretory Component

Two cases of breast tumors with a uniform solid carcinoid pattern and argyrophilic dense-core granules were analyzed by immunohistochemistry in order to compare their characteristics with known features of other carcinoid tumors and ordinary breast carcinomas. The tumors were positive for keratin-type intermediate filaments, neuron-specific enolase and alpha-chain of human chorion gonadotropin but negative for vimentin and S-100 protein. Laminin was found only in a rim between tumor cell islands and stroma but not among the cells. It is concluded that these tumors are histologically, ultrastructurally and immunohistochemically similar to other carcinoid tumors. The present results suggest that both breast carcinoids and carcinomas may have a common precursor in the mammary secretory unit.

Topics: Aged; Breast Neoplasms; Carcinoid Tumor; Carcinoma; Chorionic Gonadotropin; Diagnosis, Differential; Female; Fluorescent Antibody Technique; Humans; Immunoenzyme Techniques; Keratins; Laminin; Middle Aged; Phosphopyruvate Hydratase; Staining and Labeling

Prostate acid phosphatase (PAP), prostate-specific antigen (PSA), carcinoembryonic antigen (CEA) and keratin were determined immunohistochemically in paraffin sections from 64 prostatic carcinomas fixed in formalin according to the conventional method. The results obtained with PSA led to the correct diagnosis of prostatic carcinoma in 90.7% of the cases. 80.3% of the diagnoses obtained with PAP were correct. The intensity of the staining of the marker decreased with increasing differentiation. 3 utricular carcinomas were positive for PAP and PSA. CEA and keratin may be considered unspecific tumor markers only. However, metaplastic squamous epithelium from poorly differentiated carcinomas was always positive for keratin. PAP and PSA are also suitable for differentiating between tumors of prostatic and nonprostatic origin and could thus be successfully used to determine immunohistochemically the histogenesis of 15 invasive, poorly differentiated carcinomas of the prostate and bladder. PSA again proved to be a more specific epithelial marker than PAP.

Topics: Acid Phosphatase; Adenocarcinoma; Antigens, Neoplasm; Carcinoembryonic Antigen; Carcinoma; Humans; Immunoenzyme Techniques; Keratins; Male; Prostate-Specific Antigen; Prostatic Neoplasms

Mucoepidermoid carcinoma of the thyroid (MECT) has been recently recognized as a pathological entity. The origin of MECT is unknown but the morphology of this tumour closely resembles features seen in the ultimobranchial body (UB) vestiges. Recent studies in man have shown strong evidence that the so-called solid cell nests (SCN) of the thyroid may correspond to the human UB vestiges. To investigate whether these vestiges are the site of origin of this tumour a comparative study on SCN and MECT was undertaken. One hundred autopsied thyroids cut at 2-3 mm intervals were studied for the presence of SCN. Histochemical (H & E, Alcian blue-PAS, Mayer mucicarmine) and immunohistochemical studies (calcitonin, epidermal keratin) were performed in SCN and four cases of MECT. Sixty percent of thyroids were found to have SCN. They were mainly composed of epidermoid-like cells arranged in solid structures or lining cystic cavities, tubular and follicular structures. Solid clusters usually showed lumina containing PAS-positive and mucin-positive cell debris. Mucin stains also revealed mucinous cells placed around lumina filled by mucosubstances. Characteristic PAS-positive rounded bodies were found filling lumina as well as within some apical epidermoid-like cells, mucinous cells and cell debris. An obvious transition between these cells, cell debris and mucosubstances filling the lumina was noticed; suggesting degenerative changes undergone by the epidermoid-like cell. MECT basically presented all histological and histochemical features shown by SCN, furthermore, calcitonin containing cells were observed in 54% of SCN, while a metastatic MECT also showed scattered C cells within solid islands. The presence of epidermal keratin in all SCN and MECT, together with the previous findings, are strong evidence that MECT could originate in the SCN or human UB vestiges.

Topics: Animals; Calcitonin; Carcinoma; Epidermis; Histocytochemistry; Humans; Keratins; Thyroid Neoplasms; Ultimobranchial Body

Forty-nine cases encompassing 16 different types of malignant lymphoma were examined for their intermediate filament protein (IFP) type by indirect immunofluorescence microscopy of cryostat sections. In all cases, vimentin was shown to be the only IFP type detectable in these tumours. Lymphomas are negative for keratin and desmin, which are characteristic for benign and malignant epithelial or muscular tissues respectively. In addition, eighteen cases are described in which antibodies to intermediate filament proteins were used successfully to distinguish between lymphoma and metastatic carcinoma where differential diagnosis was difficult or impossible on the basis of routine histology.

Topics: Adolescent; Adult; Aged; Antibodies; Carcinoma; Child; Desmin; Diagnosis, Differential; Female; Fluorescent Antibody Technique; Histocytochemistry; Humans; Immunoenzyme Techniques; Intermediate Filament Proteins; Keratins; Lymphoma; Male; Microscopy, Fluorescence; Middle Aged; Vimentin

Five large cell malignant neoplasms were studied by immunohistochemistry and electron microscopy. Ultrastructural examination demonstrated numerous circumferential microvilli in 3 cases and a more polarized distribution in 2 cases. The tumor cells in 2 cases demonstrated the surface glycoprotein T29/33, indicative of a hematopoietic neoplasm. Two cases (including one positive for T29/33) contained intracytoplasmic IgG-kappa. Anti-keratin staining using both polyclonal and monoclonal antibodies was negative. Two patients are alive and in remission after treatment for lymphoma. One died with tumor following a progressive course, and one has been lost to follow-up. A fifth patient died of tumor and at autopsy was found to have a disseminated pancreatic tumor. Microvilli around large malignant cells have been commonly associated with epithelial tumors; however, our findings indicate that, in the absence of intercellular junctions and tonofilaments, the possibility of malignant lymphoma should be considered and pursued immunohistochemistry.

Topics: Aged; Carcinoembryonic Antigen; Carcinoma; Diagnosis, Differential; Female; Follow-Up Studies; Humans; Immunoenzyme Techniques; Immunoglobulins; Keratins; Lymph Nodes; Lymphoma; Male; Mesentery; Microscopy, Electron; Microvilli; Middle Aged

Topics: Carcinoma; Humans; Keratins; Leukoplakia, Oral; Mouth Diseases; Mouth Mucosa; Mouth Neoplasms

Carcinomas of different origin have been tested in immunofluorescence microscopy with the monoclonal murine antibodies CK1-CK4, which recognize a single cytokeratin polypeptide (human cytokeratin No. 18) present in simple but not in stratified squamous epithelia, and with the monoclonal antibody KG8.13 and guinea pig kerA antibodies, both of which recognize a variety of cytokeratins common to almost all epithelial cell types. Tumors derived from simple epithelia, including adenocarcinomas and some other tumors such as ductal breast carcinomas, were strongly stained by all three antibodies. So was a transitional carcinoma of the bladder. In contrast, basal cell epithelioma, cloacogenic carcinoma, and squamous cell carcinoma of skin, tongue, and esophagus appeared negative with CK1-CK4 but positive with the other two antibodies. Other squamous cell carcinomas derived from epiglottis and cervix uteri showed a mixture of positive and negative cells when tested with CK1-CK4, although all tumor cells were positive when tested with KG8.13 and with kerA. Thus, use of an appropriate collection of cytokeratin antibodies with different specificities not only allows tumors of epithelial origin to be distinguished from other tumor types but, in addition, allows a further subdivision of carcinomas in relation to their histologic origin.

Topics: Adenocarcinoma; Animals; Antibodies, Monoclonal; Antibody Specificity; Carcinoma; Carcinoma, Transitional Cell; Colonic Neoplasms; Fluorescent Antibody Technique; Guinea Pigs; Histocytochemistry; Humans; Intermediate Filament Proteins; Keratins; Mice; Urinary Bladder Neoplasms

Monoclonal antibodies against cytokeratins, isolated from human callus, were prepared. Here we describe the characterization of three of these monoclonal antibodies (Clones 77, 78, and 80) with special emphasis on the staining characteristics of a number of normal epithelial tissues and a series of tumors. On thin sections and in immunoblotting experiments our monoclonal antibodies showed different specificities. In immunoblots Clone 80 stained more bands in preparations of cytokeratin from callus, cultured keratinocytes, and a metastasis of a lung carcinoma than Clones 77 and 78. In this last cytokeratin preparation Clones 77 and 78 each stained a separate band not stained by Clone 80. In normal tissues Clone 80 stained all types of epithelia except myoepithelium and podocytes of glomeruli. Clone 78 stained mainly squamous epithelium. Clone 77 stained differentiated squamous epithelium, transitional epithelium, ductal epithelium, and parenchymatous epithelium. These results confirm the heterogeneity of cytokeratins. In neoplasms Clone 77 was positive with adenocarcinoma and squamous cell carcinoma. Clone 78 stained squamous cell carcinoma and well-differentiated adenocarcinoma. Clone 80 stained all epithelial tumors, including anaplastic carcinoma, and is therefore useful in tumor diagnosis.

Topics: Animals; Antibodies, Monoclonal; Antibody Specificity; Bony Callus; Carcinoma; Diagnosis, Differential; Epithelial Cells; Histocytochemistry; Humans; Immunoenzyme Techniques; Intermediate Filament Proteins; Keratins; Mice; Mice, Inbred BALB C

Light-microscopic immunocytochemistry and electron microscopy demonstrated that adenocarcinomas (AC) and squamous cell (epidermoid) carcinomas (SCCs) of human lung contained keratin proteins in the form of tonofilament bundles. However, moderately differentiated (md) SCCs contained abundant keratin, whereas poorly differentiated (pd) SCCs and all ACs contained lesser amounts. Lung tumors with the diagnosis of AC or SCC, as defined by WHO criteria, were also analyzed by immunoprecipitation techniques for the presence of keratin proteins. Regardless of the degree of tumor differentiation, SCCs contained a 44 kd keratin which was lacking in ACs. Interestingly, normal bronchial epithelium also contained the same 44 kd keratin. In addition, as SCCs became more differentiated, they exhibited even greater differences in the profile of synthesized keratins. Specifically, the relative abundance of the intermediate-sized keratins (57 and 59 kd) was increased in the md SCCs. Although keratin protein patterns appear to be a valuable adjunct in distinguishing AC from SCC, their usefulness as a diagnostic tool will require survey of a larger number of poorly differentiated tumors.

Topics: Adenocarcinoma, Bronchiolo-Alveolar; Bronchi; Carcinoma; Carcinoma, Squamous Cell; Epidermis; Histocytochemistry; Humans; Immunochemistry; Immunoenzyme Techniques; Keratins; Lung Neoplasms; Microscopy, Electron; Precipitin Tests

The clinical and morphologic features of four cases of spindle cell carcinoma of the breast are presented, and the comparable features of 35 previously reported cases are reviewed. All tumors contained histologically malignant squamous carcinoma that tended to blend with a spindle cell "pseudosarcomatous" stroma. Patients with this rare tumor tend to present at the same age as patients with other histologic types of breast carcinoma, but the spindle cell tumors are somewhat larger. Although the number of reported patients is too small to serve as a basis for firm conclusions, the prognosis appears similar to that for patients with conventional infiltrating duct carcinoma of the breast.

Topics: Aged; Breast Neoplasms; Carcinoma; Cell Nucleus; Epithelium; Female; Humans; Keratins; Middle Aged; Necrosis; Prognosis

The presence of intermediate filament proteins of cytokeratin/prekeratin type and vimentin type was evaluated in non-neoplastic thyroid glands and in different types of thyroid neoplasms. Follicular epithelium of both normal and goitrous thyroids showed a strong reaction with anticytokeratin antibodies that widely cross-react with various simple epithelia. On the other hand, in normal thyroid, there were only occasionally (in one of 12 cases) solitary cells reacting with antibodies to epidermal prekeratin. In nodular goiters, such cells were often seen (eight of 18), especially among the lining cells of cysts, and in chronic thyroiditis in all (12 of 12) cases. Only the stromal cells and intraluminal macrophages reacted with antibodies to vimentin. Neoplastic cells of papillary carcinomas showed a positive staining reaction both with antibodies to cytokeratins and to epidermal prekeratin. Follicular carcinoma cells, although positive for cytokeratins, could generally not be stained with antibodies to epidermal prekeratin. Medullary carcinoma cells also showed cytokeratin positivity and, only occasionally, positivity for epidermal prekeratin. Anaplastic carcinomas were also reactive with antibodies to cytokeratin but, for the most part, were negative for epidermal prekeratin. Interestingly, some neoplastic cells of all types of thyroid carcinomas also appeared to contain vimentin, as shown with both polyclonal and monoclonal antivimentin antibodies. In contrast to carcinomas, the intermediate filaments of thyroid sarcomas and lymphomas were only of vimentin type. Furthermore, it was found that the papillary structures in benign goiters were only reactive with cytokeratin antibodies and lacked, in contrast to papillary carcinomas, epidermal prekeratin-like immunoreactivity. Hence, the analysis of intermediate filament proteins of thyroid tumors can be utilized to differentiate between papillary and follicular carcinomas and between benign and malignant papillary lesions as well as between anaplastic thyroid carcinomas and sarcomas or lymphomas.

Topics: Adenocarcinoma; Carcinoma; Carcinoma, Papillary; Chronic Disease; Epithelium; Fluorescent Antibody Technique; Goiter, Nodular; Humans; Intermediate Filament Proteins; Keratins; Lymphoma; Protein Precursors; Sarcoma; Thyroid Gland; Thyroid Neoplasms; Thyroiditis; Vimentin

One hundred and twenty seven cases of lung tumors were studied by the immunoperoxidase technique for the presence of CEA and beta-HCG. Twenty-nine of these tumors were additionally stained for keratin and SP1, CEA and SP1 could be demonstrated in 80% of the studied cases, while beta-HCG was found in only 9%. SP1 revealed an almost identical staining pattern to CEA and keratin was found only in squamous cell carcinomas. The tissue positivity of none of these three markers correlated with tumor size, lymphnodal involvement or histological type.

Topics: Adenocarcinoma; Aged; Bronchial Neoplasms; Carcinoembryonic Antigen; Carcinoid Tumor; Carcinoma; Carcinoma, Small Cell; Carcinoma, Squamous Cell; Chorionic Gonadotropin; Female; Histocytochemistry; Humans; Keratins; Lung Neoplasms; Male; Middle Aged; Pregnancy Proteins; Pregnancy-Specific beta 1-Glycoproteins

A total of 43 cases undifferentiated large cell tumours presenting in lymph nodes were stained by immunoperoxidase techniques using antibodies against keratin and a leucocyte-associated glycoprotein. In 26 cases diagnosed histologically as metastatic carcinoma, staining with the keratin antibody suggested a squamous cell origin in 11 cases. This was supported by microscopic observation of intracellular filaments in seven cases. In 15 patients in whom the original diagnosis was uncertain, a definite diagnosis was possible in all cases following immunoperoxidase staining with the two antibodies and most of these proved to be large cell lymphomas. In two cases a potentially major diagnostic error was detected. It is suggested that the staining of undifferentiated human neoplasms using combinations of antibodies reactive with epithelial and lymphoid cells should result in much greater diagnostic accuracy in the field of large cell tumours presenting in lymph nodes.

Topics: Adolescent; Adult; Aged; Antibodies; Carcinoma; Female; Humans; Immunoenzyme Techniques; Keratins; Leukocytes; Lymph Nodes; Lymphatic Metastasis; Lymphoma; Male; Middle Aged; Prospective Studies

We investigated the value of prekeratin immunostaining in establishing the diagnosis of undifferentiated carcinoma of the nasopharyngeal type (lymphoepithelioma). As in squamous cell carcinoma of the nasopharynx, all seven lymphoepithelial carcinomas stained for prekeratin whereas other look-alike but histogenetically different neoplasms (malignant lymphoma, esthesioneuroblastoma, and small round cell sarcomas) did not stain. In addition to confirming the squamous epithelial nature of lymphoepithelioma, our findings indicated that immunoperoxidase staining for prekeratin is a useful diagnostic tool in the differential diagnosis of nasopharyngeal carcinomas in general and lymphoepithelioma in particular.

Topics: Animals; Antibodies; Carcinoma; Histocytochemistry; Humans; Immunoenzyme Techniques; Keratins; Nasopharyngeal Neoplasms; Protein Precursors; Rabbits

Topics: Adult; Carcinoma; Female; Humans; Keratins; Keratosis; Leukoplakia, Oral; Lichen Planus; Male; Middle Aged; Mouth Diseases; Mouth Mucosa; Mouth Neoplasms; Nicotiana; Plants, Toxic; Precancerous Conditions

An infrared spectrum of the calcified epithelioma excised from the eyelid of a three-year old girl was observed. Main absorption peaks were assigned as proteins and calcium phosphate. The crystallinity of calcium phosphate was 41%. The relative content of proteins and calcium phosphate was monitored as 7.4:1, reproducing the spectrum of the calcified epithelioma with a mixture of keratin and calcium phosphate. An epithelioma taken from the trunk of a 41-year-old man showed no calcification and the infrared spectrum of this epithelioma showed no absorption peaks of calcium phosphate.

Topics: Adult; Calcinosis; Calcium Phosphates; Carcinoma; Child, Preschool; Eyelid Neoplasms; Female; Humans; Keratins; Male; Neoplasm Proteins; Skin Neoplasms; Spectrophotometry, Infrared

Two cases of olfactory neuroblastoma mixed with other neoplastic elements are reported. One tumor contained foci of adenocarcinoma and of ganglioneuroblastoma in addition to an undifferentiated small cell component consistent with neuroblastoma; the other tumor histologically resembled small cell undifferentiated carcinoma with foci of squamous differentiation, but was shown by electron microscopy to be neuroblastoma. The histogenesis and treatment of mixed tumors of this type are discussed.

Topics: Adenocarcinoma; Aged; Carcinoma; Carcinoma, Small Cell; Cytoplasm; Humans; Keratins; Male; Nasopharyngeal Neoplasms; Neuroblastoma; Nose Neoplasms

A histological review of 72 undifferentiated thyroid tumors was performed in order to discover small cell anaplastic carcinomas and Non-Hodgkin lymphomas. Cases suspected to be lymphoma were examined for the presence of Ig and keratin and lectins with a PAP-procedure. Among the 72 cases, 68 (94,5%) were anaplastic carcinomas of various types. Four cases (5,5%) were diffuse small cell tumors, which had previously been regarded as anaplastic carcinomas. All four could be identified as Non-Hodgkin lymphomas by histology, immunohistochemistry, repeat biopsy or autopsy. The findings suggest that the majority of small cell anaplastic thyroid tumors are lymphomas and that true anaplastic small cell carcinoma of the thyroid must be extremely rare. Its diagnosis requires electronmicroscopy and/or immunohistochemistry to demonstrate the epithelial nature of tumor cells.

Topics: Adenocarcinoma; Biopsy; Carcinoma; Carcinoma, Small Cell; Carcinoma, Squamous Cell; Diagnosis, Differential; Humans; Immunoenzyme Techniques; Immunoglobulins; Keratins; Lymphoma; Lymphoma, Large B-Cell, Diffuse; Lymphoma, Non-Hodgkin; Thyroid Gland; Thyroid Neoplasms

Nasopharyngeal carcinoma (NPC) provides a unique opportunity to evaluate distinctive epidemiologic features and a possible etiologic relationship with Epstein-Barr virus (EBV) in human malignancy. The lack of a uniformly accepted pathologic classification for NPC has limited the application of this data, although the World Health Organization (WHO) developed a classification that may solve this problem. Monoclonal keratin antibodies were used for staining of NPC for evaluation of its assistance in diagnosis and classification. In the present immunohistochemical study, monoclonal keratin antibodies, designated AE1, AE2, and AE3, and a polyclonal keratin antibody (RAK) were used for study of the presence of keratin in 121 cases of NPC obtained from China and the United States. AE1 monoclonal antibody, which recognizes keratin protein classes 56.5K, 50K, and 40K, was shown to be the most sensitive and specific for NPC tumor cells among the keratin antibodies studied. In addition, some different keratin expression patterns could be identified between different kinds of epithelium and different tumor groups, with possible relevance to the histogenesis of the histologic subtypes of NPC.

Topics: Antibodies, Monoclonal; Carcinoma; Humans; Immunoenzyme Techniques; Keratins; Nasopharyngeal Neoplasms; Nasopharynx

With indirect immunofluorescence microscopy it is possible to visualize intermediate-sized filaments which show a cell-specific distribution and in this manner establish a light-microscopical diagnosis in certain cases which are difficult or impossible to differentiate using conventional methods. We applied the same method to tumours of the head and neck region. Intermediate-sized filaments were studied in four malignant lymphomas, seven carcinomas and four metastases of carcinomas. Malignant lymphomas showed a positive reaction with antibodies to vimentin, carcinomas a positive reaction with antibodies to keratin. Using a monoclonal antibody against a single keratin polypeptide (cytokeratin 18) a further subdivision of the carcinomas was possible. The keratinizing squamous cell carcinoma and two non-keratinizing squamous cell carcinomas showed a positive reaction with the conventional antibody against keratin, but a negative reaction with the monoclonal antibody against cytokeratin 18. One adenocarcinoma, two anaplastic carcinomas and one lymphoepithelial carcinoma were positive with the conventional antibody against keratin and with the monoclonal antibody against cytokeratin 18. Thus lymphoepithelial carcinomas and anaplastic carcinomas should probably not be regarded as special variants of squamous cell carcinoma. In all metastases the same intermediate-sized filaments were demonstrable as in the primary tumour. Certain advantages of immunofluorescence microscopy when compared to diagnostic electron microscopy are discussed.

Topics: Adenocarcinoma; Antibodies, Monoclonal; Carcinoma; Carcinoma, Squamous Cell; Cytoskeleton; Diagnosis, Differential; Fluorescent Antibody Technique; Head and Neck Neoplasms; Humans; Keratins; Lymphatic Metastasis; Lymphoma, Non-Hodgkin; Microscopy, Electron; Vimentin

Cigarette smoking is known to be an important etiologic factor in several lung diseases; however, the number of smokers who develop these diseases represents a small segment of the smoking population. It is possible that evidence of inhalation-induced injury to bronchial epithelial cells of smokers will be reflected in the proteinaceous products of these cells, thereby identifying a high-risk subgroup. We have tested this hypothesis by analysis of 2 proteins, free secretory component (FSC) and the keratins, in lavage fluids obtained from 4 groups of subjects: 30 normal nonsmokers, 15 asymptomatic smokers, 22 symptomatic smokers, and 40 carcinoma patients. Among symptomatic smokers, FSC relative to total protein (FSC/TP) was depressed compared with that in nonsmokers and asymptomatic smokers. The keratins were detected only in symptomatic smokers and correlated with pack/years of smoking history (p = 0.017). Carcinoma patients had depressed FSC/TP and detectable keratin (33 of 38 patients studied). Lung sections from carcinoma patients studied immunohistochemically revealed an apparent inverse relationship between tissue FSC and keratins. This inverse relationship was borne out by analysis of these proteins in the lavage fluid of cancer patients (r = -0.4, p = 0.04). Thus, in cancer patients, immunohistochemical evidence of airway injury correlates with bronchial lavage levels of mucosal epithelial cell proteins. It is possible that smokers with altered levels of these proteins may be the ones at increased risk of smoking-associated lung disease.

Topics: Adolescent; Adult; Aged; Bronchi; Carcinoma; Enzyme-Linked Immunosorbent Assay; Epithelium; Glycoproteins; Humans; Keratins; Lung Neoplasms; Middle Aged; Smoking; Therapeutic Irrigation

Surgical specimens of the salivary gland tumor were studied by immunohistochemical techniques using the anti-keratin antibody and the anti-myosin antibody. In the normal tissue, keratin was localized predominantly in the duct epithelial cells and myosin in the myoepithelial cells. According to the immunohistochemical staining patterns, the tumors were able to be divided into two groups: one group consisted of pleomorphic adenoma, adenoid cystic carcinoma, and adenocarcinoma which showed a mixture of keratin- and myosin-positive cells, respectively, mimicking the structures of the intercalated duct; the other comprised monomorphic adenoma and mucoepidermoid tumor which disclosed keratin-positive cells predominantly, resembling the constituent of the excretory duct. These results were mostly consistent with the "bicellular theory" that the salivary tumors generate from the intercalated duct reserve cells and the excretory duct reserve cells.

Topics: Adenocarcinoma; Adenolymphoma; Adenoma, Pleomorphic; Carcinoma; Carcinoma, Adenoid Cystic; Humans; Immunoenzyme Techniques; Keratins; Myosins; Salivary Gland Neoplasms; Salivary Glands

A 76-year-old man underwent a subtotal parotidectomy for removal of a 3 cm. multicystic mass. The tumor was a salivary gland carcinoma, with both infiltrating and intraductal/intra-acinar components, exhibiting three histologic patterns: cribriform, papillary, and comedo-like. Immunohistochemical stain for keratin by the immunoperoxidase technique was strongly reactive in the vast majority of the tumor cells, indicating ductal differentiation of the tumor. Ultrastructural studies indicated primarily ductal differentiation of the tumor cells, with additional areas of acinous and myoepithelial differentiation.

Topics: Animals; Carcinoma; Carcinoma, Intraductal, Noninfiltrating; Chick Embryo; Humans; Immunoenzyme Techniques; Keratins; Male; Microscopy, Electron; Parotid Neoplasms

Metastatic tumor cells of epithelial origin present in effusions from human serous cavity fluids (ascites or pleural fluid) were examined for their intermediate-sized filament types by using antibodies to keratin, vimentin, and desmin in the indirect immunofluorescence technique. Solid epithelial tumors (both primary carcinomas and their metastases) contain keratin intermediate-sized filaments exclusively. However, when these cells are present in ascitic or pleural fluid, they also express vimentin, which occurs in a fibrillar organization. The possible effects of this additional, but temporary, cytoskeleton on metastatic growth or aggressiveness (or both) are discussed.

Topics: Carcinoma; Cytoskeleton; Fluorescent Antibody Technique; Humans; Intermediate Filament Proteins; Keratins; Neoplasm Metastasis; Neoplasms; Vimentin

Immunocytochemical stains for three epithelial cell markers--keratin, epithelial membrane antigen (EMA) and carcinoembryonic antigen (CEA)--have been examined on paraffin-embedded material from 14 patients with nasopharyngeal carcinoma (NPC). Tumour cells staining positively for keratin were found in all cases and for EMA in eight; two tumours contained CEA-positive cells. Seven cases of Hodgkin's disease and 24 non-Hodgkin's lymphomas were uniformly negative. Keratin is the most reliable epithelial marker for identifying NPC and excluding lymphoma. The regular finding of stainable keratin in non-keratinising and anaplastic NPC supports the view that NPC is a homogeneous group exhibiting variable degrees of squamous differentiation.

Topics: Antigens; Carcinoembryonic Antigen; Carcinoma; Cell Membrane; Diagnosis, Differential; Epithelium; Hodgkin Disease; Humans; Immunoenzyme Techniques; Keratins; Lymphoma; Nasopharyngeal Neoplasms

Fifty-two primary carcinomas of the lung were studied by electron microscopy and by an immunoperoxidase method, using an anti-human keratin antiserum. The results were compared with light microscopic observations. One-third of the carcinomas of the lung showed ultrastructural evidence of both glandular and squamous differentiation. The group of small cell carcinomas was found to be particularly heterogenous ultrastructurally with only three out of eight tumors showing neurosecretory-type granules. Indirect immunoperoxidase staining revealed presence of a keratin-type protein in the vast majority of carcinomas, including foci of small cell carcinomas. Our studies emphasize the heterogeneity and frequent intermixing of the four major categories of lung carcinomas: squamous cell carcinomas, adenocarcinomas, small cell carcinomas, and large cell carcinomas. It is suggested that all these tumors might be derived from pluripotential "reserve" bronchial or bronchioalveolar cells. The segregation of small cell carcinomas from other groups continues to be justified on pragmatic grounds because these carcinomas constitute a group of predominantly small fast-replicating cells amenable to chemotherapy.

Topics: Adenocarcinoma; Carcinoma; Histocytochemistry; Humans; Immune Sera; Immunoenzyme Techniques; Keratins; Lung Neoplasms; Male; Microscopy; Middle Aged

Frozen sections of human renal carcinomas were studied in indirect immunofluorescence using antibodies against intermediate filaments of cytokeratin, desmin and vimentin type, and against proximal tubular brush border and distal tubular Tamm-Horsfall glycoprotein antigens, as well as with fluorochrome-labeled lectins in an attempt to study the origin and stage of differentiation of renal carcinomas. Eighty per cent of the renal carcinomas expressed the brush border antigens, whereas the Tamm-Horsfall glycoprotein could not be found. Antibodies against epidermal cytokeratins reacted only with collecting ducts in normal kidney, whereas antibodies against cytokeratins of Madin-Darby canine kidney epithelial cell line also reacted with glomerular and tubular epithelium. In 93% of the carcinomas tumor cells showed reactivity with both types of antikeratin antibodies. Vimentin, the cytoskeletal protein of mesenchymal cells, was present in the carcinoma cells of 53% of the tumors, although it was not present in normal tubular epithelium. Moreover, vimentin was expressed together with cytokeratin in the carcinoma cells in 57% of the keratin-positive samples as judged by double immunostaining, whereas the muscle type of intermediate filament protein, desmin, was not seen in the malignant cells. Binding sites for Lotus tetragonolobus agglutinin and soybean agglutinin, normally present in the cells of proximal tubules, were lacking or only faintly detectable in the neoplastic cells. Dolichos biflorus agglutinin, normally present in collecting ducts, was not detected in the tumors. The results show that most renal carcinomas express cytokeratin antigens as a sign of their epithelial origin and also show characteristics of proximal tubular cells. On the other hand, the results indicate that lectin-binding sites typical for normal differentiated tubular cells are profoundly modified in renal carcinomas. Ulex europaeus agglutinin did not bind to the malignant cells but decorated the endothelial cells of the tumors.

Topics: Antigens; Carcinoma; Desmin; Fluorescent Antibody Technique; Humans; Intermediate Filament Proteins; Keratins; Kidney Neoplasms; Lectins; Microvilli; Receptors, Mitogen; Vimentin

The light microscopic, electron microscopic and histochemical features of a highly malignant colonic tumor resected from a 39 year old man are presented. The tumor was composed predominantly of undifferentiated cells with focally admixed neuroendocrine, exocrine and squamous cells, occasionally arranged in an organoid manner. Histochemically the tumor contained argyrophilic cells as well as cells that reacted positively with the antibodies to alpha-1-antitrypsin, alpha-1-antichymotrypsin, carcinoembryonic antigen and lysozyme. The term "stem cell carcinoma of the intestine" is proposed for this highly malignant tumor composed of undifferentiated cells exhibiting only focally their multidirectional developmental capacity.

Topics: Adult; alpha 1-Antichymotrypsin; alpha 1-Antitrypsin; Carcinoembryonic Antigen; Carcinoma; Chymotrypsin; Colonic Neoplasms; Histocytochemistry; Humans; Immunologic Techniques; Keratins; Male; Microscopy, Electron; Muramidase; Staining and Labeling

Cytokeratins are one of the intermediate cytoplasmic filaments which contribute to the cytoskeleton. Keratins have recently been demonstrated in normal and neoplastic tissues as well as in human cell lines. It has been suggested that the cellular location of keratin may reflect tissue-specific or epithelial type differentiation. Twenty-three examples of human ovaries containing the full spectrum of epithelial proliferations from inflammatory reactive processes to malignant neoplasia were studied for the cellular distribution of cytokeratin using antisera to human keratin. Nineteen cases contained immunoreactive keratin which was limited to the epithelial cells: 2/2 inflammatory, 8/10 benign tumors, 5/7 borderline tumors, 4/4 carcinomas. There was marked regional heterogeneity in keratin expression such that adjacent morphologically-identical cells could be functionally distinguished by the immunoreactive staining. The predominant cellular localization of keratin varied between histological tumor types in the benign neoplasms: serous = apical, subciliary; endometrioid = apical; mucinous = basal. This pattern was lost in the cytological progression to borderline and malignant tumors. In borderline tumors, the most intense reactivity was noted in areas of cellular atypia and proliferation. In borderline and malignant tumors, keratin was usually present in basal cytoplasmic regions contiguous with stroma.

Topics: Carcinoma; Cell Division; Epithelium; Female; Humans; Keratins; Ovarian Neoplasms; Tissue Distribution

Antisera against total keratin extracts of human callus have been used to identify keratins in lung tumours of different histological type. Forty-three were classified by the WHO scheme. Keratin immunoreactive cells were identified in all 8 epidermoid carcinomas; 6 out of 12 large cell carcinomas; 2 out of 6 adenocarcinomas; 2 out of 15 small cell carcinomas and in the only muco-epidermoid carcinoma. These cases demonstrate the heterogeneity of phenotypic expression in lung tumours not recognisable without the use of immunohistochemical techniques.

Topics: Adenocarcinoma; Bronchial Neoplasms; Carcinoma; Carcinoma, Small Cell; Carcinoma, Squamous Cell; Humans; Immune Sera; Keratins; Lung Neoplasms; Phenotype

Forty cases of nasopharyngeal neoplasia were analyzed using immunohistochemical staining employing keratin antibodies. Using this probe the tumors were classified as being keratin-positive or negative. In this study, all squamous cell carcinomas labeled with keratin antibodies whether they were classified as keratinizing or nonkeratinizing by usual staining methods. In contrast, lymphoid and mesenchymal tumors of the nasopharynx did not label with keratin antibodies. Thus, the presence of keratin proteins as detected by immunohistochemical means on paraffin-embedded tissues appears to be a useful, reliable, and sensitive method for aiding in the accurate diagnosis and classification of nasopharyngeal neoplasms.

Topics: Antibodies; Carcinoma; Carcinoma, Squamous Cell; Enzyme-Linked Immunosorbent Assay; Humans; Immunoenzyme Techniques; Keratins; Nasopharyngeal Neoplasms

To elucidate the role of keratin modification in tumor promotion, we investigated the keratin polypeptide patterns of mouse epidermis, papillomas, and carcinomas throughout an initiation-promotion experiment. The epidermal keratin modifications induced by repetitive 12-O-tetradecanoylphorbol-13-acetate treatments in both initiated and noninitiated mouse skin were essentially identical to those observed with a single 12-O-tetradecanoylphorbol-13-acetate application. These changes were even more pronounced in epidermal papillomas. In addition, the keratins of the papillomas displayed greater charge heterogeneity, particularly among the high-molecular-weight keratins (Mr 60,000 to 62,000). As the experiment progressed, there appeared to be a selective loss of one group of high-molecular-weight keratins (Mr 62,000) in some of the papillomas. Interestingly, the carcinomas that appeared at this time had significant reduction in both groups of high-molecular-weight keratins. In fact, the keratin profiles of carcinomas were very similar to the patterns observed in basal cells after a single 12-O-tetradecanoylphorbol-13-acetate treatment of adult epidermis. This may indicate that the program of keratin expression of a carcinoma becomes permanently fixed at a basal cell pattern. Changes in keratin patterns may serve as a biochemical marker of malignant progression in mouse epidermis.

Topics: Animals; Carcinogens; Carcinoma; Female; Keratins; Mice; Mice, Inbred Strains; Molecular Weight; Neoplasms, Experimental; Papilloma; Skin; Skin Neoplasms; Tetradecanoylphorbol Acetate

Topics: Animals; Antibodies; Biopsy, Needle; Carcinoma; Cytoskeleton; Fluorescent Antibody Technique; Humans; Keratins; Muscle Proteins; Neoplasm Metastasis; Neoplasms; Neoplasms, Experimental; Sarcoma; Vimentin

A rabbit antiserum prepared against human keratins isolated from calluses was applied to sections of 108 neoplasms using indirect immunofluorescence and immunoperoxidase technics. The vast majority of epithelial neoplasms were strongly positive for keratin-type proteins, even in the absence of obvious keratinization or squamous differentiation as revealed by light microscopy. This keratin-positivity was invariably correlated with the identification of intermediate-sized filaments arranged in loose or dense bundles in the cytoplasm of neoplastic epithelial cells. Keratin-negative neoplasms included nevi, malignant melanomas, carcinoid tumors, malignant lymphomas, and a variety of connective-tissue tumors. Immunologic identification of keratin-type proteins was particularly helpful in establishing the epithelial nature of "undifferentiated" malignant tumors, including oat cell carcinomas.

Topics: Adenocarcinoma; Animals; Carcinoma; Carcinoma, Basal Cell; Carcinoma, Squamous Cell; Carcinoma, Transitional Cell; Humans; Immunoenzyme Techniques; Keratins; Rabbits; Skin Neoplasms; Urinary Bladder Neoplasms

This paper describes the use of a panel of seven monoclonal antibodies (selected so as to include reagents reactive with both epithelial and lymphoid cells) for distinguishing between anaplastic carcinoma and high grade lymphoma. Details are given of the immunohistological reactions of these antibodies against a wide range of both normal and malignant tissues and of a number of practical instances in which use of the antibody panel enabled a diagnosis to be made when routine histological examination had been inconclusive.

Topics: Adult; Aged; Antibodies, Monoclonal; Antigens, Neoplasm; Carcinoembryonic Antigen; Carcinoma; Diagnosis, Differential; Female; Histocompatibility Antigens; Histocompatibility Antigens Class II; HLA-DR Antigens; Humans; Immunoenzyme Techniques; Keratins; Lymphoma; Male

56 thyroid gland tumours and non neoplastic alterations were studied for keratin and thyroglobulin staining, using the indirect immunoperoxidase method on serial formalin fixed paraffin embedded sections. Papillary carcinomas showed a strong reaction with anti-keratin serum but a weak reaction with anti-thyroglobulin serum. Follicular adenomas and carcinomas showed virtually no reaction for keratin but a strong reaction for thyroglobulin. Undifferentiated and medullary carcinomas did not react with either antiserum, except for single cells in two undifferentiated carcinomas which reacted with anti-keratin serum. In nodular goiters, hyperplastic follicles showed little or no reaction with anti-keratin serum and strong reaction with anti-thyroglobulin serum. It is suggested that this virtually type-specific staining for keratin or thyroglobulin may be related to different degrees of cellular differentiation and organelle content in the tumour cells.

Topics: Adenocarcinoma; Carcinoma; Carcinoma, Papillary; Diagnosis, Differential; Goiter, Nodular; Graves Disease; Histocytochemistry; Humans; Immune Sera; Immunochemistry; Keratins; Thyroglobulin; Thyroid Diseases; Thyroid Neoplasms; Thyroiditis

Intermediate filaments (IF) are tissue-specific in so far that epithelial, mesenchymal, muscle and neural tissue types can be distinguished by the use of specific antibodies to keratin, vimentin, desmin and neurofilaments or glial filaments respectively. We have examined the possibility of using these sera in the differential diagnosis of human malignant tumors. Using antisera to human skin keratin and bovine lens vimentin we could differentiate between carcinomas (keratin +) and sarcomas (vimentin +). Furthermore, we could show that when cells become malignant and metastasize they retain their original IF and do not develop additional IF systems. We conclude that antibodies to IF proteins are powerful tools in the hands of a pathologist as an additional method to improve identification of tumors and their metastases.

Topics: Antibodies, Neoplasm; Carcinoma; Cytoskeleton; Diagnosis, Differential; Fluorescent Antibody Technique; Humans; Intermediate Filament Proteins; Keratins; Sarcoma; Vimentin

Antibodies to human and bovine epidermal prekeratin and antibodies to mouse liver cytokeratin component D (Mr 49 000) have been applied in indirect immunofluorescence microscopy on sections of human tumors of mammary gland and liver. In non-neoplastic mammary gland all epithelial cells were stained with these antibodies. In pre-invasive and invasive ductal and lobular carcinomas a cell population was observed which was not significantly stained with antibodies to epidermal prekeratin but did strongly react with antibodies to liver cytokeratin D. In the liver, the antibodies to epidermal prekeratin as well as those directed against liver cytokeratin D strongly decorated bile duct epithelia. In contrast, significant staining of the hepatocytes was only achieved with antibodies to liver cytokeratin D. This different staining reaction was maintained in liver tumors of hepatocellular and cholangiocellular origin. Antibodies to vimentin stained mesenchymal cells and tumors of mesenchymal derivation but reacted not significantly with any of the epithelial and carcinoma cells examined. The difference is of practical importance for the discrimination between anaplastic carcinomas and sarcomas of unknown origin. Cytokeratin could also be detected by antibody staining using the peroxidase-antiperoxidase (PAP) technique in formaldehyde-fixed and paraffin-embedded material of skin, gastrointestinal, respiratory, urinary and genital tract as well as various glands, liver and kidney. Examples of positive reactions were shown in a squamous cell carcinoma, a basalioma and a pleomorphic adenoma of the parotis. It is concluded that the immunohistochemical analysis of intermediate filament proteins has diagnostic potential in clinical pathology and may help to elucidate histogenesis and differentiation of tumors and possibly also prognosis of tumor growth. It is further suggested to use antibodies recognizing different subsets of proteins of the cytokeratin family in order to distinguish between different types of carcinomas.

Topics: Adenoma, Pleomorphic; Breast Neoplasms; Carcinoma; Carcinoma, Basal Cell; Carcinoma, Squamous Cell; Female; Fluorescent Antibody Technique; Humans; Intermediate Filament Proteins; Keratins; Liver Neoplasms; Parotid Neoplasms; Protein Precursors; Sarcoma; Skin Neoplasms

Fifty primary gastrointestinal and breast carcinomas, four embryonal rhabdomyosarcomas, six nonmuscular mesenchymal malignant tumors and one mesothelioma have been studied to determine what type of intermediate filaments they express, using affinity purified antibodies to prekeratin, vimentin and desmin and FITC or peroxidase labeled second antibodies. The tissues were alcohol fixed and paraffin embedded before use. In all carcinoma cases the tumor cells are stained by antibodies to prekeratin, while the vimentin antibody only decorates the stroma. Prekeratin positive tumor cells are not only seen in well differentiated tumors, but also in signet ring cell carcinomas. In the case of rhabdomyosarcoma the tumor cells clearly were decorated by antibodies to desmin, while the vimentin antibody only stained very few tumor cells. In cases of nonmuscular mesenchymal tumors, the tumor cells could only be labeled by antibodies to vimentin and not by antibodies to prekeratin or desmin. In biphasic tumors like mesothelioma, different parts of the tumor were separated by antibodies to prekeratin and vimentin.

Topics: Adenocarcinoma, Mucinous; Breast Neoplasms; Carcinoma; Child; Cytoskeleton; Desmin; Female; Gastrointestinal Neoplasms; Humans; Intermediate Filament Proteins; Keratins; Mesothelioma; Neoplasms; Neoplasms, Germ Cell and Embryonal; Protein Precursors; Rhabdomyosarcoma; Sarcoma; Vimentin

The intermediate-sized filaments can be divided into several groups which are characteristic of different types of tissues (e.g.: epithelial, mesenchymal, muscle, astrocytic and neural origin). Antibodies specific for some of these filament types have been used to analyse a group of salivary gland tumours. Prekeratin-positive cells were seen in the normal gland, cystadenolymphomas, mucoepidermoid tumours, and squamous cell carcinomas which are all tumours of epithelial origin. The pleomorphic adenomas showed the presence of some cells which appeared to contain both prekeratin and vimentin. The results are discussed with respect to their histogenetic implications.

Topics: Adenoma; Carcinoma; Carcinoma, Squamous Cell; Cytoskeleton; Desmin; Fluorescent Antibody Technique; Humans; Intermediate Filament Proteins; Keratins; Protein Precursors; Salivary Gland Neoplasms; Salivary Glands; Vimentin

Rabbit antisera to human 40-63 000 MW epidermal keratin, one batch with restricted distribution of reactivity from an initial (aK1) and one with "broad spectrum" distribution of reactivity from a late bleeding (aK), and to "luminal epithelial antigen" (aLEA) were applied to formalin fixed paraffin embedded sections of human normal and neoplastic mammary and salivary glands using an indirect immunoperoxidase method. aK1 reacted with myoepithelial cells, aLEA with luminal epithelial cells and aK with both cell types in normal mammary and salivary gland. In breast carcinomas the majority of intraluminal and infiltrating carcinoma cells reacted with aLEA but not with aK1 which reacted only with surrounding myoepithelial cells. aK reacted with both myoepithelial cells and with intraluminal and infiltrating tumour cells. In the salivary gland adenomas the majority of cells reacted with aK, and those cells arranged in a tubular fashion reacted with aLEA.

Topics: Adenoma; Breast Neoplasms; Carcinoma; Carcinoma, Intraductal, Noninfiltrating; Cytoskeleton; Epithelium; Female; Humans; Immunoenzyme Techniques; Keratins; Parotid Neoplasms; Salivary Gland Neoplasms

Immunoelectron microscope cytochemistry was carried out on 2% paraformaldehyde fixed, 50 mu sections of normal urothelium and bladder carcinoma cells in culture using antisera raised in rabbits to human 40-63 000 MW epidermal "broad spectrum" keratin and calf urothelial "luminal epithelial antigen" (aLEA) Both the unconjugated and indirect immunoperoxidase-DAB techniques were used before routine embedding. The localisation of both keratin and luminal epithelial antigen (LEA) was similar in normal and neoplastic cells and reaction product was associated not only with tonofilaments but also lining membrane vesicles and on fine filaments in the cytoplasmic ground substance.

Topics: Animals; Carcinoma; Epithelium; Humans; Keratins; Mice; Mice, Inbred C57BL; Microscopy, Electron; Neoplasms, Experimental; Rats; Rats, Inbred Strains; Urinary Bladder; Urinary Bladder Neoplasms

Pale cell carcinoma, a hormone-dependent mammary tumor in GR mice, consists mostly of islands of pale cells and dark cells, interrupted by a few areas containing keratinized cells. In this study the pale cells (electron-lucent), were arranged in bands adjacent to vascular spaces, while the dark cells, which produced mammary tumor virus, were clustered around lumens. A morphometric analysis revealed that pale cells were larger than dark cells and had other differences that indicated they were swollen. The areas having keratinized cells (or cells displaying squamous cell differentiation) resulted from a transformation of certain pale cells, perhaps in response to injury. The cells developed large desmosomes, accumulated tonofilaments, and sometimes displayed keratohyalin granules; and although most pale cells did not fully keratinize, a few did. Moreover, they remained within pale cell carcinomas that had regressed.

Topics: Animals; Carcinoma; Female; Keratins; Mammary Neoplasms, Experimental; Mice; Neoplasms, Hormone-Dependent

Intraspecific human cell hybrids were created by fusing normal epidermal keratinocytes with carcinoma (HeLa) cells. All of the hybrids were epithelial in morphology and exhibited a bright cytoskeletal pattern after indirect immunofluorescent labelling by antibody against keratin. Like the normal parental cells, the hybrid populations had organized arrays of microfilaments, and expressed low levels of surface fibronectin, predominantly in short "stitches" at cell boundaries. None of the cells expressed collagen type I, as expected of epithelial cells. Subcutaneous injection into nude mice revealed that the tumorigenic phenotype was initially suppressed in certain of the hybrids. However, cells of these lineages tested at later population doublings, and other hybrid clones tested at early population doublings, formed very small, non-progressive nodules, Histologically, these nodules resembled moderately to well-differentiated squamous-cell carcinomas. The properties in vitro and in vivo of these epithelial hybrids are compared to those of human fibroblast X HeLa hybrids.

Topics: Animals; Carcinoma; Carcinoma, Squamous Cell; Cell Fusion; Chromosomes; Collagen; Cytoskeleton; Fibroblasts; Fibronectins; Fluorescent Antibody Technique; HeLa Cells; Humans; Hybrid Cells; Keratins; Mice; Mice, Nude; Neoplasm Transplantation; Neoplasms, Experimental; Phenotype; Skin

Forty-three tumors were investigated by means of immunofluorescence with the use of antibodies against the following different classes of intermediate-sized (10 nm) filament proteins: 1) cytokeratins, 2) vimentin, and 3) desmin. In general, the immunologic features of tumor-cell intermediate filaments are those present in their tissue of origin. It can be seen, therefore, that, during neoplastic transformation, there are no major changes in the synthesis of the type of intermediate filament proteins when compared to normal tissues. Immunologic identification of these proteins furnishes the surgical pathologist with a quick and clear-cut way to differentiate tumors of mesenchymal origin from epithelial neoplasms, and in particular to distinguish between malignant lymphomas and lymph node metastases of undifferentiated carcinomas.

Topics: Adult; Animals; Antibodies; Breast Neoplasms; Carcinoma; Cytoskeleton; Desmin; Female; Guinea Pigs; Humans; Keratins; Male; Mice; Microtubules; Middle Aged; Muscle Proteins; Neoplasms; Protein Precursors; Sarcoma; Skin Neoplasms; Vimentin

Topics: Carcinoma; Female; Humans; Keratins; Lymphatic Metastasis; Prognosis; Time Factors; Uterine Cervical Neoplasms

Nonglandular carcinomas of the nasopharynx originate in the epithelium of that anatomical region. Although numerous morphological patterns exist at the level observable by light microscopy, ultrastructurally, all have features of squamous-cell carcinoma. The most useful and consistent classification on the basis of light microscopy is that which separates keratinizing squamous carcinomas from nonkeratinizing carcinomas. Approximately 25% of tumours have abundant and easily recognized keratin. The nonkeratinizing types are more confusing, since many variants exist, both from tumour to tumour and, frequently, within the same tumour. Variable tissue reactions to infiltrating tumours, ranging from marked desmoplasia to complete absence of reaction, add to the confusion. The descriptive names applied to the variants of nonkeratinizing squamous carcinomas are well engraved in medical communications, and there is little chance that they will be abandoned.

Topics: Carcinoma; Carcinoma, Squamous Cell; Carcinoma, Transitional Cell; Epithelium; Humans; Keratins; Nasopharyngeal Neoplasms; Nasopharynx

Topics: Carcinoma; Erythroplasia; Histocytochemistry; Humans; Keratins; Keratosis; Leukoplakia, Oral; Lichen Planus; Melanins; Smoking

Topics: Biopsy, Needle; Carcinoma; Female; Humans; Jaw Neoplasms; Keratins; Keratosis; Male; Mandibular Neoplasms; Maxillary Neoplasms; Mitosis; Neoplasm Recurrence, Local; Odontogenic Cysts; Radiography

Topics: Animals; Benz(a)Anthracenes; Carcinoma; Glycolysis; Keratins; Lactates; Male; Mice; Oxygen Consumption; Skin Neoplasms

Topics: Basement Membrane; Carcinoma; Dermatology; Diagnosis, Differential; Esterases; Fluorescent Antibody Technique; Glycogen; Histocytochemistry; Humans; Keratins; Keratoacanthoma; Keratosis; Lupus Erythematosus, Discoid; Mast-Cell Sarcoma; Psoriasis; Skin; Skin Diseases; Skin Neoplasms; Sweat Glands; Urticaria

Topics: Animals; Carcinoma; Goats; Keratins; Lung Neoplasms; Metaplasia; Microscopy; Mucins; Retrospective Studies

Topics: Adolescent; Adult; Biopsy; Carcinoma; Humans; Keratins; Male; Middle Aged; Plants, Medicinal; Plants, Toxic; Podophyllum; Skin Neoplasms; Wound Healing

Topics: Animals; Carcinoma; Keratins; Neoplasms; Papilloma; Rabbits; Tumor Virus Infections