bromochloroacetic-acid and Carcinoma--Squamous-Cell

Submucosal glands (SMGs) present throughout human esophagus with clusters at either the upper third or lower third of the organ. SMGs tend to atrophy with age, and neoplasms arising in these glands are rare. In order to bring convenience to diagnosis, we summarize the histopathologic characteristics of all esophageal submucosal gland tumors (SGTs). Due to the morphological similarity, the nomenclature of salivary tumors is adopted for SGTs. However, there is great confusion about the definition and histogenesis of these tumors, especially the malignant subtypes. In the literature, esophageal mucoepidermoid carcinoma and adenoid cystic carcinoma usually adjoin the surface squamous epithelium and coexist with intraepithelial neoplasia or invasive squamous cell carcinoma (SCC). In addition, the typical gene alterations of salivary tumors have not been reported in these SGTs. Therefore, we propose to apply stringent diagnostic criteria to esophageal SGTs so as to exclude mimickers that are SCCs with various degree of SMG differentiation.

Topics: Aged, 80 and over; Atrophy; Carcinoma in Situ; Carcinoma, Adenoid Cystic; Carcinoma, Mucoepidermoid; Carcinoma, Squamous Cell; Esophageal Neoplasms; Esophagus; Humans; Keratins; Male; Mucin-5B; Neoplasms, Glandular and Epithelial; Retrospective Studies

Keratins, the epithelial-predominant members of the intermediate filament superfamily, are expressed in a pairwise, tissuespecific and differentiation-dependent manner. There are 28 type I and 26 type II keratins, which share a common structure comprising a central coiled coil α-helical rod domain flanked by two nonhelical head and tail domains. These domains harbor sites for major posttranslational modifications like phosphorylation and glycosylation, which govern keratin function and dynamics. Apart from providing structural support, keratins regulate various signaling machinery involved in cell growth, motility, apoptosis etc. However, tissue-specific functions of keratins in relation to cell proliferation and differentiation are still emerging. Altered keratin expression pattern during and after malignant transformation is reported to modulate different signaling pathways involved in tumor progression in a context-dependent fashion. The current review focuses on the literature related to the role of keratins in the regulation of cell proliferation, differentiation and transformation in different types of epithelia.

Topics: Acetylation; Animals; Apoptosis; Carcinoma, Squamous Cell; Cell Differentiation; Cell Proliferation; Cell Transformation, Neoplastic; Epithelial Cells; Gene Expression Regulation, Neoplastic; Glycosylation; Humans; Keratins; Neoplasms; Phosphorylation; Protein Processing, Post-Translational; Protein Structure, Secondary; Signal Transduction

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

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

A 79-year-old Japanese woman presented with an ulcerated, brown-red nodule in the center of a sharply demarcated, tan-brown plaque situated on the left side of her right breast. Histologically, the plaque demonstrated an acanthosis with an intraepidermal epithelioma of Borst-Jadassohn. Small oval nests of bland-appearing basophilic cells in the periphery gradually enlarged into nests of various sizes and irregular shapes, composed of densely cohesive, atypical basophilic cells above the central nodule. The atypical keratinocytes shifted to atypical spindle cells beneath the acanthotic epidermis, penetrating deep into the subcutaneous tissue. In addition to vimentin and p63, the spindle cells were positive for several cytokeratin (CK) markers, including AE1/AE3, 34βE12 and CK5/6, which showed more intense signals closer to the epidermis. Basophilic cells in the clonal nests were positive for p63, AE1/AE3, 34βE12 and CK5/6. The MIB-1 index was estimated at approximately 40-50% in both the bland-appearing and the atypical basophilic cells. We describe the first case of spindle cell squamous cell carcinoma arising in an intraepidermal epithelioma expressed by clonal Bowen's disease, which was difficult to differentiate from clonal seborrheic keratosis.

Topics: Aged; Biomarkers, Tumor; Bowen's Disease; Breast; Carcinoma, Squamous Cell; Dermoscopy; Diagnosis, Differential; Epidermal Cells; Epidermis; Female; Humans; Immunohistochemistry; Keratinocytes; Keratins; Keratosis, Seborrheic; Skin Neoplasms

Although clinical history and morphologic appearance should be the initial considerations when evaluating small round blue cell tumors of the sinonasal tract, the final diagnosis often hinges on immunohistochemical findings. Unfortunately, interpretation of stains in these tumors is fraught with numerous pitfalls and limitations. This article presents an approach to sinonasal small round blue cell tumors based on four common immunohistochemical patterns: cytokeratin positivity, squamous marker positivity, neuroendocrine marker positivity, and cytokeratin negativity.

Topics: Biomarkers, Tumor; Carcinoma, Adenoid Cystic; Carcinoma, Squamous Cell; Diagnosis, Differential; Humans; Keratins; Nasal Cavity; Papillomavirus Infections; Paranasal Sinus Neoplasms

Metaplastic Breast Carcinoma (MBC) is a group of rare breast cancers; squamous cell carcinoma (SCC) is its most common member. Due to rarity of the condition, frequent case reports have been published of late. In the last one year alone, there were about a dozen such reports. Here we report a case of primary squamous cell carcinomain a 62-year-old female, with a 3.5cm mass in the left breast. Biopsy and mastectomy reports confirmed Metaplastic carcinoma, with 21 benign lymph nodes.. The tumour was triple negative and cytokeratin 5/6 positive. We are reporting the first case of squamous cell carcinoma of breast from our region, and we recommended large multi centre studies.

Topics: Breast Neoplasms; Carcinoma, Squamous Cell; Female; Humans; Keratins; Middle Aged

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

Mycosis fungoides (MF) is a relatively rare cutaneous T-cell malignancy. Only two cases of MF with marked eosinophilia have been reported. In addition, MF with concomitant squamous cell carcinoma (SCC) occurring in the site of MF has not been reported. The author reports herein a very rare case of MF in the plaque stage showing pronounced eosinophilic infiltration, folliculotropic pattern, and in situ development of poorly differentiated squamous cell carcinoma (SCC). A 75-year-old man was found to show high prostate specific antigen (PSA, 13 hg/ml) and prostatic biopsy showed well differentiated prostatic adenocarcinoma of Gleason score 6. Imaging techniques showed no metastatic lesions. He was treated by estrogen therapy. At 80 years, he consulted our hospital because of erythematous patch in the trunk. Biopsy showed mild infiltrations of lymphocyte and eosinophils. The lesion disappeared spontaneously. At 82 years, he consulted our hospital of because of erythematous patch at the back, and biopsy showed mildly atypical lymphocytes positive for CD20 and CD45, but negative for CD30, CD45RO, S100 protein, and cytokeratin (CK). Lymphoma was suspected but not definite. The lesions spontaneously disappeared. At 86 ages, he also consulted our hospital because of plaques in the face. Biopsy showed proliferation of atypical lymphocytes, marked infiltration of mature eosinophils, marked infiltration of these cells in the fair follicles (folliculotropism), and poorly differentiated invasive SCC arising from follicular cells. An immunohistochemical analysis showed that the atypical lymphocytes are T-lymphoma cells with T-cell markers, cyclinD1, p53, and high Ki67 labeling (50%) but without B-cell markers, NK-cell markers and plasma cell markers. The eosinophils were mature, and lacked p53 and showed low Ki67 labeling (4%). The carcinoma was positive for CK, p53, cyclinD1, and high Ki67 labeling (35%). A diagnosis of MF in the plaque stage with marked non-neoplastic eosinophilic infiltration, marked folliculotropism, and coexistent poorly differentiated invasive SCC was made by the author. Post-biopsy imaging techniques showed no metastasis or lymphadenopathy in the body. The patient was now treated by chemotherapy.

Topics: Aged, 80 and over; Biomarkers, Tumor; Biopsy; Carcinoma, Squamous Cell; Cell Movement; Comorbidity; Cyclin D1; Drug Therapy; Eosinophils; Hair Follicle; Humans; Keratins; Male; Mycosis Fungoides; Neoplasms, Multiple Primary; Skin Neoplasms; Tumor Suppressor Protein p53

Topics: Aged; Carcinoma, Medullary; Carcinoma, Squamous Cell; Diagnosis, Differential; Gastrectomy; Humans; Keratins; Lymphoma; Melanoma; Middle Aged; Neoplasm Staging; Retrospective Studies; RNA, Viral; Stomach Neoplasms

Papillary squamous cell carcinoma (SCC) (PSCC) of the oral mucosa is a relatively rare but distinct variant of SCC of head and neck. The objectives of this study were to describe the clinicopathologic and immunohistochemical features of a series of patients with oral PSCC and to review the literature on this topic. Retrospective review of patients with clinical and pathologic diagnosis of PSCC (n = 12) between 2000 and 2008 in our institution was conducted. The outcome analysis in a mean follow-up of 56 months (range, 24-131 months) was performed. These patients were 7 women and 5 men, and the mean age at diagnosis was 72.9 years (range, 53-83 years). The cheek and the gingiva were the predominant sites of involvement. At the end of follow-up, 4 patients were found to have local recurrence, and 3 were dead of disease. The estimated 3- and 5-year survival was 91.7% and 76.4% for the whole series, respectively. Histopathologically, the papillary pattern consisted of multiple, thin, delicate filiform, finger-like papillary projections with fibrovascular cores. Besides, the exophytic pattern consisted of the broad-based bulbous to "cauliflower-like" exophytic growth with rounded projections. Immunohistochemically, positivity for CKpan, CKhmw (high molecular weight), and p53, yet negativity for CK8, vimentin, desmin, smooth muscle actin, and S-100 was observed in PSCC. In conclusion, 2 specific histopathologic growth patterns of oral PSCC were identified to separate from conventional SCC. Patients with PSCC have a favorable outcome in relation to exophytic nature and limited invasion of the tumor.

Topics: Aged; Aged, 80 and over; Carcinoma, Papillary; Carcinoma, Squamous Cell; Cheek; Female; Gingiva; Humans; Kaplan-Meier Estimate; Keratins; Male; Middle Aged; Mouth Mucosa; Mouth Neoplasms; Retrospective Studies; Survival Rate; Tumor Suppressor Protein p53

Topics: Aged; Aged, 80 and over; Carcinoma, Squamous Cell; Cell Proliferation; Female; Head and Neck Neoplasms; Humans; Immunohistochemistry; Keratins; Male; Melanoma; Nose Neoplasms; S100 Proteins; Skin Neoplasms; Squamous Cell Carcinoma of Head and Neck

Thyroid carcinomas have been found incidentally in the cervical lymph nodes during surgery for head and neck squamous cell carcinoma (SCC). Such carcinomas have been considered a metastatic focus for malignant transformation of heterotopic thyroid tissue. We report on cases of so-called occult thyroid carcinoma in the cervical lymph nodes, and review the relevant literature.. We encountered 3 cases of incidental papillary carcinoma in the cervical lymph nodes of patients with oral SCC, and consequently reviewed 75 previously reported cases.. Among 148 patients with oral SCC who had undergone cervical lymph node dissection, 3 were diagnosed with occult thyroid carcinoma. Papillary carcinomas were found in 3, 10, and 3 lymph nodes in cases 1, 2, and 3, respectively. Computed tomography showed 2 tumor-like shadows and 1 calcified mass in the thyroid gland in cases 2 and 3, respectively. These shadows did not enlarge during the 3 to 5 years of observation, and all patients are alive, without any events related to the neck and thyroid gland. Among the reviewed cases, approximately two fifths were histopathologically or clinically free from thyroid carcinoma. Progressive thyroid carcinoma was not detected in any patient.. We propose the possibility that thyroid carcinoma in the cervical lymph nodes is not necessarily metastatic, but may occasionally arise from heterotopic thyroid tissue.

Topics: Aged; Carcinoma, Papillary; Carcinoma, Squamous Cell; Choristoma; Diagnosis, Differential; Histocytochemistry; Humans; Incidental Findings; Keratins; Lymph Nodes; Male; Middle Aged; Mouth Neoplasms; Neck; Neck Dissection; Thyroglobulin; Thyroid Gland; Thyroid Neoplasms

Pre-treatment serum squamous cell carcinoma antigen [SCC] levels are elevated in 28-88% of patients with squamous cell cervical cancer, and are related to tumour stage, tumour size, depth of stromal invasion, lymph-vascular space status, parametrial involvement and lymph node status. The clinical relevance of pre-treatment serum SCC assay is still debated. Some authors reported that it has no prognostic value, some others found that it is related to survival at univariate analysis, and some others detected that is an independent prognostic variable for survival. Serial SCC measurements reflect both the tumour response to treatment and the clinical outcome of patients. Increasing SCC levels can precede the clinical diagnosis of recurrent disease in 46-92% of the cases, with a mean lead time ranging from 2 to 8 months. According to some authors serum SCC assay during the follow-up does not improve the cure rate of patients who will ultimately develop a recurrence. However, it has been recently reported that the performance of a positron emission tomography [PET] in patients with asymptomatic SCC elevation can sometimes allow an earlier diagnosis of relapse with a survival benefit. SCC is a more sensitive serum tumour marker than CYFRA 21-1 for squamous cell cervical cancer in most series. Pre-treatment CA 125 levels are raised in 20-75% of patients with cervical adenocarcinoma, and reflect tumour stage, tumour size, histological grade, cervical stromal invasion, lymph-vascular space status and lymph node status. Elevated serum CA 125 has been also detected in patients with squamous cell cervical cancer, but with a positivity rate lower than that found in patients with cervical adenocarcinoma. Pre-treatment CA 125 levels appear to have a prognostic value, and rising serum CA 125 during follow-up may precede or be coincident with the clinical diagnosis of recurrent cervical adenocarcinoma. Serum levels of vascular endothelial growth factor [VEGF] are often elevated in patients with cervical cancer, and decrease significantly after successful treatment. However, the clinical relevance of serum VEGF assay is still investigational.

Topics: Antigens, Neoplasm; Biomarkers, Tumor; CA-125 Antigen; Carcinoma, Squamous Cell; Female; Follow-Up Studies; Humans; Keratin-19; Keratins; Neoplasm Proteins; Prognosis; Serpins; Uterine Cervical Neoplasms; Vascular Endothelial Growth Factor A

Head and neck squamous cell carcinoma (HNSCC) is the sixth most common malignancy and is a major cause of cancer morbidity and mortality worldwide. Oral cancer is the most predominant malignancy in the Indian subcontinent due to the widespread habits of chewing tobacco and related products. Patients with oral tumours have a high risk of early locoregional relapse. Early detection of disease progression remains a challenging task mainly due to the lack of adequate early prognostic markers. CEA, SCC Ag, CA-125, serum cytokeratin (CK) fragments, Cyfra 21-1 (CK 19), TPS (CK 18), TPA (CK 8, 18, and 19) etc. are being used as serum markers for the prediction of prognosis of various malignancies. This review presents the available literature on serum CK markers in different malignancies evaluates their utility in the management of oral cancer, and identifies the lacunae which need to be addressed to develop sensitive and specific assays for early detection of recurrence, prognosis, and treatment monitoring.

Topics: Biomarkers, Tumor; Carcinoma, Squamous Cell; Female; Humans; India; Keratins; Lymphatic Metastasis; Male; Mouth Neoplasms; Neoplasm Staging; Prognosis; Tobacco, Smokeless

Primary intracranial squamous cell carcinoma is extremely rare, with most of the cases arising from malignant transformation of an epidermoid or a dermoid cyst. We report here a case of a 45-year-old male patient who presented with 1-month history of intermittent headache and recent onset of altered sensorium. Imaging revealed a midline posterior fossa mass lesion compressing the fourth ventricle and causing hydrocephalus. A provisional diagnosis of dermoid cyst was considered. Histopathological examination revealed a squamous cell carcinoma possibly arising from an underlying epidermoid cyst. This entity is being reported for its rarity.

Topics: Brain Diseases; Calcinosis; Carcinoma, Squamous Cell; Cell Transformation, Neoplastic; Cholesterol; Cranial Fossa, Posterior; Diagnosis, Differential; Epidermal Cyst; Fourth Ventricle; Humans; Keratins; Male; Middle Aged; Skull Base Neoplasms; Tomography, X-Ray Computed

Topics: Carcinoma, Squamous Cell; Humans; Keratins; Keratoacanthoma; Keratosis; Photography; Skin Neoplasms; Warts

We present a brief review of epithelioid trophoblastic tumor, a rare trophoblastic neoplasm derived from chorionic-type intermediate trophoblastic cells that typically presents in reproductive-age women between 1 and 18 years following a previous gestation. Histologic features include a nodular growth pattern of monomorphic, epithelioid cells within a hyaline matrix. Areas of necrosis and mitotic activity (0-9 mitoses per 10 high-power fields) are additional features of this neoplasm. Positive immunostaining for p63 and cytokeratin, frequent location in the lower uterine segment and endocervix, as well as the epithelioid appearance can lead to confusion with squamous cell carcinoma. Inhibin-alpha is typically expressed, as well as focal, more variable expression of other trophoblastic markers including beta-human chorionic gonadotropin, human placental lactogen, placental alkaline phosphate, and Mel-CAM (CD148). The clinical behavior of this rare form of gestational trophoblastic disease is difficult to predict. Although most cases follow a benign course following resection, there is a potential for metastatic disease.

Topics: Adult; Biomarkers, Tumor; Carcinoma, Squamous Cell; Diagnosis, Differential; Epithelioid Cells; Female; Humans; Immunohistochemistry; Keratins; Membrane Proteins; Mitosis; Necrosis; Pregnancy; Trophoblastic Tumor, Placental Site; Uterine Neoplasms

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

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

The increasing interest in the so-called sentinel node concept, which has recently been adapted to squamous cell carcinomas of the upper aerodigestive tract, can be explained by encouraging results in other tumor entities. Although the publications on this topic do not yet allow a final judgment on the significance of sentinel lymphadenectomy in head and neck squamous cell carcinoma, early results emphasize the importance of this new diagnostic and therapeutic concept. The basic prerequisite is a detailed knowledge of the existing method-specific limitations in this anatomic region. Critical and careful evaluation of the sentinel node concept is mandatory prior to its application to other tumor entities. Sentinel lymphadenectomy for head and neck cancer may prove helpful if the indications for its use are clearly defined.

Topics: Carcinoma, Squamous Cell; Head and Neck Neoplasms; Humans; Immunohistochemistry; Keratins; Lymph Nodes; Lymphatic Metastasis; Radionuclide Imaging; Sentinel Lymph Node Biopsy; Tonsillar Neoplasms

This review is concerned with the usefulness and the problem of biomarkers for cancer of digestive organs. Carcinoembryonic antigen (CEA) is a most popular and useful tumor marker for cancer of digestive organs. Squamous cell carcinoma (SCC) antigen and CYFRA have been reported as a useful tumor marker for esophageal cancer. CEA and CA 19-9 are a good prognostic factor in gastric cancer patients. The post-operative increase of serum CEA can be a predictive marker for the patients of colorectal cancer. Development of a radioimmunoassay for highly sensitive detection of tumor markers, they are considered to be useful for monitoring after treatment. But are not useful for the early diagnosis. The diagnosis of hepatocellular carcinoma (HCC) is based mainly on serological markers, such as alpha-fetoprotein and PIVKA-II. The two are useful complementary markers of HCC because they do not correlate with each other. But the problem of the false-positive rate for the patients with chronic hepatitis or liver cirrhosis is still remained. A typical marker of pancreatic and bile duct cancer is carbohydrate antigen, but the sensitivity of these markers is only 50%. Recent molecular biological analysis may be used as effective biomarkers in the diagnosis, prognosis, therapy, and risk assessment of digestive cancer.

Topics: alpha-Fetoproteins; Antigens, CD19; Antigens, Neoplasm; Biomarkers; Biomarkers, Tumor; Carcinoembryonic Antigen; Carcinoma, Hepatocellular; Carcinoma, Squamous Cell; Colorectal Neoplasms; Digestive System Neoplasms; Esophageal Neoplasms; Female; Humans; Keratin-19; Keratins; Lewis X Antigen; Liver Neoplasms; Pancreatic Neoplasms; Prognosis; Protein Precursors; Prothrombin; Stomach Neoplasms

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

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

Esophageal squamous cell carcinoma in situ (SCCIS) with diffuse pagetoid features is a recently recognized rare variant of squamous cell carcinoma. A histopathological study of a specimen from a 70-year-old male Japanese patient is reported. The patient died of respiratory failure due to rapidly progressing metastatic pulmonary tumors of unknown origin 73 days after the onset of hemosputum. Autopsy disclosed widespread metastasis of choriocarcinoma in the absence of tumors of the testes or other common sites of germ cell tumors. Elevation of human chorionic gonadotropin (hCG-beta) levels was later detected in the stored serum. Serial histological evaluation of the entire esophagus revealed a small primary site of choriocarcinoma in a background of diffuse SCCIS, mainly of pagetoid type, accompanied by several small foci of submucosally invasive squamous cell carcinoma and primary mucoepidermoid carcinoma. These stimulated nodal metastasis independently of the choriocarcinoma. The SCCIS did not alter the gross mucosal appearance. This is the first reported case of diffuse pagetoid SCCIS combined with choriocarcinoma. Morphological findings and previous studies suggest that the extensive SCCIS of the esophagus resulted from pagetoid spread of tumor cells. The invasive squamous cell carcinoma, mucoepidermoid carcinoma and choriocarcinoma are suggested to have originated from the overlying SCCIS.

Topics: Aged; alpha-Fetoproteins; Autopsy; Carcinoma, Mucoepidermoid; Carcinoma, Squamous Cell; Choriocarcinoma; Chorionic Gonadotropin, beta Subunit, Human; Esophageal Neoplasms; Fatal Outcome; Humans; Immunohistochemistry; Keratins; Male; Paget Disease, Extramammary; Tissue Polypeptide Antigen

We describe a case of solitary papilloma of the bronchus and provide a review of 38 similar cases reported in Japan. A 70-year-old man complained of cough and sputum. Chest X-rays and CT scans revealed atelectasis of the right middle lobe. On bronchoscopy, a polypoid tumor was found at the orifice of the bronchus of the right middle lobe. The tumor was histologically diagnosed as a squamous papilloma with moderate atypia. Because of elevated tumor markers and the reported high incidence of malignant changes in papillomas, the tumor was endoscopically resected by electrosurgical snare. While this procedure resulted in improvement of atelectasis, the chest CT taken subsequently revealed a mass adjacent to the resected polypoid tumor in the middle lobe bronchus. Percutaneous needle biopsy followed by histopathological examination confirmed the tumor to be a squamous cell carcinoma. Only three cases of malignant changes in papillomas have been previously reported in Japan. Electrosurgical snare, which allows the identification of tissue at the tumor base, should be the treatment of choice rather than YAG laser surgery.

Topics: Aged; Antigens, Neoplasm; Antineoplastic Combined Chemotherapy Protocols; Biomarkers, Tumor; Biopsy, Needle; Bronchial Neoplasms; Carcinoma, Squamous Cell; Cisplatin; Combined Modality Therapy; Contraindications; Disease Progression; Electrosurgery; Humans; Keratins; Male; Mitomycin; Neoplasm Proteins; Papilloma; Parkinson Disease, Secondary; Pneumonectomy; Pulmonary Atelectasis; Serpins; Tomography, X-Ray Computed; Vindesine

Topics: Adolescent; Biomarkers, Tumor; Carcinoma, Squamous Cell; Diagnosis, Differential; Diagnostic Errors; Gingival Neoplasms; Humans; Keratins; Male; Microscopy, Electron; Myosins; Neoplasm Proteins; Rhabdomyosarcoma

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

A 57-year-old woman presented with a 10 x 10 cm anterior mediastinal mass. The tumor had invaded the pericardium, both lungs and the left brachiocephalic vein, and was treated by partial resection and postoperative radiation therapy. Pathological examination of the tumor revealed squamous cell carcinoma with a spindle cell sarcomatous component. Immunohistochemically, keratin and epithelial membrane antigen were positive in both the spindle cell sarcomatous areas and the squamous cell carcinomatous area and thus, a diagnosis of thymic carcinoma of sarcomatoid type was made. The patient died of recurrent disease 1 year after surgery. This case is the seventh reported in the English literature. Because of the poor outcome, adjuvant therapy is recommended.

Topics: Carcinoma, Squamous Cell; Female; Humans; Immunohistochemistry; Keratins; Middle Aged; Mucin-1; Neoplasm Invasiveness; Sarcoma; Thymus Neoplasms

Sclerosing mucoepidermoid carcinoma with eosinophilia (SMECE) is a recently recognized malignant neoplasm of the thyroid gland. Two additional cases of this condition which occurred in a 70-year-old woman and a 69-year-old woman are presented. The case of the 70-year-old woman (patient 1) is the first report of distant metastasis, besides lymph node metastasis, for this type of tumor. The patient initially presented with a thyroid mass, and the thyroid gland with surrounding cervical lymph nodes was removed. Because of focal keratin "pearl" formation, the tumor was misinterpreted as a metastatic squamous cell carcinoma to the thyroid. Approximately 4 years later, the patient developed a left supraclavicular mass and lung densities. A pathological fracture of the right humeral head followed, and the left supraclavicular mass recurred along with newly developed subcutaneous nodules on the chest wall and arm. Open lung and bone biopsies revealed metastatic SMECE, which was morphologically identical to that of the thyroid mass. The 69-year-old woman (patient 2) had, in 1983, undergone thyroidectomy with left radical neck dissection; this had been diagnosed as follicular carcinoma of the thyroid with lymph node involvement. After multiple isolated lymph nodes metastases, the patient developed locally extensive, recurrent tumor that showed microscopic features of SMECE. Review of the previous thyroid tumor and lymph nodes revealed the same type of histology. To our knowledge, only a single report containing eight cases of this distinctive carcinoma of the thyroid has been published. Herein we describe characteristic morphological features of two additional cases of this rare malignancy, one with distant metastasis, and we review the related literature.

Topics: Aged; Carcinoma, Mucoepidermoid; Carcinoma, Squamous Cell; Diagnosis, Differential; Eosinophilia; Female; Humans; Immunohistochemistry; Keratins; Lung Neoplasms; Sclerosis; Thyroid Neoplasms; Thyroiditis, Autoimmune

In Okinawa, a subtropical island in southern Japan, squamous cell carcinoma (SCC), especially the well-differentiated form, is prevalent, while this form is relatively rare in both the mainland and other countries (e.g. United States of America). More patients with SCC from Okinawa, moreover, were positive for human papillomavirus (HPV) DNA by polymerase chain reaction (PCR) (79%), and harbored HPV types 6, 16 and 18, in combination. On the other hand, less than 30% of the mainland patients were positive for HPV DNA by PCR. Those patients who were positive all harbored only one HPV type. Furthermore, in Okinawa, there were a significant number of cases with adenosquamous carcinoma, and they too were positive for HPV DNA. The SCC and the adenocarcinoma cells adjacent to the SCC component in these cases were also positive for HPV DNA, and such adenocarcinoma cells were enlarged in size with relatively wide cytoplasm. The authors postulate that HPV infects adenocarcinoma cells and changes them to enlarged cells, followed by squamous metaplasia. In this report, HPV DNA was transfected to adenocarcinoma cells (cultured cell lines) and this showed that HPV causes squamous metaplasia. In addition, aberrant expression of p53 was demonstrated in a large number of the SCC cases in Okinawa. The enlarged adenocarcinoma cells adjacent to the SCC components in adenosquamous carcinomas also showed aberrant expression of p53. The recent advances in the studies of anti-oncogenes, p53, etc. and oncogenes are outlined. It is to be noted that the molecular mechanisms of carcinogenesis in the lung have been studied in general, classifying lung tumors into two groups, namely, small cell carcinoma (SCLC) and non-small cell carcinoma (NSCLC). However, because human lung cancer is represented by a wide variety of histologic types, molecular genetic studies according to a more detailed histological subclassification is needed.

Topics: Adult; Aged; Aged, 80 and over; Animals; Blotting, Southern; Blotting, Western; Carcinoma, Adenosquamous; Carcinoma, Squamous Cell; Female; Humans; In Situ Hybridization; Japan; Keratins; Lung Neoplasms; Male; Metaplasia; Mice; Mice, SCID; Middle Aged; Mutation; Papillomaviridae; Transfection; Tumor Cells, Cultured; Tumor Suppressor Protein p53

Topics: Animals; Carcinoma, Squamous Cell; Cell Differentiation; Cervix Uteri; Female; Intestinal Mucosa; Keratins; Metaplasia; Phenotype; Precancerous Conditions; Rats; Rats, Wistar; Urodela; Uterine Cervical Neoplasms

Topics: Adult; Carcinoma, Squamous Cell; Cell Transformation, Neoplastic; Humans; Keratins; Male; Mandibular Diseases; Mandibular Neoplasms; Neoplasm Invasiveness; Odontogenic Cysts

A case of carcinosarcoma arising in the skin of the left arm of a 69-year-old woman is reported with a review of the literature. The tumor was composed of low-differentiated squamous cell carcinoma, which was intermingled with a pleomorphic sarcoma. The carcinomatous component had keratin and lacked vimentin, whereas the phenotype of the sarcomatous portion was the reverse. The former presented additionally focal expression of S-100 protein, which was lacking in other portions of the carcinoma. The phenotypic data, supplemented by p53 immunostaining, which was present in both components, suggest their common origin in this tumor.

Topics: Aged; Arm; Carcinoma, Squamous Cell; Carcinosarcoma; Cell Nucleus; Chromatin; Coloring Agents; Epithelium; Female; Humans; Keratins; Mitosis; Organelles; Phenotype; S100 Proteins; Sarcoma; Skin Neoplasms; Tumor Suppressor Protein p53; Vimentin

Clinical and experimental experience indicate that differentiation and malignancy are inversely correlated. However, more recent experimental studies using mouse and human keratinocyte systems have demonstrated that complete or even substantial loss in overall epithelial differentiation is not a prerequisite for malignant growth of cancer cells. Major defects in differentiation are also not a prerequisite for premalignant stages, in particular for cell immortalization, which is considered an early and essential step in the transformation process. Moreover, progressive dedifferentiation, often associated with advanced tumor stages, is also found in immortalized cell lines which are, however, nontumorigenic. On the other hand, malignant cell lines may have maintained a high degree of their normal differentiation program and sensitivity to differentiation modulators. However, to date no transformed keratinocyte cell lines with completely normal differentiation have been observed. Since epidermal keratinization is a very complex process involving many different parameters and is fully expressed only under in vivo conditions, an exact and quantitative comparison of such ill-defined phenomena (differentiation and malignancy) is still problematic. Obviously, both phenomena are under separate control and not causally linked. Nevertheless, a better understanding of factors and mechanisms regulating differentiation and of their disturbance in carcinogenesis would offer new possibilities to design novel tumor therapeutic strategies in the field of differentiation therapy.

Topics: Biomarkers; Carcinoma, Squamous Cell; Cell Differentiation; Cell Survival; Cell Transformation, Neoplastic; Disease Progression; Epidermal Cells; Epithelial Cells; Humans; Keratins; Neoplasm Proteins; Neoplasms; Protein Precursors; Skin Neoplasms; Tumor Cells, Cultured

Six cases of squamous cell carcinoma arising in the head and neck of patients infected with the human immunodeficiency virus are described. This article reports the first two cases of primary intraosseous squamous cell carcinoma associated with infection with human immunodeficiency virus. Clinical presentation, results of imaging studies, histologic characteristics, therapies applied, and the clinical follow-up are described in detail for each of the six cases. These data are evaluated through a review of the current literature.

Topics: Acquired Immunodeficiency Syndrome; Adult; Biomarkers, Tumor; Carcinoma, Squamous Cell; CD4-CD8 Ratio; Female; Head and Neck Neoplasms; HIV Infections; Humans; Immunocompromised Host; Keratins; Male; Mandibular Neoplasms; Middle Aged; Mouth Neoplasms

CYFRA is a new marker which measures a fragment of cytokeratin 19 in the serum by an immune radiometric method. The test is based on the preservation of the cytokeratin expression on the epithelial cells during the course of malignant transformation. In immuno-histochemistry the antibodies which selectively recognise cytokeratin react with all histological types of bronchial cancer. The presence of cytokeratin in the serum of patients suffering from cancer would be linked to their liberation during the course of cellular death. The threshold of specificity for CYFRA 21-1 is 3.3.3.6 ng/ml in a population suffering from benign respiratory diseases. The study performed in bronchial cancer produced the following conclusions: the marker is, above all, useful for epidermoid cancer; it is more discriminating than other markers to separate bronchial cancers and non-malignant respiratory disease. An elevated level of CYFRA 21-1 is predictive of advanced disease but does not permit any prediction as to inoperability. In 65% of cases, variations of CYFRA 21-1 are concordant with the stage of the disease during chemotherapy. Finally, elevated levels of CYFRA 21-1 predict a poor prognosis independent of the state of the disease.

Topics: Biomarkers, Tumor; Bronchial Diseases; Bronchial Neoplasms; Carcinoma, Squamous Cell; Cell Transformation, Neoplastic; Gene Expression Regulation, Neoplastic; Humans; Immunoradiometric Assay; Keratins; Peptide Fragments; Prognosis; Sensitivity and Specificity

The major value of intermediate filaments (IFs) in biological and applied research lies in their high order of cell and tissue specificity. This is particularly well illustrated in keratin (K) expression in various oral epithelia. Although the original class of IF is usually conserved in tissues after neoplastic transformation, epithelia show a tendency to shift their pattern of keratin expression in a manner which, while not predictable with precision, may sometimes be of diagnostic or prognostic significance. This review compares the keratins in normal oral epithelia, which show a mainly site-dependent expression, with those in squamous cell carcinoma. Key changes in the latter are the presence of simple epithelial keratins, K8 and K18 (occasional K7), reduced expression of differentiation-linked keratins (K1, K10, K4 and K13) and a tendency for down-regulation of primary keratins, K5 and K14. Moderate and severe dysplasias also tend to exhibit K8 and K18 with concomitant disordered expression of differentiation-linked keratins. There are reports of similar changes after neoplastic transformation in other mucosal sites and skin. Before this information can be applied diagnostically in immunocytochemical studies, the anti-keratin antibodies must be fully characterised and their interaction with the relevant tissue, both frozen and conventionally processed, should be evaluated.

Topics: Carcinoma, Squamous Cell; Humans; Intermediate Filaments; Keratins; Mouth Mucosa; Mouth Neoplasms; Neoplasm Proteins; Precancerous Conditions

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

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

Topics: Carcinoma, Basal Cell; Carcinoma, Squamous Cell; Humans; Keratinocytes; Keratins; Reference Values; Skin Neoplasms

Squamous differentiation in poral adnexal neoplasms is a rare event. Two cases are presented of malignant eccrine poroma in which areas of squamous differentiation showing the features of squamous cell carcinoma were present. The areas of squamous differentiation were found within the invasive components of the lesions and appeared to result from direct transformation of the poral epithelial cells. A review of the literature on this unusual phenomenon is presented.

Topics: Acrospiroma; Aged; Aged, 80 and over; Carcinoma, Squamous Cell; Cell Nucleus; Cell Transformation, Neoplastic; Cytoplasm; Cytoplasmic Granules; Foot Diseases; Humans; Hyalin; Keratinocytes; Keratins; Male; Neoplasm Invasiveness; Sweat Gland Neoplasms; Thigh

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

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

Topics: Carcinoma, Squamous Cell; Cell Differentiation; Cell Transformation, Neoplastic; Cellular Senescence; Epithelial Cells; Epithelium; Humans; Intermediate Filament Proteins; Intermediate Filaments; Keratins

Carcinoid neoplasms, although rare, have to be considered in the differential diagnosis of neoplasms of the larynx. The total number of cases reviewed and listed in the present article is 47. The gross appearance of carcinoid tumours is not characteristic and does not differ from that of other malignant neoplasms of the larynx. Under the light microscope various types can be distinguished, which are described and illustrated in this review article. Available material of five previously published cases and of one new case have been re-examined under the electron microscope and by modern histochemical and immunohistochemical methods. The ultrastructural presence of neurosecretory granules and of argyrophilia by the Grimelius technique were uniformly positive, together with monoclonal antibodies for somatostatin and keratin. These special methods offer a reliable basis for the diagnosis of neuroendocrine neoplasms to which carcinoid tumours belong. The treatment of carcinoid neoplasms of the larynx is surgical.

Topics: Adult; Aged; Aged, 80 and over; Carcinoid Tumor; Carcinoma, Squamous Cell; Cytoplasmic Granules; Diagnosis, Differential; Female; Humans; Immunohistochemistry; Keratins; Laryngeal Neoplasms; Male; Middle Aged; Neoplasm Staging; Prognosis; Somatostatin

A case of spindle cell squamous cell carcinoma of the tongue in a 4-year-old boy is presented. The diagnosis is supported by immunohistochemical demonstration of cytokeratins within the tumor cells. The authors believe this report represents the first case of "nonkeratinizing" spindle cell squamous carcinoma of the tongue in the first decade of life.

Topics: Carcinoma, Squamous Cell; Child, Preschool; Humans; Keratins; Male; Tongue Neoplasms

Topics: Animals; Carcinoma, Squamous Cell; Cell Differentiation; Cell Line; Cells, Cultured; Dihydroxycholecalciferols; Epidermal Cells; Epidermis; Humans; Hydroxycholecalciferols; Keratins; Kinetics; Vitamin D

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

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

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

Topics: Animals; Antigens, Polyomavirus Transforming; Antigens, Viral, Tumor; Breast; Carcinoma, Squamous Cell; Cell Survival; Cell Transformation, Neoplastic; Cell Transformation, Viral; Cells, Cultured; Epithelium; Female; Humans; Keratins; Male; Methods; Oncogene Proteins, Viral; Oncogenes; Organ Specificity; Phenotype; Pregnancy; Simian virus 40; Skin

Ten cell lines established from surgical specimens of human squamous carcinomas of the tongue and larynx have been investigated with respect to their motility, ultrastructure, karyotypes, certain biochemical features, interaction with normal epithelial and stromal elements and capacity to infiltrate three-dimensional organoid systems. All the cell lines have maintained several morphological and biochemical characteristics indicating a common origin, although the extent to which each line displays this heritage is variable. The phenotypes of each of the individual cell lines are, however, notably stable. Data are provided for epithelial surface markers (including epidermal growth factor, EGF) and for the synthesis and release of prostaglandins and proteases which may be involved in invasive mechanisms. Encounters between the cell lines and organoid substrata (embryonic chick heart spheroids, human amnion, chick chorioallantoic membrane) are described: the results indicate a scale of invasiveness ranging from lack of penetration to full-thickness infiltration by cells showing various distinctive growth patterns. Correlation between in vitro and in vivo findings is discussed, and it is suggested that the biological heterogeneity of the lines may reflect inherent properties of the original carcinoma cell populations which are more distinctly expressed in vitro.

Topics: Aged; Animals; Bone and Bones; Calcium-Binding Proteins; Carcinoembryonic Antigen; Carcinoma, Squamous Cell; Cartilage; Cell Communication; Cell Line; Cell Movement; Chick Embryo; Epidermal Growth Factor; Female; Humans; Karyotyping; Keratins; Laryngeal Neoplasms; Male; Membrane Proteins; Microscopy, Electron; Middle Aged; Mucin-1; Tongue Neoplasms

10 pleomorphic adenomas of the human parotid gland were transplanted on several groups of nude mice. For comparative reasons, 10 other pleomorphic adenomas, a neurinoma and a chordoma and transplants of squamous cell carcinomas and of normal salivary gland tissue were also analysed. In the primary tumours and in the transplants, the presence of keratin, carcinoembryonic antigen, tissue polypeptide antigen, lactoferrin, lysozyme, immunoglobulins, secretory component, amylase, fibronectin and of several lectin-receptors (PNA, WGA, HPA, Ulex europaeus) was sought. The immunohistological observations show that many of the features of a pleomorphic adenoma are constant under the conditions of transplantation. In the transplanted tumour, the same heterogeneity as in the primary tumours can be observed. Autoradiographic studies show little labelling with 3-H thymidine, which is in good accordance with the biological behaviour of the tumour. The distribution of fibronectin shows an interesting association with myoepithelial-like cells. Our results support the hypothesis that the histogenetic origin of the pleomorphic adenoma is a cell pool of the terminal ductal segment. A differentiation towards ductal cells (with production of secretory substances) and towards myoepithelial cells (associated with large amounts of basal membrane like substances) is observed.

Topics: Adenoma, Pleomorphic; Animals; Autoradiography; Carcinoembryonic Antigen; Carcinoma, Squamous Cell; Cell Division; Fibronectins; Histocytochemistry; Humans; Immunochemistry; Immunoglobulin A; Immunoglobulin A, Secretory; Immunoglobulin G; Immunoglobulin M; Keratins; Lactoferrin; Lectins; Mice; Mice, Nude; Muramidase; Neoplasm Transplantation; Salivary Gland Neoplasms; Tetradecanoylphorbol Acetate; Transplantation, Heterologous

Vitamin A deficiency or benzo(a)pyrene instillation into tracheas of Syrian golden hamsters causes squamous metaplasia of tracheobronchial epithelium, normally a mucous secretory tissue. In the present studies, we have employed a tracheal organ culture system and have reproduced the in vivo phenomenon of squamous metaplasia during culturing under vitamin A free conditions as well as after carcinogen treatment. The squamous metaplasia induced by vitamin A deficiency, both in vivo and in vitro, was accompanied by an overall increase in keratin synthesis. Vitamin A deficient tracheas were shown to contain keratins of 50, 48, 46.5 Kd detected with the antibody AE1, and 58, 56 and 52 Kd detected with AE3. These proteins were either absent or present in much less quantity in control tracheas. In deficient tracheas 60 kd keratin was found to be located specifically in squamous suprabasal cells, and 55 and 50 Kd keratin proteins were found in a greatly expanded basal cell compartment. Following carcinogen exposure, the appearance of 60 kd keratin and the enhanced expression of 50 and 55 Kd keratins preceded the squamoid metaplastic response as detected morphologically. Both the keratin changes and the morphological changes were prevented by retinoid treatment.

Topics: Animals; Carcinoma, Squamous Cell; Cell Differentiation; Cricetinae; Epithelial Cells; Epithelium; Keratins; Mesocricetus; Metaplasia; Organ Culture Techniques; Trachea; Vitamin A; Vitamin A Deficiency

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

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

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

Nineteen patients with carcinoma cuniculatum are presented. Of these, 17 were male and two were female. The age range was from 26 to 73 years with a mean of approximately 54 years. Sixteen tumours were located on the foot, the other three were situated on the knee, wrist and finger respectively. The pathological features of carcinoma cuniculatum are described and the aetiology of the tumour is discussed.

Topics: Adult; Aged; Carcinoma, Squamous Cell; Cytoplasmic Granules; Female; Foot Diseases; Humans; Inflammation; Keratins; Male; Middle Aged; Mitosis; Neoplasm Invasiveness; Skin Neoplasms

Topics: Age Factors; Carcinoma, Squamous Cell; Cell Membrane; Cell Nucleus; Cervix Mucus; Cervix Uteri; Chromatin; Cytoplasm; Female; Herpes Simplex; Humans; Hyperplasia; Inflammation; Keratins; Metaplasia; Pregnancy; Trichomonas Infections

The leucine rich repeats and immunoglobulin-like protein 1 (LRIG1) is a newly discovered negative regulator of epidermal growth factor receptor (EGFR) and a proposed tumor suppressor. It is not universally downregulated in human cancers, and its role in neoplastic transformation and tumorigenesis is not well-documented. In this study, we show the expression of LRIG1 as a novel potential marker for neoplastic transformation in ocular-surface squamous neoplasia (OSSN). The following two groups were included in this study: 1) benign group (3 cases; 1 with papilloma and 2 with dysplasia) and 2) malignant group (3 cases with squamous cell carcinoma (SCC)). In both groups, immunofluorescence analysis was firstly performed for keratins 4, 12, 13, and 15 to characterize the state of differentiation, and for Ki67 to evaluate the proliferation activity. Subsequently, LRIG1 and EGFR expression was analyzed. Either keratin 4 and/or 13, both non-keratinized epithelial cell markers, were generally expressed in both groups, except for 1 severe SCC case. Keratin 15, an undifferentiated basal cell marker, was more strongly expressed in the malignant cases than in the benign cases. The Ki67 index was significantly higher (P<0.002) in the malignant group (33.2%) than in the benign group (10.9%). LRIG1 expression was limited to basal epithelial cells in normal corneal epithelial tissue. Interestingly, LRIG1 was expressed throughout the epithelium in all the benign cases. In contrast, its expression was limited or totally disappeared in the malignant cases. Inversely, EGFR staining was faintly expressed in the benign cases, yet strongly expressed in the malignant cases. Malignant tissue with proliferative potential presented EGFR overexpression and inverse downregulation of LRIG1, consistent with LRIG1 being a suppressor of neoplastic transformation by counteracting the tumor growth property of EGFR. Our findings indicate that downregulation of LRIG1 is possibly a novel potential marker of transformation and tumorigenesis in OSSN cases.

Topics: Adult; Aged; Aged, 80 and over; Animals; Biomarkers, Tumor; Carcinoma, Squamous Cell; Cell Transformation, Neoplastic; Down-Regulation; ErbB Receptors; Eye Neoplasms; Eye Proteins; Female; Gene Expression Regulation, Neoplastic; Humans; Keratins; Male; Membrane Glycoproteins; Middle Aged; Neoplasm Proteins

Cytokeratin 7 (CK7) and Cam 5.2 are often used to differentiate extramammary Paget's disease (EPD) from squamous cell carcinoma (SCC) in situ because they are generally considered to be expressed in the former but not in the latter. However, we have encountered CK7+ and Cam 5.2+ SCCs.. We evaluated CK7, Cam 5.2 and Ber-Ep4 expression in SCC and EPD.. We found significant CK7 and Cam 5.2 positivity in SCCs, particularly in those with a pagetoid pattern. Only one case expressed Ber-Ep4.. We conclude that CK7 and Cam 5.2 expression may occur in SCC. A panel including Ber-Ep4 is advisable for immunohistochemical differentiation of EPD from SCC.

Topics: Biomarkers; Biomarkers, Tumor; Carcinoma, Squamous Cell; Female; Gene Expression Regulation; Humans; Keratin-7; Keratins; Male; Neoplasm Proteins; Skin Neoplasms

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

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

This article describes the use of tissue-engineered mucosal grafts instead of split-thickness skin grafts after freeing of the tongue in patients who had previous resection of an oral squamous cell carcinoma and initial primary wound closure.. Tissue-engineered mucosal grafts, up to 75 cm2 in size, were cultured from biopsy specimens of the hard palate in 6 patients, starting 3 to 4 weeks before the operation. After freeing of the tongue, the engineered mucosa was implanted on the wound surface by using vaseline gauze as carrier and fixed with an intraoral gauze wound dressing.. A good glossoalveolar sulcus was formed in 5 patients, resulting in good mobility of the tongue and a satisfactory denture-bearing surface. In 1 patient, there was a disturbance of wound healing, leading to severe shrinkage of the glossoalveolar sulcus and very limited improvement in tongue mobility. Preoperative bromodeoxyuridine (BrdU) labeling of the graft and postoperative immunohistochemical staining of biopsy specimens from the grafted areas with anti-BrdU showed that the cultured cells are integrated into the newly formed mucosal epithelium. Postoperative histologic investigations showed a differentiation process in the grafted mucosal epithelium, with a change in the expression of cytokeratins. At 6 months postoperatively, the typical pattern of normal nongrafted mucosa was regained.. This investigation provides evidence that tissue-engineered mucosal cells can serve as a graft for large intraoral wounds. Complete intraoral lining is quickly reestablished, and normal epithelial differentiation is seen in the graft area within a 6-month postoperative period.

Topics: Adult; Aged; Biomedical Engineering; Biopsy; Bromodeoxyuridine; Carcinoma, Squamous Cell; Cell Culture Techniques; Female; Histocytochemistry; Humans; Keratinocytes; Keratins; Male; Middle Aged; Mouth Floor; Mouth Mucosa; Mouth Neoplasms; Pilot Projects; Tongue; Vestibuloplasty

The aim of the study was to investigate if a short-term administration of high-dose Tamoxifen (Tam) could affect the expression of biologically relevant biochemical parameters in cervical cancer tissue.. The study was conducted in 24 patients with histologically confirmed cervical tumors. Biopsies were obtained by colposcopy on day 0 in all patients, who then received either 80 mg/die or 160 mg/die for 5 consecutive days until the second biopsy was obtained. Immunohistochemistry was performed with antiestrogen receptor (ER), anti-Ki67, anticaspase cleavage product of keratin 18 (M30), and anti-CD31 monoclonal antibodies.. Eleven (45.8%) of 24 cervical tumors were ER positive. The percentage of Ki67-positive tumor cells in pre-Tam biopsies was significantly higher than the percentage in the corresponding posttreatment biopsies (z = 4.29, P = 0.0001). No difference in the pretreatment percentage of Ki67-positive cells according to ER status was found. The percentage of M30 positivity was higher in post-Tam than in pre-Tam biopsies. Microvessel density values in pre-Tam biopsies were significantly higher than corresponding values in posttreatment tissues (z = -3.72, P = 0.0002). The reduction in the percentage of Ki67-positive tumors was significantly (z = 3.58, P = 0.0003) higher in ER-positive than in ER-negative tumors, whereas no difference in Tam-induced reduction of microvessel density values according to ER status (z = -0.18, P = 0.85) was found. Tam treatment did not induce any change of M30 positivity in ER-positive tumors, whereas in ER-negative tumors, it produced a significant (P = 0.015) increase in the percentage of M30-positive cells in post-Tam versus pre-Tam biopsies.. A short-term treatment with Tam at doses 4-8-fold higher than those in conventional schemes is associated with modifications of biological parameters associated with tumor cell proliferation, apoptosis, and neoangiogenesis in cervical cancer.

Topics: Adult; Aged; Antineoplastic Agents, Hormonal; Apoptosis; Blood Vessels; Carcinoma, Squamous Cell; Dose-Response Relationship, Drug; Female; Humans; Immunohistochemistry; Keratins; Ki-67 Antigen; Middle Aged; Platelet Endothelial Cell Adhesion Molecule-1; Receptors, Estrogen; Tamoxifen; Uterine Cervical Neoplasms

Micrometastasis (MM) and tumor cell microinvolvement (TCM) in the lymph node were immunohistochemically evaluated using the cytokeratin (CK) antibody between a surgery group (n=20; 929 lymph nodes) and a chemotherapy group (n=20; 1052 lymph nodes). The incidence of MM+/-TCM in the surgery and chemotherapy groups was 50.0 (10/20) and 55.0% (11/20), respectively. Limiting the analysis to TCM alone revealed that the incidence in the chemotherapy group (10.0%; 2/20) was significantly lower than that in the surgery group (40.0%; 8/20; P=0.032). Preoperative chemotherapy in this regime was not effective, except for some patients with TCM alone.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Squamous Cell; Cisplatin; Combined Modality Therapy; Esophageal Neoplasms; Esophagectomy; Female; Fluorouracil; Follow-Up Studies; Humans; Immunohistochemistry; Keratins; Leucovorin; Lymphatic Metastasis; Male; Middle Aged; Neoadjuvant Therapy; Survival Rate; Treatment Outcome

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

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

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

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

Topics: Aged, 80 and over; Biomarkers, Tumor; Carcinoma, Squamous Cell; Endoscopic Ultrasound-Guided Fine Needle Aspiration; Female; Humans; Keratins; Liver; Prognosis

Differentiated vulvar intraepithelial neoplasia (dVIN) is a human papillomavirus-independent lesion with the potential for rapid progression to invasive squamous cell carcinoma (SCC). The histopathologic features of dVIN are diverse, have overlapping characteristics with lichen sclerosus (LS) and lichen simplex chronicus (LSC), and may be diagnosed by dermatopathologists or gynecologic pathologists because of the vulva's anatomic location.. To identify the salient histopathologic features of dVIN, particularly those that predict progression to SCC, and to evaluate interobserver agreement in diagnosing dVIN within the same subspecialty and across subspecialties.. One general surgical pathologist, 2 pathology-trained dermatopathologists, and 1 gynecologic pathologist blinded to the final diagnoses were asked to record 20 histopathologic features and to provide their final interpretations on cases of dVIN (n = 65), LS (n = 126), LSC (n = 112), and LS with LSC (n = 6).. Interobserver agreement for the 4 diagnoses and 10 histopathologic features was moderate. Logistic regression analysis indicated that keratin pearls, basal pleomorphism, and basal layer disarray were independent variables for diagnosing dVIN (coefficients 1.95, 1.97, and 0.91, respectively; P < .001) and progression to SCC (coefficients 1.96, 1.20, and 1.08, respectively; P < .001).. There is no single histopathologic feature pathognomonic for dVIN; however, the presence of keratin pearls, basal pleomorphism, and basal layer disarray should raise high suspicion for dVIN and concurrent SCC. Expertise in both dermatologic and gynecologic pathology is beneficial for diagnosing dVIN.

Topics: Carcinoma in Situ; Carcinoma, Squamous Cell; Female; Humans; Keratins; Observer Variation; Vulvar Neoplasms

In head and neck squamous cell carcinoma (HNSCC), salvage neck dissection (ND) is required after primary chemoradiation in case of residual nodal disease. Upon histopathological examination, viability of tumor cells is assessed but little is known about other prognostic histopathological features. In particular, the presence of swirled keratin debris and its prognostic value is controversial. The aim of this study is to examine histopathological parameters in ND specimens and correlate them with patient outcome to determine the relevant parameters for histopathological reporting.. Salvage ND specimen from a cohort of n = 75 HNSCC (oropharynx, larynx, hypopharynx) patients with prior (chemo) radiation were evaluated on H&E stains for the following parameters: viable tumor cells, necrosis, swirled keratin debris, foamy histiocytes, bleeding residues, fibrosis, elastosis, pyknotic cells, calcification, cholesterol crystals, multinucleated giant cells, perineural, and vascular invasion. Histological features were correlated with survival outcomes.. Only the presence / amount (area) of viable tumor cells correlated with a worse clinical outcome (local and regional recurrence-free survival, (LRRFS), distant metastasis-free survival, disease-specific survival, and overall survival, p < 0.05) in both the univariable and multivariable analyses.. We could confirm the presence of viable tumor cells as a relevant negative prognostic factor after (chemo) radiation. The amount (area) of viable tumor cells further substratified patients with worse LRRFS. None of the other parameters correlated with a distinctive worse outcome. Importantly, the presence of (swirled) keratin debris alone should not be considered viable tumor cells (ypN0).

Topics: Carcinoma, Squamous Cell; Head and Neck Neoplasms; Humans; Keratins; Lymphatic Metastasis; Neoplasm Recurrence, Local; Neoplasm Staging; Prognosis; Retrospective Studies; Squamous Cell Carcinoma of Head and Neck

Oral squamous cell carcinoma (OSCC) is one of the most common malignancies affecting the head-and-neck region, regional lymph nodes being an important prognostication factor dictating the survival rate. Despite an array of modalities used, clinically, radiographically and routine histopathologically, the detection of micro-metastasis (2-3 mm tumour cell deposits) in the lymph nodes often escapes identification. The presence of few of these tumour epithelial cells in the lymph nodes drastically increases mortality and alters treatment plan. Hence, the identification of these cells is of major prognostic significance for a patient. Thus, the present study was aimed to evaluate and detect the efficacy of the immunohistochemical (IHC) marker [cytokeratin (CK) AE1/AE3] over routine Hematoxylin & eosin (H & E) staining in detecting micro-metastasis in the lymph nodes of OSCC cases.. The IHC marker CK cocktail (AE1/AE3) did not demonstrate any positive reactivity for the target antigen in all the 100 H & E stained lymph node sections evaluated in the present study.. This study was undertaken to check the efficacy of IHC (CK cocktail AE1/AE3) in the detection of micro-metastasis in lymph nodes that are found to be negative in routine H&E stained sections. The findings of this study suggest that the IHC marker AE1/AE3 did not prove to be useful to detect micro-metastasis in this study population.

Topics: Carcinoma, Squamous Cell; Eosine Yellowish-(YS); Head and Neck Neoplasms; Hematoxylin; Humans; Immunohistochemistry; Keratins; Lymph Nodes; Lymphatic Metastasis; Mouth Neoplasms; Squamous Cell Carcinoma of Head and Neck

Bowen disease, one of the common skin cancers, is defined as squamous cell carcinoma in situ, characterized by atypical keratinocytes occupying the full thickness of the epidermis, and predominantly occurs on sun-protected skin. There is no existing data on the impact of tumour and immune cell interactions or cytokeratin expression on the pathology of Bowen disease.. We analysed dynamic changes in cytokeratin expression and immune cell composition during the development and progression of Bowen disease.. Analysis was performed using immunohistochemistry and electron microscopy for samples from 140 patients with Bowen disease and 20 patients with invasive squamous cell carcinoma. We evaluated cytokeratin expression, the number of infiltrating immune cells and amyloid deposition by immunohistochemistry, and the ultrastructural relationship between tumour cells and immune cells by electron microscopy.. The results showed that the expression of CK14 is associated with tumour progression, keratotic status and amyloid deposition and that the expression of CK10 is associated with accumulation of immune cells in Bowen disease. The findings of electron microscopy indicated repeated battles involving immune cells in response to tumour invasion.. The expression of cytokeratins, hyperkeratosis, inflammatory infiltration and amyloid deposition are useful findings indicating the "stage" in Bowen disease.

Topics: Anus Neoplasms; Bowen's Disease; Carcinoma, Squamous Cell; Humans; Keratins; Keratosis

Myxoid spindle cell squamous cell carcinoma is a rare variant of squamous cell carcinoma that can pose diagnostic challenges because of its unusual morphology. In this article, we report the case of a 68-year-old man who presented with a slow-growing, fungating mass on the right tibia at the site of his long-standing draining sinus tract. Biopsy revealed a malignant spindle cell tumor with prominent myxoid stroma and areas containing thin-walled blood vessels with a curvilinear appearance. The immunohistochemical profile indicated that the neoplastic cells were positive for a variety of keratins (MNF116, Cam 5.2, AE1/AE3, 34βE12, and CK5/6) and transcriptional markers classically expressed in squamous cell carcinomas (p63 and p40). The tumor cells were negative for melanocytic and mesenchymal markers smooth muscle antibody, S100, caldesmon-h, desmin and CD34. Together, the clinical history, histologic appearance, and immunohistochemical panel was diagnostic of a myxoid spindle cell squamous cell carcinoma. The main differential diagnosis was myxofibrosarcoma. In addition to this clinical case, we also outline the current state of knowledge on this rare entity and discuss the importance of recognizing a Marjolin ulcer in this scenario.

Topics: Adult; Aged; Biomarkers, Tumor; Carcinoma, Squamous Cell; Fibrosarcoma; Histiocytoma, Malignant Fibrous; Humans; Immunohistochemistry; Keratins; Male; Osteomyelitis

An 11-year-old spayed female Miniature Schnauzer dog was presented with loss of a claw caused by a nail bed mass. Histopathological evaluation revealed that the mass comprised neoplastic squamous cells with abundant cytoplasmic melanin pigment. Immunohistochemically, the neoplastic cells were positive for cytokeratin and negative for vimentin and ionized calcium-binding adaptor molecule 1, supporting a diagnosis of pigmented squamous cell carcinoma. To our knowledge, this is the first report of subungual pigmented squamous cell carcinoma in animals.

Topics: Animals; Carcinoma, Squamous Cell; Dog Diseases; Dogs; Female; Keratins; Nail Diseases; Skin Diseases; Skin Neoplasms

Topics: Carcinoma, Squamous Cell; Humans; Immunohistochemistry; Keratins; Mohs Surgery; Skin Neoplasms

While most cases of cutaneous squamous cell carcinoma (cSCC) are benign, invasive cSCC is associated with higher mortality and is often more difficult to treat. As such, understanding the factors that influence the progression of cSCC are important. Aggressive cancers metastasize through a series of evolutionary changes, collectively called the epithelial-to-mesenchymal transition (EMT). During EMT, epithelial cells transition to a highly mobile mesenchymal cell type with metastatic capacities. While changes in expression of TGF-β, ZEB1, SNAI1, MMPs, vimentin, and E-cadherin are hallmarks of an EMT process occurring within cancer cells, including cSCC cells, EMT within tissues is not an "all or none" process. Using patient-derived cSCC and adjacent normal tissues, we show that cells within individual cSCC tumors are undergoing a hybrid EMT process, where there is variation in expression of EMT markers by cells within a tumor mass that may be facilitating invasion. Interestingly, cells along the outer edges of a tumor mass exhibit a more mesenchymal phenotype, with reduced E-cadherin, β-catenin, and cytokeratin expression and increased vimentin expression. Conversely, cells in the center of a tumor mass retain a higher expression of the epithelial markers E-cadherin and cytokeratin and little to no expression of vimentin, a mesenchymal marker. We also detected inverse expression changes in the miR-200 family and the EMT-associated transcription factors ZEB1 and SNAI1, suggesting that cSCC EMT dynamics are regulated in a miRNA-dependent manner. These novel findings in cSCC tumors provide evidence of phenotypic plasticity of the EMT process occurring within patient tissues, and extend the characterization of a hybrid EMT program occurring within a tumor mass. This hybrid EMT program may be promoting both survival and invasiveness of the tumors. A better understanding of this hybrid EMT process may influence therapeutic strategies in more invasive disease.

Topics: Biomarkers, Tumor; Cadherins; Carcinoma, Squamous Cell; Cell Line, Tumor; Epithelial-Mesenchymal Transition; Humans; Keratins; Skin Neoplasms; Vimentin

Cytokeratin 10 (CK10) is a type I acidic low molecular weight cytokeratin which is mainly expressed in keratinizing squamous epithelium of the skin. Variable levels of CK10 protein have been described in squamous carcinomas of different sites and in some other epithelial neoplasms. To comprehensively determine the prevalence of CK10 expression in normal and neoplastic tissues, a tissue microarray containing 11,021 samples from 131 different tumor types and subtypes was analyzed by immunohistochemistry. CK10 immunostaining was detectable in 41 (31.3 %) of 131 tumor categories, including 18 (13.7 %) tumor types with at least one strongly positive case. The highest rate of positive staining was found in squamous cell carcinomas from various sites of origin (positive in 18.6 %-66.1 %) and in Warthin tumors of salivary glands (47.8 %), followed by various tumor entities known to potentially exhibit areas with squamous cell differentiation such as teratomas (33.3 %), basal cell carcinomas of the skin (14.3 %), adenosquamous carcinomas of the cervix (11.1 %), and several categories of urothelial neoplasms (3.1 %-16.8 %). In a combined analysis of 956 squamous cell carcinomas from 11 different sites of origin, reduced CK10 staining was linked to high grade (p < 0.0001) and advanced stage (p = 0.0015) but unrelated to HPV infection. However, CK10 staining was not statistically related to grade (p = 0.1509) and recurrence-free (p = 0.5247) or overall survival (p = 0.5082) in 176 cervical squamous cell carcinomas. In the urinary bladder, CK10 staining occurred more commonly in muscle-invasive (17.7 %) than in non-invasive urothelial carcinomas (4.0 %-6.0 %; p < 0.0001). In summary, our data corroborate a role of CK10 as a suitable marker for mature, keratinizing squamous cell differentiation in epithelial tissues. CK10 immunohistochemistry may thus be instrumental for a more objective evaluation of the clinical significance of focal squamous differentiation in cancer.

Topics: Biomarkers, Tumor; Carcinoma, Adenosquamous; Carcinoma, Squamous Cell; Female; Humans; Immunohistochemistry; Keratins; Urothelium

The genetic features of primary lymphoepithelioma-like carcinoma (LELC) of the upper urinary tract have not been systematically explored. In this study, tumor mutation profiling was performed using whole-genome sequencing in two patients with LELC of the renal pelvis. Novel candidate variants relevant to known disease genes were selected using rare-variant burden analysis. Subsequently, a population-based study was performed using the Surveillance, Epidemiology, and End Results (SEER), PubMed, MEDLINE, Embase, and Scopus databases to explore clinical features and prognostic risk factors. Immunohistochemical analysis revealed seven positive cytokeratin-associated markers in tumor cells and five positive lymphocyte-associated markers in and around the tumor area. Sub-sequently, we identified KDM6A as the susceptibility gene and LEPR as the driver gene by Sanger sequencing in case 2 of LELC of the renal pelvis. Three mutation sites of the existing targeted drugs were screened: CA9, a therapeutic target for zonisamide; ARVCF, a therapeutic target for bupropion; and PLOD3, a therapeutic target for vitamin C. In a population-based study, patients with primary LELC of the upper urinary tract had clinical outcomes similar to those of patients with primary upper urinary tract urothelial carcinoma (UUT-UC) before and after propensity score matching at 1 : 5. Focal subtype was an independent prognostic factor for the overall survival of patients with LELC of the upper urinary tract. The carcinogenesis of primary LELC may be due to different genetic variations, including single-nucleotide variants, insertion and deletions, structural variations, and repeat regions, which may provide the basis for clinical diagnosis and treatment. The prognosis of LELC in the upper urinary tract is similar to that of UUT-UC. We suggest that the focal subtype can serve as a prognostic factor for LELC of the upper urinary tract; however, further studies are required to confirm this.

Topics: Ascorbic Acid; Bupropion; Carcinoma, Squamous Cell; Carcinoma, Transitional Cell; Histone Demethylases; Humans; Keratins; Kidney Pelvis; Nucleotides; Prognosis; Urinary Bladder Neoplasms; Zonisamide

Fanconi anemia (FA) patients frequently develop oral squamous cell carcinoma (OSCC). This cancer in FA patients is diagnosed within the first 3-4 decades of life, very often preceded by lesions that suffer a malignant transformation. In addition, they respond poorly to current treatments due to toxicity or multiple recurrences. Translational research on new chemopreventive agents and therapeutic strategies has been unsuccessful partly due to scarcity of disease models or failure to fully reproduce the disease. Here we report that Fanca gene knockout mice (Fanca

Topics: Animals; Carcinoma, Squamous Cell; Disease Models, Animal; Fanconi Anemia; Head and Neck Neoplasms; Keratins; Mice; Mice, Knockout; Mouth Neoplasms; Squamous Cell Carcinoma of Head and Neck

FAM83H is essential for amelogenesis, but recent reports implicate that FAM83H is involved in the tumorigenesis. We previously clarified that TRIM29 binds to FAM83H to regulate keratin distribution and squamous cell migration. However, little is known about FAM83H in normal/malignant skin keratinocytes.. To investigate the expression of FAM83H in cutaneous squamous cell carcinoma (SCC) and its physiological function.. Immunohistochemical analysis and RT-PCR of human SCC tissues were performed. Next, we examined the effect of FAM83H knockdown/overexpression in SCC cell lines using cell proliferation, migration, and invasion assay. To investigate the molecular mechanism, immunoprecipitation of FAM83H was examined. Further, Immunofluorescence staining was performed. Finally, we examined the correlation between the expressions of FAM83H and the keratin distribution.. FAM83H expression was lower in SCC lesions than in normal epidermis and correlated with differentiation grade. The mRNA expression levels of FAM83H in SCC tumors were also lower than in normal epidermis. The knockdown of FAM83H enhanced SCC cell migration and invasion, whereas the overexpression of FAM83H led to decreases in both. Furthermore, the knockdown of FAM83H enhanced the cancer cell metastasis in vivo. FAM83H formed a complex with TRIM29 and keratins. The knockdown of FAM83H altered keratin distribution and solubility. Clinically, the loss of FAM83H correlates with an altered keratin distribution.. Our findings reveal a critical function for FAM83H in regulating keratin distribution, as well as in the migration/invasion of cutaneous SCC, suggesting that FAM83H could be a crucial molecule in the tumorigenesis of cutaneous SCC.

Topics: Animals; Carcinoma, Squamous Cell; Cell Line, Tumor; Cell Movement; Cell Proliferation; DNA-Binding Proteins; Epidermis; Female; Gene Expression; Gene Knockdown Techniques; Humans; Keratinocytes; Keratins; Mice; Mice, Inbred BALB C; Neoplasm Grading; Neoplasm Invasiveness; Neoplasm Metastasis; Neoplasm Transplantation; Proteins; RNA, Messenger; Skin Neoplasms; Transcription Factors

Mice have served as an excellent model to understand the etiology of lung cancer for years. However, data regarding dual-stage carcinogenesis of lung squamous cell carcinoma (SCC) remain elusive. Therefore, we aim to develop pre-malignant (PM) and malignant (M) lung SCC in vivo using N-nitroso-tris-chloroethylurea (NTCU). BALB/C mice were allotted into two main groups; PM and M groups which received treatment for 15 and 30 weeks, respectively. Then, the mice in each main group were allotted into three groups; control, vehicle, and cancer (n = 6), which received normal saline, 70% acetone, and 0.04 M NTCU by skin painting, respectively. Histopathologically, we discovered a mix of hyperplasia, metaplasia, and dysplasia lesions in the PM group and intracellular bridge; an SCC feature in the M group. The M group was positive for cytokeratin 5/6 protein which confirmed the lung SCC subtype. We also found significantly higher (P < 0.05) epithelium thickness in the cancer groups as compared to the vehicle and control groups at both the PM and M. Overall, this study discovered that NTCU is capable of developing PM and M lung SCC in mice model at appropriate weeks and the vehicle group was suggested to be adequate as control group for future research.

Topics: Animals; Biomarkers, Tumor; Carcinogens; Carcinoma, Non-Small-Cell Lung; Carcinoma, Squamous Cell; Carmustine; Disease Models, Animal; Epithelium; Female; Immunohistochemistry; Keratins; Lung Neoplasms; Mice; Mice, Inbred BALB C

In skin containing hair follicles, specialized epithelial structures known as "touch domes (TDs)" are located where the Merkel cells are clustered. We explored the histogenetic relationship between intraepidermal and dermal Merkel cell carcinomas (MCCs) and investigated which transformed progenitor cells can develop into intraepidermal MCC. We encountered an association between an extremely rare case of dermal and intraepidermal MCC with squamous cell carcinoma, which was examined using standard immunohistochemical methods with various epithelial, neuroendocrine, and TD markers including several immunohistochemical markers. Differential expression levels of CK20 and CD56 were found between intraepidermal and dermal MCCs, indicating molecularly distinct MCC populations. CK15 and CK17, expressed in TDs, were partially expressed in the intraepidermal neuroendocrine component at the tumor periphery in intraepidermal MCC with squamous cell carcinoma. These differences may suggest that the origin of dermal and intraepidermal MCCs is different under pathological conditions. We hypothesize that intraepidermal MCC is derived from tissue-specific stem cells localized within TDs.

Topics: Aged, 80 and over; Biomarkers, Tumor; Carcinoma, Merkel Cell; Carcinoma, Squamous Cell; Cell Lineage; Female; Humans; Immunohistochemistry; Keratins; Merkel Cells; Neoplasms, Complex and Mixed; Neoplastic Stem Cells; Skin Neoplasms

Topics: Adult; Aged; Aged, 80 and over; Biomarkers, Tumor; Carcinoma, Squamous Cell; Female; Humans; Immunohistochemistry; Keratins; Male; Margins of Excision; Middle Aged; Mohs Surgery; Neoplasm Invasiveness; Neoplasm Recurrence, Local; Retrospective Studies; Skin; Skin Neoplasms

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

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

Sentinel lymph node biopsy is gaining increasing acceptance as a less morbid way to assess lymph node status in patients with endometrial carcinoma, compared with full pelvic node dissection. The sentinel nodes are usually subjected to ultrastaging, with sections taken at multiple levels from each block and immunstaining for keratin performed, in order to detect micrometastses. We report a case of an 80-yr-old woman who underwent a right sentinel lymph node biopsy at the time of surgery for clinically and radiologically apparent stage I endometrial endometrioid adenocarcinoma. The immunostains for AE1/AE3 performed on the 2 right pelvic sentinel lymph nodes were positive, corresponding to subcapsular acellular keratin on hematoxylin and eosin; however, carcinoma cells could not be identified on the hematoxylin and eosin-stained slides. Immunomarkers for Ber-EP4 and EMA, both of which were strongly expressed in the endometrial carcinoma cells, were negative on the nodal tissue, and we concluded that the sentinel lymph nodes were negative for metastatic carcinoma, despite the positive keratin immunostains. To our knowledge, this unusual finding is not described in the literature; recognition of this phenomenon and study of additional cases is warranted.

Topics: Aged, 80 and over; Carcinoma, Endometrioid; Carcinoma, Squamous Cell; Cell Differentiation; Endometrial Neoplasms; Endometrium; Female; Humans; Hysterectomy, Vaginal; Keratins; Salpingo-oophorectomy; Sentinel Lymph Node; Sentinel Lymph Node Biopsy

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

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

This study aims to perform differential protein expression analysis of serum samples from Oral Squamous Cell Carcinoma (OSCC) patients and healthy controls in search of potential diagnostic and/or prognostic biomarker(s).. OSCC is usually diagnosed late, which results in poor survival and high mortality. Identification of non-invasive prognostic biomarkers is of utmost importance for early diagnosis and proper management of the disease; hence we used a proteomic approach to identify potential biomarkers from serum.. Serum samples (OSCC n=45 and control n=30) were depleted, and proteins were separated using 2-D gel electrophoresis followed by identification by mass spectrometric analysis. Gene expression analysis of identified proteins in malignant and normal tissue was also performed to complement proteomics studies.. Among differentially expressed proteins, up-regulation of heat shock protein alpha (HSP90α) from the serum of oral cancer patients was observed. We also observed elevated levels of Haptoglobin (HP) along with downregulation of Type II keratin cytoskeletal 1(KRT1) and serum albumin (ALB) in oral cancer patients. Gene expression studies on identified proteins in malignant and normal tissue revealed a similar pattern with the exception of KRT1. We believe that elevated levels of serum HSP90 alpha might be used as a potential biomarker.. Our findings suggest a contribution of HSP90 alpha and other identified proteins in oral pathology as pro/anti-apoptotic modulators, thus considering their potential as predictive biomarkers.

Topics: Biomarkers, Tumor; Carcinoma, Squamous Cell; Early Detection of Cancer; Gene Expression Regulation, Neoplastic; Haptoglobins; HSP90 Heat-Shock Proteins; Humans; Keratins; Mouth Neoplasms; Prospective Studies; Proteomics; Serum Albumin; Tandem Mass Spectrometry

Squamous cell carcinoma is the most common malignant tumor of the uterine cervix with a well-documented link to infection with human papillomaviruses (HPV). According to a recent classification, there are several morphological variants of cervical squamous carcinoma, without reference to sarcomatoid squamous cell carcinoma, which is well described in other organs.. In this paper, we describe an extremely rare case of a 77-year-old woman with primary malignant cervical tumor displaying biphasic histomorphology with an epithelioid and sarcomatoid part; the latter was immunohistochemistry positive for cytokeratin and vimentin. The association with a high-grade squamous intraepithelial lesion and molecular proof of HPV33 infection in the tumor tissue supported our diagnosis of carcinoma with partial sarcomatoid differentiation.. We report a rare case of a primary cervical epithelial tumor with a partial sarcomatoid phenotype, an unequivocal HPV infection, and an associated precancerous lesion in the cervical mucosa. This is the first description of an HPV33 infection underlying a biphasic epithelioid-sarcomatous tumor of the uterine cervix. The terminology overlap between sarcomatoid carcinoma and carcinosarcoma is also discussed.

Topics: Aged; Carcinoma, Squamous Cell; Carcinosarcoma; Cell Differentiation; Cervix Uteri; Female; Humans; Keratins; Papillomavirus Infections; Sarcoma; Uterine Cervical Neoplasms

Adenosquamous carcinoma of the pancreas (ASCAP) is characterized by conventional pancreatic ductal adenocarcinoma (PDAC) and squamous carcinoma components with at least 30% of the tumour showing squamous differentiation. To get further insight into the histogenesis of these lesions, we analysed the cellular organization of ASCAP compared to PDACs. Using Immunohistochemistry and triple immunofluorescence labelling studies for keratins, p63, p40, MUC1, MUC2, MUC5AC, Ki67, and EGFR we demonstrate that many ASCAPs contain a transitional zone between the K8/18-positive adenocarcinomatous component and the p63+ /p40+ /K5/K14+ squamous component initiated by the expression of p63 in K8/18+ adenocarcinomatous cells and the appearance of basally located p63+ K5/14+ cells. p63+ K5/14+ cells give rise to fully developed squamous differentiation. Notably, 25% of conventional PDACs without histologically recognizable squamous component contain foci of p63+ p40+ and K5/14+ cells similar to the transitional zone. Our data provide evidence that the squamous carcinoma components of ASCAPs originate from pre-existing PDAC via transdifferentiation of keratin K8/18-positive glandular cells to p63-, p40-, and keratin K5/14-positive squamous carcinoma cells supporting the squamous metaplasia hypothesis. Thus our findings provide new evidence about the cellular process behind squamous differentiation in ASCAPs.

Topics: Aged; Aged, 80 and over; Carcinoma, Adenosquamous; Carcinoma, Squamous Cell; Cell Differentiation; Female; Humans; Keratins; Male; Middle Aged; Pancreatic Neoplasms

Topics: Biomarkers, Tumor; Biopsy; Calcinosis; Carcinoma, Squamous Cell; Humans; Immunohistochemistry; Keratins; Mouth Neoplasms

The role of Cytokeratin fraction 21-1 (CYFRA 21-1) as a tumour marker for head and neck cancer is still a matter of research. The aim of the present study was to evaluate the clinical impact of CYFRA 21-1 for patients with oropharyngeal squamous cell carcinoma (OSCC).. Data of 180 patients with an initial diagnosis of OSCC of any stage between 2003 and 2017 were retrospectively analysed regarding the association between pretherapeutic CYFRA 21-1 levels, clinical characteristics, overall and disease-free survival. Additionally, the potential of CYFRA 21-1 for the detection of recurrent disease in the follow-up was evaluated. The cut-off value was set at 3.3 ng/ml. The median follow-up time was 2.85 years.. A significant correlation of the CYFRA 21-1 concentration at the time of diagnosis and the N-stage was detected (p = 0.01). Patients with CYFRA 21-1 levels > 3.3 ng/ml at first diagnosis showed a significantly shorter overall survival. In the case of disease-progression, a significant increase of CYFRA 21-1 value was found compared to post-therapeutic CYFRA 21-1 levels (9.1 ng/ml versus 5.1 ng/ml; p < 0.01). CYFRA 21-1 level after treatment showed only a low sensitivity of 32% and a specificity of 78% for tumour recurrence.. CYFRA 21-1 correlates with the tumour stage and, therefore, the survival of OSCC patients. Posttreatment CYFRA21-1 seems not to be a suitable predictor of tumour recurrence in the further course of the disease. However, a sudden increase of CYFRA 21-1 during follow-up may indicate a tumour recurrence in the individual patient.

Topics: Antigens, Neoplasm; Biomarkers, Tumor; Carcinoma, Squamous Cell; Head and Neck Neoplasms; Humans; Keratin-19; Keratins; Lung Neoplasms; Neoplasm Recurrence, Local; Retrospective Studies; Sensitivity and Specificity; Squamous Cell Carcinoma of Head and Neck

Topics: Antineoplastic Combined Chemotherapy Protocols; Ascites; Biomarkers, Tumor; Carcinoma, Squamous Cell; Cisplatin; Docetaxel; Female; Gastroscopy; Gene Expression; Humans; Keratins; Lymphatic Metastasis; Membrane Proteins; Middle Aged; NF-KappaB Inhibitor alpha; Stomach; Stomach Neoplasms; Tomography, X-Ray Computed

Tumor budding (TB) is a promising prognostic marker in many cancers including oral squamous cell carcinoma. The evaluation of TB in preoperative diagnostic biopsies has been proven be possible; therefore, the association of TB with other morphological features can represent an important aid in the previous treatment decision. This study aims to evaluate TB in oral squamous cell carcinoma (OSCC) biopsies, assessing its association with other morphological characteristics of the sample. A total of 56 cases of OSCC were investigated. In hematoxylin and eosin-stained slides, morphological features including histopathological grading and mode of invasion were evaluated in the deep invasive front. Moreover, immunohistochemistry was performed with anti-multi-cytokeratin antibody helping in the identification of TB, which was graded as low-intensity or no TB and high-intensity TB. Descriptive and bivariate analyses were performed, and the level of significance was set at 5%. The tongue was the most-affected site with 29 (51.7 %) tumors. The predominant mode of invasion (27-48.2 %) was by groups of neoplastic cells without clear boundaries. Of the cases investigated, 37 (66.1 %) were high-intensity TB, which was associated with the mode of invasion of the tumors (p < 0.05). All cases with the worst mode of invasion showed high-intensity TB. Preliminary results showed the potential of morphological features, such as TB and mode of invasion, evaluated in diagnostic specimens of OSCC, aiding in the treatment decision to select patients who could benefit from more-aggressive treatments.

Topics: Adult; Biopsy; Carcinoma, Squamous Cell; Female; Head and Neck Neoplasms; Humans; Immunohistochemistry; Keratins; Male; Middle Aged; Mouth Neoplasms; Squamous Cell Carcinoma of Head and Neck

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Carcinoma, Squamous Cell; Child; Female; Follow-Up Studies; Humans; Keratins; Male; Middle Aged; Nasopharyngeal Neoplasms; Prognosis; Radiotherapy; Retrospective Studies; SEER Program; Survival Rate; Time Factors; Young Adult

There is currently no definite clinical implication for the subtypes of lung squamous cell carcinoma according to the 2015 WHO classification. This study aimed to investigate postoperative recurrence of the two major subtypes of lung squamous cell carcinoma: keratinizing squamous cell carcinoma (KSCC) and nonkeratinizing squamous cell carcinoma (NKSCC).. We identified the patients with KSCC and NKSCC who had undergone complete resection in Shanghai Chest Hospital between April 2015 and June 2016. Disease-free survival (DFS) was compared using Kaplan-Meier statistical analysis. Variables selected by univariate analysis were evaluated in multivariate analysis using the Cox proportional hazard model.. A total of 334 patients included 231 (69.2%) cases with KSCC and 103 (30.8%) cases with NKSCC. There were more smokers in keratinizing than nonkeratinizing subtype (84.8% versus 72.8%, p = 0.009). The percentage of stage Ⅲ was higher in NKSCC than that in KSCC (35% versus 22.9%, p = 0.012). The 2-year DFS rates of stage Ⅰ, stage Ⅱ and stage Ⅲ were 90.1%, 66.4% and 37.7% in KSCC, 83.3%, 67.7% and 52.8% in NKSCC, respectively. There were no significant differences of 2-year DFS rates between KSCC and NKSCC. Furthermore, KSCC and NKSCC had no significant differences in recurrence patterns and metastatic sites.. There were no significant differences of postoperative recurrence between KSCC and NKSCC.

Topics: Aged; Biomarkers, Tumor; Carcinoma, Squamous Cell; Chemotherapy, Adjuvant; Female; Humans; Immunohistochemistry; Keratins; Lung Neoplasms; Male; Middle Aged; Neoplasm Invasiveness; Neoplasm Recurrence, Local; Neoplasm Staging; Radiotherapy, Adjuvant

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

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

Bone morphogenetic protein 6 (BMP6) has unique properties regarding structure and function in supporting bone formation during development and adult life. Despite its known role in various malignant tumors, the prognostic significance of BMP6 expression in oral squamous cell carcinoma (OSCC) remains unknown. The aim of the study was to investigate immunohistochemical expression of BMP6 in OSCC in correlation with clinical and pathological parameters, disease recurrence and survival. In addition, we investigated other parameters in order to identify prognosticators of neck metastases and final outcome. The study included 120 patients with clinically T1-3N0 OSCC who were primarily surgically treated between 2003 and 2008. There were 99 (82.5%) male and 21 (17.5%) female patients. The five-year disease-specific survival for the whole cohort was 79.7%. Tumors smaller than 2 cm in diameter showed higher incidence of strong BMP6 expression. No statistical correlation was observed between other clinico-pathological factors and BMP6 expression. Expression of BMP6 was not associated with disease recurrence and survival. BMP6 may not serve as prognosticator of final outcome or recurrence in clinically node-negative OSCC subjects. In multivariate analysis predictors of poorer survival were positive surgical margin, moderate tumor cell differentiation and pathological involvement of levels IV and/or V.

Topics: Adult; Aged; Aged, 80 and over; Bone Morphogenetic Protein 6; Carcinoma, Squamous Cell; Cohort Studies; Female; Head and Neck Neoplasms; Humans; Immunohistochemistry; Keratins; Male; Middle Aged; Mouth Neoplasms; Multivariate Analysis; Neoplasm Metastasis; Neoplasm Recurrence, Local; Prognosis

To identify cytokeratins (CK) of significant correlations with clinical and histopathologic prognostic parameters in oral and oropharyngeal squamous cell carcinoma (SCC).. The sample consisted of 100 cases retrieved from the archives of the Pathology Department/ King Hussein Cancer Center/Amman/ Jordan. Recorded data included: age, gender, location, grade, depth of invasion, the presence of epithelial dysplasia, tumor size, lymph node metastasis, number of positive lymph nodes, distant metastases, clinical stage, local recurrence, treatment modalities and 5-year survival rate. Immunohistochemical staining of 7 cytokeratins: 8, 10, 13, 14, 16, 18, and 19 was performed using standard protocols. Stained sections were digitized and analyzed using ImageJ-color deconvolution to identify the percentage of cytokeratin-positive area (score). Statistical tests used were: student t-test, analysis of variance, bivariate analysis and logistic regression.. Lower CK8,18, 19 scores correlated with lower 5-year survival rate. Higher CK19 and lower CK 10, 14, 16 scores were associated with distant metastasis. Increased CK8, 18, 19 scores correlated with higher stage and with higher depth of invasion. Increased CK18 scores correlated with increased local recurrence. Higher CK10, 13, 16 scores correlated with well-differentiated grade. Higher CK19 and lower CK16 scores were associated with adjacent epithelial dysplasia. Regression analysis showed that better 5-year survival rate was significantly correlated with increased CK16, decreased CK18 and 19 scores.. Expression scores of a panel of cytokeratin are potential prognostic indicators for 5-year survival and correlates with other prognostic parameters.

Topics: Adult; Aged; Aged, 80 and over; Analysis of Variance; Carcinoma, Squamous Cell; Female; Gingiva; Humans; Immunohistochemistry; Jordan; Keratin-10; Keratin-13; Keratin-14; Keratin-16; Keratin-18; Keratin-19; Keratin-8; Keratins; Lymphatic Metastasis; Male; Middle Aged; Mouth Neoplasms; Neoplasm Staging; Oropharynx; Prognosis; Regression Analysis; Survival Rate; Young Adult

Cutaneous carcinosarcoma is a rare biphasic tumor comprising malignant epithelial and heterologous mesenchymal elements. Data on the clinical and histopathologic characteristics of this tumor in Asian populations are not available. The purpose of this study was to investigate the clinicopathologic and immunohistochemical features of cutaneous carcinosarcoma in the Korean population.. We retrospectively reviewed the records of 11 patients with cutaneous carcinosarcoma who were diagnosed from 2006 to 2016.. The mean patient age at diagnosis was 71.5 years (range, 43-96 years) and there was a men predilection. The most common site of cutaneous carcinosarcoma was the head and neck (8/11, 72.7%). Histopathologically, most tumors showed a characteristic morphology consisting of two types of tumor cells, varied differentiated epithelial cells (such as basal or squamous cells) and spindle cells with transition zones between the two components. These two cell types also demonstrated variable immunohistochemical characteristics.. Although the number of cases in this study was limited, our results provide valuable insight into the clinical and histopathologic characteristics of cutaneous carcinosarcoma in the Korean population.

Topics: Adult; Aged; Aged, 80 and over; Carcinoma, Basal Cell; Carcinoma, Squamous Cell; Carcinosarcoma; Female; Humans; Immunohistochemistry; Keratins; Male; Middle Aged; Republic of Korea; Retrospective Studies; Tumor Suppressor Protein p53

To systematically describe the clinical and histopathological features of a case series of conjunctival carcinomatous lesions underlying as-and also masquerading-pyogenic granuloma.. Nine cases of conjunctival carcinomatous lesions underlying a pyogenic granuloma (which were clinically predominant) were retrospectively identified. Patients' records were analysed for demographic data, clinical appearance and the postoperative course. Formalin-fixed paraffin-embedded specimens were routinely processed and stained with H&E and periodic acid-Schiff. Immunohistochemical stains for cytokeratin were performed in selected cases.. All nine tumours were located in the conjunctiva (bulbar, tarsal, limbal conjunctiva) of patients between 44 and 80 years. The lesions exhibited clinical features of pyogenic granuloma which dominated the clinical appearance. Additional features comprised a papillomatous appearance of the adjacent conjunctiva, a more whitish aspect of the lesion and a history of squamous cell carcinoma (SCC) respectively surgery for other entities. Histopathological analysis revealed a carcinomatous lesion (conjunctival intraepithelial neoplasia or SCC) at the base of a classic pyogenic granuloma in all nine cases. Surgical removal (R0 resection) was performed. Three cases received adjuvant mitomycin C or interferon α2b treatment. Two lesions locally recurred within 2 years after initial presentation.. Carcinomatous lesions may be accompanied by a pyogenic granuloma which may dominate the clinical pictures. As the tumour is usually located at the base of the lesion, a complete surgical excision followed by histopathological analysis is mandatory for each lesion appearing as conjunctival pyogenic granuloma.

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Agents; Biomarkers, Tumor; Carcinoma in Situ; Carcinoma, Squamous Cell; Chemotherapy, Adjuvant; Conjunctival Neoplasms; Diagnosis, Differential; Female; Granuloma, Pyogenic; Humans; Interferon alpha-2; Keratins; Male; Middle Aged; Mitomycin; Retrospective Studies

Perineural invasion (PNI) is associated with high risk keratinocyte carcinomas. Identification of PNI during Mohs surgery is important for staging and post-adjuvant treatment decisions but can be challenging. To confirm or exclude PNI suspected on hematoxylin and eosin sections, we performed immunohistochemical double staining on Mohs frozen sections. Neural marker SOX10 and pan-cytokeratin marker AE1/AE3 were combined in a simultaneous assay using species-specific (mouse and rabbit) antibodies and horseradish peroxidase and alkaline phosphatase detection systems. Of 23 Mohs cases with suspected PNI, 18 were confirmed to have definitive nerve involvement by tumor using double staining. Double staining frozen tissue is feasible and can be beneficial for real time confirmation of PNI during Mohs.\ \ J Drugs Dermatol. 2019;18(3):262-264.

Topics: Carcinoma, Basal Cell; Carcinoma, Squamous Cell; Frozen Sections; Humans; Immunohistochemistry; Keratins; Mohs Surgery; Neoplasm Invasiveness; Peripheral Nerves; Skin; Skin Neoplasms; SOXE Transcription Factors

Imaging nuclei of keratinocytes in the stratified squamous epithelium has been a subject of intense research since nucleus associated cellular atypia is the key criteria for the screening and diagnosis of epithelial cancers and their precursors. However, keratinocyte nuclei have been reported to be either low scattering or high scattering, so that these inconsistent reports might have led to misinterpretations of optical images, and more importantly, hindered the establishment of optical diagnostic criteria. We disclose that they are generally low scattering in the core using Micro-optical coherence tomography (μOCT) of 1.28-μm axial resolution in vivo; those previously reported "high scattering" or "bright" signals from nuclei are likely from the nucleocytoplasmic boundary, and the low-scattering nuclear cores were missed possibly due to insufficient axial resolutions (~4μm). It is further demonstrated that the high scattering signals may be associated with flattening of nuclei and cytoplasmic glycogen accumulation, which are valuable cytologic hallmarks of cell maturation.

Topics: Animals; Carcinoma, Squamous Cell; Cell Nucleus; Cervix Uteri; Cytoplasm; Epidermis; Epithelium; Esophagus; Female; Glycogen; Humans; In Vitro Techniques; Keratinocytes; Keratins; Light; Mouth Mucosa; Rats; Rats, Sprague-Dawley; Scattering, Radiation; Swine; Tomography, Optical Coherence; X-Ray Microtomography

A 10-year-old female American Pit Bull dog was diagnosed with metastatic undifferentiated carcinoma of the scapula. Immunohistochemistry showed positive immunoexpression for cytokeratins (AE1/AE3, 34BE12, CK7) and vimentin, confirming squamous cell carcinoma. No evidence of nodules was found in the complete physical examination and imaging procedures conducted. The patient was diagnosed with carcinoma of unknown primary origin. Amputation and adjuvant chemotherapy with doxorubicin and piroxicam were performed, but the patient died of respiratory failure after 737 days of diagnosis. Necropsy confirmed undifferentiated carcinoma infiltrating the lungs and kidneys, and showing the same immunoexpression as the tumor in the scapula. Amputation associated with chemotherapy extended the overall survival time of this patient.

Topics: Amputation, Surgical; Animals; Biomarkers, Tumor; Bone Neoplasms; Carcinoma, Squamous Cell; Dogs; Drug Therapy; Female; Immunohistochemistry; Keratins; Kidney Neoplasms; Lung Neoplasms; Neoplasms, Unknown Primary; Scapula; Vimentin

Keratinization is a routinely reported histologic feature in head and neck cancer. In contrast to numerous clinicopathologic parameters, the prognostic value of keratinization in oral squamous cell carcinoma (OSCC) is rarely reported in the literature. The purpose of this study was to review the outcome of patients with OSCC with a special focus on the degree of keratinization.. In this retrospective cohort study, we evaluated the medical records at the Department of Oral and Maxillofacial Surgery, Jena University Hospital, and investigated the outcome of patients with OSCC with disease-free survival and disease-specific survival according to the degree of keratinization. This research also analyzed common clinical and histologic parameters such as age, gender, tumor site, T category, N category, resection margin, lymphovascular invasion, and extracapsular spread. Descriptive statistics were performed, and survival was calculated by the Kaplan-Meier method. Prognostic factors were analyzed by multivariate Cox analysis.. In the sample of 151 OSCC patients, with a median age of 57.5 years and a male-female ratio of 4.03:1, 119 had tumors with no or low keratinization (K0 to K2) and 32 had tumors with good or high keratinization (K3 or K4). More recurrences were seen in patients with OSCC with low keratinization (P = .0008). The 5-year disease-free survival rate was significantly decreased for OSCC with low keratinization (52.9%) compared with good or high keratinization (93.2%) (P = .0008). The 5-year disease-specific survival rate was reduced to 66.1% (P = .0136) for patients with OSCC with low keratinization. Multivariate analysis showed that extracapsular spread (P = .001) and keratinization (P = .002) are independent, significant prognostic factors for recurrence in OSCC.. Besides extracapsular spread, the degree of keratinization seems to be an important prognostic factor for recurrence and survival in OSCC. Our results indicate that the degree of keratinization should be considered in decisions regarding treatment and prognosis for OSCC.

Topics: Carcinoma, Squamous Cell; Female; Humans; Keratins; Lymphatic Metastasis; Male; Margins of Excision; Middle Aged; Mouth Neoplasms; Neoplasm Grading; Neoplasm Invasiveness; Neoplasm Staging; Prognosis; Retrospective Studies; Survival Rate

Tumor budding is a morphological marker of cancer invasion, defined as the presence of isolated or small clusters of neoplastic cells at the tumor invasive front. This study aimed to evaluate the association between intensity of tumor budding and cell proliferation in oral squamous cell carcinoma (OSCC).. Immunohistochemistry was employed in 163 OSCC samples to detect the cell proliferation marker Ki-67 and multicytokeratin (to identify OSCC cells in tumor budding evaluation). The Mann-Whitney test was used to evaluate differences in the cell proliferation index between samples with high-intensity tumor budding and samples with low-intensity or no tumor budding. In samples with high-intensity tumor budding, the Wilcoxon test was used to evaluate differences in the cell proliferation index between the budding area and the area outside the budding. The chi-square test assessed the association between cell proliferation index and intensity of tumor budding.. The cell proliferation index was higher in samples with high-intensity tumor budding than in samples with low-intensity or no tumor budding (P < .05). Tumors with high-intensity tumor budding showed a higher cell proliferation index in the budding area than in the area outside the budding (P < .05). Finally, samples showing high-intensity tumor budding were associated with high cell proliferation index (P < .05).. Cell proliferation is positively associated with intensity of tumor budding in OSCC. Moreover, in tumors showing high-intensity tumor budding, the budding area is the location of higher cell proliferation. These findings reinforce the hypothesis that tumor budding is associated with the biological behavior of OSCC.

Topics: Biomarkers, Tumor; Carcinoma, Squamous Cell; Cell Proliferation; Female; Humans; Immunohistochemistry; Keratins; Ki-67 Antigen; Male; Middle Aged; Mouth Neoplasms; Pathology, Clinical; Staining and Labeling

A 61-year-old man presented with a dome-shaped nodule, 1.2 cm in size, with a central crater covered by keratinous material near the left lateral malleolus. Histological findings demonstrated a basophilic circular cone in the center, surrounded and sharply demarcated by a broad eosinophilic area. The central conical mass was composed mainly of atypical basaloid cells intermingled with scattered atypical sebaceous cells with scalloped nuclei and microvesicular cytoplasms, suggesting sebaceous carcinoma. The peripheral area consisted of atypical keratinizing squamoid cells without sebaceous cells, suggesting invasive squamous cell carcinoma. Atypical sebaceous cells were positive for adipophilin. Atypical basaloid cells were positive for 34βE12 and CAM5.2. Peripheral squamoid cells were positive for 34βB4 and 34βE12 throughout, and were positive for LHP1 in the superficial layer. We herein describe the first case of extraocular sebaceous carcinoma accompanied by invasive squamous cell carcinoma, which might have arisen from biphasic differentiation of cancer stem cells.

Topics: Adenocarcinoma, Sebaceous; Ankle; Biomarkers; Carcinoma, Squamous Cell; Chromosomal Proteins, Non-Histone; Humans; Keratins; Male; Middle Aged; Neoplastic Stem Cells; Perilipin-2; Sebaceous Gland Neoplasms; Sebaceous Glands

For squamous cell carcinoma (SCC) treated using Mohs micrographic surgery (MMS), interpretation of haematoxylin and eosin-stained frozen sections can be challenging. In these situations, ancillary use of immunostaining is a useful tool for the Mohs surgeon. However, use of immunostaining in MMS laboratories is limited, mainly because current manual immunostaining platforms are subject to operator error, and automated immunostaining, albeit accurate, is too slow for inclusion in MMS. In this report, we describe a novel 1-hour protocol for rapid frozen section immunocytochemistry, using the pancytokeratin markers AE1/AE3. This protocol has been specifically designed to integrate the speed of manual techniques and the accuracy of automated platforms, making it a valuable addition to the MMS laboratory. We propose that in selected or histologically challenging cases, there is a role for the use of this novel protocol, allowing the Mohs surgeon to more confidently declare tumour clearance, thus preventing further unnecessary surgery and preserving healthy tissue.

Topics: Aged, 80 and over; Biomarkers, Tumor; Carcinoma, Squamous Cell; Frozen Sections; Humans; Immunohistochemistry; Keratins; Male; Mohs Surgery; Skin Neoplasms

Keratinising squamous cell metaplasia (KSCM) is an uncommon diagnosis in the West. Patients typically present with lower urinary tract symptoms: haematuria (visible and non-visible), dysuria, urgency and frequency. Investigation is rigid cystoscopy. Abnormal bladder wall tissue should be resected and biopsies sent for histopathology to confirm KSCM. This is a preneoplastic condition with strong associations with squamous cell carcinoma. Due to a significant lag time, annual cystoscopy with multiple biopsies is recommended.

Topics: Aged, 80 and over; Biopsy; Carcinoma, Squamous Cell; Cystoscopy; Early Detection of Cancer; Humans; Keratins; Male; Metaplasia; Time Factors; Urinary Bladder; Urinary Bladder Neoplasms

Cytokeratins with epitopes in common with those of alpha (acidic and basic) mammalian keratins have been immunohistochemically demonstrated in the epidermis of reptiles. However, there are no reports of immunohistochemical staining patterns of alpha-keratins in other tissues from reptiles. Because the epithelial tumours usually retain the keratin patterns of their normal epithelial origin, it is necessary to know in advance these patterns in the major normal epithelia and organs. We used anti-alpha human keratin AE1 and AE3 monoclonal antibodies to study the staining patterns of alpha-keratins in the major normal epithelia and organs from two reptile species [the bearded dragon (Pogona vitticeps) and the loggerhead sea turtle (Caretta caretta)]. We also studied the immunolocalization of alpha-keratins in squamous cell carcinomas (SCCs) in a bearded dragon and two loggerhead turtles.. Acidic alpha-keratin (AE1 positive) was detected in many of the epithelial tissues of the bearded dragons; however, the detection of basic alpha-keratin (AE3 positive) was much more limited. Alpha-keratins were detected in a greater number of tissues of loggerhead turtles compared with those observed in bearded dragons. In the bearded dragon SCC, all layers of the nests of neoplastic cells, including the cornified layer of the keratin pearls, were strongly reactive with the AE1 antibody. However, a weak reactivity using the AE3 antibody was detected in the basal and intermediate layers of these nests. In the cutaneous SCCs of both sea turtles, acidic alpha-keratin was detected in the basal and suprabasal layers, and in all of the invasive neoplastic cords, while basic alpha-keratin was mainly detected in the invasive neoplastic cords. The pattern observed in the metastases in both turtles consisted of immunohistological detection of acidic alpha-keratin in all metastatic foci, and limited or lack of detection of basic alpha-keratin.. This study provides, for the first time, information about the immunohistochemical staining patterns of alpha-keratins in normal tissues from bearded dragons and loggerhead sea turtles, and confirms the usefulness of AE1 and AE3 monoclonal antibodies in these reptile species. The use of these antibodies also contributed to a better characterization of SCCs in these species.

Topics: Animals; Antibodies, Monoclonal; Carcinoma, Squamous Cell; Epidermis; Intestinal Mucosa; Keratins; Lizards; Male; Skin Neoplasms; Turtles

The diagnosis of cutaneous epithelial tumors (CETs) in dogs is based on predominant histological differentiation patterns. However, the expression of a broad panel of antigens has not been comprehensively examined with immunohistochemistry. The present study aims to establish a comprehensive expression profile and identify useful diagnostic markers for each CET type. Cytokeratin (CK), stem cell, and other associated markers were immunohistochemically examined in 110 canine CETs. Among these, CK16 was useful for differentiating between basal and squamous cell carcinomas. Acantholytic squamous cell carcinomas were positive for CK8, CK18, and CK19, suggesting their close association with the apocrine duct. Unlike their benign counterparts, sebaceous carcinomas coexpressed CK5/6 and adipophilin. Smooth muscle actin (SMA) and p63 immunostaining were useful for accurately distinguishing between glandular and ductal differentiation in apocrine tumors. A case of apocrine carcinoma and malignant myoepithelioma was identified using anti-SMA antibodies. Stem cell expression profiles (CK8, CK15, CK19, and CD34) of hair follicle tumors were discrete and indicative of their anatomic origins. The effectiveness of immunohistochemistry for tumor diagnosis was further confirmed by hierarchical cluster analysis, through which selected markers were able to sort CETs into specific groups: CK5/6, CK8, CK14, CK16, CK18, CK19, p63, adipophilin, and SMA sorted tumors of epidermal, apocrine, or sebaceous origin; while CK8, CK14, CK15, CK16, CK19, CD34, and p63 sorted hair follicle tumors in agreement with their histological differentiation. In conclusion, the present study provides comprehensive immunohistochemical information, which could complement histomorphological features for the future classification of canine CETs.

Topics: Animals; Biomarkers, Tumor; Carcinoma, Basal Cell; Carcinoma, Squamous Cell; Cluster Analysis; Dog Diseases; Dogs; Epithelial Cells; Keratin-18; Keratin-19; Keratin-8; Keratins; Skin; Skin Neoplasms; Stem Cells

We here report the case of a 54-year old woman presenting with a swelling in the left forearm occurred eight weeks before and rapidly increasing in volume. Clinical examination showed ulcero-budding painless purplish skin lesion measuring 2 cm along its longer axis (A). The patient underwent simple biopsy. Histological examination showed dyskeratosic, disorganized, hyperplastic epithelium with cytonuclear abnormalities, suggesting malignant transformation. Given the absence of infiltration in the chorion and the presence of hyperkeratosis, the diagnosis of keratoacanthoma was made. Resection of the tumor was indicated to confirm or deny this diagnosis. Histological examination revealed a protruding epithelial tumor-like lesion circumscribed by two species of lateral "bird beaks" delineating a crater filled with many layers of keratin. The crater was bordered by hyperplastic epithelium. The crater base was characterized by irregular papillomatous projections as well as by few cellular strands which seemed to shred in the underlying dermis. These were basophilic made up of cells displaying a certain degree of cytonuclear abnormalites arranged in one or two peripheral areas and, in their center, some eosinophilic, keratin, homogeneous cells, few mitoses as well as many horny globes, most often completely keratinized (B). The diagnosis of keratoacanthoma was retained. Keratoacanthoma is a well defined anatomo-clinical entity which can be very difficult to distinguish from squamous cell carcinoma, whose incidence is three times higher. A distinction between these two lesions is necessary due to their different management.

Topics: Biopsy; Carcinoma, Squamous Cell; Diagnosis, Differential; Female; Forearm; Humans; Keratins; Keratoacanthoma; Middle Aged; Skin Neoplasms

: TRIM29 (tripartite motif-containing protein 29) is a TRIM family protein that has been implicated in breast, colorectal, and pancreatic cancers. However, its role in stratified squamous epithelial cells and tumors has not been elucidated. Here, we investigate the expression of TRIM29 in cutaneous head and neck squamous cell carcinomas (SCC) and its functions in the tumorigenesis of such cancers. TRIM29 expression was lower in malignant SCC lesions than in adjacent normal epithelial tissue or benign tumors. Lower expression of TRIM29 was associated with higher SCC invasiveness. Primary tumors of cutaneous SCC showed aberrant hypermethylation of

Topics: Animals; Biomarkers, Tumor; Carcinogenesis; Carcinoma, Squamous Cell; Cell Line, Tumor; Cell Movement; Cell Proliferation; DNA Methylation; DNA-Binding Proteins; Gene Expression Regulation, Neoplastic; Head and Neck Neoplasms; Humans; Keratinocytes; Keratins; Mice; Mice, Nude; Neoplasm Invasiveness; Neoplasm Metastasis; Neoplasm Transplantation; Prognosis; Proteins; RNA, Small Interfering; Transcription Factors

Expression profiling was performed to delineate and characterize the impact of malignancy by comparing tissues from three sites of head and neck cancer of each patient, also determining interindividual variability.. Genome-wide analysis was carried out covering the expression of 25,832 genes with quantification for each site of seven patients with tonsillar or oropharyngeal squamous cell carcinoma. Immunohistochemical analysis was performed for adhesion/growth-regulatory galectins, three pro-inflammatory chemo- and cytokines and keratins.. Up- and down-regulation was found for 281 (tumor vs. normal) and 276 genes (transition zone vs. normal), respectively. The profile of the transition zone had its own features, with similarity to the tumor. Galectins were affected in a network manner, with differential regulation and interindividual variability between patients, also true for keratins and the chemo- and cytokines.. These results underline special features at each site of specimen origin as well as the importance of analyzing galectins as a network and of defining the expression status of the individual patient prior to reaching clinically relevant conclusions.

Topics: Aged; Carcinoma, Squamous Cell; Cytokines; Epithelium; Female; Galectins; Gene Expression Profiling; Genome, Human; Humans; Keratins; Male; Middle Aged; Oropharyngeal Neoplasms

Malignancy of the middle ear is a rare condition with limited data available for clinical guidance.. Retrospective evaluation of a large national database.. Deidentified national cancer database.. Subjects with diagnosis of malignancy of the middle ear in the National Cancer Database between 2004 and 2012.. Demographic information and tumor characteristics were evaluated. The primary endpoint of interest is overall survival.. The most common histology was squamous cell carcinoma (SCC) (50%). Multivariable Cox proportional hazard analysis found the following variables had a significant negative impact on overall survival: age (HR 1.04 95% CI [1.02-1.05]), squamous cell carcinoma, not otherwise specified (NOS) (HR 2.08 95% CI [1.30-3.32]), squamous cell carcinoma, keratinizing, NOS (HR 4.20 95% CI [2.14-8.24]), embroynal rhabdomyosarcoma, NOS (HR 4.96 95% CI [1.17-21.11]), and unknown extension (HR 2.87 95% CI [1.22-6.74]). For patients of SCC who underwent surgery, 30 had positive margins and 29 underwent adjuvant radiation. For these, no survival advantage was found with the addition of chemotherapy, regardless of node status.. Malignancy of the middle ear is a rare condition with prognosis that depends on histology. The most common histology, SCC, is associated with the poorest overall survival. Evaluation of large national datasets can add significantly to the understanding of such uncommon tumors.

Topics: Adult; Aged; Carcinoma, Squamous Cell; Databases, Factual; Ear Neoplasms; Ear, Middle; Female; Humans; Kaplan-Meier Estimate; Keratins; Male; Middle Aged; Multivariate Analysis; Prognosis; Proportional Hazards Models; Radiotherapy; Radiotherapy, Adjuvant; Retrospective Studies; United States

The expression of the hair follicle stem cell marker CD34 was analyzed in five different head and neck squamous cell carcinoma (HNSCC) cell lines with different antibodies. All HNSCC cell lines expressed CD34 on their cell surface. After cell cycle synchronization via serum starvation, we observed cyclic CD34 expression in HNSCC cells dependent on cell cycle progression via immunofluorescent staining and flow cytometric analysis. Investigation of the CD34(+) and CD34(-) HNSCC populations revealed most of the cells in S-phase and G2/M-Phase in CD34(+) cells in contrast to CD34(-) cells. Knockdown of CD34 in HNSCC cells led to diminished clonal expansion in a colony forming assay after subjecting the cells to ionizing radiation. Furthermore, knockdown of CD34 after cell cycle synchronization induced high CK1, CK4, and CK5 gene expression and downregulation of CK10 gene expression as shown by Taqman

Topics: Antigens, CD34; Carcinoma, Squamous Cell; Cell Line, Tumor; Cell Proliferation; Gene Expression; Head and Neck Neoplasms; Humans; Keratins; Radiation Tolerance

Desmoplastic squamous cell carcinoma (DSCC) as a rare subtype of cutaneous SCC has specific histological features, characterized by columns, bands, and strands of squamoid cells infiltrating a dense collagenous stroma. To decrease the high rates of local recurrence in DSSC, improvement of diagnostic methods is highly demanded. Objective was to evaluate whether immunohistochemistry (IHC) is suited to increase diagnostic accuracy. A total number of 18 patients were included in this study. After recutting of the original paraffin blocks, parallel staining of serial sections with conventionally H&E and cytokeratin AE1/AE3-immunohistochemical staining was performed. Results were evaluated by an experienced dermatohistopathologist. In 55.6% (n = 10), the margins of 3D-histology still showed no evidence of neoplastic lesions in both stainings. In contrast, we found neoplastic lesions in 5 of 18 cases (27.8%) with cytokeratin AE1/AE3 staining, while H&E-staining remained negative. In addition, neoplastic lesions were found in both, H&E as well as cytokeratin AE1/AE3 staining in three cases (16.7%). The data presented show improvement of diagnosis in 27.8% of cases using IHC and 3D-histology. This method is suitable to improve the diagnosis of DSCC.

Topics: Biomarkers, Tumor; Biopsy; Carcinoma, Squamous Cell; Female; Humans; Imaging, Three-Dimensional; Immunohistochemistry; Keratins; Male; Margins of Excision; Predictive Value of Tests; Reproducibility of Results; Retrospective Studies; Skin Neoplasms

Multipotent stromal cells (MSCs) are envisioned as a powerful therapeutic tool. As they home into tumors, secrete trophic and vasculogenic factors, and suppress immune response their role in carcinogenesis is a matter of controversy. Worldwide oral squamous cell carcinoma (OSCC) is the fifth most common epithelial cancer. Our aim was to determine whether MSC administration at precancerous stage modifies the natural progression of OSCC. OSCC was induced in Syrian hamsters by topical application of DMBA in the buccal pouch. At papilloma stage, the vehicle or 3×10

Topics: Animals; Apoptosis; Bone Marrow Cells; Carcinoma, Squamous Cell; Caspase 3; Cell Dedifferentiation; Cell Line, Tumor; Cell Proliferation; Cricetinae; Disease Progression; Down-Regulation; Epithelial Cells; Female; Hyperplasia; Immunophenotyping; Keratins; Ki-67 Antigen; Leukocyte Common Antigens; Male; Mesenchymal Stem Cell Transplantation; Mesenchymal Stem Cells; Mesocricetus; Mouth Neoplasms; Papilloma; Phenotype; Transcriptome; Transplantation, Homologous

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

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

Granular cell tumor is a rare benign tumor that can present a pseudoepitheliomatous hyperplasia of the covering epithelium. This lesion is not encapsulated and can be characterized by a pseudo invasive growth pattern, represented by the tumoral cells that infiltrate between adjacent connective tissue elements. Diagnostic difficulties may arise because histopathological features of the pronounced pseudoepitheliomatous hyperplasia can be confused with a well-differentiated oral squamous cell carcinoma. The aim of this case report is to demonstrate the role of an immunohistochemical panel in the diagnosis of a granular cell tumor in the tongue with clinical and microscopic features resembling an oral squamous cell carcinoma.. A 44-year-old white man with a history of heavy smoking and alcohol abuse presented an ulcerated nodular lesion in the dorsum of the tongue. The lesion was asymptomatic with fast growth. The clinical diagnosis was an oral squamous cell carcinoma. An incisional biopsy was performed and the ensuing histopathological analysis showed a pseudoepitheliomatous hyperplasia in the overlying epithelium mimicking the invasion of epithelial tumor cells into the connective tissue as in an oral squamous cell carcinoma. Immunohistochemical antibodies (S-100, vimentin, CD68, p53, Ki-67, E-cadherin, collagen IV and cytokeratin AE1/AE3) were used to characterize molecular aspects of the lesion. Strong staining of S-100 protein, CD68, vimentin, E-cadherin and low proliferative activity observed with Ki-67 expression confirmed the diagnosis of a granular cell tumor. The patient was submitted to surgical excision of the whole lesion. At a 12-month check-up, there was no evidence of recurrence.. This case report showed that the immunohistochemical profile was helpful in determining the clinical behavior of the tumor and establishing the final diagnosis with appropriate treatment.

Topics: Adult; Antigens, CD; Antigens, Differentiation, Myelomonocytic; Cadherins; Carcinoma, Squamous Cell; Collagen Type IV; Granular Cell Tumor; Humans; Hyperplasia; Immunohistochemistry; Keratins; Ki-67 Antigen; Male; S100 Proteins; Tongue; Tongue Neoplasms; Tumor Suppressor Protein p53; Vimentin

Topics: Carcinoma, Squamous Cell; Cell Cycle; Cell Line, Tumor; Humans; Keratins; Laryngeal Neoplasms

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

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

The cytology of oral squamous cell carcinoma (SCC) is challenging because oral SCC cells tend to be well differentiated and lack nuclear atypia, often resulting in a false negative diagnosis. The purpose of this study was to establish practical cytological parameters specific to oral SCCs.. We reviewed 123 cases of malignancy and 53 of non-neoplastic lesions of the oral mucosa, which had been diagnosed using both cytology and histopathology specimens. From those, we selected 12 SCC and 4 CIS cases that had initially been categorized as NILM to ASC-H with the Bethesda system, as well as 4 non-neoplastic samples categorized as LSIL or ASC-H as controls, and compared their characteristic findings. After careful examinations, we highlighted five cytological parameters, as described in Results. Those 20 cytology samples were then reevaluated by 4 independent examiners using the Bethesda system as well as the 5 parameters.. Five cytological features, (i) concentric arrangement of orangeophilic cells (indicating keratin pearls), (ii) large number of orangeophilic cells, (iii) bizarre-shaped orangeophilic cells without nuclear atypia, (iv) keratoglobules, and (v) uneven filamentous cytoplasm, were found to be significant parameters. All malignant cases contained at least one of those parameters, while none were observed in the four non-neoplastic cases with nuclear atypia. In reevaluations, the Bethesda system did not help the screeners distinguish oral SCCs from non-neoplastic lesions, while use of the five parameters enabled them to make a diagnosis of SCC.. Recognition of the present five parameters is useful for oral SCC cytology. Diagn. Cytopathol. 2017;45:406-417. © 2017 Wiley Periodicals, Inc.

Topics: Adult; Aged; Aged, 80 and over; Carcinoma, Squamous Cell; Cell Nucleus; Cytoplasm; Diagnosis, Differential; Female; Histocytochemistry; Humans; Keratins; Male; Middle Aged; Mouth Mucosa; Mouth Neoplasms

The aim of this study was to investigate the relationship the expression of cytokeratins (CK10 and CK13) and the cell proliferation index determined by Ki-67 of lip squamous cell carcinoma and actinic cheilitis with different degrees of dysplasia.. Forty-five paraffin-embedded actinic cheilitis with and without dysplasia and 20 lip squamous cell carcinoma were analyzed by immunohistochemistry using anti-human anti-CK10, anti-CK13, and anti-Ki-67 antibodies.. The majority of actinic cheilitis showed immunopositivity for CK10 and CK13 with decrease or loss of expression in dysplastic areas. In lip squamous cell carcinoma of the lip, heterogeneous expression of CK13 and immunonegativity for CK10 were observed. There was a statistically significant difference between CK10 expression in lip squamous cell carcinoma and in actinic cheilitis with or without dysplasia (p < 0.001). The cell proliferation index was higher in actinic cheilitis with dysplasia and lip squamous cell carcinoma than in actinic cheilitis without epithelial dysplasia. A significant correlation was found between the intensity of the epithelial dysplasia and the cell proliferation index (p < 0.001).. These results provide evidence that there is a downregulation of CK10 expression in dysplastic areas of patients with actinic cheilitis and in those with lip squamous cell carcinoma (LSCC) and that the index of cell proliferation, determined by Ki-67, is directly correlated with the intensity of the epithelial dysplasia.. Altogether, these results suggest that CK10 expression and the epithelial cell proliferation index can help to identify malignant transformation in the lip region.

Topics: Carcinoma, Squamous Cell; Cell Proliferation; Cell Transformation, Neoplastic; Cheilitis; Humans; Keratins; Lip Neoplasms

Cross-contamination during or early after establishment of a new cell line could result in the worldwide spread of a misidentified cell line. Therefore, newly established cell lines need to be authenticated by a reference standard method. This study was conducted to investigate the authenticity of a newly established epithelial cell line of human esophageal squamous cell carcinoma (ESCC) called YM-1 using short tandem repeat (STR) DNA profiling method. Primary human ESCC epithelial cells were cultured from the fresh tumor tissue of an adult female patient. Growth characteristics and epithelial originality of YM-1 cells were studied. Genomic DNA was isolated from YM-1 cells harvested at passage 22 and ESCC donor tumor sample on two different days to prevent probable DNA contamination. STR profiling was performed using AmpFℓSTR® Identifiler® Plus PCR Amplification Kit. To address whether YM-1 cells undergo genetic alteration as the passage number increases, STR profiling was performed again on harvested cells at passage 51. YM-1 cells grew as a monolayer with a population doubling time of 40.66 h. Epithelial originality of YM-1 cells was confirmed using ICC/IF staining of cytokeratins AE1/AE3. The STR profile of the ESCC donor tumor sample was the same with YM-1 cells at passage 22. However, STR profile of the donor tumor sample showed an off-ladder (OL) allele in their D7S820 locus. Also, re-profiling of YM-1 cells at passage 51 showed a loss of heterozygosity (LOH) at D18S51 locus. This suggests that long-term culture of cell lines may alter their DNA profile. Comparison of the DNA fingerprinting results in DSMZ, and ATCC STR profiling databases confirmed unique identity of YM-1 cell line. This study provides an easy, fast, and reliable procedure for authentication of newly established cell lines, which helps in preventing the spread of misidentified cells and improving the reproducibility and validity of experiments, consequently.

Topics: Carcinoma, Squamous Cell; Cell Line, Tumor; DNA Fingerprinting; DNA, Neoplasm; Esophageal Neoplasms; Female; Humans; Keratins; Loss of Heterozygosity; Microsatellite Repeats; Middle Aged; Reference Standards; Reproducibility of Results; Time Factors; Tumor Cells, Cultured

Topics: Biomarkers, Tumor; Carcinoma, Neuroendocrine; Carcinoma, Small Cell; Carcinoma, Squamous Cell; Cyclin-Dependent Kinase-Activating Kinase; Cyclin-Dependent Kinases; Diagnosis, Differential; Female; Gene Expression; Humans; Keratins; Membrane Proteins; Middle Aged; Nuclear Proteins; Oropharyngeal Neoplasms; Synaptophysin; Thyroid Nuclear Factor 1; Transcription Factors

To date, a number of potential biomarkers for lung squamous cell cancer (SCC) have been identified; however, sensitive biomarkers are currently lacking to detect early stage SCC due to low sensitivity and specificity. In the present study, we compared the 7 serum proteomic profiles of 11 SCC patients, 7 chronic obstructive pulmonary disease (COPD) patients and 7 healthy smokers as controls to identify potential serum biomarkers associated with SCC and COPD. Two-dimensional difference gel electrophoresis (2D-DIGE) and mass-spectrometric analysis (MS) using an affinity column revealed two candidate proteins, haptoglobin (HP) and apolipoprotein 4, as biomarkers of SCC, and α-1-antichymotrypsin as a marker of COPD. The iTRAQ technique was also used to identify SCC-specific peptides. HP protein expression was significantly higher in SCC patients than in COPD patients. Furthermore, two HP protein peptides showed significantly higher serum levels in SCC patients than in COPD patients. We established novel polyclonal antibodies for the two HP peptides and subsequently a sandwich enzyme-linked immunosorbent assay (ELISA) for the quantification of these specific peptides in patient and control sera. The sensitivity of detection by ELISA of one HP peptide (HP216) was 70% of SCC patients, 40% of COPDs patients and 13% of healthy controls. We also measured CYFRA, a cytokeratin fragment clinically used as an SCC tumor marker, in all the 28 cases and found CYFRA was detected in only seven SCC cases. However, when the measurement of HP216 was combined with that of CYFRA, 100% (10 of 10 patients) of SCC cases were detected. Our proteomic profiling demonstrates that the SCC-specific HP peptide HP216 may potentially be used as a diagnostic biomarker for SCC.

Topics: Adult; Aged; alpha 1-Antichymotrypsin; Apolipoproteins A; Biomarkers, Tumor; Carcinoma, Squamous Cell; Case-Control Studies; Electrophoresis, Gel, Two-Dimensional; Enzyme-Linked Immunosorbent Assay; Haptoglobins; Humans; Keratins; Lung Neoplasms; Male; Mass Spectrometry; Middle Aged; Peptide Fragments; Proteome; Pulmonary Disease, Chronic Obstructive; Smoking

We have developed an automatic and objective method for detecting human oral squamous cell carcinoma (OSCC) tissues with Raman microspectroscopy. We measure 196 independent Raman spectra from 196 different points of one oral tissue sample and globally analyze these spectra using a Multivariate Curve Resolution (MCR) analysis. Discrimination of OSCC tissues is automatically and objectively made by spectral matching comparison of the MCR decomposed Raman spectra and the standard Raman spectrum of keratin, a well-established molecular marker of OSCC. We use a total of 24 tissue samples, 10 OSCC and 10 normal tissues from the same 10 patients, 3 OSCC and 1 normal tissues from different patients. Following the newly developed protocol presented here, we have been able to detect OSCC tissues with 77 to 92% sensitivity (depending on how to define positivity) and 100% specificity. The present approach lends itself to a reliable clinical diagnosis of OSCC substantiated by the "molecular fingerprint" of keratin.

Topics: Biomarkers, Tumor; Carcinoma, Squamous Cell; Humans; Keratins; Mouth Neoplasms; Spectrum Analysis, Raman

Primary squamous cell carcinoma (SCC) of the liver is very rare, and few cases have been reported in Korea. Primary SCC of the liver is known to be associated with hepatic cysts and intrahepatic stones. A 71-year-old male was admitted to our hospital, and a abdominal computed tomography scan revealed a 10 × 6 cm mass in the liver. Analysis of a biopsy sample suggested SCC, and so our team performed a thorough workup to find the primary lesion, which was revealed hepatoma as a pure primary SCC of the liver with multiple distant metastases. The patient was treated with one cycle of radiotherapy, transferred to another hospital for hospice care, and then died 1 month after discharge.

Topics: Abdomen; Aged; Carcinoma, Squamous Cell; Humans; Immunohistochemistry; Keratins; Liver Neoplasms; Male; Palliative Care; Positron-Emission Tomography; Tomography, X-Ray Computed

Patients with head and neck squamous cell carcinoma (HNSCC) present different responses to chemotherapy and radiotherapy. One explanation may be the differences in the individual rates of stem cell-like cells.. We included patients with HNSCC and tumor progression or relapse. Tumor samples were obtained before and after primary chemotherapy, and immunohistochemical analyses were performed for CD44, HLA class I (HLA-I), pancytokeratin, and phosphorylated epidermal growth factor receptor (p-EGFR). Differences in expression between the first and second specimens were assessed.. Expression between the first and second specimens varied as follows: CD44 increased by 14.67% (95% confidence interval, CI: 6.94 to 22.40; p < 0.01); HLA-I decreased by 16.72% (95% CI: -23.87 to -9.47; p < 0.01); pancytokeratin decreased by 24.91% (95% CI: -32.8 to -17.7; p < 0.01), and p-EFGR expression decreased by 12.30% (95% CI: -20.61 to -3.98; p < 0.005).. Among patients with HNSCC, there is an enrichment of cells with stem-like markers in relapsed tumors when compared with the primary tumor. This finding should be considered when developing treatment strategies.

Topics: Adult; Aged; Biomarkers, Tumor; Carcinoma, Squamous Cell; Disease Progression; ErbB Receptors; Female; Head and Neck Neoplasms; Histocompatibility Antigens Class I; Humans; Hyaluronan Receptors; Keratins; Male; Middle Aged; Neoplasm Recurrence, Local; Neoplastic Stem Cells

Granular cell tumor (GCT) of the oral cavity is a benign lesion. Half of oral GCTs demonstrate pseudocarcinomatous hyperplasia (PCH) of the mucosa which can mimic invasive islands of oral squamous cell carcinoma (SCC). Such similarity can be confusing when diagnosing or evaluating the two conditions, potentially leading to misdiagnosis or misclassification. Indeed, several misdiagnosed cases of oral GCT have been reported in the literature as OSCC or malignant oral GCT that resulted in unnecessary aggressive treatment for the affected patients. The aim of this study was to investigate if the cytokeratin pattern of the PCH can help in differentiating GCT from oral SCC. To distinguish between these two entities, we examined 12 patient specimens of oral GCT-PCH and oral SCC histologically and via immunohistochemistry (IHC) for CK13, CK17 and P75. The results suggest that the cytokeratin profile of PCH is similar to that of oral SCC. Therefore, consideration of IHC findings for epithelial markers alone may lead to erroneous diagnosis; thus, the presence of the granular tumor underneath the PCH and its immunopositivity for P75 or other neural definition markers can be essential to identify the underlying tumor and exclude oral SCC. Finally we recommend more studies on the molecular biology of PCH to understand how it can mimic oral SCC histologically without harboring its malignant phenotype clinically, which could have significant translational potential for understanding invasive oral SCC.

Topics: Biomarkers, Tumor; Carcinoma, Squamous Cell; Diagnosis, Differential; Granular Cell Tumor; Humans; Hyperplasia; Immunoenzyme Techniques; Keratins; Mouth Neoplasms; Neoplasm Staging; Prognosis

Oral cancer is aggressive and invasive. The 5-year survival rate is around 50% and has not improved in over 50 years. One-third of oral cancer patients develop local and/or regional tumor recurrence following treatment. We continue to use our multicellular spheroid (MCS) model to better understand how the extracellular matrix contributes to epithelial to mesenchymal transition and how hypoxia contributes to the progression of oral squamous cell carcinoma (SCC).

Topics: Carcinoma, Squamous Cell; Cell Hypoxia; Cell Line, Tumor; Epithelial-Mesenchymal Transition; Fibronectins; Humans; Keratins; Models, Theoretical; Spheroids, Cellular; Tongue Neoplasms; Vimentin

Esophageal squamous cell carcinoma (ESCC) is an aggressive malignancy with a poor prognosis due to its highly invasive and metastatic potential. The molecular pathogenesis underlying the invasive mechanism of ESCC is not well known because of the lack of existing models to study this disease. p120-Catenin (p120ctn) and the epidermal growth factor receptor (EGFR) have each been implicated in several cancers, including ESCC. p120ctn is down-regulated in 60% of ESCC tumors, whereas EGFR is the most commonly overexpressed oncogene in ESCC. For these reasons, we investigated the cooperation between p120ctn and EGFR and its effect on ESCC invasion. We show that p120ctn down-regulation is commonly associated with EGFR overexpression. By using a three-dimensional culture system, we demonstrate that the inverse relationship between p120ctn and EGFR has biological implications. Specifically, p120ctn down-regulation coupled with EGFR overexpression in human esophageal keratinocytes (EPC1-PE) was required to promote invasion. Morphological comparison of EPC1-PE cells grown in three-dimensional culture and human ESCC revealed identical features, including significantly increased cellularity, nuclear grade, and proliferation. Molecular characteristics were measured by keratin expression patterns, which were nearly identical between EPC1-PE cells in three-dimensional culture and ESCC samples. Altogether, our analyses have demonstrated that p120ctn down-regulation and EGFR overexpression are able to mimic human ESCC in a relevant three-dimensional culture model.

Topics: Antigens, CD; Cadherins; Carcinoma, Squamous Cell; Catenins; Cell Culture Techniques; Cell Line, Tumor; Cell Movement; Delta Catenin; Down-Regulation; Epithelium; ErbB Receptors; Esophageal Neoplasms; Esophageal Squamous Cell Carcinoma; Gene Expression Profiling; Gene Expression Regulation, Neoplastic; Humans; Immunohistochemistry; Keratins; Neoplasm Invasiveness

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

Squamous cell carcinoma (SSC) of the head and neck is the sixth most common cancer and is rarely diagnosed in early stages. The transcription factor Krϋppel-like factor 4 (Klf4) suppresses cell proliferation and promotes differentiation. Inducible mice carrying an oral-specific ablation of Klf4 (K14-CreER(tam) /Klf4(flox/flox) ) develop mild dysplastic lesions and abnormal differentiation in the tongue. Aiming to analyze whether Klf4 cooperate in oral chemical carcinogenesis,we applied 4-nitroquinoline 1-oxide (4NQO), a tobacco surrogate, to this conditional Klf4 knockout mice.. K14-CreER(tam) /Klf4(flox/flox) and control mice were treated with 4NQO for 16 weeks and monitored until week 30. Histopathological samples were used for diagnostic purposes and immunofluorescence detection of epithelial differentiation markers.. 4NQO-treated K14-CreER(tam) /Klf4(flox/flox) mice (Klf4KO 4NQO) showed a significant weight loss and developed more severe dysplastic lesions than control mice with 4NQO (P < 0.005). The Klf4KO 4NQO showed a tendency to higher incidence of oral SCC and a marked keratinization pattern in dysplasias, in situ carcinomas and SCC. Also, tongues derived from Klf4KO 4NQO mice exhibited reduced terminal differentiation as judged by cytokeratin 1 staining when compared with 4NQO-treated controls.. Klf4 ablation results in more severe dysplastic lesions in oral mucosa, with a tendency to higher incidence of SCC, after chemical carcinogenesis. We show here, in a context similar to the human carcinogenesis, that absence of Klf4 accelerates carcinogenesis and correlates with the absence of cytokeratin 1 expression. These results suggest a potential role for KLF4 as a tumor suppressor gene for the tongue epithelium.

Topics: 4-Nitroquinoline-1-oxide; Animals; Carcinogenesis; Carcinogens; Carcinoma, Squamous Cell; Cell Differentiation; Disease Models, Animal; Gene Expression; Head and Neck Neoplasms; Keratins; Kruppel-Like Factor 4; Kruppel-Like Transcription Factors; Mice; Mice, Inbred C57BL; Mice, Knockout; Mouth Mucosa; Mouth Neoplasms; Precancerous Conditions; Squamous Cell Carcinoma of Head and Neck; Tongue Neoplasms

Oral squamous cell carcinomas (OSCC) induced in F344 rats by 4-nitroquinoline-1-oxide (4-NQO) demonstrate considerable phenotypic similarity to human oral cancers. Gene expression studies (microarray and PCR) were coupled with methylation analysis of selected genes to identify molecular markers of carcinogenesis in this model and potential biochemical and molecular targets for oral cancer chemoprevention. Microarray analysis of 11 pairs of OSCC and site-matched phenotypically normal oral tissues from 4-NQO-treated rats identified more than 3500 differentially expressed genes; 1735 genes were up-regulated in rat OSCC versus non-malignant tissues, while 1803 genes were down-regulated. In addition to several genes involved in normal digestion, genes demonstrating the largest fold increases in expression in 4-NQO-induced OSCC include three lipocalins (VEGP1, VEGP2, LCN2) and three chemokines (CCL, CXCL2, CXCL3); both classes are potentially druggable targets for oral cancer chemoprevention and/or therapy. Down-regulated genes in 4-NQO-induced OSCC include numerous keratins and keratin-associated proteins, suggesting that alterations in keratin expression profiles may provide a useful biomarker of oral cancer in F344 rats treated with 4-NQO. Confirming and extending our previous results, PTGS2 (cyclooxygenase-2) and several cyclooxygenase-related genes were significantly up-regulated in 4-NQO-induced oral cancers; up-regulation of PTGS2 was associated with promoter hypomethylation. Rat OSCC also demonstrated increased methylation of the first exon of APC2; the increased methylation was correlated with down-regulation of this tumor suppressor gene. Overexpression of pro-inflammatory chemokines, hypomethylation of PTGS2, and hypermethylation of APC2 may be causally linked to the etiology of oral cancer in this model.

Topics: 4-Nitroquinoline-1-oxide; Animals; Carcinoma, Squamous Cell; Chemokines; Cyclooxygenase 1; Cyclooxygenase 2; DNA Methylation; Gene Expression Regulation, Neoplastic; Genes, Tumor Suppressor; Keratins; Lipocalins; Male; Membrane Proteins; Mouth Neoplasms; Oligonucleotide Array Sequence Analysis; Promoter Regions, Genetic; Rats, Inbred F344; Tongue; Transcriptome

A 30-year-old man presented with lesions on his oral mucosa and soles. There were no similar complaints in his family members. The dermatological examination revealed follicular hyperkeratosis on his trunk and upper extremities and flesh-colored, firm cystic lesions on his axillae. He had focal, painful, hyperkeratotic areas sited particularly on both his soles and palms. In addition to these, leukokeratosis and ulcerative areas on buccal, labial mucosa, tongue, and at corners of the mouth, and complete loss of teeth was observed. The proximal layering was revealed on all of his nails. The laboratory investigations produced normal results except the deficiency of immunoglobulin A. The psychiatric examination revealed mild mental retardation. Keratin gene (KRT6a, KRT6b, KRT16, and KRT17) mutations for pachyonychia congenita were negative. He got removable dental prosthesis because of inadequate alimentation. Squamous cell cancer developed on lower lip mucosa during follow-up. We present an individual who had different nail dystrophy, epidermal cysts, mental retardation, blepharitis, complete loss of teeth, and negative keratin gene mutations for pachyonychia congenita and developed squamous cell cancer on the oral leukokeratosis lesions. We think that the present case may be an unusual new type of pachyonychia congenita.

Topics: Adult; Carcinoma, Squamous Cell; Epidermal Cyst; Humans; Intellectual Disability; Keratins; Keratosis; Leukoplakia, Oral; Lip Neoplasms; Male; Mouth, Edentulous; Oral Ulcer; Pachyonychia Congenita; Syndrome

Chronic venous leg ulcers (VLU), especially long-lasting non-healing ulcers, are among the risk factors for squamous cell carcinoma (SCC). Malignant transformation of a VLU is a rare finding and the relative risk of carcinomatous transformation is quite low (about 5.8). SCC arising in the context of a VLU has a particularly aggressive behavior. A 76-year-old male patient with no relevant medical familial history, with chronic venous insufficiency CEAP C6 for 10 years [recurrent leg ulcers with favorable outcome (healing) after specific local and systemic treatment], showing for about three years one ulcerated lesion located on the anterior upper third of the right calf non-responsive to specific treatment, which subsequently increased their size and merged. Biopsy sample was taken. Histopathology showed epidermal acanthosis, papillomatosis, intense parakeratosis, pseudoepitheliomatous hyperplasia, dysplasia and moderately differentiated squamous cell carcinoma with areas of acantholysis. Immunohistochemistry (Ki67, EMA, cytokeratin 34βE12 and p63) was performed and all types of immunostaining were moderately to intense positive. Above-knee leg amputation and specific oncologic treatment were proposed as possible curative solutions but the patient refused. Ten months after diagnosis and discharge form the Department of Dermatology, the patient died. Patients with chronic venous leg ulcers and clinically suspicious lesions should be evaluated for malignant transformation of the venous lesion. When diagnosed, malignancy complicating a chronic venous leg ulcer requires a resolute treatment as it may be fatal.

Topics: Aged; Amputation, Surgical; Carcinoma, Squamous Cell; Cell Transformation, Neoplastic; Fatal Outcome; Humans; Immunohistochemistry; Keratins; Ki-67 Antigen; Leg; Leg Ulcer; Male; Mucin-1; Risk Factors; Skin Neoplasms; Transcription Factors; Tumor Suppressor Proteins; Varicose Ulcer

Topics: Biomarkers, Tumor; Carcinoma, Squamous Cell; Conjunctival Neoplasms; Fluorescent Dyes; Humans; Keratins; Microscopy, Confocal; Rose Bengal; Staining and Labeling

To evaluate the effectiveness of sentinel lymph node biopsy (SLNB) as an optimal staging method in oral and oropharyngeal squamous cell carcinoma (OOSCC) and the impact of the extent of SLN involvement on the decision for neck dissection (ND).. A prospective cohort study was performed in 96 consecutive patients with stage T1 to T4N0M0 OOSCC (mean follow-up, 62.9 months). SLN localization was determined using cervical lymphoscintigraphy and single-photon emission computed tomography. Patients underwent SLNB examination and ND. The ND specimen was investigated by hematoxylin and eosin (H&E) staining and the SLNs were investigated using H&E staining and step-serial sectioning and cytokeratin antibodies AE1 and AE3. The statistical study calculated the sensitivity and negative predictive value (NPV). The sample size of 96 patients was calculated for a 95% confidence interval with an accuracy of ±2% and an estimated a priori sensitivity of 99% compared with the benchmark. The impact of extent of SLN involvement on the decision for ND was analyzed by χ(2) test. A logistic regression model was used to assess the association of predictor variables with SLN involvement and neck disease.. The diagnostic accuracy, sensitivity, NPV, and negative likelihood ratio were 95%, 88%, 94%, and 0.06. The statistical comparison between the extent of metastatic involvement of the SLN and neck disease was important for SLN macrometastasis (odds ratio = 11.9), but not for SLN micrometastasis (odds ratio = 0.93).. SLNB examination is an excellent staging method in OOSCC. The present data indicate a very small risk of additional lymph node metastasis with SLN micrometastasis.

Topics: Adult; Aged; Aged, 80 and over; Carcinoma, Squamous Cell; Cohort Studies; Decision Making; Female; Follow-Up Studies; Humans; Keratins; Lymph Nodes; Lymphatic Metastasis; Lymphoscintigraphy; Male; Middle Aged; Mouth Neoplasms; Neck Dissection; Neoplasm Staging; Oropharyngeal Neoplasms; Predictive Value of Tests; Prospective Studies; Radiopharmaceuticals; Sensitivity and Specificity; Sentinel Lymph Node Biopsy; Technetium; Tomography, Emission-Computed, Single-Photon

The invasion of cancer cells into the surrounding normal tissue is one of the defining features of cancer. While the phenomena of tumour budding, epithelial-mesenchymal transition and the presence of myofibroblasts have independently been shown to be related to a poor prognosis of oral carcinomas, their relationship has not been examined in detail.. Paraffin-embedded tissues from 28 patients with oral squamous cell carcinomas were stained with antibodies to cytokeratin, α-SMA, vimentin, E-cadherin, N-cadherin and Twist and evaluated for their expression in relation to invasive cancer cells and the surrounding tumour stroma.. A direct, histological relationship between invading, budding tumour cells and myofibroblasts was occasionally seen but was not a general feature. Most of the budding tumour cells at the invasive front had a decreased expression of E-cadherin, but we did not find that this was associated with a consistent or clear increase in either N-cadherin or vimentin. We therefore suggest that the budding of tumour cells is not dependent upon either myofibroblasts or a complete epithelial-mesenchymal transition and that these phenomena most likely represent separate processes in tumour progression.

Topics: Actins; Animals; Cadherins; Carcinoma, Squamous Cell; Cell Line, Tumor; Cell Movement; Epithelial-Mesenchymal Transition; Goats; Head and Neck Neoplasms; Humans; Keratins; Mice; Mouth Neoplasms; Muscle, Smooth; Myofibroblasts; Paraffin Embedding; Prognosis; Rabbits; Single-Cell Analysis; Squamous Cell Carcinoma of Head and Neck; Twist-Related Protein 1; Vimentin

Atypical fibroxanthoma (AFX) is an uncommon cutaneous neoplasm of pleomorphic myofibroblast-like cells. Diagnosis requires exclusion of other undifferentiated spindle and pleomorphic cell neoplasms by immunohistochemistry. We report two patients with p63-non-reactive spindle cell neoplasms which resembled AFX but demonstrated anomalous dot-like immunolabeling with antibodies to high molecular weight keratin and keratin 5. One case recurred locally, suggesting such lesions may behave aggressively. Whether these lesions represent keratin-positive dermal sarcomas or poorly differentiated carcinomas is debatable. Regardless of exact classification, our experience suggests such cases should be managed as high-risk non-melanoma skin cancers.

Topics: Aged; Carcinoma, Squamous Cell; Diagnosis, Differential; Histiocytoma, Malignant Fibrous; Humans; Immunohistochemistry; Keratins; Male; Membrane Proteins; Mohs Surgery; Neoplasm Recurrence, Local; Nevus, Spindle Cell; Skin Neoplasms; Xanthomatosis

Cytokeratins (CK) are abundant in keratinized cells, particularly CK14 and CK19, which are expressed in stratified squamous epithelial cells. In this study, expression of CK14 and 19 was examined in human epithelial and dysplastic tissues. Surgical specimens from patients with clinically diagnosed oral leukoplakia or early cancer were stained with hematoxylin and eosin and classified into normal, low grade dysplasia (LGD), high grade dysplasia (HGD), or squamous cell carcinoma (SCC). The sections were examined by immunostaining and reverse transcription-polymerase chain reaction (RT-PCR) for CK14 and CK19. Expression and the results of RT-PCR for CK14 showed a decrease in the order of LGD, HGD, and SCC, whereas those of CK19 showed an increase in that order. These results suggest that decreased expression of CK14 and increased expression of CK19 serve as indicators of potential for malignant transformation.

Topics: Carcinogenesis; Carcinoma, Squamous Cell; Epithelial Cells; Humans; Keratin-14; Keratin-19; Keratins; Mouth Neoplasms

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

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

Oral squamous cell carcinoma (OSCC) has contributed 90% of oral cancer worldwide. In situ histological evaluation of tissue sections is the gold standard for oral cancer detection. Formation of keratinization and keratin pearl is one of the most important histological features for OSCC grading. This paper aims at developing a computer assisted quantitative microscopic methodology for automated identification of keratinization and keratin pearl area from in situ oral histological images. The proposed methodology includes colour space transform in YDbDr channel, enhancement of keratinized area in most significant bit (MSB) plane of Db component, segmentation of keratinized area using Chan-Vese model. The proposed methodology achieves 95.08% segmentation accuracy in comparison with (manually) experts-based ground truths. In addition, a grading index describing keratinization area is explored for grading OSCC cases (poorly, moderately and well differentiated).

Topics: Animals; Carcinoma, Squamous Cell; Diagnostic Imaging; Humans; Keratins; Mouth Neoplasms; Neoplasm Grading

Solar ultraviolet irradiation is an environmental carcinogen that causes skin cancer. Caspase-7 is reportedly expressed at reduced levels in many cancers. The present study was designed to examine the role of caspase-7 in solar-simulated light (SSL)-induced skin cancer and to elucidate its underlying molecular mechanisms. Our study revealed that mice with genetic deficiency of caspase-7 are highly susceptible to SSL-induced skin carcinogenesis. Epidermal hyperplasia, tumor volume and the average number of tumors were significantly increased in caspase-7 knockout (KO) mice compared with SKH1 wild-type mice irradiated with SSL. The expression of cell proliferation markers, such as survivin and Ki-67, was elevated in SSL-irradiated skin of caspase-7 KO mice compared with those observed in SSL-exposed wild-type SKH1 mouse skin. Moreover, SSL-induced apoptosis was abolished in skin from caspase-7 KO mice. Two-dimensional gel electrophoresis, followed by matrix-assisted laser desorption/ionization-time-of-flight analysis of skin tissue lysates from SSL-irradiated SKH1 wild-type and caspase-7 KO mice revealed an aberrant induction of keratin-17 in caspase-7 KO mice. Immunohistochemical analysis of skin tumors also showed an increase of keratin-17 expression in caspase-7 KO mice compared with SKH1 wild-type mice. The expression of keratin-17 was also elevated in SSL-irradiated caspase-7 KO keratinocytes as well as in human basal cell carcinomas. The in vitro caspase activity assay showed keratin-17 as a substrate of caspase-7, but not caspase-3. Overall, our study demonstrates that genetic loss of caspase-7 promotes SSL-induced skin carcinogenesis by blocking caspase-7-mediated cleavage of keratin-17.

Topics: Animals; Carcinoma, Squamous Cell; Caspase 7; Cells, Cultured; Epidermis; Female; Gene Knockout Techniques; Keratinocytes; Keratins; Male; Mice, Inbred BALB C; Mice, Inbred C57BL; Mice, Knockout; Proteolysis; Radiation Injuries, Experimental; Skin Neoplasms; Sunlight; Tumor Burden

Four cases of tumors in which cell internalization was frequently visualized are reported: one feline mammary carcinoma, one feline cutaneous squamous cell carcinoma, one canine pulmonary squamous cell carcinoma and one canine pleural mesothelioma. Cell internalization was observed by cytology in two of these cases (the feline mammary tumour and the pleural effusion in the canine mesothelioma) and by histopathology in all but the canine mesothelioma. Immunohistochemical staining for pancytokeratin was positive for both internalized and host cells, while E-cadherin expression was frequently absent, although internalized cells occasionally stained positive. This cell-to-cell interaction seems to be associated with tumors displaying a strong epithelial-mesenchymal transitional phenotype, in which cancer cells become engulfed by other cancer cells. Such event could be regarded as an important hallmark of very high malignancy.

Topics: Animals; Biomarkers, Tumor; Biopsy; Cadherins; Carcinoma, Squamous Cell; Cat Diseases; Cats; Cytophagocytosis; Dog Diseases; Dogs; Female; Immunohistochemistry; Keratins; Lung Neoplasms; Male; Mammary Neoplasms, Animal; Mesothelioma; Pleural Neoplasms; Skin Neoplasms

Five-year survival rates for oral squamous cell carcinoma (OSCC) are 30% and the mortality rate is 50%. Immunohistochemistry panels are used to evaluate proliferation, vascularization, apoptosis, HPV infection, and keratin expression, which are important markers of malignant progression. Keratins are a family of intermediate filaments predominantly expressed in epithelial cells and have an essential role in mechanical support and cytoskeleton formation, which is essential for the structural integrity and stability of the cell. In this study, we analyzed the expressions of keratins 17 and 19 (K17 and K19) by immunohistochemistry in tumoral and non-tumoral tissues from patients with OSCC. The results show that expression of these keratins is higher in tumor tissues compared to non-tumor tissues. Positive K17 expression correlates with lymph node metastasis and multivariate analysis confirmed this relationship, revealing a 6-fold increase in lymph node metastasis when K17 is expressed. We observed a correlation between K17 expression with disease-free survival and disease-specific death in patients who received surgery and radiotherapy. Multivariate analysis revealed that low expression of K17 was an independent marker for early disease relapse and disease-specific death in patients treated with surgery and radiotherapy, with an approximately 4-fold increased risk when compared to high K17 expression. Our results suggest a potential role for K17 and K19 expression profiles as tumor prognostic markers in OSCC patients.

Topics: Biomarkers, Tumor; Carcinoma, Squamous Cell; Disease-Free Survival; Epithelial Cells; Female; Humans; Keratins; Lymphatic Metastasis; Male; Middle Aged; Mouth Neoplasms; Neoplasm Recurrence, Local; Prognosis

Oral squamous cell carcinoma (OSCC) is one of the most prevalent cancers worldwide. Laminin-5 gamma 2 chain (laminin-5 γ2) is a protein associated to a migratory phenotype in epithelial neoplastic cells. Stromal myofibroblasts also play a significant role in tumor invasion, due to its ability to modify the extracellular matrix. Tumor budding is a morphologic marker of tumor invasion. The aim of this study was to evaluate the expression of laminin-5 γ2 in OSCC and its association with intensity of tumor budding and density of stromal myofibroblasts.. Paraffin-embedded archival samples of 57 OSCC patients were evaluated. Immunohistochemistry was employed to detect laminin-5 γ2, alpha smooth muscle actin (marker of stromal myofibroblasts), and multicytokeratin (to identify OSCC cells in tumor budding evaluation). Laminin-5 γ2 expression and its association with intensity of tumor budding and density of stromal myofibroblasts were analyzed. Association among intensity of tumor budding and density of stromal myofibroblasts was also evaluated.. Higher laminin-5 γ2 expression was associated with high-intensity tumor budding (P < 0.05) and with higher density of stromal myofibroblasts (P < 0.05). Moreover, high-intensity tumor budding was associated with higher density of stromal myofibroblasts (P < 0.05).. In OSCC, higher laminin-5 γ2 expression is associated with high-intensity tumor budding and with higher density of stromal myofibroblasts, suggesting that this expression is related to the establishment of an invasive phenotype of neoplastic cells and a permissive environment for tumor invasion in this neoplasia.

Topics: Actins; Adult; Aged; Aged, 80 and over; Carcinoma, Squamous Cell; Cell Count; Female; Humans; Immunohistochemistry; Keratins; Laminin; Male; Middle Aged; Mouth Neoplasms; Myofibroblasts; Neoplasm Invasiveness

Sarcomatoid carcinoma (SC) is a variant of head and neck squamous cell carcinoma characterized by a prominent and sometimes exclusive spindle cell component. Distinction from a sarcoma or reactive stroma can be problematic, particularly in cases in which the conventional component is not obvious. The value of immunohistochemistry is limited because of the loss of cytokeratin expression in a sizable percentage of cases. Staining for p63 can enhance detection of epithelial differentiation, but its usefulness is offset by expression in various soft tissue proliferations. Staining for p40--a squamous-specific isoform of p63--could potentially improve diagnostic accuracy. Immunohistochemistry for pancytokeratin, p63, and p40 was performed on 37 head and neck SCs, 201 soft tissue neoplasms, and 40 reactive stromal proliferations. The SCs were also stained for p16 in the event that some of the tumors were human papillomavirus (HPV) related. HPV in situ hybridization was performed on p16-positive cases. Twenty-three of 37 (62%) SCs were positive for pancytokeratin, 23 of 37 (62%) were positive for p63, and 20 of 37 (54%) were positive for p40. Compared with p63, p40 staining was less likely to be observed in soft tissue tumors (5% vs. 30%) and reactive stromal proliferations (0% vs. 30%). HPV16 was detected in 3 of 10 (30%) SCs of the oropharynx but in none of the nonoropharyngeal SCs. p40 staining does not improve the sensitivity for diagnosing SC, but it does diminish the risk of misdiagnosing a sarcoma or reactive stroma as SC. The presence of a sarcomatoid variant of HPV-related oropharyngeal cancer points to HPV testing as a useful diagnostic tool for atypical spindle cell proliferations of the oropharynx.

Topics: Biomarkers, Tumor; Carcinoma, Squamous Cell; Cell Proliferation; Cyclin-Dependent Kinase Inhibitor p16; Diagnosis, Differential; DNA, Viral; Head and Neck Neoplasms; Human papillomavirus 16; Human Papillomavirus DNA Tests; Humans; Immunohistochemistry; In Situ Hybridization; Keratins; Oropharyngeal Neoplasms; Papillomavirus Infections; Predictive Value of Tests; Protein Isoforms; Stromal Cells; Transcription Factors; Tumor Suppressor Proteins

Cancer chemoprevention is defined as the use of chemicals or dietary components to block, inhibit, or reverse the development of cancer in normal or pre-neoplastic tissue. Mentha extract (ME) has antioxidant and antiperoxidant properties. This study was held to investigate the protective and anticancer effect of Mentha leaves aqueous extract on oral epithelium of mice tongues.. A total of 80 Egyptian albino mice were divided into three groups. Group I served as control (not subjected to any kind of treatment), and groups II and III were subjected to two-stage chemical carcinogenesis through topical application of dimethylbenz[a]anthracene (DMBA) followed by formaldehyde on dorsal and ventral surfaces of tongues for 9 weeks. Mentha leaves extract was administrated to group III at the same time of cancer induction. Histological changes were assessed in H&E sections at 3-week intervals. The anticarcinogenic effect of Mentha piperita was tested using immunostain with anticaspase antibody.. The oral administration of ME reduced the appearance of dysplastic cellular changes with 61% and inhibited tumor incidence with 100%. Group I showed moderate-to-strong cytoplasmic caspase expression. At 6-week interval, group II showed weak-to-moderate caspase expression, while sections from group III showed moderate-to-strong caspase expression. High significant statistical difference in the total score of caspase 3 expression was found between specimens obtained from animals sacrificed at 6 weeks in groups I, II, and III (P = 0.001**).. Our study demonstrated that Mentha piperita has inhibited the initiation and promotion of oral dysplastic lesions.

Topics: 9,10-Dimethyl-1,2-benzanthracene; Animals; Anticarcinogenic Agents; Antioxidants; Basement Membrane; Carcinogenesis; Carcinogens; Carcinoma, Squamous Cell; Caspase 3; Chemoprevention; Connective Tissue; Epithelium; Formaldehyde; Hyperplasia; Keratins; Male; Mentha piperita; Mice; Phytotherapy; Plant Extracts; Protective Agents; Tongue; Tongue Neoplasms

Lymph node metastasis is a prominent clinical feature of tongue squamous cell carcinoma (TSCC) and is associated with a higher mortality rate. Carcinoma-associated fibroblasts (CAFs), a major component of the tumor microenvironment (TME), play an important role in tumor progression, and are associated with a poor prognosis. The aim of this study was to examine the role of CAFs in promoting the invasion of TSCC through the epithelial-to-mesenchymal transition (EMT).. A series of matched CAF and normal fibroblast (NF) pairs were assessed for cell morphology and for the expression of alpha smooth muscle actin (α-SMA), stromal cell-derived factor-1 (SDF1), fibroblast-activating protein (FAP), vimentin, and cytokeratin (CK) markers. Transwell assays, Western blot analysis, reverse transcription-PCR, and immunofluorescence staining were used to assess the role of CAFs, as compared to that of NFs, in promoting proliferation, migration, invasion, and EMT in TSCC.. Both CAF and NF primary cultures expressed vimentin but not CK. CAFs showed significantly higher α-SMA protein levels, SDF1 secretion, and mRNA levels of α-SMA, SDF1, and FAP. We also found that co-culture with CAFs enhanced the proliferation and invasion of SCC9 cells. Moreover, co-culture with CAFs induced upregulation of the EMT markers fibronectin and vimentin, downregulation of E-cadherin, and enhanced invasion in SCC9 cells.. These results suggest that CAFs induce EMT marker expression and functional changes in TSCCs.

Topics: Actins; Adult; Aged; Antigens, Neoplasm; Cadherins; Carcinoma, Squamous Cell; Cell Line, Tumor; Cell Movement; Cell Proliferation; Cell Shape; Cells, Cultured; Chemokine CXCL12; Coculture Techniques; Endopeptidases; Epithelial-Mesenchymal Transition; Female; Fibroblasts; Fibronectins; Gelatinases; Humans; Keratins; Lymphatic Metastasis; Male; Membrane Proteins; Middle Aged; Neoplasm Invasiveness; Serine Endopeptidases; Tongue Neoplasms; Tumor Microenvironment; Vimentin

Nasopharyngeal squamous cell carcinoma (NPSCC) is uncommon in non-endemic regions. Two major histologic subtypes are recognized: keratinizing (K-NPSCC) and nonkeratinizing (NK-NPSCC). We hypothesize that significant differences exist between the 2 in terms of demographic, clinicopathologic, survival, and prognostic features. We aim to show that differentiating between the 2 subtypes is perhaps the most important first step at the time of diagnosis.. Using a retrospective cohort design, the U.S. National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) registry was used to extract data on the 2 major subtypes of NPSCC. Frequency, incidence, and relative survival (RS) were analyzed comparatively. Regression analysis was conducted and hazard ratios (HRs) calculated.. A total of 1624 cases were identified: 1234 (76.0%) cases of NK-NPSCC and 390 (24.0%) cases of K-NPSCC. Five-year RS was 60.6% for NK-NPSCC and 40.5% for K-NPSCC. Regression analysis revealed K-NPSCC to be a poor prognostic factor (HR 2.1; 95% confidence interval, 1.8-2.6; p < 0.0001). Other factors associated with a poor prognosis included female gender in K-NPSCC, age greater than 44 years in both groups, and advanced-stage disease at diagnosis. Favorable prognostic factors included Asian/Pacific Islander race, and treatment with radiation therapy. Higher histologic grade did not portend a worse prognosis for either group.. NPSCC remains an uncommon malignancy in the United States. K-NPSCC and NK-NPSCC represent 2 different histologic entities with important clinical differences. K-NPSCC carries a worse overall prognosis when compared to NK-NPSCC.

Topics: Age Factors; Asian People; Carcinoma, Squamous Cell; Cohort Studies; Diagnosis, Differential; Female; Humans; Keratins; Male; Middle Aged; Nasopharyngeal Neoplasms; Native Hawaiian or Other Pacific Islander; Neoplasm Staging; Prognosis; Retrospective Studies; Risk; Sex Factors; Survival Analysis; United States

Hsp90α (heat shock protein 90α), one of the important molecular chaperones in cancer cell signal transduction, has been a new candidate target for cancer therapy. Cyclin B1, the client protein of Hsp90α, plays a key role as a mitotic cyclin in the G2-M phase transition during the cell cycle progression. However, the relationship between the level of HSP90α and cyclin B1, the location of Hsp90α and cyclin B1 in prognosis of esophageal squamous cell carcinoma (ESCC) has not been examined. Here, we demonstrate that the diagnostic significance of Hsp90α and cyclin B1 by immunohistochemistry and the association of Hsp90α and cyclin B1 expression in ESCC. In the specimens from 105 ESCC patients (81 stained with Hsp90α antibody by Immunohistochemistry, 65 with cyclin B1 antibody, and among them, 41 paired specimens were stained with Hsp90α and cyclin B1 respectively, and then checked for the correlation of the level and location of Hsp90α and cylcin B1. The positivity rate of Hsp90α and cyclin B1 expression were 96.3% (78 of 81) and 84.6% (55 of 65) respectively. Both of them, the expression levels are associated with the clinical pathological stage (Hsp90α, p=0.027; cyclin B1, p=0.007). No association was found between Hsp90α or cyclin B1 and gender, age, tumor location. As to TMN stage, there is no association with the level of Hsp90α, However, cyclin B1 expression is significantly related to tumor status (p=0.002). Interestingly, Hsp90α expression was negatively correlated to cyclin B1 expression (Gamma=-0.692, p=0.007) in the keratin pearls though there is a positive correlation in the other areas of tumor (Gamma=0.503, p=0.015), which suggest Hsp90α might play diverse roles in the cyclin B1 expression and cyclin B1 related cell cycle regulation in the different area of tumor. These findings demonstrated that the expression of Hsp90α, cyclin B1 protein is associated with tumor malignancy and prognosis for patients with human esophageal squamous cell carcinoma, and Hsp90α might be involved in cyclin B1 expression regulation and cell cycle regulation in keratin peal formation of ESCC.

Topics: Adult; Aged; Aged, 80 and over; Biomarkers, Tumor; Carcinoma, Squamous Cell; Cyclin B1; Cytoplasmic Structures; Esophageal Neoplasms; Female; Gene Expression Regulation, Neoplastic; HSP90 Heat-Shock Proteins; Humans; Immunohistochemistry; Kaplan-Meier Estimate; Keratins; Male; Middle Aged; Neoplasm Staging; Prognosis; Retrospective Studies; Survival Rate

We have reported that neutrophilic infiltration was associated with round-shaped dyskeratosis foci, a kind of keratin pearl, of oral carcinoma in situ and that those inflammatory cells are recruited from intra-epithelially entrapped blood vessels. Based on these lines of evidence, we have formulated a hypothesis that keratin pearls are terminally degraded by neutrophils. To confirm this hypothesis, we investigated immunohistochemically stepwise degradation of keratin pearls in oral squamous cell carcinoma (SCC) to clarify any other type scavenger cells in addition to neutrophils are involved in this particular degradation process.. Neutrophils (neutrophil elastase) and macrophage subpopulations (CD68, CD163 and CD204) were immunohistochemically localized in 30 cases of oral SCC with typical round-shaped keratin pearls. SCC cells were revealed by immunohistochemistry for keratin (K) 17, and blood vessels were demonstrated by CD31.. Keratin pearl degradation process was divided into four steps: (i) intact stage: no macrophage infiltration but minimal neutrophils were found in keratin pearls; (ii) neutrophil recruit stage: no macrophage infiltration but focal neutrophilic infiltration within the pearls; (iii) neutrophil predominant stage: dense neutrophil infiltration with minimal macrophages and segregated keratinized cancer cells strongly positive for K17; and (iv) macrophage predominant stage: dense infiltration of CD68-, CD163 (mononuclear)- and CD204 (multinucleated)-positive macrophages engulfing detached keratinized SCC cells.. Keratin pearl degradation in oral SCC is strictly regulated by two types of scavenger cells: neutrophils, which perform initial tasks, and macrophages, which reciprocally take over from neutrophils the role to finalize the degradation processes.

Topics: Antigens, CD; Antigens, Differentiation, Myelomonocytic; Carcinoma, Squamous Cell; Humans; Keratin-17; Keratins; Leukocyte Elastase; Macrophage Activation; Macrophages; Mouth Neoplasms; Neutrophil Infiltration; Neutrophils; Platelet Endothelial Cell Adhesion Molecule-1; Proteolysis; Receptors, Cell Surface; Receptors, Scavenger; Scavenger Receptors, Class A

An adult, gravid, female pigtailed macaque (Macaca nemestrina) presented for facial swelling centered on the left mandible that was approximately 5 cm wide. Differential diagnoses included infectious, inflammatory, and neoplastic origins. Definitive antemortem diagnosis was not possible, and the macaque's condition worsened despite supportive care. Necropsy findings included a mandibular mass that was locally invasive and expansile, encompassing approximately 80% of the left mandibular bone. The mass replaced portions of the soft palate, hard palate, sinuses, ear canal, and the caudal-rostral calvarium and masseter muscle. Histologically, the mass was a neoplasm that was poorly circumscribed, unencapsulated, and infiltrative invading regional bone and soft tissue. The mass consisted of polygonal squamous epithelial cells with intercellular bridging that breached the epithelial basement membrane and formed invasive nests, cords, and trabeculae. The mitotic rate averaged 3 per 400× field of view, with occasional bizarre mitotic figures. Epithelial cells often exhibited dyskeratosis, and the nests often contained compact lamellated keratin (keratin pearls). The neoplasm was positive via immunohistochemistry for pancytokeratin, variably positive for S100, and negative for vimentin, smooth muscle actin, and desmin. The gross, histologic, and immunohistochemical findings were consistent with an aggressive oral squamous cell carcinoma. The neoplasm was negative via PCR for papilloma virus. In general, neoplasia in macaques is rare. Although squamous cell carcinomas are one of the most common oral neoplasia in many species, to our knowledge this case represents the first reported oral squamous cell carcinoma in a pigtailed macaque.

Topics: Animals; Carcinoma, Squamous Cell; Fatal Outcome; Female; Immunohistochemistry; Keratins; Macaca nemestrina; Monkey Diseases; Mouth Neoplasms

Topics: Aged; Carcinoma, Squamous Cell; Humans; Keratins; Male; Middle Aged; Mucin-1; Neoplasms, Multiple Primary; Parotid Neoplasms; Skin Neoplasms

To examine the cytokeratin expression in cervical lymph nodes of patients with mandibular gingival squamous cell carcinoma and its clinical significance.. The data of 42 cases with mandibular gingival squamous cell carcinoma after operation from July 2009 to December 2012 were included. Forty-two patients (male = 27, formale = 15) were included, with a mean age of 54.1 years (range 27-77). The lesions were staged (stage I:9, stage II:16, stage III:6, stage IV:11). The cervical lymph nodes were examined by immunohistochemistry and HE. The cytokeratin expression in the lymph nodes was analyzed.. The rates of lymph nodes metastasis detected by routine HE staining, serial sections HE staining and IHC were 8.0% (47/585), 9.6% (56/585) and 12.8% (75/585), respectively. There was significant difference (χ(2) = 7.17, P < 0.01) in the diagnosis of lymph nodes metastasis between IHC and routine HE staining, There was no significant difference between IHC and serial HE staining (χ(2) = 3.10, P > 0.05). Metastasis occurred mainly in the Level I, II and III. Nineteen lymph nodes in 12 patients were found micrometastasis with IHC. Serial sections and routine HE staining did not find micrometastasis.. CK markers is sensitive in detecting lymph node metastasis of mandibular gingival squamous cell carcinoma.

Topics: Adult; Aged; Carcinoma, Squamous Cell; Gingiva; Gingival Neoplasms; Humans; Immunohistochemistry; Keratins; Lymph Nodes; Lymphatic Metastasis; Male; Mandible; Middle Aged; Neck; Neoplasm Staging; Staining and Labeling

Oral squamous cell carcinoma (OSCC) and canine acanthomatous ameloblastoma (CAA) represent two epithelium-derived neoplasms that affect the oral cavity of dogs. The expression of cytokeratins (CKs) and calretinin has been previously established in the canine tooth bud and odontogenic tumours. The aim of this study was to characterize the CK and calretinin expression profile of OSCC in comparison to CAA and canine tooth bud tissues. Samples from 15 OSCC and 15 CAA cases, as well as 6 tooth buds and 2 normal gingival tissues were examined. OSCC CK expression was consistent with the CK expression profile of CAA and canine tooth bud tissue. Calretinin was positively expressed in 10 of 15 OSCC cases, with 5 cases demonstrating high staining intensity. Only 2 of 15 CAA cases demonstrated mild-moderate staining intensity. The statistically significant difference in staining pattern and intensity of calretinin in OSCC and CAA can help distinguish between these two tumour types.

Topics: Ameloblastoma; Animals; Antibodies, Monoclonal; Calbindin 2; California; Carcinoma, Squamous Cell; Dog Diseases; Dogs; Immunohistochemistry; Jaw Neoplasms; Keratins; Mouth Neoplasms; Tooth; Universities

The objective of this study was to evaluate the potential detection of circulating tumor cells (CTCs) using the CellSearch (CS) Assay™ in patients with locally advanced head and neck squamous cell carcinoma (HNSCC) and then to identify the clinical factors predictive of the presence of CTCs. The presence and number of CTCs were determined using the CS system before treatment, and in 10 healthy individuals (control group). The CS system was able to successfully identify the presence of CTCs in 8 of 49 patients (16 %) before therapy. No CTC was found in the control group. CTCs were detected before therapy in 1 of 19 patients (5 %) with N0 tumor and in 7 of 30 patients (23 %) with N1-2c tumor (p = 0.12; Fisher's exact test). CTCs were identified in a relatively low proportion of patients with locally advanced HNSCC.

Topics: Aged; Antigens, Neoplasm; Biomarkers, Tumor; Carcinoma, Squamous Cell; Case-Control Studies; Cell Adhesion Molecules; Cell Count; Epithelial Cell Adhesion Molecule; Female; Head and Neck Neoplasms; Humans; Keratins; Male; Middle Aged; Mouth Neoplasms; Neoplasm Staging; Neoplastic Cells, Circulating; Oropharyngeal Neoplasms; Prognosis; Squamous Cell Carcinoma of Head and Neck

The purpose of this study was to assess the predictability of sentinel lymph node biopsy (SNB) for oral squamous cell carcinoma (OSCC) when pathologic processing is performed without serial step sectioning.. We prospectively enrolled 36 patients with T1 or T2 cN0 OSCC into this institutional review board-approved prospective cohort study, and they underwent gamma probe-guided SNB in addition to selective neck dissection. The rate of patients with negative SNB results whose neck dissection was also negative for metastasis (negative predictive value) was the primary endpoint.. Of the 28 patients whose sentinel lymph nodes were found to be pathologically and clinically node negative by routine hematoxylin-eosin stain and immunohistochemistry, 27 were found to have no other pathologically positive nodes, corresponding to a negative predictive value of 96%.. The results of this study suggest that SNB performed without the use of thin serial step sectioning may accurately predict neck stage in OSCC.

Topics: Adult; Aged; Aged, 80 and over; Carcinoma, Squamous Cell; Cohort Studies; Coloring Agents; Eosine Yellowish-(YS); Fluorescent Dyes; Hematoxylin; Humans; Immunohistochemistry; Keratins; Lymph Nodes; Lymphatic Metastasis; Microtomy; Middle Aged; Mouth Neoplasms; Neck Dissection; Neoplasm Staging; Predictive Value of Tests; Prospective Studies; Radionuclide Imaging; Radiopharmaceuticals; Sentinel Lymph Node Biopsy; Technetium Tc 99m Sulfur Colloid; Young Adult

In humans, activation-induced cytidine deaminase (AID) expression results due to inflammation and this deaminase activity is also involved in carcinogenesis. The aim of this study is to investigate the correlation between AID expression and the clinical classification of oral cancer tissues.. The current study investigated the correlation between AID expression and the clinical classification of oral cancer tissues from 27 patients who underwent surgical resection using immunohistochemistry. Specific AID expression and its induction by cytokine stimulation were investigated in cultured HSC oral cancer cell lines by reverse transcriptase PCR.. AID expression was detected in 10 of 27 specimens (37.0%). AID expression was more frequently detected in early-stage cancer, especially in early stage T, than in late-stage cancer (T1/T2 vs. T3/4; P = 0.0493, N0 vs. N1/2/3; P = 0.0793). HSC-2, a nonmetastatic oral cancer cell line, abundantly expressed endogenous AID, whereas no such expression was observed in HSC-3, a metastatic oral cancer cell line. Moreover, AID expression was substantially induced in HSC-2 cells by stimulation of an inflammation-related cytokine, TNF-α.. Aberrant AID expression in the oral epithelium would contribute to the initiation of oral squamous cell carcinoma. Avoiding persistent AID inducible condition such as frequent cleaning of oral cavity would play an important role for the prevention of developing oral cancer.

Topics: Carcinoma, Squamous Cell; Cell Line, Tumor; Cytidine Deaminase; Humans; Keratins; Mouth Neoplasms; Neoplasm Staging; Tumor Necrosis Factor-alpha; Up-Regulation

The hedgehog signaling pathway (HH) is involved in tumorigenesis in a variety of human malignancies. In head and neck squamous cell carcinomas (HNSCC), Hh overexpression was associated with poor prognosis. Therefore, we analyzed the effect of Hh signaling blockade with cyclopamine on colony formation of cells from HNSCC samples.. HNSCC biopsies were cultured alone for reference or with serial dilutions of cyclopamine (5-5,000 nM), docetaxel (137.5-550 nM), or cisplatin (1,667-6,667 nM) and their binary combinations. Cytokeratin-positive colonies were counted after fluorescent staining.. Cyclopamine concentration-dependently inhibited HNSCC ex vivo [(IC50) at about 500 nM]. In binary combinations, cyclopamine additively enhanced the suppressive effects of cisplatin and docetaxel on HNSCC colony formation.. Our findings define SMO--a Hh component- as a potential target in HNSCC and suggest the utility of Hh targeting in future multimodal treatment regimens for HNSCC.

Topics: Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Squamous Cell; Cisplatin; Docetaxel; Female; Head and Neck Neoplasms; Hedgehog Proteins; Humans; KB Cells; Keratins; Male; Molecular Targeted Therapy; Receptors, G-Protein-Coupled; Signal Transduction; Smoothened Receptor; Taxoids; Tumor Cells, Cultured; Tumor Stem Cell Assay; Veratrum Alkaloids

To evaluate the expression of cytokeratin 19(CK19) and connexin 43(Cx43) in various stages of oral carcinogenesis and investigate the relationship of CK19 and Cx43 in the process of oral cancer.. 4-nitroquinoline-1-oxide(4NQO) was used to induce oral carcinogenesis in the mucosa of SD rats and immunohistoche-mical technique was used to study the expression of CK19 and Cx43 in various stages of oral carcinogenesis.. The CK19 positive staining were distributed in the basal cell layer in the normal rat lingual mucosa. While CK19 positive staining were distributed in cytoplasm of supra-basal layers in the mild dysplasia, moderate dysplasia and severe dysplasia. In oral squamous cell carcinoma(OSCC) tissue, CK19 were expressed in all the stratum of epithelium. The positive rate of CK19 in normal, mild, moderate, severe dysplasia and OSCC tissues were respectively 30.00%, 50.00%, 58.33%, 80.00%, and 91.67%. With the lesions getting worse, the positive rate and the intensity of CK19 raised significantly (P<0.05). In normal tongue mucosa, Cx43 proteins were mainly expressed in the membrane of the epithelial cells of the rat tongue. It was weakly positive in the basal cell layer, increased in the stratum spinosum and stratum granulosum, and negative in the stratum corneum. Compared with normal epithelia, the expression of Cx43 in dysplastic and OSCC epithelia decreased significantly. The positive rate of Cx43 in normal, mild, moderate, severe dysplasia and OSCC tissues were respectively 100.00%, 85.71%, 66.67%, 40.00%, and 33.33%. The expression of Cx43 was significantly decreased with severity increasing (P<0.05).. The expression of CK19 protein significantly increases with the development of rat tongue carcinoma, suggesting that CK19 is associated with carcinogenesis. The expression of Cx43 protein dramatically decrease with the development of rat tongue carcinoma, suggesting that the abnormal expression of Cx43 protein is associated with oral mucosa carcinoma origination. The expression of CK19 and Cx43 has negative correlation. Combined detection of CK19 and Cx43 has an important role in the early diagnosis of OSCC and can help to improve the sensitivity and specificity of the early diagnosis of OSCC.

Topics: 4-Nitroquinoline-1-oxide; Animals; Carcinogenesis; Carcinoma, Squamous Cell; Connexin 43; Epithelial Cells; Epithelium; Keratin-19; Keratins; Male; Mouth Mucosa; Mouth Neoplasms; Oxides; Rats; Rats, Sprague-Dawley; Tongue; Tongue Neoplasms

Keratins play a major role in several cellular functions. Each tissue type expresses a specific set of keratins. The immense potential of keratins as diagnostic and prognostic markers for different cancers is emerging. Oral cancer is the fifteenth most common cancer worldwide. However, comprehensive information on the profile of keratins in the oral cavity is not available. Several independent reports have identified keratins using antibody based techniques which have pitfalls due to the cross reactivity of the antibodies to this set of very homologous proteins. A few recent proteomic studies have reported the identification of keratins in head and neck cancer. Majority of the studies have used tissues from the head and neck region without specifying subsites. This study reports the analysis of enriched preparations of keratins from cancer of the gingivo buccal complex (GBC) using MS, 2DE, WB, silver staining of 2DE gels and IHC. Our study reveals the absence of K4 and K13 and presence of K14, K16, and K17, in cancers of the GBC and combination of these expression patterns in the cut margins. This report also shows that K13 is glycosylated. This well characterized profile of keratins may have potential to be used in clinics.. In recent years the immense potential of keratins as diagnostic and prognostic markers for different cancers is emerging. However, comprehensive information on the profile of keratins in the oral cavity is not available. Several independent reports have identified keratins using only antibody based techniques which have pitfalls due to the cross reactivity of the antibodies to this set of very homologous proteins. This study reports the analysis of enriched preparations of keratins from a subsite of the oral cavity, the gingivo buccal complex (GBC) using mass spectrometry, 2DE, western blotting, silver staining of 2DE gels and IHC. The proteomic analysis shows the absence of K4 and K13 and presence of K14, K16, and K17 in cancers of the GBC and combination of these expression patterns in the cut margins. This well characterized profile of keratins from the gingivo buccal complex provides defined markers which may have potential to be used in the clinics.

Topics: Adult; Aged; Biomarkers; Biomarkers, Tumor; Carcinoma, Squamous Cell; Female; Gene Expression Profiling; Gene Expression Regulation, Neoplastic; Gingiva; Glycosylation; Head and Neck Neoplasms; Humans; Keratins; Male; Middle Aged; Mouth Mucosa; Mouth Neoplasms; Neoplasm Metastasis; Proteomics

To investigate the reasons for the occurrence of the pink-color sign of iodine-unstained lesions.. In chromoendoscopy, the pink-color sign of iodine-unstained lesions is recognized as useful for the diagnosis of esophageal squamous cell carcinoma. Patients with superficial esophageal neoplasms treated by endoscopic resection were included in the study. Areas of mucosa with and without the pink-color sign were evaluated histologically. The following histologic features that were possibly associated with the pink-color sign were evaluated. The keratinous layer and basal cell layer were classified as present or absent. Cellular atypia was classified as high grade, moderate grade or low grade, based on nuclear irregularity, mitotic figures, loss of polarity, chromatin pattern and nuclear/cytoplasmic ratio. Vascular change was assessed based on dilatation, tortuosity, caliber change and variability in shape. Vessels with these four findings were classified as positive for vascular change. Endoscopic images of the lesions were captured immediately after iodine staining, 2-3 min after iodine staining and after complete fading of iodine staining. Quantitative analysis of color changes after iodine staining was also performed.. A total of 61 superficial esophageal neoplasms in 54 patients were included in the study. The lesions were located in the cervical esophagus in one case, the upper thoracic esophagus in 10 cases, the mid-thoracic esophagus in 33 cases, and the lower thoracic esophagus in 17 cases. The median diameter of the lesions was 20 mm (range: 2-74 mm). Of the 61 lesions, 28 were classified as pink-color sign positive and 33 as pink-color sign negative. The histologic diagnosis was high-grade intraepithelial neoplasia (HGIN) or cancer invading into the lamina propria in 26 of the 28 pink-color sign positive lesions. There was a significant association between pink-color sign positive epithelium and HGIN or invasive cancer (P = 0.0001). Univariate analyses found that absence of the keratinous layer and cellular atypia were significantly associated with the pink-color sign. After Bonferroni correction, there were no significant associations between the pink-color sign and presence of the basal membrane or vascular change. Multivariate analyses found that only absence of the keratinous layer was independently associated with the pink-color sign (OR = 58.8, 95%CI: 5.5-632). Quantitative analysis was performed on 10 superficial esophageal neoplasms with both pink-color sign positive and negative areas in 10 patients. Pink-color sign positive mucosa had a lower mean color value in the late phase (pinkish color) than in the early phase (yellowish color), and had similar mean color values in the late and final phases. These findings suggest that pink-color positive mucosa underwent color fading from the color of the iodine (yellow) to the color of the mucosa (pink) within 2-3 min after iodine staining. Pink-color sign negative mucosa had similar mean color values in the late and early phases (yellowish color), and had a lower mean color value in the final phase (pinkish color) than in the late phase. These findings suggest that pink-color sign negative mucosa did not undergo color fading during the 2-3 min after iodine staining, and underwent color fading only after spraying of sodium thiosulfate.. The pink-color sign was associated with absence of the keratinous layer. This sign may be caused by early fading of iodine staining.

Topics: Aged; Aged, 80 and over; Carcinoma, Squamous Cell; Cell Nucleus; Color; Cytoplasm; Duodenoscopy; Esophageal Neoplasms; Esophageal Squamous Cell Carcinoma; Esophagoscopy; Female; Humans; Iodine; Keratins; Male; Middle Aged; Mitosis; Mucous Membrane; Staining and Labeling; Time Factors

Keratins are structural marker proteins with tissue specific expression; however, recent reports indicate their involvement in cancer progression. Previous study from our lab revealed deregulation of many genes related to structural molecular integrity including KRT76. Here we evaluate the role of KRT76 downregulation in oral precancer and cancer development.. We evaluated KRT76 expression by qRT-PCR in normal and tumor tissues of the oral cavity. We also analyzed K76 expression by immunohistochemistry in normal, oral precancerous lesion (OPL), oral squamous cell carcinoma (OSCC) and in hamster model of oral carcinogenesis. Further, functional implication of KRT76 loss was confirmed using KRT76-knockout (KO) mice.. We observed a strong association of reduced K76 expression with increased risk of OPL and OSCC development. The buccal epithelium of DMBA treated hamsters showed a similar trend. Oral cavity of KRT76-KO mice showed preneoplastic changes in the gingivobuccal epithelium while no pathological changes were observed in KRT76 negative tissues such as tongue.. The present study demonstrates loss of KRT76 in oral carcinogenesis. The KRT76-KO mice data underlines the potential of KRT76 being an early event although this loss is not sufficient to drive the development of oral cancers. Thus, future studies to investigate the contributing role of KRT76 in light of other tumor driving events are warranted.

Topics: Adult; Animals; Carcinogenesis; Carcinoma, Squamous Cell; Cricetinae; Disease Models, Animal; Female; Gene Expression Profiling; Gene Expression Regulation, Neoplastic; Humans; Hyperplasia; Immunohistochemistry; Keratins; Male; Mice; Mice, Knockout; Middle Aged; Mouth Mucosa; Mouth Neoplasms; Neoplasm Grading; Neoplasm Staging; Prognosis; Reproducibility of Results

A combined squamomelanocytic tumor is an exceedingly rare occurrence; little is known about its pathogenesis. A definitive diagnosis can only be made via histological examination. We describe herein an 83 year-old man who was discovered to have this combined tumor and recommend the appropriate management for such a lesion.

Topics: Aged, 80 and over; Biomarkers, Tumor; Carcinoma, Squamous Cell; Facial Neoplasms; gp100 Melanoma Antigen; Humans; Keratins; Male; MART-1 Antigen; Melanins; Melanoma; Melanoma-Specific Antigens; Neoplasms, Multiple Primary; S100 Proteins; Skin Neoplasms

The study was aimed at analysing and identifying the proteins that are differentially expressed in oral squamous cell carcinoma (OSCC) compared to adjacent non-tumour tissue.. Two-dimensional (2D) sodium dodecyl sulphate-polyacrylamide gel electrophoresis accompanied by mass spectrometry (matrix-assisted laser desorption/ionisation-time-of-flight mass spectrometry and liquid chromatography-tandem mass spectrometry) was used to analyse and identify the differentially expressed proteins in 10 pairs of tumours and adjacent non-tumour tissues from five cases of early-stage and five cases of late-stage OSCC. The statistical differences of the protein spots were analysed by the Wilcoxon signed-rank test. A validation study using immunohistochemistry and quantitative real-time reverse transcription-polymerase chain reaction (qRT-PCR) was performed.. A total of 68 proteins (63 up-regulated, five down-regulated) were differentially expressed in early-stage disease, and 39 proteins (37 up-regulated, two down-regulated) were significantly altered in late-stage disease. Among these, 14 proteins were altered in both groups. A total of 44 proteins were identified, including heat shock proteins (HSPs: Hsp90, HSPA5 and HSPA8), keratins (K1, K6A and K17), tubulin, cofilin 1, 14-3-3σ and metabolic enzymes. These proteins are involved in various cellular processes essential for cell growth, survival and cell migration. The validation study on α-tubulin and 14-3-3σ using immunohistochemistry and KIAA1199 expression using real-time RT-PCR confirmed the results in proteomics analysis.. The study identified many proteins, both known and unknown, for cancer cell processes. At least two proteins, KIAA1199 and Horf6, are novel for oral cancer.

Topics: Biomarkers, Tumor; Carcinoma, Squamous Cell; Down-Regulation; Electrophoresis, Gel, Two-Dimensional; Endoplasmic Reticulum Chaperone BiP; Gene Expression Regulation, Neoplastic; Heat-Shock Proteins; Humans; Hyaluronoglucosaminidase; Immunohistochemistry; Keratins; Mouth Neoplasms; Peroxiredoxin VI; Proteins; Proteomics; Real-Time Polymerase Chain Reaction; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; Thailand; Tubulin; Up-Regulation

Malignant tumors represent one of the most important medical problems, due to the increased mortality rate, life quality alteration, and the lack of a curable treatment. Skin neoplasm ranks first most frequent top primary tumor, summing a higher percentage than any other neoplastic location. It is also known, the fact that, in our country, gastric adenocarcinoma represents the most encountered tumor of the digestive tube. Our case, male, 49-year-old, comes from a rural area, was diagnosed with and surgically treated, within one year, for gastric adenocarcinoma (intestinal type gastric carcinoma) and squamous cell carcinoma (at the level of the lower lip). A high number of etiologic agents are associated with different risks in developing a carcinoma with squamous cells at the level of the head and the neck, and a gastric carcinoma (our patient is known to suffer from gastric ulcer and Helicobacter pylori, for more than 20 years, and he is a chronic consumer of alcohol and nicotine).

Topics: Carcinoma, Squamous Cell; Humans; Keratins; Male; Middle Aged; Mucins; Postoperative Care; Stomach Neoplasms

Primary intra-osseous carcinoma (PIOC) is a rare tumor, defined as squamous cell carcinoma that develops in the jaw bones, having no initial connection to adjacent skin or mucosa. It is locally aggressive, with metastases to regional lymph nodes, (28% of cases) and lung (5% of cases) at the time of diagnosis. Its origin may be di novo or from other odontogenic tumors. The maxillary bones have epithelial tissues; therefore this neoplasm is located exclusively on this site, predominantly in the jaw. PIOC diagnostic criteria are strict and include: squamous cell carcinoma histopathology, lack of commitment and sinus mucosa, ruling out the possibility of metastasis from a distant site with a thorough clinical study and complementary methods. The treatment is, whenever possible, oncologic resection, additional radio and / or chemotherapy. Reconstructive surgery with graft and / or prostheses for aesthetic and functional are also required. We report the case of a 72 years old man who consulted for sore jaw three months after molar extraction. Curettage biopsy was performed and then resected mandible with lymphadenectomy. Histopathological examination showed a poorly differentiated squamous cell carcinoma, infiltrating jawbone with morphological findings linking him to residual odontogenic cyst and metastatic lymph nodes in 15 of 48 isolates. Postoperative radiotherapy was performed, he died at 30 months of diagnosis by progressive deterioration.

Topics: Aged; Biopsy; Carcinoma, Squamous Cell; Fatal Outcome; Humans; Jaw Neoplasms; Keratins; Male; Maxillary Neoplasms

Basaloid squamous cell carcinoma is a rare and aggressive variant of squamous cell carcinoma, which mostly occurs in the upper aerodigestive tracts. Basaloid squamous cell carcinoma also typically arises in the anal canal, but is extremely rare in the lower gastrointestinal tract. A 70-year-old man presented with loose stool and intermittent hematochezia 2 months ago. Colonoscopy showed an ulceroinfiltrative mass on the rectosigmoid colon from 16 cm to 18 cm above the anal verge. Conventional colonoscope could not pass through the lesion but it was possible with pediatric colonoscope. Abdominal CT scan showed 1.6 cm sized wall thickening with circumferential luminal narrowing in the rectosigmoid colon and multiple ill-defined low density masses in both lobes of the liver. Therefore, colon cancer with liver metastasis was suspected. However, basaloid cells were noted on histologic examination, and they were weakly positive for synaptophysin on immunohistochemical study. After palliative lower anterior resection, histologic examination of the resected specimen revealed basaloid differentiation with keratin pearls, and tumor cells were positively stained with high molecular weighted cytokeratin (34BE12) and CK 5/6. Thus, the patient was finally diagnosed with basaloid squamous cell carcinoma of rectosigmoid colon with distant metastases.

Topics: Aged; Carcinoma, Squamous Cell; Colonoscopy; Colorectal Neoplasms; Humans; Immunohistochemistry; Keratins; Liver Neoplasms; Lung Neoplasms; Male; Positron-Emission Tomography; Synaptophysin; Tomography, X-Ray Computed

Topics: Carcinoma, Squamous Cell; Child; Cysts; Diagnosis, Differential; Epithelium; Female; Follow-Up Studies; Humans; Keratin-19; Keratin-5; Keratin-6; Keratin-7; Keratins; Neoplasm Recurrence, Local; Reoperation; Submandibular Gland; Submandibular Gland Neoplasms; Transcription Factors; Tumor Suppressor Protein p53; Tumor Suppressor Proteins

The cytopathologic diagnosis of basaloid squamous cell carcinoma can be problematic as there are several components of the differential diagnosis that share common cytomorphologic features. In this study, we report the fine-needle aspiration (FNA) findings of 16 basaloid squamous cell carcinoma cases and compare those cases to 16 cases of small cell carcinoma. To our knowledge, this is the largest series of basaloid squamous cell carcinoma FNA cases ever reported. The following cytomorphologic features were compared for both tumors: cohesive tissue fragments, single cells, adenoid cystic-like features (cribriform pseudoglandular lumina with hyaline materials), necrosis, nuclear size, nuclear molding, nucleoli, cytoplasm, and the presence of single keratinized cells. Adenoid cystic-like features and the presence of single keratinized cells were specific for basaloid squamous cell carcinoma (P < 0.05).

Topics: Aged; Biopsy, Fine-Needle; Carcinoma, Small Cell; Carcinoma, Squamous Cell; Cell Nucleus; Cytoplasm; Female; Gastrointestinal Neoplasms; Humans; Keratins; Male; Middle Aged; Necrosis; Respiratory Tract Neoplasms

The objective of this study is to evaluate the incidence of occult nodal micrometastases in N0 laryngeal squamous cell carcinoma using cytokeratin immunohistochemical analysis (CKIHA) and its influence on the overall occult metastatic rate. This is a prospective cohort study. A total number of 30 patients with N0 stage laryngeal cancer underwent 46 selective neck dissections for elective treatment of the neck. Nodes found to be negative using routine histopathological examination were evaluated for the presence of micrometastasis using CKIHA. The occult micrometastasis rate for all cases was 26.7 % which significantly increased the overall occult metastasis rate to 50 % (P = 0.014). The micrometastasis rate was 30.8, 25 and 20 % for glottic, supraglottic and transglottic tumors, respectively, which increased the overall occult metastasis rate to 53.8, 50 and 40 % but without statistical impact. The micrometastasis rate was 35.7 and 23.1 % in T3 and T4 tumors, respectively, and this increased the overall occult metastasis rate to 50 and 61.5 % with statistical influence in T3 tumors (P = 0.046). Micrometastasis upstaged the neck in 7 (23.3 %) patients with statistical impact on the PN stage (P = 0.007). The overall occult nodal metastasis rate in N0 laryngeal cancer is underestimated. Nodal micrometastasis may be missed during routine histopathological examination and can be detected using CKIHA.

Topics: Adult; Aged; Aged, 80 and over; Carcinoma, Squamous Cell; Cohort Studies; Head and Neck Neoplasms; Humans; Immunohistochemistry; Keratins; Laryngeal Neoplasms; Male; Middle Aged; Neck Dissection; Neoplasm Micrometastasis; Neoplasm Staging; Prospective Studies; Sensitivity and Specificity; Squamous Cell Carcinoma of Head and Neck

This is a case report of a cutaneous horn, which was difficult to diagnose as benign or malignant. It demonstrates how these lesions can be approached in terms of diagnosis and management.

Topics: Carcinoma, Squamous Cell; Cheek; Diagnosis, Differential; Facial Neoplasms; Humans; Keratins; Keratoacanthoma; Male; Middle Aged; Radiotherapy, Adjuvant; Skin Neoplasms

Bone marrow-derived stem cells (BMDCs) have the ability to differentiate into lung epithelial cells in response to damage; however, their role in squamous cell carcinoma (SCC) formation is unknown. This study aimed to determine whether BMDC-derived lung epithelial cells could contribute to SCC formation. A model of lung SCC induced with N-nitrosodiethylamine (NDEA) in recipient female mice transplanted with green fluorescent protein (GFP)-positive BMDCs from male donors was established. Incorporation of BMDCs in lung tissue was determined using immunohistochemistry and immunofluorescence to detect GFP expression and fluorescence in situ hybridization to Y chromosomes. BMDC appeared at three stages of lung SCC progression: metaplasia, dysplasia, and carcinoma. There was a significantly higher proportion of GFP-positive (GFP(+)) cells within SCC than was found in metaplasia and dysplasia 16 weeks post-transplantation (both P < 0.017); GFP(+) BMDCs were also observed in clusters within several SCC nests. Furthermore, most GFP(+) cells in SCC were pancytokeratin-positive (PCK(+)) epithelial cells, and some exhibited proliferative activity as determined by Ki67 staining (9.7 ± 3.92 %). The presence of GFP(+)Ki67(+)PCK(+) cells within SCC nests suggested that some donor BMDCs differentiated into proliferating epithelial cells. Finally, analysis of p63 expression, a marker of SCC cells, indicated that the presence of GFP(+)p63(+) cells (green) in inner parts of the SCC. These findings strongly suggest that BMDC-derived lung epithelial cells could participate in lung SCC formation and partially contribute to tumor growth, which might have significant potential implications for both clinical cancer therapy using BMDCs.

Topics: Animals; Bone Marrow Cells; Bone Marrow Transplantation; Carcinoma, Squamous Cell; Cell Differentiation; Cell Movement; Cell Proliferation; Cell Transformation, Neoplastic; Diethylnitrosamine; Epithelial Cells; Female; Green Fluorescent Proteins; Keratinocytes; Keratins; Ki-67 Antigen; Lung Neoplasms; Male; Mice; Mice, Inbred C57BL; Phosphoproteins; Stem Cells; Trans-Activators

Macrophage migration inhibitory factor (MIF) is a pleiotropic cytokine with pro-inflammatory functions and involved in tumorigenesis. The aim of this study was to evaluate the expression and localization of the macrophage MIF in oral squamous carcinoma (OSC). In addition, the relationship between MIF expression and clinicopathological parameters such as survival data, tobacco use, alcohol habits, TNM stage, tumor graduation, and peritumoral inflammatory infiltrate were evaluated.. Using immunohistochemistry, expression and localization of MIF was detected in 44 specimens of OSC. The absolute number and relative proportions of MIF-positive cells detected were also determined separately for tumor parenchyma vs. stroma. All counts were determined from 10 consecutive high-power fields using an integration graticule. Moreover, some parameters were analyzed separately for lip and intra-oral cancers.. Migration inhibitory factor-positive cells were observed in both the tumor parenchyma and in inflammatory cells of all specimens. In contrast, MIF expression was not detected in tumoral nests associated with poorly differentiated tumors. In specimens of lip cancer, a greater number of MIF-positive stromal immune cells were detected than in intra-oral cancer specimens (Mann-Whitney test, P = 0.049).. Oral squamous carcinoma cells consistently express MIF independent of their location. Lip tumors presented more MIF-positive peritumoral inflammatory cells, similar to control, suggesting that immunological differences in leukocyte activation exist between in lip and intra-oral cancers.

Topics: Alcohol Drinking; Carcinoma, Squamous Cell; Cell Count; Cohort Studies; Epithelium; Female; Humans; Inflammation; Keratins; Leukocytes; Leukoplakia, Oral; Lip Neoplasms; Macrophage Migration-Inhibitory Factors; Male; Middle Aged; Mouth Neoplasms; Neoplasm Grading; Neoplasm Staging; Smoking; Stromal Cells; Survival Rate

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

The migratory ability of tumor cells requires cytoskeletal rearrangement processes. Epidermal growth factor receptor (EGFR)-signaling tightly correlates with tumor progression in head and neck squamous cell carcinomas (HNSCCs), and has previously been implicated in the regulation of cytokeratin (CK) expression. In this study, HNSCC cell lines were treated with EGF, and CK expression levels were monitored by Western blot analysis. Changes in cellular morphology were documented by fluorescence- and atomic force microscopy. Some of the cell lines demonstrated an EGF-dependent modulation of CK expression levels. Interestingly, regression of some CK subtypes or initial up-regulation followed by downregulation at higher EGF-levels could also be observed in the tested cell lines. Overall, the influence of EGF on CK expression levels appeared variable and cell-type-dependent. Real-time cellular analysis of EGF-treated and -untreated HNSCC cell lines demonstrated a rise over time in cellular impedance. In three of the EGF-treated HNSCC cell lines, this rise was markedly higher than in untreated controls, whereas in one of the cell lines the gain of cellular impedance was paradoxically reduced after EGF treatment, which was found to correlate with changes in cellular morphology rather than with relevant changes in cellular viability or proliferation. After treating HNSCC cells with EGF, CK filaments frequently appeared diffusely distributed throughout the cytoplasm, and in some cases were found in a perinuclear localization, the latter being reminiscent to observations by other groups. In summary, the data points to a possible role of EGFR in modulating HNSCC cell morphology.

Topics: Carcinoma, Squamous Cell; Cell Line, Tumor; Cell Shape; Cell Survival; Epidermal Growth Factor; Head and Neck Neoplasms; Humans; Keratinocytes; Keratins; Microscopy, Atomic Force; Phenotype; Plakophilins; Squamous Cell Carcinoma of Head and Neck

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

Topics: Aged; Antigens, Neoplasm; Biomarkers, Tumor; Bone Marrow; Carcinoma, Squamous Cell; Cell Adhesion Molecules; Epithelial Cell Adhesion Molecule; Female; Head and Neck Neoplasms; Humans; Keratins; Lymph; Lymph Nodes; Lymphatic Metastasis; Male; Microscopy, Fluorescence; Middle Aged; Polymerase Chain Reaction; Reproducibility of Results

To determine the feasibility of viable storage of head and neck squamous cell carcinoma (HNSCC) for regrowth of cells in culture.. Laboratory-based translational study.. Methods for intermediate-term frozen storage of viable HNSCC were explored using small pieces of primary tumor and dissociated HNSCC cells after short-term culture. Viable cells after freezing were confirmed by adherence to tissue culture plates, cell morphology, and increased cell or colony density. Two cultures were immunostained for cytokeratin to confirm epithelial origin of viable cultured cells after freezing.. Six primary HNSCCs (two oral cavity, three larynx, one oropharynx) and two HNSCCs that had been passaged through a xenograft (two oral cavity) were dissociated to single cells and grown in short-term cell culture for 0 to 12 passages. After short-term culture, cells were frozen for up to 8 months, thawed, and replated. Frozen cells derived from all tumors (six primary and two xenografts) were successfully replated with cultures lasting >7 days with seven of eight tumors presenting increased colony or cell density over 1 week of growth after freezing. In total, 15 of 15 tested samples derived from six primary and two xenografted HNSCCs were viable after freezing.. In the current study, we show that biopreservation of primary or xenografted HNSCC using short-term cell culture is feasible. Initial short-term cell culture was required for successful storage and viability of frozen cells. These proof-of-principle studies, if more widely implemented, could improve preclinical testing of new therapies for HNSCC.

Topics: Carcinoma, Squamous Cell; Cryopreservation; Feasibility Studies; Head and Neck Neoplasms; Humans; Immunohistochemistry; Keratins; Laryngeal Neoplasms; Mouth Neoplasms; Oropharyngeal Neoplasms; Squamous Cell Carcinoma of Head and Neck; Tissue Banks; Transplantation, Heterologous; Tumor Cells, Cultured

Basaloid squamous cell carcinoma (BSCC) is rare variant of oral squamous cell carcinoma (OSCC) with predilection for upper aerodigestive tract. Although it is characterized by distinct histologic features it is often confused with conventional OSCC and other basaloid tumors. The study aims to establish differentiating features of BSCC with oral basaloid tumors using immunohistochemical (IHC) markers. This retrospective study included 34 cases, including BSCC, OSCC, and basaloid tumors. IHC staining was performed with primary antibodies against cytokeratin (CK) 19, 14, 8/18, α-smooth muscle actin (αSMA), p53, and MMP-9. A prominent CK 19, 14, and 8/18 expression was observed in BSCC as compared with basaloid tumors suggesting of basal cell origin with undifferentiated type of tumor cells. Expression of αSMA was intense in tumor cells of myoepithelial differentiation but lacked in BSCC. The intense expression of p53 and MMP-9 was noted in all basaloid malignancies. Considering standard histologic criteria in diagnosing BSCC, when in confusion with other basaloid tumors, IHC markers gain importance. Hence, enhanced expression of CK 19, 8/18, and 14 and coexistence of p53 and MMP-9 expression and negativity for αSMA suggest an accurate diagnosis of BSCC.

Topics: Actins; Aged; Biomarkers, Tumor; Carcinoma, Squamous Cell; Diagnosis, Differential; Female; Humans; Immunohistochemistry; Keratins; Male; Matrix Metalloproteinase 9; Middle Aged; Mouth Neoplasms; Neoplasms, Basal Cell; Tumor Suppressor Protein p53

Squamous cell carcinoma, a malignant proliferation of keratinocytes, can be found in many regions of the body covered by stratified squamous epithelium and in areas covered by other epithelia but which had undergone squamous metaplasia. Squamous cell carcinoma has many variants.. We, retrospectively, reviewed the case file and histological features of a 75 year old trader with a rare variant of squamous cell carcinoma arising from an old surgical scar.. The 75-year-old African female trader presented to the hospital with three and a-half month history of a swelling in the anterior aspect of the left leg arising from an old surgical scar. Clinical examination showed an irregularly shaped ulcer measuring 14 x 16 cm with an everted edge and a hyperpigmented floor. Histologic sections of the specimen showed the infiltration of the papillary and reticular dermis of the skin by sheets of atypical spindle cells with areas of squamous differentiation. There was a contiguous area of capillary-like structures constituting about 30% of the sections examined. The neoplastic cells were positive for vimentin and cytokeratin but were negative for CD34. The diagnosis was pseudoangiosarcomatous squamous cell carcinoma.. This tumour can be found in Africans and in an old surgical scar. It can coexist with other variants of squamous cell carcinoma. There may be need in the future to add a new mixed variant to the current classification scheme.

Topics: Aged; Carcinoma, Squamous Cell; Cicatrix; Female; Hemangiosarcoma; Humans; Immunohistochemistry; Keratins; Retrospective Studies; Skin Neoplasms; Vimentin

Primary lymphoepithelioma-like carcinoma (LELC) of the lung is an extremely rare disease that occurs more commonly in Asians, and is composed of undifferentiated carcinoma with prominent lymphoid stroma. LELC is reported to be closely associated with Epstein-Barr virus (EBV) infection. A case is presented here in which bronchial brushing smears in a 70-year-old man, revealed large clusters of neoplastic cells with scant cytoplasm. The nuclei were large, hyperchromatic, of irregular contour and with prominent nucleoli. Also identified were prominent intratumoral lymphoid infiltration and brisk mitotic figures. We detected EBV-coded small RNA in situ hybridization in smears. A cytologic diagnosis of a LELC was suggested. Further evaluation and immunohistochemical studies were conducted on formalin-fixed, paraffin-embedded material. Cords or nests of large neoplastic cells with enlarged nuclei and prominent nucleoli with marked lymphoid infiltration and lymphoid stroma were identified on H&E sections. Immunohistochemically, the tumor cells showed diffuse and strong membranous staining for CK(AE1/AE3), CK5/6, CK34βE12, Napsin A and Bcl-2 but were negative for CK7, CK14, CK20, EMA, TTF-1, chromogranin A, synaptophysin and CD56. The proliferative index with MIB-1 was around 60%, and the p53 positive cells around 20%. The diagnosis of primary LELC of the lung was confirmed based on cytopathologic, histopathologic, immunohistochemical and EBER results, and a detailed systemic examination to exclude possible extrapulmonary (nasopharyngeal) origin. We report the cytopathological features of LELC of the lung and demonstrate here for the first time the positivity of the EBER with RNA-ISH method in smears with emphasis on differential diagnostic considerations.

Topics: Aged; Aspartic Acid Endopeptidases; Biomarkers, Tumor; Carcinoma, Squamous Cell; Cell Nucleus; Cell Proliferation; Cytoplasm; Diagnosis, Differential; Herpesvirus 4, Human; Humans; Immunohistochemistry; In Situ Hybridization; Keratins; Lung Neoplasms; Male; RNA, Viral

Topics: Adult; Aged; Carcinoma, Squamous Cell; Epithelial Cells; Female; Follow-Up Studies; gp100 Melanoma Antigen; Humans; Keratins; Lymphatic Metastasis; Male; MART-1 Antigen; Melanins; Melanocytes; Melanoma-Specific Antigens; Middle Aged; Mouth Floor; Mouth Mucosa; Mouth Neoplasms; S100 Proteins; Tongue Neoplasms

We present two cases of spindle cell squamous cell carcinoma, which were derived from solar keratosis and burn scar in two elderly Japanese patients, respectively. The tumors involved the whole dermis and subcutis in connection with the overlying epidermis. They were composed mainly of anaplastic spindle cells partially forming storiform patterns. The tumor cells were diffusely positive for vimentin and cytokeratin 8/18 (clone CAM5.2, simple epithelial cytokeratin), but negative for cytokeratin 1/5/10/14 (clone 34βE12, stratified epithelial cytokeratin). Ultrastructural analysis of a patient demonstrated desmosomes and tonofilaments in the tumor cells. Although spindle cell squamous cell carcinoma is usually positive for vimentin, detailed cytokeratin profile is controversial. The present cases revealed immunohistochemistry not expressing stratified but simple epithelial cytokeratin and vimentin. We should be reminded of the efficacy of simple epithelial cytokeratin immunoreactivity in spindle cell squamous cell carcinoma.

Topics: Aged; Carcinoma, Squamous Cell; Female; Humans; Immunohistochemistry; Keratins; Male; Skin Neoplasms; Vimentin

In this retrospective study, the aim was to compare individual histopathologic parameters of malignancy between nonmetastatic and metastatic squamous cell carcinoma of the tongue.. Sixty-two cases of squamous cell carcinoma of the tongue were selected and examined according to the system established by Brandwein-Gensler et al (Am J Surg Pathol 29:167, 2005) and included the pattern of invasion (most to least favorable), lymphocytic infiltration, perineural invasion, risk score, keratinization, eosinophilia, perivascular invasion, and tumor thickness.. The least favorable pattern had no association with nodal metastasis (P > .05). The scarcity or density of the lymphocytic infiltration, perineural invasion, and a risk score ≥ 3 were associated with nodal metastasis (P < .05). Keratinization, eosinophilia, perivascular invasion, and tumor thickness had no association with nodal metastasis (P > .05). A significant positive correlation was found between the pattern of invasion and perineural invasion and between the pattern of invasion and tumor thickness (P < .05).. The scarcity or density of the lymphocytic infiltration, perineural invasion, and histopathologic risk score may be helpful as parameters of histologic malignancy for the evaluation of metastatic and nonmetastatic squamous cell carcinoma of the tongue.

Topics: Adult; Aged; Aged, 80 and over; Carcinoma, Squamous Cell; Chemotaxis, Leukocyte; Eosinophilia; Female; Follow-Up Studies; Humans; Inflammation; Keratins; Lymphatic Metastasis; Lymphocytes; Male; Microvessels; Middle Aged; Neoplasm Invasiveness; Neoplasm Recurrence, Local; Peripheral Nerves; Retrospective Studies; Risk Assessment; Survival Rate; Tongue Neoplasms

Although down-regulation of GNG7 in cancer was reported before, its role in carcinogenesis is poorly understood. It belongs to a family of large G-proteins that may be involved in cell-contact-induced growth arrest and function in tumor suppression. In the present study, we stained immunohistochemically 188 tumors derived from larynx or floor of the mouth for GNG7 protein and confronted it with clinicopathologic data. Moreover, we performed bisulfite pyrosequencing to analyze GNG7 promoter methylation. We identified recurrent loss of GNG7 protein expression in 68/188 (36%) cases and promoter hypermethylation in (42/98; 43%) primary tumors, predominantly in young patients (p < 0.001). Loss of GNG7 expression correlated with hypermethylation of GNG7 promoter region (p < 0.001). Moreover, loss of GNG7 protein expression correlated with tumor size (p = 0.012) and lack of cervical metastasis (p = 0.02) whereas sustained expression correlated with keratinization (p = 0.008). Taken together, loss of GNG7 protein expression is a frequent event in head and neck cancer. Moreover, our data suggest that hypermethylation of the promoter region of GNG7 is probably the mechanism of the observed inactivation.

Topics: Adult; Aged; Aged, 80 and over; Carcinoma, Squamous Cell; DNA Methylation; DNA, Neoplasm; Female; Gene Expression Regulation, Neoplastic; GTP-Binding Protein gamma Subunits; Head and Neck Neoplasms; Humans; Immunohistochemistry; Keratins; Male; Middle Aged; Promoter Regions, Genetic; Sequence Analysis, DNA; Tumor Burden; Uterine Cervical Neoplasms

Nonkeratinizing morphology in oropharyngeal squamous cell carcinoma (NKSCC) strongly correlates with human papillomavirus and p16 status, but as a unique diagnostic entity is not widely recognized by pathologists. We sought to prospectively examine the performance of a new histological typing system during 1 year of routine clinical practice (Aim 1) and also its reproducibility amongst six head and neck pathologists using a 40 case test set (Aim 2).. The three histological types were: Type 1 (keratinizing), Type 2 (nonkeratinizing with maturation) and Type 3 (nonkeratinizing). For Aim 1, there were 85 cases. p16 immunohistochemistry was positive in five of the 18 (27.8%) cases classified as Type 1, 18 of the 19 (94.7%) as Type 2, and 47 of the 48 (97.9%) as Type 3. For Aim 2, agreement among pathologists on the test cases was best for types 1 and 3 (kappa values 0.62 and 0.56; P < 0.0001) and lowest for type 2 (kappa 0.35; P < 0.0001). All 21 cases classified as NK SCC (type 3) by any of the reviewers was p16 positive.. Pathologists can recognize NK SCC with good agreement, and when a pathologist classifies a tumour as NK SCC, this reliably predicts p16 positivity.

Topics: Biomarkers, Tumor; Carcinoma, Squamous Cell; Humans; Keratins; Observer Variation; Oropharyngeal Neoplasms; Prospective Studies; Reproducibility of Results; Tumor Suppressor Protein p14ARF

The distinction of porocarcinoma from squamous cell carcinoma is clinically relevant but can often be a diagnostic dilemma. Current markers reported to be helpful in diagnosing porocarcinoma include carcinoembryonic antigen and cytokeratin 7; however, their expression has been demonstrated in 30% to 80% and 13% to 22% of squamous cell carcinoma cases, respectively. In this study, we assessed immunohistochemical expression of cytokeratin 7, cytokeratin 15, cytokeratin 19, CAM 5.2, carcinoembryonic antigen, and nestin in 67 cases (39 porocarcinomas and 28 moderately differentiated squamous cell carcinomas) to determine their use as histologic adjuncts. Expression of carcinoembryonic antigen, cytokeratin 19, cytokeratin 7, CAM 5.2, cytokeratin 15, and nestin was seen in 77%, 67%, 64%, 51%, 49%, and 13% of porocarcinomas, respectively; and in 57%, 18%, 26%, 32%, 30%, and 37% of squamous cell carcinomas, respectively. Of these, cytokeratin 19 was the most specific (specificity, 82%) in detecting porocarcinomas, and carcinoembryonic antigen was the most sensitive (sensitivity, 77%). By χ(2) test, statistically significant P values (<.05) were observed for cytokeratin 7, cytokeratin 19, and nestin in the distinction of porocarcinoma from squamous cell carcinoma. However, in a logistic regression and stepwise selection for predicting a porocarcinoma, statistical significance was observed only for cytokeratin 19 (P = .0003). In conclusion, we found cytokeratin 19 to be a helpful marker in the distinction of porocarcinoma from squamous cell carcinoma, although a focal staining pattern can be seen in a third of cases. The diagnostic sensitivity and specificity appear to be significantly improved using a selected panel of immunohistochemical stains that include cytokeratin 7, cytokeratin 19, and nestin.

Topics: Adult; Aged; Aged, 80 and over; Biomarkers, Tumor; Carcinoembryonic Antigen; Carcinoma, Squamous Cell; Diagnosis, Differential; Eccrine Porocarcinoma; Female; Humans; Intermediate Filament Proteins; Keratins; Male; Middle Aged; Nerve Tissue Proteins; Nestin; Sensitivity and Specificity; Skin Neoplasms; Sweat Gland Neoplasms

In this study, we report 2 pediatric cases of nuclear protein of the testis (NUT) midline carcinoma (NMC) suggestive of pulmonary origin: case 1 was a 14-year-old Japanese boy and case 2 was a 7-year-old Japanese girl. Initial symptoms of both cases were prolonged cough and chest pain, and the case 2 patient also complained of lumbago and lumbar mass due to bone metastases. Imaging studies revealed that pulmonary tumors from both patients were located at the hilar region of the lower lobe. Biopsies of the tumors showed undifferentiated carcinoma in case 1 and combined undifferentiated and squamous cell carcinoma in case 2. Despite intensive treatment with chemotherapy and radiation, progression of neither tumor was controlled, and both patients died of the tumors at 1 year (case 1) and 4 months (case 2) after onset of disease. Both tumors were diffusely positive for p63 and NUT expression and were partially positive for various cytokeratins. Reverse transcription polymerase chain reaction analysis and subsequent direct sequencing revealed that the bromodomain-containing protein 4-NUT chimeric gene was present in tumor tissue of both patients, leading to a diagnosis of NMC. The tumor cells of case 1 were also positive for thyroid transcription factor-1 expression, but those of case 2 were negative. Histologic examination of the surgically removed lung tumor of case 1 indicated that the origin of the tumor was basal cells of the bronchiolar epithelia.

Topics: Adolescent; Biomarkers, Tumor; Biopsy; Carcinoma, Squamous Cell; Cell Differentiation; Child; Disease Progression; Fatal Outcome; Female; Humans; Immunohistochemistry; Keratins; Lung Neoplasms; Male; Neoplasm Proteins; Nuclear Proteins; Oncogene Proteins; Oncogene Proteins, Fusion; Reverse Transcriptase Polymerase Chain Reaction; Spinal Neoplasms; Thyroid Nuclear Factor 1; Time Factors; Tomography, X-Ray Computed; Transcription Factors; Treatment Outcome; Tumor Suppressor Proteins

To investigate whether the neoplastic spindle cells in nasopharyngeal carcinoma (NPC) are associated with the process of epithelial-mesenchymal transition (EMT).. We used immunohistochemistry to analyse the expression of cytokeratin, E-cadherin, β-catenin, vimentin, fibronectin, Snail1, Slug and aldehyde dehydrogenase 1 (ALDH1) in 115 cases of NPC in which there were neoplastic spindle cells; in 47 cases a neoplastic squamous cell component was also present. There was no significant difference in the expression of cytokeratin observed in the neoplastic spindle cells (P = 0.644), compared to the squamous component whereas E-cadherin expression was reduced. By contrast, the expression of β-catenin, vimentin, fibronectin, Snail1, Slug and ALDH1 was up-regulated in the spindle cells (all P = 0.000). Furthermore, E-cadherin expression was associated negatively with β-catenin (P < 0.001), vimentin (P < 0.001), fibronectin (P < 0.001), Slug (P < 0.001) and ALDH1 (P < 0.001) in neoplastic spindle cells, but did not correlate with Snail1 expression (P = 0.093).. Our findings demonstrate for the first time that EMT might play an important role in the development of neoplastic spindle cells in NPC.

Topics: Adolescent; Adult; Aged; Aldehyde Dehydrogenase 1 Family; beta Catenin; Biomarkers, Tumor; Cadherins; Carcinoma, Squamous Cell; Disease Progression; Epithelial-Mesenchymal Transition; Female; Fibroblasts; Fibronectins; Humans; Immunohistochemistry; Isoenzymes; Keratins; Male; Middle Aged; Nasopharyngeal Neoplasms; Neoplasm Invasiveness; Retinal Dehydrogenase; Snail Family Transcription Factors; Transcription Factors; Vimentin; Young Adult

Human papillomavirus (HPV)-related oropharyngeal squamous cell carcinoma has unique biology and better outcomes. p16 immunostaining is used as a surrogate marker for transcriptionally active HPV. Although diffuse staining is generally accepted as positive, the significance of partial staining has not been established, nor has the cutoff for extent of p16 staining that should be used to identify a tumor as HPV-related. From three other large studies utilizing p16 immunohistochemistry, we identified all cases with partial positive staining. The p16-stained slides were reviewed by three study pathologists for staining (nuclear and cytoplasmic) extent (in quartiles), and also for percentage that was confluent (ie, back-to-back cell staining). Tumors were histologically typed (keratinizing, non-keratinizing, or non-keratinizing with maturation) and tested for high-risk HPV by RNA in-situ hybridization and reverse-transcriptase PCR. For the 16 cases, there were two 4+(13%), five 3+(31%), six 2+(38%), and three 1+(19%) p16 staining tumors. Extent of staining ranged from 5 to 90% of cells positive with 25% or more confluent staining in 4/16 (25%). Of the 16 (31%) cases, 5 were HPV-related on the basis of RNA in-situ hybridization and reverse-transcriptase PCR. All of these cases had >50% p16 staining, 4/5 (80%) had more than 25% confluent staining, and 4/7 (57%) had non-keratinizing histological features. Only one of the p16 1+/2+ tumors was HPV RNA-positive (by reverse-transcriptase PCR only and low level). All 1+/2+ cases were keratinizing type or undifferentiated. By sensitive detection methods, most partial p16-positive squamous cell carcinoma cases with >50% staining harbor transcriptionally active HPV, and most HPV+ tumors have significant amounts of confluent staining. Cases with <50% p16 staining and lacking significant confluent staining rarely harbor HPV. These results support that greater than 75% p16 staining or, alternatively, >50% staining combined with >25% confluent areas, are suitable cutoffs for defining positivity.

Topics: Alphapapillomavirus; Biomarkers, Tumor; Carcinoma, Squamous Cell; Combined Modality Therapy; Cyclin-Dependent Kinase Inhibitor p16; DNA, Viral; Female; Humans; Immunohistochemistry; In Situ Hybridization; Keratins; Lymph Nodes; Male; Middle Aged; Neoplasm Grading; Oropharyngeal Neoplasms; Papillomavirus Infections; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; RNA, Viral

The diagnostic criteria for tricholemmal carcinoma remain controversial, and even the existence of tricholemmal carcinoma has been the subject of debate. Follicular (infundibular) squamous cell carcinoma (SCC) is a distinctive subset of SCC, which develops solely with folliculocentricity, and displays the features of conventional SCC without tricholemmal differentiation.. To examine the existence of pure folliculocentric SCCs showing tricholemmal differentiation, that is, tricholemmal carcinoma.. In total, 812 SCCs were examined, and those meeting the following diagnostic criteria were selected: (i) pure folliculocentricity without any associated Bowen's disease or actinic keratosis; (ii) composition primarily of lightly eosinophilic cells or clear cells containing glycogen; (iii) columnar lightly eosinophilic or clear cells aligned in a palisade along a discernible basement membrane; (iv) tricholemmal keratinization; (v) glycogen contained within the pale/clear cells; and (vi) cytological atypia and or infiltrative growth. We also evaluated whether the immunohistochemical profile [cytokeratin (CK)1, CK10, CK17, CD34 and D2-40] seen in normal hair follicles was retained in the selected lesions.. Only two lesions met the criteria. The immunohistochemical profile of the normal outer root sheath cells was generally retained in these lesions, except for CD34.. Tricholemmal carcinoma is a rare occurrence, but it does exist, and at least one type of tricholemmal carcinoma is considered to be related to follicular (infundibular) SCC.

Topics: Aged; Biomarkers, Tumor; Carcinoma, Squamous Cell; Humans; Immunohistochemistry; Keratins; Male; Middle Aged; Skin Neoplasms

For rapid, intra-operative pathological margin assessment to guide staged cancer excisions, multimodal confocal mosaic scan image wide surgical margins (approximately 1 cm) with sub-cellular resolution and mimic the appearance of conventional hematoxylin and eosin histopathology (H&E). The goal of this work is to combine three confocal imaging modes: acridine orange fluorescence (AO) for labeling nuclei, eosin fluorescence (Eo) for labeling cytoplasm, and endogenous reflectance (R) for marking collagen and keratin. Absorption contrast is achieved by alternating the excitation wavelength: 488 nm (AO fluorescence) and 532 nm (Eo fluorescence). Superposition and false-coloring of these modes mimics H&E, enabling detection of cutaneous squamous cell carcinomas (SCC). The sum of mosaic Eo+R is false-colored pink to mimic the appearance of eosin, while the AO mosaic is false-colored purple to mimic the appearance of hematoxylin in H&E. In this study, mosaics of 10 Mohs surgical excisions containing invasive SCC, and five containing only normal tissue were subdivided for digital presentation equivalent to 4 × histology. Of the total 50 SCC and 25 normal sub-mosaics presented, two reviewers made two and three type-2 errors (false positives), respectively. Limitations to precisely mimic H&E included occasional elastin staining by AO. These results suggest that confocal mosaics may effectively guide staged SCC excisions in skin and other tissues.

Topics: Absorption; Acridine Orange; Artifacts; Carcinoma, Basal Cell; Carcinoma, Squamous Cell; Collagen; Cytoplasm; Eosine Yellowish-(YS); False Positive Reactions; Humans; Keratins; Microscopy, Confocal; Mohs Surgery; Neoplasm Invasiveness; Reproducibility of Results; Skin; Skin Neoplasms

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

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

Sinonasal non-keratinizing squamous cell carcinoma (SCC), previously designated as transitional cell carcinoma or cylindrical cell carcinoma, is an uncommon malignant neoplasm with distinct histopathological features, considered to be a low-grade malignancy that usually occurs in elderly patients. Extensive local invasion is uncommon. Here we report a case of 90-year-old woman whose original presentation was as erythematous nasal skin nodules, biopsy of which showed a dermal tumor with features of sinonasal non-keratinizing SCC. No epidermal dysplasia was present. A subsequent computed tomography scan confirmed the presence of an endophytic tumor on the nasal sidewall. The initial presentation of sinonasal non-keratinizing SCC as a skin lesion is previously unreported to our knowledge. Diagnosis in this context requires accurate evaluation of the histopathology as well as a comprehensive knowledge of pathology specific to this anatomic location.

Topics: Aged, 80 and over; Biomarkers, Tumor; Carcinoma, Squamous Cell; Diagnosis, Differential; Female; Humans; Keratins; Neoplasm Invasiveness; Paranasal Sinus Neoplasms; Skin; Skin Neoplasms

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

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

Esophageal squamous cell carcinoma (ESCC) is considered one of the most aggressive cancers with poor prognosis. The high molecular weight cytokeratin 34βE12 (CK34βE12) is recognized by the antibody, that is expressed in the cytoplasm of epithelial basal cells, and has been considered as a potential marker for prostate cancer, breast cancer, and basaloid carcinoma of the lung. However, there are no clinicopathological studies investigating CK34βE12 expression at the invasive front of ESCC. In this study, we examined 170 surgically resected cases of ESCC to clarify the clinicopathological significance of CK34βE12 expression. CK34βE12 expression was found in 85.3% (145/170) of ESCC cases and was significantly correlated with lymph node metastasis (66.2% [96/145], P = 0.034), depth of tumor invasion (57.9% [84/145], P = 0.042), and differentiation (82.1% [119/145], P = 0.013). These results indicated that CK34βE12 expression is a good indicator of lymph node metastasis, depth of tumor invasion, and differentiation in case of ESCC.

Topics: Adult; Aged; Aged, 80 and over; Carcinoma, Squamous Cell; Disease Progression; Esophageal Neoplasms; Female; Gene Expression Regulation, Neoplastic; Humans; Keratins; Lymphatic Metastasis; Male; Middle Aged; Neoplasm Staging; Prognosis

Topics: Carcinoma, Squamous Cell; Female; Humans; Keratins; Male; Skin Neoplasms; Vimentin

Papillary squamous cell carcinoma (PSCC) has rarely been reported in the oral cavity. Herein reported is a case of PSCC in the mandibular gum. A 70-year-old man consulted our hospital because of a papillary tumor in the left mandibular gum. Physical examination revealed an exophytic papillary tumor of the left mandibular gum, and an excision of the tumor was performed. Grossly, the tumor was exophytic and papillary, and measured 1 x 1 x 0.8 cm. Microscopically, the tumor showed exophytic papillary proliferation with fibrovascular cores and consisted of atypical squamous epithelial cells. The tumor cells showed hyperchromasia, nuclear atypia, mitotic figures, apoptotic bodies, cancer pearls, and individual keratinization. Mild stromal invasion was seen. Immunohistochemically, the tumor cells were positive for pancytokeratin AE1/3, pancytokeratin CAM5.2, p63, p53, and Ki-67 (labeling index=40%), but negative for human papilloma virus (HPV). HPV in situ hybridization revealed no signals. Therefore, PSCC was diagnosed. The lateral and vertical margins are negative for tumor cell. The pathological diagnosis was PSCC. The patient was healthy and free from tumor three months after the operation.

Topics: Aged; Biomarkers, Tumor; Carcinoma, Papillary; Carcinoma, Squamous Cell; Gingiva; Gingival Neoplasms; Humans; Keratins; Ki-67 Antigen; Male; Mandible; Transcription Factors; Treatment Outcome; Tumor Suppressor Protein p53; Tumor Suppressor Proteins

A 29-year-old woman presented from another hospital with a 10-month history of an enlarging left-sided facial mass. Computed tomographic scan revealed a mass in the superficial lobe of the left parotid gland with left-sided cervical lymphadenopathy. The patient received a total left parotidectomy and a selective neck dissection. Histopathologic slides revealed lymphoepithelial carcinoma (LEC) that stained positive for cytokeratin, as well as Epstein-Barr virus (EBV). An LEC of the parotid is a rare salivary gland tumor accounting for less than 1% of all salivary gland tumors. As reaffirmed in our case, LEC is more common in women, occurs primarily in the parotid gland, and has an ethnic predilection. Histologic analysis reveals an infiltrative, poorly differentiated tumor nestled in a lymphoid stroma, with near 100% positivity for EBV in endemic areas. Complete resection of this poorly differentiated carcinoma followed by postoperative radiation is essential for local control.

Topics: Adult; Carcinoma, Squamous Cell; Female; Herpesvirus 4, Human; Humans; Keratins; Lymphoproliferative Disorders; Neck Dissection; Parotid Gland; Parotid Neoplasms

Scale-crust, also termed "keratin crust", appears as yellowish-to-tan scale on the skin's surface. It is caused by hyperkeratosis and parakeratosis in inflamed areas of squamous cell carcinoma in situ (SCCIS, Bowen's disease) and is a critical dermoscopy feature for detecting this skin cancer. In contrast, scale appears as a white-to-ivory detaching layer of the skin, without crust, and is most commonly seen in benign lesions such as seborrheic keratoses (SK). Distinguishing scale-crust from ordinary scale in digital dermoscopy images holds promise for early SCCIS detection and differentiation from SK. Reported here are image analysis techniques that best characterize scale-crust in SCCIS and scale in SK, thereby allowing accurate separation of these two dermoscopic features. Classification using a logistic regression operating on color features extracted from these digital dermoscopy structures can reliably separate SCCIS from SK.

Topics: Area Under Curve; Carcinoma, Squamous Cell; Databases, Factual; Dermoscopy; Diagnosis, Differential; Humans; Image Processing, Computer-Assisted; Keratins; Keratosis, Seborrheic; Logistic Models; ROC Curve; Skin Neoplasms

P-cadherin belongs to the family of Ca(2+)-dependent homophilic glycosylated cell adhesion molecules. In the normal oral epithelium it shows a strong expression in the basal cell layer which gradually decreases in the suprabasal cell layers. The exact role of P-cadherin during the development and homeostasis of the oral epithelium has not been elucidated, yet. Here, we show for the first time that P-cadherin controls differentiation by regulating cytokeratin (CK) 1/10 expression in primary oral keratinocytes (POK) from normal, but interestingly not in POKs from oral squamous cell carcinoma (OSCC) tissue. SiRNA knockdown of P-cadherin in normal POKs revealed a strong upregulation of CK1/10 expression on mRNA and protein level. In contrast, E-cadherin knockdown in normal oral keratinocytes did not show any influence on CK1/10 expression. Moreover, in comparison with normal control keratinocytes normal oral keratinocytes with reduced P-cadherin expression displayed an enhanced expression and a stronger nuclear staining of C/EBP-beta, a well-known regulator of CK1/10 expression in keratinocytes. Furthermore, after P-cadherin knockdown in normal POKs the promoter activity of a C/EBP-responsive luciferase construct was significantly higher than in normal POKs with regular P-cadherin expression. Additionally, we noticed a proliferation advantage in normal oral keratinocytes in contrast to keratinocytes with diminished P-cadherin expression. However, the inverted effect was seen in tumor derived primary oral keratinocytes. In summary, we show that P-cadherin contributes to the keratinocyte differentiation in the oral epithelium by influencing the CK1 and CK10 expression via C/EBP-beta-mediated signaling in normal but not in tumor derived oral keratinocytes from OSCC patients.

Topics: Cadherins; Carcinoma, Squamous Cell; CCAAT-Enhancer-Binding Protein-beta; Cell Differentiation; Cell Line; Cell Line, Tumor; Cell Proliferation; Humans; Keratinocytes; Keratins; Mouth Mucosa; Mouth Neoplasms; Promoter Regions, Genetic; RNA, Messenger; RNA, Small Interfering; Signal Transduction; Up-Regulation

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

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

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

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

Current treatments for nonmelanoma skin cancer include surgery, Mohs micrographic surgery, radiation, cryosurgery, photodynamic therapy, local chemotherapy and application of immunomodulators such as imiquimod. However, all have a 5-year recurrence rate of 1-40%. Gene therapy for the treatment of skin cancers is a promising new approach, as delivery of the vectors to the skin is simple and safety issues can be properly addressed.. To develop an ex-vivo organ culture system for basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) tumours, and to test the feasibility of applying oncolytic viruses to these tumours.. We first optimized conditions for the maintenance of BCC and SCC tissues in organ culture, and demonstrated viability of the tissues ex vivo for 3-7 days. The tropism of two potential oncolytic viral vectors, herpes simplex virus type 1 (HSV-1) and adenovirus (AD), was next evaluated.. Immunohistological analysis revealed that HSV-1 targeted tumour cells that expressed p63 and did not express keratin 15 or keratin 14 markers of keratinocytes. Further examination indicated that uninfected BCC and SCC tissues express two isoforms of p63 mRNA, and HSV-1 infection specifically enhanced expression of the TAp63 isoform. Furthermore, following infection, both HSV-1 and AD induced apoptosis in the BCC and SCC cells as indicated by the induction of activated caspase-3.. The results indicated a specific pattern of viral tropism to skin cancer cells that are critical for maintenance of the tumour. This new experimental system should aid in the analysis of new therapeutic modalities, such as oncolytic viruses, for future treatment of these skin tumours.

Topics: Adenoviridae; Apoptosis; Carcinoma, Basal Cell; Carcinoma, Squamous Cell; Caspase 3; Herpesvirus 1, Human; Humans; Immunohistochemistry; Keratinocytes; Keratins; Organ Culture Techniques; Skin Neoplasms; Trans-Activators; Transcription Factors; Tumor Suppressor Proteins; Viral Tropism

Besides worse prognosis of bladder cancer with squamous differentiation (pure squamous cell carcinoma (SCC) or mixed urothelial carcinoma (UC/SCC)), high-grade non-keratinising squamous differentiation is difficult to identify in haematoxylin-eosin stainings. This study aims to validate routine immunohistochemical markers for squamous differentiation in a larger cohort of patients. Tissue microarrays of 89 pure SCCs and mixed UC/SCCs, 66 urothelial carcinomas (UC), precursor lesions and normal urothelium were stained for cytokeratin (CK) 5/6, CK 5/14, CK 7, CK 20 and uroplakin III. Electron microscopy was performed to confirm the differentiation. Pure SCCs displayed staining throughout the epithelium for CK 5/6 (76.6% (36/47)) and CK 5/14 (95.8% (46/48)), focal staining for CK 7 (28.9% (13/45)) and no staining for CK 20 and uroplakin III (both 0% (0/48)). UCs exhibited a basal or diffuse staining for CK 5/6 (30.2% (16/53)) and CK 5/14 (57.1% (32/56)), focal positivity for CK 7 (83.6% (46/55)), CK 20 (50.9% (29/57)) and uroplakin III (21.8% (12/55)). Each marker discriminated SCC and UC significantly (p < 0.01). A third subgroup rarely showed full epithelial staining for CK 5/6 (14.3% (1/7)) and CK 5/14 (28.6% (2/7)), focal staining for CK 7 (85.7% (6/7)) and no staining for CK 20 and uroplakin III (both 0% (0/7)). Electron microscopy could prove both, SCC and UC characteristics, revealing a transient type. A staining pattern with CK 5/6- and CK 5/14-positivity plus CK 20- and uroplakin III-negativity identified squamous differentiation in bladder tumours and revealed a third type of squamous transdifferentiation.

Topics: Biomarkers, Tumor; Carcinoma in Situ; Carcinoma, Squamous Cell; Carcinoma, Transitional Cell; Cell Count; Cell Differentiation; Cystectomy; Humans; Keratins; Phenotype; Prognosis; Tissue Array Analysis; Urinary Bladder Neoplasms; Urothelium

Darier's disease (DD) is an inherited autosomal-dominant skin disorder characterized histologically by loss of adhesion between keratinocytes. DD is typically caused by mutations in sarcoendoplasmic reticulum Ca(2+)-ATPase isoform 2 (SERCA2), a major regulator of intracellular Ca(2+) homeostasis in the skin. However, a defined role for SERCA2 in regulating intercellular adhesion remains poorly understood. We found that diminution of SERCA2 function by pharmacological inhibition or siRNA silencing in multiple human epidermal-derived cell lines was sufficient to disrupt desmosome assembly and weaken intercellular adhesive strength. Specifically, SERCA2-deficient cells exhibited up to a 60% reduction in border translocation of desmoplakin (DP), the desmosomal cytolinker protein necessary for intermediate filament (IF) anchorage to sites of robust cell-cell adhesion. In addition, loss of SERCA2 impaired the membrane translocation of protein kinase C α (PKCα), a known regulator of DP-IF association and desmosome assembly, to the plasma membrane by up to 70%. Exogenous activation of PKCα in SERCA2-deficient cells was sufficient to rescue the defective DP localization, desmosome assembly, and intercellular adhesive strength to levels comparable to controls. Our findings indicate that SERCA2-deficiency is sufficient to impede desmosome assembly and weaken intercellular adhesive strength via a PKCα-dependent mechanism, implicating SERCA2 as a novel regulator of PKCα signaling.

Topics: Calcium; Carcinoma, Squamous Cell; Cell Adhesion; Cell Communication; Cell Line, Tumor; Darier Disease; Desmoplakins; Desmosomes; Humans; Intermediate Filaments; Keratins; Mouth Neoplasms; Protein Kinase C-alpha; RNA, Small Interfering; Sarcoplasmic Reticulum Calcium-Transporting ATPases; Signal Transduction

Basaloid squamous cell carcinoma (BSCC), an aggressive tumor of the aerodigestive tract, was described over 20 years ago, and its defining histologic parameters remain largely unchanged. While rare reports have noted cutaneous metastatic deposition, primary tumors have not been previously described.. Although most cutaneous malignancies with basaloid features comprise variants of basal cell carcinomas, a subset exhibit histologic attributes suggestive of more aggressive tumors. We evaluated 3 such tumors submitted to our dermatopathology service over a 6-month period.. Immunohistochemical stains useful in differentiating the lineage of cutaneous malignancies with basaloid-appearing tumor cells were employed. Human papillomavirus (HPV) detection and typing were performed by using polymerase chain reaction and sequencing.. The tumor cells expressed high molecular weight cytokeratin (34βE12) and cytokeratin 5/6 but not Ber-EP4 or bcl-2. This pattern of immunohistochemical staining and the histologic attributes of the neoplasms are inconsistent with those expected in better defined cutaneous basaloid malignancies but are characteristic of BSCC. Two of the tumors arose in the inguinal crease of middle-aged men, and two patients were known to be immunosuppressed. HPV genotype 33 was detected in the tumor tissue from both inguinal lesions.. The number of cases available for evaluation is small and any prognostic implications therefore tenuous.. The differential diagnosis of cutaneous malignancies exhibiting basaloid cells should include BSCC, a tumor with an unusual pattern of immunohistochemical staining and a potentially poor prognosis.

Topics: Aged; Biomarkers, Tumor; Biopsy, Needle; Carcinoma, Basosquamous; Carcinoma, Squamous Cell; Diagnosis, Differential; Female; Humans; Immunohistochemistry; Keratins; Male; Middle Aged; Neoplasm Invasiveness; Neoplasm Staging; Prognosis; Risk Assessment; Sampling Studies; Skin Neoplasms; Survival Rate; Treatment Outcome

Acantholytic squamous cell carcinoma (ASCC) is an uncommon histopathologic variant of SCC, characterized by marked acantholysis, wherein the tumor cells demonstrate defective cohesion to one another in the cancer nest leading to a pseudoglandular or pseudovascular appearance. The most common site of ASCC is the sun-exposed areas of the skin. Sporadic cases of ASCC have also been reported in various mucosal membranes and organs but to our knowledge this is the first case of primary ASCC of the large bowel.. A 59-year-old woman underwent right hemicolectomy due to large tumor in cecum and initial part of the ascending colon. Microscopically, the tumor consisted of nests of focally keratinizing large, atypical, squamous epithelial cells. Approximately 70% of the tumor showed acantholytic changes and acantholysis was equally distributed through the entire tumor. Immunohistochemically tumor cells were diffusely positive for cytokeratin (CK) AE1/AE3 and focally positive for epithelial membrane antigen and syndecan 1. All other tested antibodies (CK7, CK 20, CK MNF116, E-cadherin, beta-catenin, p63, p16, CD31, CD34, CEA, estrogen, progesterone) showed negative reaction. Periodic acid Schiff and alcian blue staining showed no intracellular or extracellular mucinous material in the tumor. The diagnosis of acantholytic squamous cell carcinoma of the cecum was suspected and additional examination was recommended to exclude possibility of metastatic carcinoma. Extensive clinical examination which also included whole-body PET/CT scan showed no additional tumors. After the exclusion of possible metastatic disease the diagnosis of primary acantholytic squamous cell carcinoma of the cecum was confirmed. Six months after surgery the metastasis in small intestine and recurrence in the abdominal cavity at the site of surgery appeared and had the same morphological characteristic as the primary tumor in the cecum.. We report a unique case of ASCC arising in cecum and on this way expands the range of tumors originating in colon. Reports of more cases of colonic ASCC would possibly help to elucidate origin, clinical behavior and therapy of these tumors.

Topics: Carcinoma, Squamous Cell; Cecal Neoplasms; Colectomy; Female; Humans; Keratins; Middle Aged; Mucin-1; Syndecans; Treatment Outcome

To evaluate the immunohistochemical expression of MMP-1, -2, -7, -9 and -26 in oral squamous cell carcinomas (SCCs) according to tumour site and histological grade of malignancy.. Fifteen cases of SCC of the lower lip and 15 cases of tongue SCC were selected and divided into low grade malignancy (n = 17) and high grade malignancy (n = 13).. Higher immunohistochemical expression of MMPs by neoplastic cells was observed in tongue SCCs, with a statistically significant difference for MMP-9 (P < 0.05). High-grade SCCs showed a higher expression of MMPs, except for MMP-2, with a statistically significant difference for MMP-7 (P < 0.05) and MMP-26 (P < 0.05). In addition, a direct association was observed between morphological scores of malignancy and MMP immunoreactivity, with the association being significant for MMP-7 and MMP-26.. The present results demonstrate the important role of MMPs in the development of SCCs of the lower lip and tongue.

Topics: Carcinoma, Squamous Cell; Cell Nucleus; Disease Progression; Humans; Immunohistochemistry; Inflammation; Keratins; Lip Neoplasms; Matrix Metalloproteinase 1; Matrix Metalloproteinase 2; Matrix Metalloproteinase 7; Matrix Metalloproteinase 9; Matrix Metalloproteinases; Matrix Metalloproteinases, Secreted; Neoplasm Invasiveness; Stromal Cells; Tongue Neoplasms

We report the malignant characteristics of circulating tumor cells (CTCs) and the corresponding molecular features of the primary tumor in a patient with esophageal squamous cell carcinoma (ESCC). A 70-year-old male patient was diagnosed with TNM stage T3N0M0 ESCC. Before surgery, seven intact CTCs and 12 CTCs with a fragmented membrane were detected in 7.5 mL of peripheral blood by immunofluorescence staining. One week after radical resection of the primary tumor, four CTCs were identified in 7.5ml peripheral blood. All CTCs were confirmed as having a malignant phenotype by chromosomal analysis and routine cell staining. Ninety percent of the CTCs were found to have polysomic chromosomes 8 and 20 by fluorescence in situ hybridization (FISH). Immunofluorescence analysis showed that all of the primary tumor cells detected were cytokeratin8/18/19 (CK8/18/19)-positive, but only 1% were CD133-positive. The serum CA19-9 and CEA level were normal in the process of diseases. The patient died 6 months after surgery as a result of lung metastases and other complications. The results of this study suggest that the dynamics and malignant characteristics of both CTCs and the corresponding primary tumor during the disease process may predict tumor burden and the risk of relapse and metastasis.

Topics: AC133 Antigen; Aged; Antigens, CD; Carcinoma, Squamous Cell; Chromosome Aberrations; Chromosomes, Human, Pair 20; Chromosomes, Human, Pair 8; Esophageal Neoplasms; Fatal Outcome; Glycoproteins; Humans; Keratins; Male; Neoplastic Cells, Circulating; Peptides

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

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

Tumor budding is a readily detectable histopathological feature and has been recognized as an adverse prognostic factor in several human cancers. However, the prognostic value of tumor budding in tongue squamous cell carcinoma (TSCC) has not been reported. The purpose of this study was to assess the correlation of tumor budding with the clinicopathologic features, and the known molecular biomarkers (E-cadherin and Vimentin), as well as to evaluate its prognostic significance for TSCC.. Archival clinical samples of 230 patients with TSCC were examined for tumor budding. Immunohistochemistry analyses were performed to examine the expression of E-cadherin and Vimentin. Statistical analyses were carried out to assess the correlation of tumor budding with clinicopathologic parameters and patient survival. The potential association between tumor budding and alterations of E-cadherin and Vimentin expression was also assessed.. Of the 230 TSCC cases examined, tumor budding was observed in 165 cases (71.7%), with a mean tumor bud count of 7.5 (range from 1 to 48 buds). High-intensity budding (≥5 tumor buds) was observed in 111 cases (48.3%). Statistical analysis revealed that tumor budding was associated with tumor size (P < 0.05), differentiation (P < 0.05), clinical stage (P < 0.05), lymph node metastasis (P < 0.01), and correlated with reduced overall survival. In addition, significant associations were observed among tumor budding and the deregulation of E-cadherin (P < 0.001) and Vimentin (P < 0.001).. Tumor budding, which associates with epithelial-mesenchymal transition, is a frequent event and appears to be an independent prognostic factor in TSCC.

Topics: Biomarkers; Cadherins; Carcinoma, Squamous Cell; Cell Differentiation; Chromogenic Compounds; Epithelial-Mesenchymal Transition; Female; Follow-Up Studies; Humans; Keratins; Lymphatic Metastasis; Male; Middle Aged; Neoplasm Grading; Neoplasm Invasiveness; Neoplasm Staging; Prognosis; Retrospective Studies; Survival Rate; Tongue Neoplasms; Vimentin

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

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

Sentinel node navigation surgery (SNNS) is currently considered to provide better staging of regional metastasis. For rapid and accurate sentinel lymph node analysis, one-step nucleic acid amplification using cytokeratin 19 (CK19) has been applied, particularly in breast cancer. On the other hand, additional quantitative reverse transcription PCR targets containing cytokeratins have been reported recently in head and neck cancer. In this report, CK19 and p63 were immunohistochemically examined in primary tumours for use as molecular markers and were compared with cytokeratin 903 (CK903), cytokeratin 8/18 (CK8/18) and cytokeratin (AE1/AE3), which are used in diagnostic immunohistochemistry for head and neck squamous cell carcinoma.. The study reviewed 17 patients with T1/T2, N0 (UICC) oral squamous cell carcinoma of the tongue who were treated surgically at Kyorin University Hospital between 2002 and 2009. The intensity and proportion of tumour cells stained for CK19, CK903, p63, CK8/18 and AE1/AE3 were evaluated.. CK19 and CK8/18 staining in cytoplasm was patchy among carcinoma cells, indicating weak expression. Staining proportion for p63, CK903 and AE1/AE3 was greater than for CK19 and CK8/18, although staining intensity for CK903 was weaker than for p63 and AE1/AE3. The difference in total score between CK19 and CK8/18 staining and p63, CK903 and AE1/AE3 staining was statistically significant (p<0.001). p63 and AE1/AE3 may be better markers than CK903, CK19 and CK8/18.. This suggests that p63 is of clinical utility in SNNS and that CK19 is unsuitable for early tongue carcinoma. Further studies are needed before clinical application of these markers.

Topics: Adult; Aged; Aged, 80 and over; Biomarkers, Tumor; Carcinoma, Squamous Cell; Female; Humans; Immunohistochemistry; Japan; Keratin-18; Keratin-19; Keratin-8; Keratins; Lymph Node Excision; Lymphatic Metastasis; Male; Middle Aged; Neoplasm Staging; Nucleic Acid Amplification Techniques; Predictive Value of Tests; Prognosis; Tongue Neoplasms; Transcription Factors; Tumor Suppressor Proteins

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

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

The receptor-binding cancer antigen expressed on SiSo cells (RCAS1) is a human tumor-associated antigen that has been considered to play a crucial role in tumor progression by enabling cancer cells to evade immune surveillance. The present study aimed to evaluate the clinical significance of RCAS1 expression in mobile tongue squamous cell carcinoma (SCC).. RCAS1 protein expression was assessed immunohistochemically on 49 mobile tongue SCC tissue samples obtained from an equal number of patients and was statistically analyzed with clinicopathological characteristics and overall and disease-free patients' survival.. Enhanced RCAS1 expression was significantly associated with reduced depth of invasion (p=0.0069), low mitotic index (p=0.0251) and no evidence of muscular invasion (p=0.0098). A borderline association between RCAS1 expression and stromal inflammatory reaction was also noted (p=0.0660). RCAS1 expression was not associated with overall and disease-free survival.. Our data support evidence for possible implication of RCAS1 at the early stage of tumor progression in mobile tongue SCC, whereas the survival prediction using RCAS1 expression as a clinical marker seems uncertain for this type of malignancy.

Topics: Adult; Aged; Aged, 80 and over; Animals; Antigens, Neoplasm; Carcinoma, Squamous Cell; Disease Progression; Female; Humans; Immunohistochemistry; Keratins; Male; Middle Aged; Tongue Neoplasms

The role of CD10 needs clarification in a broader immunohistochemical battery for distinguishing atypical fibroxanthoma (AFX) from spindle cell squamous cell carcinoma (sSCC).. We retrospectively reviewed 23 cutaneous spindle cell tumors previously classified as AFX (n = 11) or as sSCC (n = 12). Each tumor was stained with CD10, S-100, p63 and two or more cytokeratin stains. Defining AFX as a diagnosis of exclusion based on multiple negative cytokeratin stains and negative p63 staining, we reclassified four squamous cell carcinomas (SCCs) as AFX. CD10 staining was reviewed and graded in all tumors.. Fifteen tumors were classified as AFX. Strongly positive CD10 staining was observed in all 15 AFXs, as well as four (50%) of the eight SCCs. Expression of p63 was seen in six sSCCs (75%).. CD10 is consistently expressed by AFX. However, CD10 is also often strongly expressed by sSCC. Positive staining with p63 favors a diagnosis of sSCC. An immunohistochemical battery useful for distinguishing AFX from sSCC may include CD10, p63 and two cytokeratin markers. However, CD10 alone should not be relied upon in the distinction of these entities.

Topics: Biomarkers, Tumor; Carcinoma, Squamous Cell; Diagnosis, Differential; Humans; Keratins; Membrane Proteins; Neprilysin; Retrospective Studies; Sarcoma; Skin Neoplasms; Xanthomatosis

Proliferation of osteoclast-like giant cells in a cutaneous squamous cell carcinoma is a rare phenomenon and so far only four cases have been reported. In previous reports, osteoclast-like giant cells were admixed with sarcomatoid component of squamous cell carcinoma and it is therefore debatable if the osteoclast-like giant cells represent a reactive phenomenon or a part of the malignant tumour. A case of cutaneous squamous cell carcinoma associated with osteoclast-like giant cells is reported. However, sarcomatous component of squamous cell carcinoma was not identified in this case. Morphologically, the osteloclast-like giant cells appeared to be benign. The localization of the squamous cell carcinoma and the osteoclastic-like giant cells were separate from one another. Immunohistochemically, squamous cell carcinoma was positive for high molecular weight cytokeratin, cytokeratin-5 and p63, whereas the osteloclast-like giant cells were positive for histiocyte marker CD68 and vimentin and negative for epithelial markers supporting a reactive nature of osteoclast-like giant cells to the cutaneous malignancy.

Topics: Aged; Antigens, CD; Antigens, Differentiation, Myelomonocytic; Biomarkers, Tumor; Carcinoma, Squamous Cell; Cell Proliferation; Giant Cells; Humans; Keratins; Male; Osteoclasts; Skin Neoplasms; Vimentin

To evaluate the use of diffusion-weighted magnetic resonance imaging (DW-MRI) for nodal staging and its impact on radiotherapy (RT) planning.. Twenty-two patients with locally advanced head and neck squamous cell carcinoma underwent contrast-enhanced computed tomography (CT), as well as MRI (with routine and DW sequences) prior to neck dissection. After topographic correlation, lymph nodes were evaluated microscopically with prekeratin immunostaining. Pathology results were correlated with imaging findings and an RT planning study was performed for these surgically treated patients. One set of target volumes was based on conventional imaging only, and another set was based on the corresponding DW-MRI images. A third reference set was contoured based solely on pathology results.. A sensitivity of 89% and a specificity of 97% per lymph node were found for DW-MRI. Nodal staging agreement between imaging and pathology was significantly stronger for DW-MRI (kappa = 0.97; 95% confidence interval [CI], 0.84-1.00) than for conventional imaging (kappa = 0.56; 95% CI, 0.16-0.96; p = 0.019, by McNemar's test). For both imaging modalities, the absolute differences between RT volumes and those obtained by pathology were calculated. Using an exact paired Wilcoxon test, the observed difference was significantly larger for conventional imaging than for DW-MRI for nodal gross tumor volume (p = 0.0013), as well as for nodal clinical target volume (p = 0.0415) delineation.. These results suggest that DW-MRI is superior to conventional imaging for preradiotherapy nodal staging of head and neck squamous cell carcinoma, and provides a potential impact on organsparing and tumor control.

Topics: Adult; Aged; Aged, 80 and over; Carcinoma, Squamous Cell; Diffusion Magnetic Resonance Imaging; Female; Head and Neck Neoplasms; Humans; Keratins; Lymphatic Metastasis; Male; Middle Aged; Neck Dissection; Neoplasm Staging; Prospective Studies; Protein Precursors; Radiotherapy Planning, Computer-Assisted; Sensitivity and Specificity; Tomography, X-Ray Computed

We compared findings of optical coherence tomography (OCT) with histopathological results of suspicious oral lesions to assess the feasibility of using OCT to identify malignant tissue. Thirty-four oral lesions from 27 patients had swept-source frequency-domain OCT. Four variables were assessed (changes in keratin, epithelial, and sub-epithelial layers, and identification of the basement membrane) and from this we calculated whether or not there were architectural changes. These data were then compared with histopathological results. Two clinicians, who were unaware of the clinical and histopathological diagnoses, decided whether biopsy was necessary. The basement membrane was recognised in only 15 oral lesions. OCT could identify diseased areas but could not provide a diagnosis or differentiate between lesions. The two clinicians, who recommended biopsy agreed in all cases. This pilot study confirms the feasibility of using OCT to identify architectural changes in malignant tissues.

Topics: Basement Membrane; Biopsy; Carcinoma, Squamous Cell; Diagnosis, Differential; Epithelium; Erythroplasia; Feasibility Studies; Humans; Image Processing, Computer-Assisted; Keratins; Leukoplakia, Oral; Mouth Mucosa; Mouth Neoplasms; Oral Ulcer; Pilot Projects; Precancerous Conditions; Tomography, Optical Coherence; Tongue Neoplasms

Ligand activation of peroxisome proliferator-activated receptor (PPAR)-beta/delta and inhibition of cyclooxygenase-2 (COX-2) activity by nonsteroidal anti-inflammatory drugs can attenuate skin tumorigenesis. There is also evidence that attenuation of skin tumorigenesis by inhibition of COX-2 activity occurs through PPARbeta/delta-independent mechanisms. The present study examined the hypothesis that combining ligand activation of PPARbeta/delta with inhibition of COX-2 activity will cooperatively inhibit chemically induced skin tumor progression using both in vivo and ex vivo models. A two-stage chemical carcinogenesis bioassay was performed in wild-type and Pparbeta/delta-null mice. After 22 weeks, cohorts of both mouse lines were divided into four experimental groups: (1) control, (2) topical application of the PPARbeta/delta ligand GW0742, (3) dietary administration of the COX-2 inhibitor nimesulide, or (4) both GW0742 and nimesulide. Ligand activation of PPARbeta/delta did not influence skin tumor progression, while a modest decrease in skin tumor multiplicity was observed with dietary nimesulide. Interestingly, the combined treatment of GW0742 and nimesulide increased the efficacy of the decrease in papilloma multiplicity for 6 weeks in wild-type mice, but this effect was not found at later time points and was not found in similarly treated Pparbeta/delta-null mice. Neoplastic keratinocyte lines cultured with GW0742 and nimesulide also exhibited enhanced inhibition of cell proliferation coincident with increased expression of Keratin messenger RNAs. Results from these studies support the hypothesis that combining ligand activation of PPARbeta/delta with inhibition of COX-2 activity can inhibit chemically induced skin tumor progression by modulating differentiation.

Topics: 9,10-Dimethyl-1,2-benzanthracene; Animals; Anticarcinogenic Agents; Carcinoma, Squamous Cell; Cell Differentiation; Cell Line, Tumor; Cell Proliferation; Cyclooxygenase 2 Inhibitors; Dinoprostone; Disease Models, Animal; Female; Keratinocytes; Keratins; Keratoacanthoma; Ligands; Mice; Mice, Inbred C57BL; Mice, Knockout; Papilloma; PPAR delta; PPAR-beta; RNA, Messenger; Skin Neoplasms; Sulfonamides; Thiazoles; Time Factors

Squamous cell carcinoma ex-pleomorphic adenoma (CXAP) is a malignant and rare mixed tumor. We report a new case.. A seventy-year-old woman consulted for a mass in the left hemi-face having evolved over the last 20years. The physical examination revealed a hard and large tumor invading all the palate. Computed tomography revealed a heterogeneous 8.5cm long maxillary mass. The diagnosis of CXAP was made on a biopsy. A histological study confirmed the diagnosis after surgical resection of the tumor, specifying its noninvasive character.. CXAP is generally located in the parotid gland; it is very rarely located in the palate. The degenerated epithelial component generally corresponds to an adenocarcinoma or an undifferentiated carcinoma; squamous-cell carcinoma is more rarely reported. The prognosis is excellent for the micro and noninvasive types. Surgery remains the treatment of choice.

Topics: Adenoma, Pleomorphic; Aged; Amyloid; Biopsy; Carcinoma, Squamous Cell; Cell Nucleus; Epithelial Cells; Female; Follow-Up Studies; Humans; Keratins; Neoplasms, Multiple Primary; Neprilysin; Palatal Neoplasms; Tomography, X-Ray Computed

Cervical lymph node metastases from unknown primary sites account for approximately 3% to 9% of all head and neck malignant lesions. Squamous cell carcinoma is the most common type of cervical metastatic carcinoma. Our aim was to investigate the possibility of determining the site of primary tumors using an immunohistochemical diagnostic panel in metastatic cervical lymph nodes. Expression profiles of cytokeratins, 5/6; 8/18; 10; 13; 14; and 19, p16, and pRb were evaluated in 101 consecutive patients with cervical nodal metastasis who had undergone neck dissection to treat known head and neck squamous cell carcinoma (primary sites: 16, oral cavity; 38, oropharynx; 26, hypopharynx; 21, larynx). Cytokeratin 10 was more frequently expressed in oral cavity primary tumors, whereas cytokeratin 19 staining was more frequently observed in tumors originated from the pharynx and larynx. The expression of p16 and altered pRb status (0% or >50%) were more frequently observed in oropharynx primary tumors. To select the best subset among the 8 antibodies tested, classification and regression tree analysis was performed. The analysis correctly classified the four primary sites (25.0% of oral cavity, 89.5% of oropharynx, 30.8% of hypopharynx, and 57.1% of larynx) using 5 variables (histologic subtype, p16, cytokeratins 10 and 19, and pRb). The p16 was the single best predictor. The classification tree method using immunostaining profiles of p16, cytokeratins 10 and 19, or pRb may be helpful in the identification of the primary site of metastatic squamous cell carcinoma with occult primary.

Topics: Adult; Aged; Aged, 80 and over; Carcinoma, Squamous Cell; Chi-Square Distribution; Female; Head and Neck Neoplasms; Humans; Immunohistochemistry; Keratins; Lymph Nodes; Lymphatic Metastasis; Male; Middle Aged; Neoplasms, Unknown Primary; Retrospective Studies; Tissue Array Analysis

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

Histological analysis of tumour resection for squamous cell carcinoma (SCC) of the tongue yields prognostic information. We analysed histological slides of biopsy and tumour resection specimens using an adapted malignancy grading score and analysed variables of neck dissections. There was moderate correlation between biopsy and tumour resection using malignancy grading scores (correlation coefficient 0.45); good agreement of tumour grade (79%), tumour depth (76%), and type of invasive front (80%), but correlation was only fair to moderate (κ=0.38, κ=0.51, and κ=0.41, respectively). Correlation of the biopsy grading score and invaded nodes in the neck, extra capsular spread, and soft tissue disease was not significant.

Topics: Adult; Aged; Aged, 80 and over; Biopsy; Carcinoma, Squamous Cell; Cell Nucleus; Cytoplasm; Female; Glossectomy; Humans; Keratins; Lymph Nodes; Lymphocytes; Male; Middle Aged; Mitosis; Neck Dissection; Neoplasm Invasiveness; Neoplasm Recurrence, Local; Neoplasm Staging; Plasma Cells; Prognosis; Tongue Neoplasms

Cutaneous malignancies may spread to underlying nerves, a process known as perineural invasion (PNI). We report a patient who was found to have PNI presenting as a cranial polyneuropathy on the contralateral side of the face many years after the resection of a squamous cell carcinoma. All diagnostic testing was unrevealing until nerve biopsy was performed. This emphasizes the long asymptomatic period between treatment of a cutaneous malignancy and detection of PNI, and the development of PNI at a site distant from the original malignancy. Biopsy of a clinically involved nerve may permit diagnosis of PNI when other studies are normal.

Topics: Aged; Carcinoma, Squamous Cell; Cranial Nerve Neoplasms; Functional Laterality; Humans; Keratins; Male; Skin Neoplasms

This study compares synchronous oral squamous cell carcinomas (OSCCs) with single primary OSCCs to assess the histopathologic parameters with a known prognostic significance.. Twenty-eight cases of synchronous OSCCs and a control group of single primary OSCCs were compared for 15 histologic prognostic variables.. Results showed significantly less amount of abnormal mitoses (synchronous-1: P = .002; synchronous-2: P = .006) and tumor-induced stroma (synchronous-1: P = .011; synchronous-2: P = .001) in synchronous OSCCs than in single primary OSCCs. Depth of invasion was considerably lower in synchronous OSCCs than in single primary OSCCs (synchronous-1: P = .007; synchronous-2: P = .002). Lymph node metastasis (synchronous-1: P = .051; synchronous-2: P = .051) was found to be rare in synchronous OSCCs compared with single primary OSCCs.. Synchronous OSCCs show less aggressive histopathologic features than single primary OSCCs.

Topics: Aged; Carcinoma, Squamous Cell; Case-Control Studies; Cell Differentiation; Female; Gingival Neoplasms; Humans; Keratins; Lip Neoplasms; Lymphatic Metastasis; Male; Middle Aged; Mitosis; Mouth Mucosa; Mouth Neoplasms; Neoplasm Invasiveness; Neoplasms, Multiple Primary; Palatal Neoplasms; Tongue Neoplasms

Invasion is a hallmark of malignancy. The aim of this study was to develop an in vitro model that can be used for experimental studies of cancer cell invasion. The organotypic oral cancer model was constructed by growing oral squamous cell carcinoma (OSCC) cells on a collagen matrix in which normal human fibroblasts were incorporated. Immunohistochemical staining of the model showed that the expression of invasion-related molecules such as phosphorylated extracellular signal-regulated kinases 1 and 2 (p-ERK1/2), cyclooxygenase-2 (COX-2), p75(NTR), and hepatocyte growth factor receptor (Met) was similar to that seen in OSCC. Treatment of the model with cobalt chloride (CoCl(2)) to mimic hypoxic conditions increased cancer cell invasion, defined as the appearance of cancer cell islands protruding into the matrix. Models treated with CoCl(2) showed increased expression of p75(NTR) and laminin-5 in the cancer cells, and a more pronounced fragmentation of collagen IV in the basal membrane area, in contrast to models that were left untreated. The results indicate that the present model is well suited for studies on cancer cell invasion in the matrix and that the addition of CoCl(2) on day 3 of the experiment is indicated because it markedly increases the invasion and improves the model.

Topics: Antigens, CD; Carcinoma, Squamous Cell; Cell Culture Techniques; Cells, Cultured; Cobalt; Collagen; Collagen Type IV; Culture Media; Cyclooxygenase 2; Fibroblasts; Humans; Hypoxia; Keratins; Laminin; Male; Middle Aged; Mitogen-Activated Protein Kinase 1; Mitogen-Activated Protein Kinase 3; Neoplasm Invasiveness; Nerve Tissue Proteins; Proto-Oncogene Proteins c-met; Receptors, Growth Factor; Receptors, Nerve Growth Factor; Tongue Neoplasms; Young Adult

The clinical relevance of the carbohydrate antigen Sialyl Lewis a (SLea) as a serum tumor marker in diagnosis and follow-up treatment is unquestioned in a broad spectra of human carcinomas. Overexpression of this antigen is combined with poor prognosis and malignant relapse. The aim of our study was the systematic investigation of SLea expression in squamous cell carcinoma of the larynx versus normal and phlogistic tissue.. Paraffin-embedded sections of normal, phlogistic and squamous cell carcinoma tissue were incubated with a monoclonal antibody against SLea. The staining reaction was performed using ABC-Peroxidase and DAB. As a positive control tissue of breast cancer was used and the negative control was performed with unspecific mouse IgM. Semiquantitative evaluations were carried out double-blinded by two independent investigators, including a pathologist.. A very faint expression of SLea (Ca19-9) in normal laryngeal tissue, a moderate upregulation in phlogistic tissue and a dramatic upregulation in some types of squamous cell carcinoma of the larynx were observed. Laryngeal cancer is the most common cancer of the upper aerodigestive tract. Most cases of laryngeal cancer are squamous cell carcinoma and can be classified into: well differentiated (more than 75% keratinization), moderately differentiated (25-75% keratinization), and poorly differentiated (<25% keratinisation) carcinomas.. The results of this study indicate that SLea is a potential tumor marker in carcinoma of the larynx.

Topics: Biomarkers, Tumor; CA-19-9 Antigen; Carbohydrates; Carcinoma, Squamous Cell; Gene Expression Regulation, Neoplastic; Humans; Immunohistochemistry; Keratins; Laryngeal Neoplasms; Lewis X Antigen; Sialyl Lewis X Antigen; Up-Regulation

It can be difficult to distinguish between primary and metastatic squamous cell carcinoma (SCC) in the lung. Surgical specimens were obtained from two groups of patients, 26 lung SCC patients without histories of any other cancer (the definite primary group) and 17 patients who had undergone surgical removal of SCC emerging in the lung after surgery for tongue SCC (the unknown group). From the former, 26 primary lung SCC were obtained. From the latter, 17 lung tumors and 15 primary tumors of the tongue were obtained. Eleven of the 17 lung tumors from the unknown group were metastatic lung SCC. All specimens were immunostained with cytokeratin (CK)5/6, CK7, CAM5.2, CK19 and p63 antibodies. The frequency of CAM5.2 and CK19 expression was significantly higher in the lung SCC of the definite primary group (21 of 26, 81% and 20 of 26, 78%, respectively) than in the metastatic lung SCC (1 of 11, 9% (P < 0.001) and 2 of 11, 18% (P = 0.003), respectively) or primary SCC of the tongue (5 of 15, 33% (P = 0.002) and 2 of 15, 13% (P < 0.001), respectively). CAM5.2 and CK19 are useful for distinguishing between primary SCC of the lung and metastases from tongue cancer.

Topics: Adult; Age Factors; Aged; Biomarkers, Tumor; Carcinoma, Squamous Cell; Chi-Square Distribution; Diagnosis, Differential; Female; Humans; Immunohistochemistry; Keratins; Lung Neoplasms; Male; Middle Aged; Tongue Neoplasms

Cervical lymph node (CLN) metastasis from oral cancer correlates with poor prognosis. Therefore, accurate assessment of CLN status is crucial in treatment planning. However, there are few reports focusing on CLN metastasis from tongue cancer. Further, the growth and progress of the tumor are known to be profoundly related to histological malignancy, tumor angiogenesis, and lymphangiogenesis. Thus, this study aimed to identify predictive factors for CLN metastasis in tongue squamous cell carcinoma (SCC). Initial biopsy specimens obtained from 30 patients with tongue SCC were examined to evaluate histological malignancy according to Anneroth's classification. In addition, blood vessel density, lymph vessel density, and lymphatic invasion in the tumor were evaluated immunohistochemically using CD31, CD34, D2-40, and AE1/AE3, and then the relationships of CLN metastasis to these parameters were investigated. Histological malignancy grade, blood vessel density, and lymphatic invasion were significantly related to CLN metastasis (P < 0.05), but there was no relationship between lymph vessel density and CLN metastasis. However, double immunostaining showed that lymphatic invasion by tumor cells was significantly related to CLN metastasis. The results indicate that Anneroth's histological malignancy grade of 16 or more, tumor blood vessel density of more than 37, and the presence of lymphatic invasion by tumor cells can be predictive factors for CLN metastases in tongue SCC.

Topics: Adult; Aged; Aged, 80 and over; Antibodies, Monoclonal; Antibodies, Monoclonal, Murine-Derived; Antigens, CD34; Biomarkers, Tumor; Blood Vessels; Carcinoma, Squamous Cell; Cell Nucleus; Female; Humans; Keratins; Lymphangiogenesis; Lymphatic Metastasis; Lymphatic Vessels; Male; Middle Aged; Mitosis; Neck; Neoplasm Invasiveness; Neoplasm Staging; Neovascularization, Pathologic; Platelet Endothelial Cell Adhesion Molecule-1; Tongue Neoplasms

To study the clinicopathologic characteristics of thymic epithelial tumors and to evaluate the diagnostic reproducibility and clinical relevance of the 2004 WHO histologic classification system.. The morphology and immunophenotype of 52 cases of thymic epithelial tumor were reviewed. The tumors were classified according to the new WHO classification system and the clinical data were analyzed.. Of the 52 cases studied, 45 were thymomas and 7 were thymic carcinomas. Amongst the 45 cases of thymoma, 6 (13.4%) were type A, 15 (33.3%) were type AB, 4 (8.9%) were type B1, 9 (20.0%) were type B2, 9 (20.0%) were type B3 and 2 (4.4%) were metaplastic thymoma. Amongst the 7 cases of thymic carcinoma, 6 were squamous cell carcinomas and 1 was neuroendocrine carcinoma. The commonest presentations were cough and chest pain. Some cases were incidentally discovered by routine physical examination. Thirteen cases (25.0%) of thymoma were associated with myasthenia gravis. CT scan showed that 49 cases (94.2%) were located in the anterior mediastinum. All cases of type A, AB and B1 thymoma and most cases of B2 thymoma appeared as well-defined homogeneous mass, whereas a few cases of type B2 thymoma and most cases of type B3 thymoma and thymic carcinoma were poorly demarcated and heterogeneous. According to Masaoka staging system, 20 cases (41.7%) belonged to stage I, 15 cases (31.3%) stage II, 11 cases (22.9%) stage III and 2 cases (4.1%) stage IV. The histologic subtypes of thymic epithelial tumors significantly correlated with the clinical stages (chi(2) = 32.5, P < 0.01).. The 2004 revision of WHO histologic classification system for thymic epithelial tumors shows a high degree of reproducibility. Correlation with the radiologic, clinical and prognostic parameters is helpful in determining the management strategy for individual patients.

Topics: Adult; Aged; Antibodies, Monoclonal; Antigens, CD20; Carcinoma, Neuroendocrine; Carcinoma, Squamous Cell; CD5 Antigens; Female; Follow-Up Studies; Humans; Keratins; Male; Middle Aged; Myasthenia Gravis; Neoplasm Recurrence, Local; Neoplasm Staging; Prognosis; Radiotherapy, Adjuvant; Retrospective Studies; Thymoma; Thymus Neoplasms; Tomography, X-Ray Computed

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

We report the first case, to our knowledge, of syringocystadenocarcinoma papilliferum with p63-verified squamous differentiation and extensive dermal invasion accompanying in situ components. An 86-year-old woman presented with a neoplasm on the neck, and the intralesional heterogeneity typical of these neoplasms led to an initial diagnosis on needle biopsy favoring squamous cell carcinoma. Excision illustrated diverse morphology, raising a broad differential diagnosis, including more common extracutaneous malignancies, such as breast, gastrointestinal, and ovarian primary tumors. Fortuitous sectioning revealed a focal connection to the skin surface with evidence of apocrine differentiation allowing final diagnosis as syringocystadenocarcinoma papilliferum. Our literature review shows the histologic and immunohistochemical features of syringocystadenocarcinoma papilliferum are not well defined outside of their clear morphologic overlap with syringocystadenoma papilliferum. We describe our findings and diagnostic pitfalls to help pathologists encountering this unusual apocrine neoplasm.

Topics: Aged, 80 and over; Biomarkers, Tumor; Carcinoma, Squamous Cell; Cell Nucleus; Cystadenocarcinoma, Papillary; Diagnosis, Differential; Female; Humans; Keratins; Membrane Proteins; Neoplasm Invasiveness; Neoplasm Recurrence, Local; Sweat Gland Neoplasms; Syringoma

Oral squamous cell carcinoma (SCC) is an aggressive tumor with a poor 5-year survival rate. Oral SCC can undergo epithelial to mesenchymal transition (EMT). We previously showed that the epithelial integrin alphavbeta6 complexes with Fyn kinase in oral SCC to promote EMT. Using immunofluorescence microscopy and Western blotting, we evaluated whether the expression of specific markers of EMT were influenced by modulating serum concentration (ie. growth factors). The SCC cultures were grown under contrasting levels of serum. In low serum (1%), Fyn promoted EMT; whereas suppression of Fyn kinase promoted the epithelial phenotype. However, when the SCC cells were grown in 10% serum, activation of Fyn had the reverse effect. Lastly, cell migration was evaluated under low serum conditions (1% FBS). Activation of Fyn promoted SCC cell migration and its suppression thwarted SCC migration toward FN. These results indicate that the activation of Fyn kinase as well as local growth factor concentration modulate EMT in oral SCC.

Topics: Blotting, Western; Cadherins; Carcinoma, Squamous Cell; Cell Communication; Cell Movement; Culture Media; Enzyme Activation; Epithelial Cells; Humans; Keratins; Mesoderm; Microscopy, Fluorescence; Mouth Neoplasms; Proto-Oncogene Proteins c-fyn; Serum; Signal Transduction

Metastatic Merkel cell carcinoma uncommonly presents with an unidentified primary tumour. We report a patient who first presented with lichenoid dermatitis and was found to have Merkel cell carcinoma involving lymph nodes with an unknown primary site. With the rising incidence of Merkel cell carcinoma, it is important to recognize unusual manifestations of this disease as they may become more common in the future.

Topics: Aged, 80 and over; Carcinoma, Merkel Cell; Carcinoma, Neuroendocrine; Carcinoma, Squamous Cell; CD56 Antigen; Comorbidity; Dermatitis; Fatal Outcome; Humans; Keratins; Lichenoid Eruptions; Lymphatic Metastasis; Male; Neoplasms, Unknown Primary; Phosphopyruvate Hydratase; Skin Neoplasms; Synaptophysin

Topics: Carcinoma, Squamous Cell; Diagnosis, Differential; Female; Gingival Neoplasms; HIV Infections; Humans; Keratins; Mandibular Neoplasms; Middle Aged

The present study aimed to investigate the membrane stabilizing effect of Thymoquinone (TQ) on cell surface glycoconjugates and cytokeratin expression against DMBA induced hamster buccal pouch carcinogenesis. 0.5% DMBA painting (three times per week) in hamster buccal pouches for 14 weeks resulted in the formation of well developed oral squamous cell carcinoma. We observed 100% tumor formation with marked abnormalities of glycoconjugates status in tumor bearing hamsters as compared to control animals. Oral administration of TQ at a dose of 30 mg/kg body weight, to DMBA painted hamsters on alternate days for 14 weeks, reduced the tumor formation as well as protected the levels of cell surface glycoconjugates in DMBA painted hamsters. The present study thus suggests that TQ has potent chemopreventive efficacy as well as protected the abnormalities on cell surface glycoconjugates during DMBA induced hamster buccal pouch carcinogenesis.

Topics: 9,10-Dimethyl-1,2-benzanthracene; Animals; Antineoplastic Agents; Benzoquinones; Carcinogens; Carcinoma, Squamous Cell; Chemoprevention; Cricetinae; Drug Evaluation, Preclinical; Glycoconjugates; Keratins; Male; Membrane Glycoproteins; Mesocricetus; Mouth Neoplasms; Neoplasms, Experimental

DeltaNp63 is an isoform of the p53 homolog p63, which lacks an amino-terminal transactivation domain. The aim of this study was to detect the deltaNp63 expression in the squamous carcinoma component of adenosquamous carcinoma and evaluate its usefulness as a specific squamous carcinoma marker.. Immunohistochemistry was used to analyze the protein expression of deltaNp63 and high molecular weight cytokeratin in paraffin-embedded tumor samples from 17 patients with well-characterized adenosquamous carcinoma.. Of 17 cases, 13 (76.5%) and 14 (82.4%) cases showed positive staining for deltaNp63 and HMWCK in the tumor cells, respectively. It was easy to discriminate the squamous carcinoma and adenocarcinoma components in all tumors. Interestingly, positive expression of deltaNp63 was detected in one case with a negative expression of HMWCK.. These findings indicated that the deltaNp63 status was useful for distinguishing squamous carcinoma from adenocarcinoma in formalin-postfixed adenosquamous carcinoma specimens.

Topics: Aged; Aged, 80 and over; Biomarkers, Tumor; Carcinoma, Adenosquamous; Carcinoma, Non-Small-Cell Lung; Carcinoma, Squamous Cell; Female; Humans; Immunoenzyme Techniques; Keratins; Lung Neoplasms; Male; Middle Aged; Neoplasm Staging; Retrospective Studies; Survival Rate; Trans-Activators; Transcription Factors; Treatment Outcome; Tumor Suppressor Proteins

to present and discuss a high-performance negative depletion method for the isolation of circulating tumor cells (CTCs) in the blood of patients with head and neck cancer and to determine the correlation between the presence of CTCs and early clinical outcome in these patients.. prospective clinical follow-up study of patients with squamous cell carcinoma of the head and neck (SCCHN) undergoing surgical intervention, who had peripheral blood examined for the presence of CTCs.. the study population comprised 48 patients diagnosed as having SCCHN and undergoing surgical intervention.. a negative depletion process to isolate and quantify CTCs from the blood of patients with SCCHN using immunomagnetic separation was developed and validated. Immunostaining for cytokeratin was performed on the enriched samples to determine the number of CTCs extracted from each patient's blood sample. Correlation of the presence of CTCs, tumor stage, nodal status, clinical characteristics, and outcome was made.. disease-free survival.. our initial data, that have a mean follow-up of 19.0 months, suggest that patients with no detectable CTCs per milliliter of blood had a significantly higher probability of disease-free survival (P = .01). There was no correlation between the presence of CTCs with regard to age, sex, tumor site, stage, or nodal involvement.. our enrichment technology, based on the removal of normal cells, has been used on the peripheral blood of patients with head and neck cancer for which follow-up data were collected. If no CTCs were present, a statistically significant improved disease-free survival was observed in SCCHN. A blood test with such a prognostic capability could have important implications in the treatment of patients with head and neck cancer.

Topics: Carcinoma, Squamous Cell; Disease-Free Survival; Female; Follow-Up Studies; Head and Neck Neoplasms; Humans; Immunohistochemistry; Immunomagnetic Separation; Keratins; Male; Middle Aged; Neoplasm Staging; Neoplastic Cells, Circulating; Prognosis; Prospective Studies

Topics: Aged, 80 and over; Antibodies, Monoclonal; Carcinoma, Squamous Cell; Diagnosis, Differential; Granuloma; Humans; Keratins; Male; Mucin-1; Skin Neoplasms

Topics: Carcinoma, Squamous Cell; Female; Follow-Up Studies; Humans; Keratin-7; Keratins; Kidney Neoplasms; Kidney Pelvis; Middle Aged; Mucin-1

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

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

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

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

Snail is a regulator of epithelial-mesenchymal transition (EMT) and considered crucial to carcinoma metastasis, myofibroblast transdifferentiation, and fibroblast activation. To investigate the role of Snail in oral squamous cell carcinoma (OSCC), its immunohistochemical expression was analysed in 129 OSCC samples and correlated to nodal metastasis, histological grade, E-cadherin, and alpha smooth-muscle-actin (alpha SMA). The results were compared to findings in 23 basal cell carcinomas (BCC). Additionally, the influence of TGF beta 1 and EGF on Snail, E-cadherin, vimentin, and alpha SMA expression was analysed in two OSCC cell lines. As a result, Snail-positive cells were mainly found in the stroma of the OSCC invasive front without statistically significant correlation to histological grade or nodal metastasis. Snail was co-localised to alpha SMA but not to E-cadherin or cytokeratin and showed a significant correlation to the loss of membranous E-cadherin. All BCCs were Snail negative. In OSCC culture, the growth-factor-mediated EMT-like phenomenon was accompanied by alpha SMA down-regulation. In summary, Snail expression in OSCC is a stromal phenomenon associated with the myofibroblast phenotype and not related to growth-factor-mediated transdifferentiation of the carcinoma cells themselves. Consequently, Snail immunohistochemistry cannot contribute to the prediction of the metastatic potential. Furthermore, stromal Snail expression is suggested to be the result of mutual paracrine interaction of fibro-/myofibroblasts and dedifferentiated carcinoma cells leading to the generation of a special type of carcinoma-associated fibroblasts.

Topics: Actins; Adult; Aged; Aged, 80 and over; Biomarkers, Tumor; Cadherins; Carcinoma, Squamous Cell; Epidermal Growth Factor; Fibroblasts; Humans; Keratins; Middle Aged; Mouth Neoplasms; Myoblasts; Snail Family Transcription Factors; Transcription Factors; Transforming Growth Factor beta1; Vimentin

The presence of psammoma bodies (PBs) in cervical smears is a rare finding. These structures have been identified in association with a wide range of benign and malignant conditions within the female genital tract. PBs in cervical smears have usually been associated with malignant serous epithelial ovarian tumors. However, many PBs associated with atypical squamous cells were detected in cervical smears of an 83-year-old woman with complaint of postmenopausal bleeding. Colposcopic examination revealed an ulceroinfiltrative growth in the cervix. Histological examination of the biopsy specimen from the growth revealed keratinizing squamous cell carcinoma with multiple and singly arranged PBs. This report suggests that cytologists should aware of the possibilities, on finding PBs associated with atypical cells in cervical specimens and report the cases accordingly.

Topics: Aged, 80 and over; Calcinosis; Carcinoma, Squamous Cell; Female; Humans; Keratins; Uterine Cervical Neoplasms; Vaginal Smears

We aimed at determining whether the expression of protease-activated receptor 2 (PAR-2) is involved in the progression of nasopharyngeal carcinoma (NPC) and correlated with latent membrane protein 1 (LMP-1), matrix metalloproteinases-9 (MMP9), and angiogenesis of tumor. PAR-2, LMP-1, and MMP9 expressions were detected in 57 biopsies of primary NPC by immunohistochemistry. The presence of Epstein-Barr virus (EBV) was determined using EBER in situ hybridization, and intratumoral microvessels were highlighted by staining endothelial cells for anti-CD34. The correlations with immunostainings and clinicopathological factors, as well as the follow-up data of patients, were analyzed statistically. Strong expression of PAR-2 in 61.4% (35/57) of the biopsies was correlated with extensive lymph node metastasis and advanced stage of NPC. The patients with PAR-2/LMP-1 or PAR-2/MMP9 dual high-expression tumors had a significant worse prognosis than those with single protein high expression and dual low or negative expression tumors (P=0.013 and 0.004, respectively). Angiogenesis in the tumor is related to overall survival of NPC patients (P=0.001), and exhibits strong PAR-2 expression or LMP-1 expression in tumors associated with increased intratumoral microvessel density (P=0.026 and 0.006, respectively). PAR-2 is a possible mediator cooperating with LMP-1 and MMP9 to influence the progression of NPC by inducing angiogenesis and promoting lymph node metastasis.

Topics: Adaptor Proteins, Signal Transducing; Adult; Aged; Biomarkers, Tumor; Carcinoma, Squamous Cell; China; Cytoskeletal Proteins; Female; Herpesvirus 4, Human; Humans; In Situ Hybridization; Intracellular Signaling Peptides and Proteins; Keratins; LIM Domain Proteins; Lymph Nodes; Lymphatic Metastasis; Male; Matrix Metalloproteinase 9; Middle Aged; Nasopharyngeal Neoplasms; Neovascularization, Pathologic; Prognosis; Receptor, PAR-2; Ribosomal Proteins; RNA-Binding Proteins; Survival Rate; Young Adult

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

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

Pathologists having drawn attention to the morphological and functional characteristics of invasive tumor front (ITF), we attempted to investigate the difference of E-cadherin expression between the ITF and center/superficial part as well as the prognostic value of E-cadherin expression at the ITF.. We performed a retrospective analysis of the correlation between E-cadherin protein expression at the ITF and center/superficial part and prognostic factors. We also detected the difference of E-cadherin expression at the ITF and center/superficial part using immunohistochemical method, which was further supported in 20 fresh OSCC samples by confocal laser microscopy and RT-PCR methods.. The expression of E-cadherin in the same tumor was heterogeneous. Both protein (t test, P

Topics: Adult; Aged; Aged, 80 and over; Cadherins; Carcinoma, Squamous Cell; Cell Nucleus; Female; Fluorescent Antibody Technique; Humans; Immunohistochemistry; Keratins; Male; Microscopy, Confocal; Middle Aged; Mouth Neoplasms; Neoplasm Invasiveness; Prognosis; Proportional Hazards Models; Retrospective Studies; Reverse Transcriptase Polymerase Chain Reaction; Young Adult

In this study, we evaluated whether the forced expression of beta6 integrin would modulate the epithelial to mesenchymal transition (EMT). When the full length beta6 integrin was expressed in poorly invasive squamous cell carcinoma SCC9 cells, the resulting SCC9/6 cells acquired a fibroblast-like morphology, increased expression of the mesenchymal marker vimentin and reduced expression of the epithelial markers keratin and E-cadherin. SCC9beta6D1 cells, which express a truncated form of beta6 subunit lacking the C-terminal 11 amino acids (AA), retained their epithelial morphology and did not alter vimentin or E-cadherin expression. This suggests that the full-length beta6 subunit can induce EMT in oral SCC cells. We previously showed that expression of beta6 increases both MMP-3 activation and tenascin-C expression and we now show that both molecules are MEK dependent. These results also demonstrate that the terminal 11 AA of beta6 contain information important for establishing an epithelial to mesenchymal transition.

Topics: Antigens, Neoplasm; Cadherins; Carcinoma, Squamous Cell; Cell Line, Tumor; Enzyme Activation; Epithelial Cells; Humans; Integrins; Keratins; MAP Kinase Kinase Kinases; Matrix Metalloproteinase 3; Matrix Metalloproteinase Inhibitors; Mesoderm; Mouth Neoplasms; Tenascin; Vimentin

We investigated p16(INK4A) expression in branchial cleft cysts and its utility in distinguishing branchial cleft cysts from metastatic head and neck squamous cell carcinomas (SCCs) in fine-needle aspiration biopsies (FNABs).. A study set comprising 41 resections (15 SCC and 26 branchial cleft cysts) and a test set of 15 FNABs (11 SCC and 4 branchial cleft cysts) were analyzed with p16(INK4A) immunohistochemistry and human papillomavirus (HPV) polymerase chain reaction (PCR)/pyrosequencing. Cases with discrepant p16(INK4A) and PCR/pyrosequencing results were further evaluated with HPV in situ hybridization (ISH). SCCs were divided into keratinizing SCC and nonkeratinizing SCC groups and site of origin.. Metastatic oropharyngeal nonkeratinizing SCC in the study set exhibited diffuse, strong p16(INK4A) (7 of 7) and HPV16 DNA positivity (6 of 6), while keratinizing SCC from the larynx and oral cavity was negative for p16(INK4A). p16(INK4A) reactivity in the branchial cleft cyst study set was characterized by focal, strong staining (6 of 21) involving the superficial squamous epithelium. HPV DNA was identified in 7 of 19 branchial cleft cyst study set cases by PCR/pyrosequencing, but these cases were negative by HPV ISH. In the test set, oropharyngeal nonkeratinizing SCC exhibited diffuse, strong p16(INK4A) (3 of 3) and HPV16 DNA (2 of 2), while metastatic keratinizing SCC was negative for p16(INK4A) and HPV DNA. All 4 FNABs of branchial cleft cysts were negative for p16(INK4A). Diffuse, strong p16(INK4A) correlated with oropharyngeal origin (P=.001) and nonkeratinizing morphology (P=.0001).. Branchial cleft cysts can exhibit focal strong reactivity limited to the superficial squamous epithelium and glandular epithelium. Although p16(INK4A) immunohistochemistry may be helpful in distinguishing oropharyngeal nonkeratinizing SCC from branchial cleft cysts in FNAB specimens, it is not helpful in cases of keratinizing SCC because these cases are typically negative for p16(INK4A).

Topics: Adolescent; Aged; Biopsy, Fine-Needle; Branchioma; Carcinoma, Squamous Cell; Cyclin-Dependent Kinase Inhibitor p16; Cysts; Diagnosis, Differential; Female; Head and Neck Neoplasms; Humans; Immunohistochemistry; Keratins; Male; Middle Aged; Oropharynx

Esophageal cancer is a frequently fatal malignancy, and is described in certain regions in Northeast India with an incidence of esophageal squamous cell carcinoma many fold higher than the rest of the population. The population in Northeast India is at higher risk due to poor nutritional status, consumption of fermented betel quid and other oral tobacco products besides smoking and alcohol intake. Cytokeratins (CKs) are the major constituents of the esophageal epithelium and may show gain or loss of CKs as the cancer progresses from normal epithelium to invasive phenotype. In this study, we studied the immunohistochemical expression of 5 CKs (CK4, CK5, CK8, CK14, and CK17) in the normal esophageal epithelium and esophageal squamous cell carcinoma from both the general population and the high-risk population of Assam in Northeast India. The CK expression profile was similar to other published data in general. Further analysis demonstrated differences in CK expression between the general and the high-risk tumor samples. CK5 and CK8 expression was altered in the high-risk population. The significance of these differences is unclear, but suggests a connection to the etiologic factors.

Topics: Carcinoma, Squamous Cell; Esophageal Neoplasms; Humans; Immunohistochemistry; India; Keratins; Risk Factors; Tissue Array Analysis

Dense inflammation can obscure nonmelanoma skin cancer (NMSC) on frozen sections, prompting removal of additional layers to ensure negative margins. Cytokeratin (CK) immunostaining in Mohs micrographic surgery (MMS) has been examined and found to be useful but is limited by lengthy 1-hour processing.. Our objective was to develop an effective ultrarapid CK frozen section immunostain to be used during MMS in cases of NMSC with dense or perineural inflammation.. An ultrarapid immunostain with a mixture of AE1/AE3 monoclonal antibodies was performed in 21 MMS cases and compared with permanent sections prepared from the same material.. The ultrarapid CK protocol stained all of the cells in each of the 21 examples of basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) in frozen tissue in a way equivalent to immunostains being applied to permanent sections.. The 19-minute CK immunohistochemistry protocol in frozen tissue appears to be as effective at labeling tumor cells of SCC and BCC as methods requiring permanent sections. It is hopeful that this technique may prevent recurrences after MMS and limit the number of Mohs layers required to obtain free margins when inflammation is abundant. It also is effective in uncovering subtle perineural invasion.

Topics: Aged, 80 and over; Antibodies, Monoclonal; Antigens, Neoplasm; Carcinoma, Basal Cell; Carcinoma, Squamous Cell; Frozen Sections; Humans; Immunohistochemistry; Keratins; Male; Mohs Surgery; Skin Neoplasms; Staining and Labeling; Time Factors

Atypical fibroxanthoma (AFX), spindle cell squamous cell carcinoma (SCSCC) and spindle cell melanoma are the primary entities in the differential diagnosis of a cytologically atypical spindle cell tumor arising on sun-damaged skin. AFX is generally regarded as a diagnosis of exclusion in this context: in the absence of S100 or keratin reactivity, a diagnosis of AFX is favored. However, keratin reactivity may be focal or even absent in SCSCC, and although numerous positive markers of AFX have been proposed, none has shown sufficient sensitivity and specificity for routine diagnostic use. We evaluated 20 AFX and 10 SCSCC with a panel of cytokeratins and p63 to assess the utility of the latter antibody in this differential diagnosis. All 10 SCSCC showed strong expression of p63, whereas all 20 AFX were p63 negative. Two additional cases (excluded from the study) were negative for keratins and S100 on initial shave biopsies, resulting in a favored diagnosis of AFX, but p63 stains performed retrospectively were positive. However, review of the excision specimens in both cases revealed deep subcutaneous extension, excluding AFX. p63 reactivity argues against the diagnosis of AFX and is therefore a useful addition to the standard immunohistochemical panel for cutaneous spindle cell neoplasms.

Topics: Aged; Aged, 80 and over; Biomarkers, Tumor; Carcinoma, Squamous Cell; Diagnosis, Differential; Female; Histiocytoma, Benign Fibrous; Humans; Immunohistochemistry; Keratins; Male; Membrane Proteins; Middle Aged; S100 Proteins; Skin Neoplasms

Topics: Carcinoma, Adenosquamous; Carcinoma, Squamous Cell; Diagnosis, Differential; Humans; Jejunal Neoplasms; Jejunum; Keratins; Male; Middle Aged

A case of orbital metastasis of cervical keratinizing squamous cell carcinoma is presented. The patient, in remission from primary cervical and ovarian cancers, presented with complaints of left eye ptosis and pain. Examination revealed the presence of a moderately tender mass along the left supra-temporal orbital rim and downward displacement of the left globe. Computed tomography revealed a poorly circumscribed mass with superior lateral wall bone loss. Excised tissue contained invasive, poorly differentiated nests of pan keratin and epithelial membrane antigen-positive squamous cells with numerous pleomorphic multinucleated giant cells. Multiple treatment regimes were unsuccessful, and the patient expired due to disease complications after 3 months.

Topics: Adult; Carcinoma, Squamous Cell; Fatal Outcome; Female; Giant Cells; Humans; Immunoenzyme Techniques; Keratins; Neoplasm Staging; Orbital Neoplasms; Tomography, X-Ray Computed; Uterine Cervical Neoplasms

Atypical fibroxanthoma (AFX) (dermal pleomorphic sarcoma) remains a somewhat controversial entity. Some authors have averred that AFX is a fiction, suggesting that such lesions merely represent misclassified examples of spindled squamous cell carcinoma. In addition, the immunoperoxidase confirmation of AFX has been less than straightforward and has historically been approached as a diagnosis of exclusion because of the lack of sensitivity and specificity of available "positive" reagents. Procollagen 1 (PC1) and CD10 represent recently developed immunoperoxidase reagents that have been forwarded as useful in this setting, and we sought to characterize our experience, both to confirm the utility of these antibodies and to compare them. Our investigation included 3 separate data sets. Group 1 consisted of a retrospective review of 98 consecutive cases in which PC1 was used in the evaluation of dermatopathology specimens in routine practice during a 13-month interval. Group 2 consisted of a direct comparison of 11 AFX, 11 dermatofibroma (DF), and 7 epithelioid dermatofibroma (EDF) using the CD10 reagent on cases identified by database search. Group 3 consisted of a retrospective review of 47 cases in which CD10 was used in routine practice during a 10-month interval. Group 1 included 47 AFX, 13 carcinomas, and 6 melanomas. PC1 expression was observed in 45 of 47 AFX (96%), with a strong reaction in 78% of cases. Among a comparison group of carcinomas, 13 of 13 displayed strong keratin immunopositivity and 11 of 13 (85%) lacked PC1 expression whereas 2 showed focal weak labeling. Six of six melanomas exhibited avid S100 expression and none labeled with PC1. In group 2, strong CD10 immunoreactivity was present in 11 of 11 AFX. Similarly, 11 of 11 DFs were also positive. In contrast, 6 of 7 cases of EDF lacked CD10 expression. Group 3 included 38 AFX and 9 miscellaneous spindle cell proliferations. Of the 38 AFX, 37 (97%) labeled with CD10 and in 34 (92%) the reaction was strong. PC1 immunostaining was also completed in 34 of 38 AFX from group 3 and 27 (79%) cases showed positive labeling. Our results confirm that both PC1 and CD10 can be used as positive markers of AFX. We believe that CD10 and PC1 immunostaining can be used as a useful adjunct to supplement the diagnosis of AFX, within the context of an immunoperoxidase panel. Not surprisingly, CD10 expression is also common in DF, a benign analog of AFX, with the exception of its epithelioid variant. In direc

Topics: Adult; Aged; Aged, 80 and over; Carcinoma, Basal Cell; Carcinoma, Squamous Cell; Collagen Type I; Diagnosis, Differential; Epithelioid Cells; Female; Histiocytoma, Benign Fibrous; Humans; Immunohistochemistry; Keratins; Male; Melanoma; Middle Aged; Neprilysin; Predictive Value of Tests; Procollagen; Reproducibility of Results; Retrospective Studies; S100 Proteins; Sarcoma; Skin Neoplasms; Xanthomatosis

To investigate the relationship among nuclear DNA content, nuclear morphology, clinical response, and radiosensitivity in nasopharyngeal carcinoma (NPC) and the suitability of image cytometric analysis of DNA content and nuclear morphology for predicting radiosensitivity of NPC prior to radiotherapy.. Nuclear DNA content and morphology features were detected by image cytometric analysis in 51 biopsy specimens of NPC prior to radiotherapy. The radiotherapeutic effect experienced by the NPC patients was classified as CR (complete response [i.e., complete tumor disappearance]) and PR (partial response [i.e., residual tumor]) according to pathologic analysis of tumor specimens after completion of the scheduled treatment.. The mean DNA index; the percentage of cells with the DNA pattern of 2C, 5C, aneuploidy respectively; the mean nuclear area; the mean nuclear perimeter and the mean nuclear diameter in the CR group were significantly higher than they were in the PR group.. DNA content and nuclear morphometry by image cytometric analysis were significantly correlated with patient outcome and radiosensitivity of NPC. Other measurements of more biomarkers for predicting the radiosensitivity of NPC await further study.

Topics: Adult; Aged; Carcinoma, Squamous Cell; Cell Nucleus; DNA, Neoplasm; Female; Humans; Image Processing, Computer-Assisted; Keratins; Male; Middle Aged; Nasopharyngeal Neoplasms; Neoplasm Staging; Remission Induction; Treatment Outcome

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

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

Squamous cell carcinoma (SCC) and basal cell carcinoma (BCC) represent the 2 most common types of nonmelanoma skin cancer. Both derive from keratinocytes but show a distinct biological behavior. Here we present transcriptional profiling data of a large cohort of tumor patients (SCC, n = 42; BCC, n = 114). Differentially expressed genes reflect known features of SCC and BCC including the typical cytokeratin pattern as well as upregulation of characteristic cell proliferation genes. Additionally, we found increased expression of interferon (IFN)-regulated genes (including IFI27, IFI30, Mx1, IRF1 and CXCL9) in SCC, and to a lower extent in BCC. The expression of IFN-regulated genes correlated with the extent of the lesional immune-cell infiltrate. Immunohistological examinations confirmed the expression of IFN-regulated genes in association with a CXCR3+ cytotoxic inflammatory infiltrate on the protein level. Of note, a small subset of SCC samples with low expression of IFN-regulated genes included most organ transplant recipients receiving immunosuppressive medication. Collectively, our findings support the concept that IFN-associated host responses play an important role in tumor immunosurveillance in the skin.

Topics: Aged; Aged, 80 and over; Carcinoma, Squamous Cell; Cell Differentiation; Cell Proliferation; Female; Gene Expression Profiling; Gene Expression Regulation, Neoplastic; Humans; Immunohistochemistry; Interferons; Keratins; Male; Middle Aged; Neoplasm Invasiveness; Neoplasms, Basal Cell; Skin Neoplasms; Transcription, Genetic

At later stages of tumor progression, epithelial carcinogenesis is associated with transition to a mesenchymal phenotype, which may contribute to the more aggressive properties of cancer cells and may be stimulated by growth factors such as epidermal growth factor and transforming growth factor-beta. Previously, we found that cells derived from a nodal metastatic squamous cell carcinoma are highly proliferative and motile in vitro and tumorigenic in vivo. In the current study, we have investigated the role of vimentin in proliferation and motility. Cells derived from nodal metastasis express high levels of vimentin, which is undetectable in tumor cells derived from a synchronous primary lesion of tongue. Vimentin expression was enhanced by epidermal growth factor and transforming growth factor-beta both independently and in combination. Use of RNA interference resulted in the generation of stable cell lines that express constitutively low levels of vimentin. RNA interference-mediated vimentin knockdown reduced cellular proliferation, migration, and invasion through a basement membrane substitute by 3-fold compared with nontargeting controls. In addition, cells with reduced vimentin reexpressed differentiation-specific keratins K13, K14, and K15 as a result of increased gene transcription as judged by quantitative PCR and promoter-reporter assays. Furthermore, cells in which vimentin expression was reduced showed a greatly decreased tumorigenic potential, as tumors developing from these cells were 70% smaller than those from control cells. The data suggest that reversal of the mesenchymal phenotype by inhibiting vimentin expression results in reexpression of epithelial characteristics and reduced tumor aggressiveness.

Topics: Animals; Carcinoma, Squamous Cell; Cell Differentiation; Cell Line, Tumor; Cell Movement; Cell Proliferation; Down-Regulation; Gene Expression Regulation, Neoplastic; Head and Neck Neoplasms; Humans; Intercellular Signaling Peptides and Proteins; Keratins; Mice; Mice, Nude; Neoplasm Metastasis; RNA Interference; RNA, Messenger; RNA, Small Interfering; Vimentin

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

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

This study was undertaken in order to evaluate histopathological and immunohistochemical (cytokeratins AE1/AE3) characteristics of parametrial invasion in patients with early stage cervical cancer.. Thirty patients with stage IB squamous cell carcinoma (SCC) of the cervix submitted to radical hysterectomy from November 2001 to September 2002 were prospectively studied. Histopathological studies were undertaken using tissue samples (n=60) taken from the parametrium, whose surgical margins were inked and the entire parametrial tissue was fixed in 10% buffered formalin and embedded in paraffin for further analysis using hematoxylin-eosin (H&E) staining. Specific patterns of parametrial involvement (continuous invasion, parametrial lymphatic vascular space invasion (LVSI) and/or parametrial lymph nodes' (PMLN) metastasis) were recorded. Parametrial samples, in which the histological examination showed no tumor involvement, were immunohistochemically assessed through monoclonal antibodies for cytokeratins AE1/AE3. Clinicopathological characteristics of the patients were also recorded.. Patient's mean age was 49+/-10 years (27-73 years). Histopathological analysis (H&E) showed parametrium involvement in 12 patients (40%) of whom 11 (92%) presented parametrial LVSI, 9 (75%) continuous invasion and 4 (33%) PMLN metastasis. Micrometastasis was detected in 3/18 (17%) of the patients with histologically negative parametrium by H&E evaluation. Parametrial involvement detected by H&E was associated with tumor recurrence (p=0.009) and survival (p=0.025). This association was not correlated with the presence of parametrial micrometastasis (p=1.00 and 1.00, respectively).. The process of parametrial spreading in patients with SCC of the cervix may develop several histopathological patterns, which are associated with clinicopathological features and prognosis. Our findings highlight the importance to ink the parametria, which is the only way to define the pattern of tumor spreading. The clinical significance of micrometastasis, detected in patients with histologically negative parametrium by H&E, remains to be clear.

Topics: Adult; Carcinoma, Squamous Cell; Connective Tissue; Female; Humans; Keratins; Middle Aged; Pelvic Floor; Pelvic Neoplasms; Prospective Studies; Sentinel Lymph Node Biopsy; Survival Analysis; Uterine Cervical Neoplasms

Squamous cell carcinoma of the mammary gland is rare in both veterinary and human medicine. Whereas human metaplastic and squamous variants are known, the objectives of the current study were to ascertain the presence of such entities in canine mammary tumors and to distinguish them from other (epidermal, sweat gland) squamous tumors that may develop in the same area. A panel of antibodies (anti-cytokeratin [CK] 19, CK 14, CK 5/6, pancytokeratin, and vimentin) was used on 18 mammary gland malignancies with squamous features and 16 malignant skin tumors (11 squamous cell carcinomas of the skin and 5 sweat glands). Fifteen of the 18 mammary carcinomas were classified as metaplastic carcinomas, and the remaining 3 were classified as squamous cell carcinomas. The 2 most useful markers to establish the histogenesis of mammary tumors were pancytokeratin and CK 19. All other antibodies were equally expressed (CK 14 and 5/6) in all histotypes. The antibody panel discriminated primary epidermal squamous tumors (pancytokeratin positive and CK 19 negative) from gland-derived squamous neoplasms (pancytokeratin positive and CK 19 positive) but failed to distinguish primary mammary tumors from other squamous tumors of glandular origin.

Topics: Animals; Carcinoma, Squamous Cell; Dog Diseases; Dogs; Keratins; Mammary Glands, Animal; Neoplasm Proteins; Neoplasms; Skin Neoplasms; Vimentin

To investigate the clinical application value of serum tumor markers detection combined with support vector machine (SVM) model in the diagnosis of oral squamous cell carcinoma.. Serum levels of neuron-specific enolase (NSE), cancer antigen 242 (CA242), cancer antigen 19-9 (CA199), carcinoembryonic antigen (CEA), tissue polypeptide antigen (TPA), cancer antigen 72-4 (CA724), cancer antigen 21-1 (CA211) and alpha fetoprotein (AFP) were detected with enzyme-linked immunosorbent assay (ELISA) and time-resolved fluoroimmunoassay (TRFIA) in 163 oral squamous cell carcinoma patients and 160 healthy persons. All the data was analyzed with SVM; the SVM models for diagnosis of oral squamous cell carcinoma were created, trained and validated by cross validation.. Among the 163 oral squamous cell carcinoma patients, there were 128 males and 35 females with the male-to-female ratio of 3.66:1; the age ranged from 30 to 85 years old with a mean age of 59.3 years old; according to the primary site of tumor, 72 cases in tongue, 34 in gingiva, 22 in buccal mucosa, 15 in palatal mucosa, 13 in floor of mouth, 4 in lip and 3 in retromolar region; according to the TNM-UICC classification, there were 33 patients at stage T1, 72 at T2, 44 at T3, 14 at T4, 119 at N0, 42 at N1, 2 at N2, 159 at M0, 4 at M1, 27 at clinical stage I, 51 at stage II, 52 at III, and 33 at IV; according to the pathological differentiation grade, 109 tumors were well differentiated, 42 were moderately differentiated and 12 were poorly differentiated. Five serum tumor markers of CA211, CA199, TPA, CA724 and NSE were selected optimally to create the optimal SVM model for diagnosis of oral squamous cell carcinoma. The accuracy, specificity, sensitivity and positive predictive value of the optimal SVM model were 88.54%, 93.13%, 84.05% and 92.57%, respectively.. From the results, SVM model combined with 5 optimal serum tumor markers is suggested to be used in the diagnosis of oral squamous cell carcinoma. Supported by Shanghai Leading Academic Discipline Project (Grant No.Y0203).

Topics: Adult; Aged; Aged, 80 and over; Antigens, Tumor-Associated, Carbohydrate; Biomarkers, Tumor; Carcinoembryonic Antigen; Carcinoma, Squamous Cell; Female; Humans; Keratins; Lung Neoplasms; Male; Middle Aged; Mouth Neoplasms; Phosphopyruvate Hydratase; Sensitivity and Specificity; Support Vector Machine

Lymphatic metastasis has always been regarded as a major prognostic indicator for disease progression and as a guide for therapeutic strategies to oral squamous cell carcinoma (OSCC), but to date, how tumor cells access and spread via the lymphatics have not been fully elucidated. Whether tumor cells metastasize by expansion and invasion of pre-existing peritumoral lymphatics or by the induction and invasion of newly formed lymphatics within tumors is controversial. In order to address this issue and find out the clinicopathological significance of intratumoral lymphangiogenesis, we investigated 86 archival specimens from patients with OSCC, quantitating lymph vessels by immunostaining with D2-40. We also quantified lymphatic invasion and examined the possible associations of all the above parameters with clinicopathological features and outcome. Higher intratumoral lymphatic density (ILD) and peritumoral lymphatic density (PLD) were both significantly associated with the presence of lymph node metastasis at the time of diagnosis and the outcome of the post-operation biopsy of 77 patients (P = 0.001). Higher ILD was significantly associated with a higher incidence of intratumoral lymphatic invasion, peritumoral lymphatic invasion and recurrence of tumor (P = 0.001 and P = 0.041 and P = 0.001, respectively). Patients with higher ILD exhibited shorter 5-year cumulative and disease-free survival (P = 0.001). Thus, lymphangiogenesis indeed occurs in oral squamous cell carcinoma; ILD might be used as an index to inflect the aggression of the disease, to evaluate the status of lymphatic metastasis, to separate patients at higher risk of an adverse clinical outcome.

Topics: Antibodies, Monoclonal; Antibodies, Monoclonal, Murine-Derived; Biomarkers, Tumor; Carcinoma, Squamous Cell; Disease-Free Survival; Endothelium, Lymphatic; Female; Humans; Immunohistochemistry; Kaplan-Meier Estimate; Keratins; Lymphangiogenesis; Lymphatic Metastasis; Male; Mouth Neoplasms; Neoplasm Invasiveness; Neoplasm Recurrence, Local; Neoplasm Staging; Prognosis; Proportional Hazards Models

Keratoacanthoma (KA) is a common keratinizing squamous cell neoplasm of unknown origin characterized by rapid growth and spontaneous involution. Trauma-induced forms have been observed with various types of skin injury. To our knowledge, reports of KA arising at tattoo sites are scarce in the literature. A 41-year-old woman with no medical history presented for a rapidly growing nodule confined to the red part of a tattoo located on the scapula. Histology showed a keratin-filled cuplike crater with an epithelial proliferation (hyperkeratosis, parakeratosis, no keratinocyte atypia). An inflammatory infiltrate in the dermis composed of lymphocytes and histiocytes intermixed with red ink-related exogenous pigments was noted. Lack of papillomatosis and viral inclusions ruled out the diagnosis of viral wart, absence of granulomatous reaction ruled out deep fungal or mycobacterial infection and lack of cytological atypia and frank architectural abnormalities did not favour a squamous cell carcinoma. KA should be included in the list of cutaneous complications related to tattooing. Diagnosis can be challenging as differential diagnoses include pseudoepitheliomatous hyperplasia and squamous cell carcinoma. Removal of the entire area, thorough histological examination and careful follow up are mandatory.

Topics: Adult; Carcinoma, Squamous Cell; Coloring Agents; Diagnosis, Differential; Female; Histiocytes; Humans; Keratinocytes; Keratins; Keratoacanthoma; Lymphocytes; Skin Diseases; Skin Neoplasms; Tattooing

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

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

The distinction between ocular sebaceous carcinoma, poorly differentiated ocular squamous cell carcinoma and ocular basal cell carcinoma can be challenging. An appropriate immunohistochemical panel may help to differentiate these lesions.. To determine the distribution and use of several immunostains in these specimens, formalin-fixed, paraffin-embedded tissue from several of each was studied using an immunohistochemical technique.. Positive staining for cytokeratin (CK)7 was seen in 100% of sebaceous carcinomas, 77.8% of basal cell carcinomas and 67.7% of squamous cell carcinomas. One hundred percent of sebaceous and basal cell carcinomas were positive for cytokeratin CAM 5.2, while only 83.3% of squamous cell carcinomas were positive. Using epithelial membrane antigen (EMA), 100% of squamous cell carcinomas and 80% of sebaceous carcinomas were positive, while basal cell carcinomas were uniformly negative. One hundred percent of basal cell carcinomas and 80% of sebaceous carcinomas were positive for Ber-EP4, while all squamous cell carcinomas were negative. Finally, 77.8%, 20% and 16.7% of basal cell carcinomas, sebaceous carcinomas and squamous cell carcinomas showed immunoreactivity for the androgen receptor.. An EMA positive, Ber-EP4 positive immunophenotype supports sebaceous carcinoma, EMA positive, Ber-EP4 negative result supports squamous cell carcinoma and an EMA negative, Ber-EP4 positive result supports basal cell carcinoma.

Topics: Adenocarcinoma, Sebaceous; Biomarkers; Biomarkers, Tumor; Carcinoma, Basal Cell; Carcinoma, Squamous Cell; Diagnosis, Differential; Eye Neoplasms; Humans; Immunohistochemistry; Keratin-7; Keratins; Mucin-1; Receptors, Androgen; Sebaceous Gland Neoplasms; Skin

Oral submucous fibrosis (OSF) is characterized by abnormal collagen metabolism in the submucosal connective tissue. Its influence on the overlying epithelium is not known but about 14% of OSF cases undergo malignant transformation to squamous cell carcinoma indicating association with abnormality of the epithelium. Here, we have defined the keratin expression profile, by immunohistochemistry and quantitative image analysis, using a panel of 22 anti-keratin monoclonal antibodies on 28 OSF samples. We observed an increase of K1 and K10 in the suprabasal layers, induction of K6 in the basal layer and complete loss of K19 in the epithelium. Furthermore, there was increased K17 expression in the suprabasal layers, which correlated with disease severity. In a subset of the most severe OSF cases (14%), K17 expression was completely lost in the basal layer which might define them to be at most risk to undergo malignant transformation. There was no detectable expression of K8, K18, K7 and K9 and the expression of K4, K13, K14, K15 and K16 did not change in OSF. We propose that the altered keratin profiles could be useful as histological diagnostic markers and provide important insights into the pathogenesis of the disease and its predisposition to malignancy.

Topics: Biomarkers; Carcinoma, Squamous Cell; Case-Control Studies; Cell Transformation, Neoplastic; Gene Expression; Humans; Immunohistochemistry; Keratin-17; Keratinocytes; Keratins; Mouth Neoplasms; Oral Submucous Fibrosis; Phenotype; Photography, Dental; Precancerous Conditions; Severity of Illness Index

In general, it has been stated that keratin (K) molecules are glycosylated. During biochemical studies of K subunits, we encountered a glycoprotein that does not judge K subunits.. This study was intended to elucidate how the above glycoprotein co-exists in the K fraction prepared from ISO-HAS (cultured angiosarcoma cell line).. We analyzed and sequenced a remarkable spot, which was shown as a glycoprotein by periodic acid Sciff's (PAS) staining, in the K fraction prepared from ISO-HAS.. The glycoprotein was identified as an N-terminal amino acid sequence covering 10 residues of the spot. A homology search showed that it was identical to that of Hsp47 (matured type), except for one amino acid (seventh amino acid: Val 7 Leu). Similar results were confirmed for four other tumorigenic cell line types. Subsequent PAS staining using the same samples after 2D-PAGE revealed no glycosylated Ks.. No glycosylated Ks were found by PAS staining in the K fraction prepared from four tumorigenic cell line types. During K preparation from cultured human tumor cell lines, Hsps might be associated with K expression in tumor cells.

Topics: Amino Acid Sequence; Amino Acid Substitution; Carcinoma, Squamous Cell; Cell Line, Transformed; Fibrosarcoma; Gene Expression Regulation, Neoplastic; Glycosylation; HeLa Cells; Hemangiosarcoma; HSP47 Heat-Shock Proteins; Humans; Keratinocytes; Keratins; Melanoma; Molecular Sequence Data; Periodic Acid-Schiff Reaction; Skin Neoplasms

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

Numerous variants of squamous cell carcinoma (SCC) have been described. We recently encountered four examples of SCC composed primarily of single, atypical cells that were cytokeratin (CK) MNF116-positive and p63-positive. One case was particularly difficult to diagnose as the single cells were obscured by a dense inflammatory infiltrate. We have also noted similar single cell infiltration toward the periphery of four additional cases of more typical SCC. These foci resemble the single tumor cells that may infiltrate at the borders of spindle cell and desmoplastic SCCs. CK MNF116 and p63 were useful in identifying each of these neoplasms. This single--cell pattern of SCC can easily be misdiagnosed, and CK MNF116 and/or p63 are diagnostically helpful in recognizing it.

Topics: Aged; Aged, 80 and over; Biomarkers, Tumor; Carcinoma, Squamous Cell; Female; Humans; Immunohistochemistry; Keratins; Male; Membrane Proteins; Middle Aged; Mohs Surgery; Neoplasm Invasiveness; Skin Neoplasms

The patient was a 63-year-old man who consulted our hospital with complaints of a cough and breathing difficulties. His chest CT revealed a 25-mm mass in his right S1 hilar area with spiculation, disseminated nodule in right lung, and pericardial effusions. Also, bronchoscope and TBLB revealed squamous cell carcinoma. This patient was diagnosed as lung cancer (cT4N3M1, stage IV), and chemotherapy was initiated. The chemotherapy was given in the order of CBDCA (AUC3) +GEM (1,000 mg/m(2)), DOC (60 mg/m(2)), and VNR (25 mg/m(2)), and the tumor response was PD. S- 1 (120 mg/body/day, continuous administration for 2 weeks followed by 1 week of rest) was chosen as fourth-line treatment, and a breast CT detected tumor size reduction following completion of the first course. However, after completion of three courses, the breast CT found tumor-enlargement again. Then the chemotherapy was changed to amrubicin (35 mg/m(2)), but the treatment was discontinued due to skin rash. We once experienced a size reduction with S-1, so S-1 (100 mg/body/day, day 1-14) plus CPT-11 (60 mg/m(2), day 1, 7, 14) combination chemotherapy was conducted at 4-week intervals. After two courses were completed, tumor size reduction was observed by breast XP and CT. The response rate was 40.0%. Currently, seven courses were completed, and we will continue this treatment due to the tumor response of SD. The S-1 single treatment and S-1+CPT-11 combination chemotherapy showed efficacy for this difficult case of NSCLC with refractoriness to multiple cancer drug chemotherapy. This combination treatment should be investigated further for its therapeutic benefit.

Topics: Antigens, Neoplasm; Antineoplastic Combined Chemotherapy Protocols; Biomarkers, Tumor; Camptothecin; Carcinoma, Squamous Cell; Drug Combinations; Drug Resistance, Neoplasm; Humans; Irinotecan; Keratin-19; Keratins; Lung Neoplasms; Male; Middle Aged; Oxonic Acid; Tegafur; Tomography, X-Ray Computed

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

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

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

We aimed to investigate whether pretreatment serum levels of squamous cell carcinoma (SCC) antigen (SCC-Ag), cytokeratin 19 (CYFRA 21-1) and two mucins (CA 15-3 and CA 125) identify patients with occult disease in early-stage SCC of the cervix. Therefore, pretreatment serum samples were obtained from 78 patients with SCC of the cervix (52 IB, 9 IIA and 18 IIB), and tumor markers were measured with commercial immunoassays. SCC-Ag, CYFRA 21-1 and CA 15-3 (analyzed as continuous variables) were significantly associated with overall (OS) and disease-free survival (DFS) in univariate analysis (p < 0.001 in all cases). Multivariate analysis identified lymph node status as the strongest predictor for OS and DFS (p < 0.001 and p = 0.001, respectively), followed by CYFRA 21-1 (p = 0.060 and p = 0.027, respectively) and CA 15-3 (p = 0.082 and p = 0.017, respectively). Clinical cutoff values for each marker were defined by maximizing the log-rank statistics for OS in the total population: 1.1 microg/l for SCC-Ag (n = 47, 60.3%), 1.4 microg/l for CYFRA 21-1 (n = 47, 60.3%), 40 U/ml for CA 15-3 (n = 11, 14.1%) and 30 U/ml for CA 125 (n = 10, 12.8%). Stage IB patients with positive SCC-Ag and CYFRA 21-1 had significantly lower OS (mean 8.3 years, 95% confidence interval, CI, 5.8-10.7 years) and DFS (mean 7.3 years, 95% CI 4.6-10 years) than all other stage IB patients (OS, mean 14.5 years, 95% CI 13.5-15.5 years; DFS, mean 13.9 years, 95% CI 12.5-15.4 years). Stage IB patients with tumors <4 cm or with negative lymph nodes and positive SCC-Ag and CYFRA 21-1 had significantly poorer OS and DFS compared to all other patients in the same group. Elevated levels of both CA 125 and CA 15-3 (3 patients) were associated with an extremely poor prognosis. In conclusion, a combination of SCC-Ag and CYFRA 21-1 may help to identify early-stage cervical cancer patients with occult disease requiring adjuvant therapy.

Topics: Adult; Aged; Aged, 80 and over; Antigens, Neoplasm; Biomarkers, Tumor; CA-125 Antigen; Carcinoma, Squamous Cell; Female; Humans; Keratin-19; Keratins; Middle Aged; Mucin-1; Neoplasm Staging; Prognosis; Risk; Serpins; Uterine Cervical Neoplasms

We report a case of exceedingly rare cutaneous neoplasm with histological features of malignancy and uncertain biological potential. The nodular, darkly pigmented facial tumor with central exulceration, size 12 x 10 x 7 mm, of the skin 61-year-old man preauricular left was completely exised. Histologically tumor consists of atypical squamous cells, which express signs of moderate to significant pleomorphism, mitotically active, with foci forming of parakeratotic horn cysts ("pearls"). Characteristically tumor also consists of large number of atypical melanocytes with multifocal pattern, inserted between atypical squamous cells, and which contain large amount of dark brown pigment melanin. Immunohistochemically, squamous cells stain positively with keratin (CK116), melanocytes were stained with S -100 protein, HMB 45, and vimentin, but failed to stain with CK 116. To our knowledge this is the sixth reported case in world literature. The follow-up time of four years no evidence of recurrence or metastasis, similar all reported cases, but it is too short period in estimation to guarantee a benign course. However, it appears that this group of neoplasm may have different prognosis from pure squamous carcinoma or malignant melanoma.

Topics: Carcinoma, Squamous Cell; Cell Differentiation; Facial Neoplasms; Humans; Keratins; Male; Medical Oncology; Melanocytes; Melanoma; Middle Aged; S100 Proteins; Skin Neoplasms; Vimentin

Primary invasive squamous cell carcinoma of the vagina is rare, and the role of human papilloma virus in its pathogenesis remains unclear. The aims of our study were to determine the distribution of human papilloma virus genotypes in 21 cases of primary invasive squamous cell carcinoma of the vagina and to correlate human papilloma virus genotype with histological subtypes. Patients' clinical records were reviewed for demographic data and the stage of the disease. Tumors (n=21) were classified according to the World Health Organization criteria. Human papilloma virus genotyping (INNO-LiPA HPV Genotyping) was performed in the whole series, and statistical analysis was performed with Fisher's Exact Test and with Student's t-test. The patients' age ranged from 36 to 88 (mean 65) years. Six cases were keratinizing squamous cell carcinoma, and 15 cases were non-keratinizing squamous cell carcinoma (seven non-keratinizing not otherwise specified, three basaloid, and five warty types). The median age of patients with keratinizing squamous cell carcinoma was 73.8 years and that of non-keratinizing squamous cell carcinoma patients was 61.5 years (P=0.08). Human papilloma virus DNA was detected in 17 cases (81%): 13 non-keratinizing squamous cell carcinoma (87%) and four keratinizing squamous cell carcinoma (67%) (P=0.31). The human papilloma virus genotypes identified were: 6, 11, 16, 18, 31, 33, 35, 40, and 58, with human papilloma virus 16 DNA the most prevalent (33%). Invasive squamous cell carcinoma of the vagina is frequently associated with human papilloma virus infection, and human papilloma virus 16 is the most common genotype. Although without statistical significance, keratinizing squamous cell carcinoma is more frequent in older patients, whereas non-keratinizing squamous cell carcinoma more frequently affects younger women. All studied histological subtypes are strongly associated with human papilloma virus infection.

Topics: Adult; Aged; Aged, 80 and over; Carcinoma, Squamous Cell; DNA, Viral; Female; Genotype; Human papillomavirus 16; Humans; Keratins; Middle Aged; Neoplasm Staging; Papillomavirus Infections; Vaginal Neoplasms

Occult foci of neoplasm cells in lymph nodes (referred to as micrometastases) in various squamous cell carcinomas may be discovered by immunohistochemistry by using anti-CKs (cytokeratine filaments) policlonal antibodies which reactive with epithelial cells. Matrix metalloproteinases (MMPs) are proteolytic family enzymes represent a group of endopeptidases which are capable to degrading components of the extracellular matrix and have been implicated as playing an important role in cancer invasion and metastases. The purpose of this study was to analyze the morphological parameters and to investigate MT1-MMP expression in laryngeal carcinoma to relate the expression to CKs in pN0 lymph nodes.. To presented the direct correlation between the morphological features of tumor front and the probability of micrometastases and prediction of prognosis we have analyzed 22 patients operated for squamous cell carcinoma of the larynx. The total score of TFG classification, tumor 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 performed.. Our study showed that the total morphologic score TFG is very useful in the prediction of micrometastases in patients with laryngeal squamous cell carcinoma. The statistical analysis has revealed a significant correlation between the total TFG score and the depth of invasion and the presence of micrometastases. Positive MT1-MMP expression in 68.2% cases was observed. There was no significant relationship for immunoexpression of MT1-MMP in examined group of patients with advanced laryngeal carcinoma and positive poliCKs stain in lymph nodes.. The results of study suggest that extended traditional pathologic evaluation by features from the TFG classification, especially the depth of invasion, could aid in diagnosis of micrometastases. The positive expression of poliCKs in the conventional pathological examination of pN0 lymph nodes appears to play an important role in determining prognosis in patients with carcinoma of the larynx.

Topics: Aged; Aged, 80 and over; Carcinoma, Squamous Cell; Female; Gene Expression; Gene Expression Regulation, Neoplastic; Humans; Immunohistochemistry; Keratins; Laryngeal Neoplasms; Lymphatic Metastasis; Male; Matrix Metalloproteinase 1; Middle Aged; Neoplasm Staging; Prognosis

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

Spindle cell carcinoma (SpCC) is a rare microscopic type of cancer of the mouth and oropharynx. Although SpCC is thought to arise from squamous cell carcinoma (SCC), it carries a worse prognosis.. To find out the difference in immunohistochemical expression of cytokeratin, vimentin and smooth-muscle actin, and mutational alterations in the K-ras oncogene between the two tumours, in an attempt to characterise SpCC.. Immunohistochemical analysis was performed by standard avidin-biotin complex method in 35 cases each of SpCCs and SCCs. DNA extracted from paraffin wax-embedded tumours was used for PCR followed by single-strand conformation polymorphism for mutational analysis of K-ras exon 1 and exon 2.. In the SpCC group, cytokeratin positivity was significantly higher in epithelial areas (52.2%) than in spindle cell areas (16.1%), whereas vimentin was more positive in spindle cell areas (18.7%) than epithelial areas (2.7%). Cells intermediate between epithelial and spindle cell areas were consistently positive for both cytokeratin and vimentin. Cytokeratin was found to be significantly more positive in SCC (72.6%) than the squamous component and spindle cell component of SpCC. In this study, no mutation was detected in the K-ras gene of either the SpCC or SCC group.. The spindle cell component of SpCC is intermixed with cells that are morphologically mesenchymal but express dual antigen-positivity characteristic of epithelial (cytokeratin) and mesenchymal (vimentin) cells. These, possibly, are cells in transition suggesting that SpCC may be a sarcomatous metaplasia of SCC.

Topics: Actins; Adult; Aged; Aged, 80 and over; Carcinoma, Squamous Cell; DNA Mutational Analysis; DNA, Neoplasm; Female; Genes, ras; Genetic Predisposition to Disease; Head and Neck Neoplasms; Humans; Immunoenzyme Techniques; Keratins; Male; Middle Aged; Neoplasm Proteins; Polymerase Chain Reaction; Polymorphism, Single-Stranded Conformational; Prospective Studies; Vimentin

Oral squamous cell carcinoma (OSCC) is the most common malignant tumour in the oral and maxillofacial region, and has a poor prognosis. Cyfra 21-1 is a useful tumour marker for squamous cell carcinoma, but the clinical value of Cyfra 21-1 in OSCC has not been confirmed. In order to investigate the diagnostic and prognostic value of serum Cyfra 21-1 in primary OSCC patients, the preoperative serum Cyfra 21-1 concentration of 100 OSCC patients and 56 healthy subjects was detected by enzyme-linked immunosorbent assay (ELISA). The cut-off value was calculated with a receiver operating characteristic (ROC) curve, and prognostic analysis was performed using the Kaplan-Meier method and Cox regression models. The preoperative serum Cyfra 21-1 concentration in OSCC patients (1.18+/-1.20 microg/L) was significantly higher (t=6.585, P<0.001) than that in healthy subjects (0.40+/-0.16 microg/L). With a cut-off value of 0.65 microg/L, the diagnostic sensitivity and specificity was 0.570 and 0.964, respectively. There was significant correlation with tumour recurrence and survival rate: the higher the serum Cyfra 21-1; the higher the tumour recurrence rate and lower the survival rate. Serum Cyfra 21-1 was an independent prognostic factor for OSCC using univariate and multivariate Cox models.

Topics: Adult; Aged; Aged, 80 and over; Analysis of Variance; Antigens, Neoplasm; Biomarkers, Tumor; Carcinoma, Squamous Cell; Case-Control Studies; Enzyme-Linked Immunosorbent Assay; Female; Humans; Kaplan-Meier Estimate; Keratin-19; Keratins; Male; Middle Aged; Mouth Neoplasms; Neoplasm Staging; Prognosis; Proportional Hazards Models; ROC Curve; Sensitivity and Specificity

This study examined potential survival differences among nasopharyngeal carcinoma (NPC) patients from various ethnicities in the United States.. A total of 2436 newly diagnosed NPC patients from 1992 to 2002 were analyzed from the population-based Surveillance, Epidemiology, and End Results (SEER) program. Five-year survival rate estimates and Kaplan-Meier survival curves were calculated. Cox proportional hazard ratios (HRs) were used to identify independent prognostic factors for survival.. By multivariate analyses, early age of diagnosis, localized stage at presentation (versus distant, HR=0.35; P<0.0001), radiation therapy (versus none; HR=0.48; P<0.0001), undifferentiated non-keratinizing carcinoma (versus keratinizing squamous cell carcinoma; HR=0.67; P<0.0001), and Chinese ethnicity (versus Caucasian; HR=0.78; P=0.0010) were associated with improved survival. Within keratinizing squamous cell carcinoma histology, the survival advantage of Chinese patients remained even after adjustment for other prognostic factors.. The significant survival advantage of Chinese NPC patients within the keratinizing squamous cell carcinoma histology contributed largely to Chinese ethnicity being an independent and favorable prognostic factor for survival in NPC.

Topics: Adolescent; Adult; Aged; Asian People; Carcinoma, Squamous Cell; Child; Child, Preschool; China; Female; Humans; Infant; Infant, Newborn; Keratins; Male; Middle Aged; Nasopharyngeal Neoplasms; Neoplasm Staging; Prognosis; SEER Program; Survival Rate; United States

Basaloid squamous cell carcinoma of the lung, an uncommon subtype of non-small cell carcinomas was introduced as a distinct entity in the recently revised World Health Organization (WHO) classification of lung tumours. This rare tumour most commonly develops in males older than 60 years. We report a 23-years-old female patient with basaloid squamous cell carcinoma of the lung who was stage IIB post-operatively. The patient is still alive and healthy 18 months after the operation. This is one of the youngest patient reported with this rare type of tumour.

Topics: Adult; Bronchoscopy; Carcinoma, Squamous Cell; Female; Follow-Up Studies; Humans; Immunohistochemistry; Keratins; Lung Neoplasms; Neoplasm Staging; Radiography; Time Factors; Treatment Outcome

Topics: Aged; Carcinoma, Squamous Cell; Humans; Immunohistochemistry; Keratins; Ki-67 Antigen; Male; Pancreas; Pancreatic Neoplasms; Pancreaticoduodenectomy

Lymphatic metastatic characteristics of oral squamous cell carcinoma are not fully understood, for instance, skip metastasis is still controversial. The purposes of the present study was to explore the accuracy and applicability of immunohistochemical stain with cytokeratin combining semi-serial sections for detection of cervical lymph node metastasis of oral squamous cell carcinoma.. Regional lymph nodes (N=1638) were obtained from 26 patients with primary oral squamous cell carcinoma who underwent five level neck dissections. Semi-serial sections at an interval of 0.5mm was performed for each lymph node and cross-detected by immunohistochemical staining with cytokeratin and traditional hematoxylin-eosin staining (H-E) and their accuracies were compared.. Of 26 patients, 21 were detected having lymphatic metastasis by H-E staining and 26 by immunohistochemical detection; Of 1638 lymph nodes, 52 metastatic lymph nodes were detected by H-E staining while 162 by immunohistochemical detection. One case with cancer of the mouth floor being defined having skip metastasis was proved having no skip metastasis by the immunohistochemical detection.. The immunohistochemical detection method with semi-serial sections has higher accuracy than the traditional H-E staining and its application may present a need to re-evaluate the neck metastatic patterns of oral squamous cell carcinoma.

Topics: Adult; Aged; Biomarkers, Tumor; Carcinoma, Squamous Cell; Eosine Yellowish-(YS); Female; Hematoxylin; Humans; Immunoenzyme Techniques; Keratins; Lymph Nodes; Lymphatic Metastasis; Male; Middle Aged; Mouth Floor; Mouth Neoplasms; Neck; Neoplasm Staging; Sensitivity and Specificity; Staining and Labeling

The aim of this study was to examine the clinical usefulness of cytokeratin 19 fragments (CYFRA 21-1) compared with squamous cell carcinoma (SCC) antigen in patients with esophageal cancer treated with radiation therapy.. Fifty-one patients with stage I-IV esophageal cancer were evaluated. CYFRA 21-1 and SCC antigen serum levels were measured at the start and the end of radiation therapy.. CYFRA 21-1 (> 3.5 ng/mL) and SCC antigen (> 1.5 ng/mL) before radiation therapy were elevated in 63% and 53% of the patients, respectively. The CYFRA 21-1 levels were significantly correlated with TNM stages, tumor depth and lymph node metastasis (P = 0.0003, P = 0.019 and P = 0.019, respectively), whereas no correlation was observed between SCC antigen and these factors. The values of CYFRA 21-1 in all patients who survived without recurrence were under the cutoff level at the end of treatment, but the values in all patients with locoregional recurrence were above the level. However, there was no significant correlation between SCC antigen level at the end of treatment and any clinical outcome.. The results suggest that the evaluation of CYFRA 21-1 would be useful not only for assessment before radiation therapy but also for monitoring after radiation therapy in the treatment for esophageal cancer.

Topics: Aged; Aged, 80 and over; Antigens, Neoplasm; Biomarkers, Tumor; Carcinoma, Squamous Cell; Esophageal Neoplasms; Female; Follow-Up Studies; Humans; Keratin-19; Keratins; Lymph Nodes; Male; Middle Aged; Neoplasm Invasiveness; Neoplasm Staging; Prognosis; Recurrence; Serpins; Time Factors; Treatment Outcome

Neoadjuvant chemotherapy (NACT) has been postulated but not yet proven to eradicate micrometastases and improve the prognosis of patients with advanced esophageal squamous cell carcinomas (ESCC). Cytokeratin immunohistochemistry of the lymph nodes of ESCC revealed immunohistochemical micrometastases (IHM) and cytokeratin deposits (CD), which are hyalinized denucleated particles considered to be cadavers of carcinoma cells. Successful chemotherapy should convert cancer cells from IHM to CD and improve the status of ESCC patients from systemic disease to regional disease.. Cytokeratin immunostaining of surgically removed lymph nodes was performed for 107 patients with node-positive ESCC, including 32 patients without preoperative treatment (Surgery group) and 75 patients undergoing NACT using CDDP, doxorubicin hydrochroride, and 5-fluorouracil (NACT group). Cytokeratin-positive staining was done for serial hematoxylin-eosin-stained sections and classified as pathologic metastasis, IHM, or CD.. CD was observed less frequently in the Surgery group than in the NACT group (6% vs 43%, P < .0001), whereas IHM was more frequent in the former (47% vs 24%, P = .019). IHM was a poor prognostic factor in both groups, whereas CD was a favorable one in the NACT group. The effect of chemotherapy on IHM was classified as eradicated, IHM(-)/CD(+); persistent, IHM(+)/CD(+); no effect, IHM(+)/CD(-); or not informative, IHM(-)/CD(-). This classification correlated well with the clinical response of the primary neoplasm, number of pathologic metastases, and postoperative survival (3-year survival rates: 78%, 18%, 0%, and 38%). IHM/CD was found to be an independent prognostic factor together with the number of pathologic metastases in the multivariate analysis.. Disappearance of IHM and the emergence of CD suggest the eradication of micrometastases by NACT. The clinical benefit of NACT was apparent for IHM(-)/CD(+) patients with node-positive ESCC.

Topics: Carcinoma, Squamous Cell; Chemotherapy, Adjuvant; Cisplatin; Doxorubicin; Esophageal Neoplasms; Fluorouracil; Humans; Immunohistochemistry; Keratins; Lymph Nodes; Lymphatic Metastasis; Neoadjuvant Therapy; Prognosis

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

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

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

Saliva is the body fluid in the oral cavity and contacts directly with oral mucosa. As a detective media, it is acceptable and non-traumatic. Cyfra 21-1, being the soluble fragment of cytokeratin 19(CK19), correlates well with oral squamous cell carcinoma (OSCC).. To investigate the saliva Cyfra 21-1 concentrations in OSCC patients and healthy persons, and the correlation between the Cyfra 21-1 concentration in saliva and the CK19 expression in tissue from OSCC patients.. Saliva Cyfra 21-1 concentration was detected by ELISA in 30 OSCC patients and 30 healthy persons; CK19 protein expression and CK19 mRNA level were, respectively, detected by immunohistochemistry and fluorescent real-time RT-PCR in cancerous and paracancerous tissues from 33 OSCC patients.. Saliva Cyfra 21-1 concentration in OSCC patients (85.95+/-78.00 microg/L) was significantly higher than that in healthy persons (42.27+/-40.84 microg/L) (P=0.009); it was also significantly higher in the patients suffering later tumour recurrence (130.95+/-66.38 microg/L) than that in the patients without tumour recurrence (74.84+/-63.45 microg/L) (P=0.023). CK19 protein expression increased significantly in OSCC tissues (P<0.001) with positive rate of 90.9%, CK19 mRNA level in cancerous tissues was 2.21 folds higher than that in paracancerous tissues (P=0.020); significant correlation was found between tissue CK19 protein expression and tissue CK19 mRNA level (P=0.003), and great correlation was found between tissue CK19 protein expression and saliva Cyfra 21-1 concentration (P=0.051).. The increased CK19 expression in OSCC tissues plays an important role in the increase of saliva Cyfra 21-1 concentration. Potential clinical value of saliva Cyfra 21-1 detection is suggested for OSCC. Further studies are encouraged to reveal the real diagnostic and prognostic value of detecting saliva Cyfra 21-1 concentration for OSCC.

Topics: Adult; Aged; Aged, 80 and over; Antigens, Neoplasm; Biomarkers, Tumor; Carcinoma, Squamous Cell; Case-Control Studies; Enzyme-Linked Immunosorbent Assay; Female; Humans; Immunohistochemistry; Keratin-19; Keratins; Male; Middle Aged; Mouth Neoplasms; Neoplasm Staging; Precancerous Conditions; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; ROC Curve; Saliva; Statistics, Nonparametric; Survival Rate

Extended histopathologic work-up has increased the detection of micrometastasis in sentinel lymph nodes in malignant melanoma and breast cancer. The aim of this study was to examine if (A) step-sectioning of the central 1000 microM at 250 microM levels with immunostaining were accurate when compared with (B) step-sectioning and immunostaining of the entire sentinel lymph node at 250 microM levels.. Forty patients with T1/T2 cN0 oral cancer were enrolled. Three patients were excluded. In one patient no sentinel lymph node was identified. The remaining two had unidentified sentinel lymph nodes due to lymphoscintigraphic and surgical sampling error. The central 1000 microM of 147 sentinel lymph nodes were step-sectioned in 250-microm intervals and stained with hematoxylin and eosin and CK-KL1. All lymph nodes were recorded as negative or positive for macrometastases or micrometastases. After inclusion of the last patient the residual tissue of the lymph nodes was totally step-sectioned at 250-microm intervals and re-classified. The tumor deposits were divided into macrometastases and micrometastases and ITC.. Method (A) upstaged 17 lymph nodes and 11 patients compared with method (B), which upstaged 22 lymph nodes and 11 patients. Seven of the patients with positive lymph nodes did not change stage. However, four lymph nodes changed from micrometastases to macrometastases. One patient changed from a micrometastasis to four micrometastases. One pN2c patient with bilateral micrometastases did not change stage, but an additional ipsilateral lymph node with a micrometastasis was identified.. Larger tumor deposits and more metastases are identified by more extensive sectioning of the sentinel lymph nodes. None of the patients was false-negative due to histopathologic sampling error, but the results indicate that central step-sectioning of the central 1000 microM cannot completely be relied upon for accurate staging of the patients.

Topics: Adult; Aged; Aged, 80 and over; Carcinoma, Squamous Cell; Coloring Agents; Eosine Yellowish-(YS); Female; Fluorescent Dyes; Follow-Up Studies; Hematoxylin; Humans; Keratins; Lymph Nodes; Lymphatic Metastasis; Male; Microtomy; Middle Aged; Mouth Neoplasms; Neoplasm Staging; Sentinel Lymph Node Biopsy; Survival Rate

To investigate the use of immunohistochemistry in distinguishing necrotizing sialometaplasia (NSM) from squamous cell (SCC) and mucoepidermoid carcinoma (MEC) by (i) the identification of myoepithelial cells and (ii) cytokeratin (CK) expression.. Thirteen cases with the histological changes of NSM, eight SCCs and eight MECs were examined with the following immunohistochemical markers: calponin, S100, smooth muscle actin (SMA), p63, CK7, CK5, CK6 and CAM5.2. The distribution and intensity of staining were recorded. Residual myoepithelial cells (best demonstrated by calponin and SMA) were identified at the periphery of the epithelial islands in all cases of NSM (although not in all islands), in contrast to MEC and SCC. S100 showed a similar pattern, although staining fewer cells. Moderate rather than extensive expression of CK7 may help to distinguish NSM from MEC.. Identification of myoepithelial cells and CK7 expression may help to distinguish NSM from its mimics.

Topics: Actins; Biomarkers; Biomarkers, Tumor; Calcium-Binding Proteins; Calponins; Carcinoma, Mucoepidermoid; Carcinoma, Squamous Cell; Diagnosis, Differential; Head and Neck Neoplasms; Humans; Immunohistochemistry; Keratins; Keratins, Type II; Membrane Proteins; Microfilament Proteins; S100 Proteins; Sialometaplasia, Necrotizing

This study was designed to evaluate one institution's experience with treatment outcomes for rectal squamous-cell carcinoma.. Using our prospective Colorectal Database, we identified patients diagnosed with rectal squamous-cell carcinoma at our institution between 1983 and 2005. Pathology was rereviewed, tumor immunophenotype was compared to control cases of anal squamous-cell carcinoma and rectal adenocarcinoma, treatment modalities and outcomes were analyzed.. Twelve patients were identified (10 females median age, 58 years). Median distal extent of tumors was 7 (range, 5-8) cm from the anal verge. Treatment included chemotherapy only (n = 1), chemoradiation only (n = 2), induction chemotherapy followed by chemoradiation and surgery (n = 2), chemoradiation followed by surgery (n = 5), and surgery followed by chemoradiation (n = 2). The chemotherapy regimen was 5-fluorouracil-based. Radiotherapy total dose was 50.4 Gy (1.8 Gy/day, daily x 5) external iliac and inguinal nodes were not included in the radiation field. Complete clinical responders to chemoradiation (n = 2) received no further treatment. All seven partial responders underwent surgery; six had complete pathologic response; nodal status in two of six was unknown because they had local excision. Immunophenotypical analysis showed similar keratin expression profile between rectal squamous-cell carcinoma (n = 5) and rectal adenocarcinoma (n = 5), which is different from anal squamous-cell carcinoma (n = 10). All patients were alive without evidence of disease at follow-up (median follow-up, 2.6 (range, 0.5-16) years).. Our data suggest that most patients treated with upfront chemoradiation therapy followed by surgery did well. Sphincter-preserving surgery is usually feasible. Clinical judgment of tumor response after chemoradiation is not completely reliable. Immunohistochemistry suggests a common cellular origin for rectal squamous-cell carcinoma and rectal adenocarcinoma, which is different from anal squamous-cell carcinoma.

Topics: Adult; Aged; Aged, 80 and over; Antimetabolites, Antineoplastic; Biomarkers, Tumor; Carcinoma, Squamous Cell; Colectomy; Female; Fluorouracil; Follow-Up Studies; Humans; Immunohistochemistry; Keratins; Male; Middle Aged; Neoplasm Staging; Prospective Studies; Radiotherapy, Adjuvant; Rectal Neoplasms; Survival Rate; Treatment Outcome; United States

Intermediate filaments are involved in cell migration and intracellular signal transduction pathways. In a variety of organs, the expression of distinct intermediary filaments are further associated with distinct steps of malignant transformation. In this study, we seeked to define the cytokeratin (Ck) expression pattern in oral leukoplakia and oral squamous cell carcinoma (OSCC). One hundred and ninety-two patients with OSCC, 117 patients with oral leukoplakia without dysplasia (OL) and 23 with oral leukoplakia with dysplasia (squamous intraepithelial neoplasia) (OLD) of the oral cavity were investigated for the immunohistochemical expression of Ck 5-6, Ck 8/18, Ck 1 Ck 10, Ck 14, Ck 19 using the tissue microarray technique. Correlations between clinical features and the expression of cytokeratins were evaluated statistically by chi2 tests. The expression of Ck 8/18, Ck 19 and Ck 1 was seen in 3.1% (Ck 8/18), 12.5% (Ck 19), 75.4% (Ck 1) of all leukoplakias, 1.0% (Ck 8/18), 9.4% (Ck 19), 76.8% (Ck 1) in OL, 13.0% (Ck 8/18), 27.3% (Ck 19), 68.4% (Ck 1) in OLD and was significantly associated with the degree of dysplasia (Ck 8/18 p<0.01; Ck 19 p<0.01; Ck 1 p<0.01) and the acquisition of invasive growth properties. The highest frequencies were observed in invasive squamous cell carcinomas. The expression of Ck 8/18 and Ck 19 in transformed oral lesions can be regarded as an early feature in the pathogenesis of invasive OSCC. However, the aberrant expression of Ck 8/18 and Ck 19 in an even higher frequency in invasive carcinomas characterizes the expression of typical glandular cytokeratins as a general progression marker in squamous cell carcinomas. These results can be interpreted as first hints that oral leukoplakias with an expression of Ck 8/18 or 19 independent of dysplasia, should be resected totally since they might indicate an increased progression potential.

Topics: Adult; Aged; Aged, 80 and over; Carcinoma, Squamous Cell; Female; Humans; Keratins; Leukoplakia; Male; Middle Aged; Mouth Neoplasms; Neoplasm Staging

For deveplopment and function of the lung, progesterone (Prog) fulfils important roles. In a recent report, immunolocalization of Prog and estrogen receptors in non-small cell lung carcinomas were examined and it was shown that the Prog receptor might be a potent prognostic factor. In the present study, a cell line with the sensitivity to Prog was established from a human lung cancer and the growth mechanism was analyzed. The proliferation of established SN96-42 cells was sensitive to Prog and antiprogesterone RU38486 inhibited their proliferation stimulated by Prog. Exposure of these cells to Prog resulted in a decreased formation of leukotriene (LT). The 5-lipoxygenase inhibitor (5-LOX), AA861, effectively stimulated SN96-42 cell proliferation and 5-LOX-catalyzed product(s), especially LTC4, inhibited SN96-42 cell proliferation caused by Prog. Prog-sensitive enhancement of SN96-42 cell proliferation is at least partly mediated through an inhibition of LT formation and these data suggest that 5-LOX and LTs play important roles in SN96-42 cell proliferation stimulated by Prog.

Topics: Carcinoma, Squamous Cell; Cell Division; Cell Line, Tumor; Humans; Keratins; Leukotrienes; Lung Neoplasms; Progesterone; Receptors, Estrogen; Receptors, Progesterone

We have studied cytokeratin (CK) expression in two cases of well-differentiated and poorly differentiated squamous cell carcinoma (SCC) arising from hidradenitis suppurativa (HS) (acne inversa). In both cases, type A (infundibular-like keratinized) epithelia were observed. In type A epithelia, CK 1 and 10 expressions were decreased, and CK 14 and 17 were detectable in the whole layers. CK 7, 8, 15, 16 and 18 were not detected in type A epithelia. In tumor nests of well-differentiated SCC, CK 1 and 10 expressions were downregulated, and CK 14 expression was upregulated. In tumor nests of poorly differentiated SCC, CK 1 and 10 were not expressed, but simple epithelial keratins (CK 8, 18 and 19) were expressed. These changes of CK expression are related to malignant transformation from the sinus tract (type A epithelium) in HS to SCC.

Topics: Aged; Biomarkers, Tumor; Carcinoma, Squamous Cell; Cell Transformation, Neoplastic; Fatal Outcome; Hidradenitis Suppurativa; Humans; Immunoenzyme Techniques; Keratins; Male; Middle Aged; Skin Neoplasms

The aim of the present study was to clinically, morphologically, and immunohistochemically correlate the expression of cytokeratins (CKs) 7, 10, 13, 14, 16, and 19 in 30 cases of tongue squamous cell carcinoma (SCC) with disease outcome, metastases, clinical stage (tumor, node, metastasis [TNM]), and histological grade of malignancy proposed by Bryne. Statistical analysis (chi2 test) showed that only histological grading was not significantly correlated with the clinical variables. CK expression varied in the samples analyzed. CK 10 expression was significantly correlated with the presence of metastases, and the expression of CK 16 was related to disease outcome and also to TNM stages III and IV. These results indicate that metastases and TNM are effective prognostic indicators. The histological grading proposed by Bryne did not reflect the biological behavior of the tongue SCC cases studied. Analysis of some intermediate CK filaments can reflect the biological behavior and aggressiveness of some tongue SCCs.

Topics: Adult; Aged; Aged, 80 and over; Biomarkers, Tumor; Carcinoma, Squamous Cell; Combined Modality Therapy; Disease-Free Survival; Female; Humans; Immunohistochemistry; Keratins; Male; Middle Aged; Remission Induction; Retrospective Studies; Survival Rate; Tongue Neoplasms

The human p63 gene codes for multiple protein isoforms and is commonly over-expressed in squamous cell carcinoma of head and neck (SCCHN). This expression is predominantly of the DeltaN- and beta-isoforms, the former lacking the p53-related transactivation domain. p63 can activate or repress transcription of p53 and p73 target genes, but also has unique transcriptional targets and, unlike other p53 family members, is required for normal development and differentiation of squamous epithelia. We have identified novel targets of p63, using microarray analysis of SCCHN cells that stably over-express individual DeltaNp63 isoforms. All three isoforms induced expression of the cancer stem cell marker, CD44, with the DeltaNp63beta isoform showing strongest induction. Using chromatin immunoprecipitation, we were unable to show direct binding of p63 to the CD44 promoter, but found that p63 specifically increased expression of CD44 lacking variant exon 2. Each of the DeltaNp63 isoforms up-regulated expression of keratins 6A and 14 and down-regulated expression of keratins 4 and 19, in keeping with their expression patterns in SCCHN. The data strengthen the idea that p63 has key roles in regulating normal and abnormal differentiation processes through both induction and repression of genes with opposite functions. The identification of up-regulation and differential splicing of CD44 following p63 over-expression indicates roles in the regulation of adhesion, metastasis and the cancer stem cell phenotype.

Topics: Carcinoma, Squamous Cell; DNA-Binding Proteins; Down-Regulation; Gene Expression Regulation, Neoplastic; Head and Neck Neoplasms; Humans; Hyaluronan Receptors; Keratins; Mouth Mucosa; Neoplasm Proteins; Oligonucleotide Array Sequence Analysis; Protein Isoforms; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; RNA, Neoplasm; Trans-Activators; Transcription Factors; Tumor Cells, Cultured; Tumor Suppressor Proteins; Up-Regulation

Topics: Biomarkers, Tumor; Carcinoma, Renal Cell; Carcinoma, Squamous Cell; Cell Transformation, Neoplastic; Humans; Keratins; Kidney Neoplasms; Male; Middle Aged; Sarcoma

Topics: Biomarkers, Tumor; Carcinoma, Small Cell; Carcinoma, Squamous Cell; Chromosome Aberrations; Diagnosis, Differential; Humans; Keratins; Lymphoma; Mucin-1; Urinary Bladder; Urinary Bladder Neoplasms

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

Poorly differentiated, spindle cell malignancies, on sun damaged skin frequently pose a diagnostic challenge for pathologists. The vast majority of these neoplasms ultimately are diagnosed as either atypical fibroxanthoma (AFX), spindle cell melanoma (SCM), and very rarely as spindle cell squamous cell carcinoma (SCSCC), leiomyosarcoma or angiosarcoma. Light microscopic clues may suggest one of these neoplasms, but subtle and overlapping characteristics often render precise diagnosis impossible based on morphological features alone. Immunohistochemistry therefore is necessary to firmly and accurately diagnose the majority of spindle cell malignancies on sun damaged skin. Aim of this case report is to highlight the practical approach to such diagnostic dilemmas.

Topics: Aged, 80 and over; Carcinoma, Squamous Cell; Diagnosis, Differential; Female; Humans; Immunohistochemistry; Keratins; Melanoma; S100 Proteins; Sarcoma; Skin Neoplasms; Vimentin; Xanthomatosis

Gap junctions (GJs) have been shown to play a role in tumor progression including a variety of keratinocyte-derived and non-keratinocyte-derived skin tumors. Here we show that the synthesis of the GJ proteins connexin 26 and connexin 30 (Cx26 and Cx30) is induced in keratinocyte-derived epithelial skin tumors whereas there is either no change or a downregulation of Cx43. Cx26, Cx30, and Cx43 are absent in non-epithelial skin tumors. Further, Cx26 and Cx30 are induced in the epidermis adjacent to malignant melanoma but absent in the epidermis adjacent to benign non-epithelial skin lesions (melanocytic nevi and angioma). The keratinocyte-derived skin tumors are very heterogeneous regarding the Cx26/Cx30 pattern in the epidermis at the periphery of the tumors. We did not observe any difference in the localization of the very similar proteins Cx26 and Cx30 but a variation in intensity of immunoreactivity. As the staining patterns of Cx26 and Cx30 antibodies are not identical to those of CK6, a marker for hyperproliferation, and CK17, a marker for trauma, we discuss that the induction of these gap junctional proteins exceeds a reflection of reactive hyperproliferative or traumatized epidermis. We further discuss the putative roles of these gap junctional proteins in tumor progression.

Topics: Animals; Bowen's Disease; Carcinoma, Basal Cell; Carcinoma, Squamous Cell; Connexin 26; Connexin 30; Connexins; Epidermis; Hemangioma; Humans; Keratinocytes; Keratins; Keratosis; Liver; Melanoma; Mice; Mice, Inbred C57BL; Microscopy, Fluorescence; Nevus, Pigmented; Skin Neoplasms; Warts

The relationship between loss of intercellular adhesion and the biologic properties of human squamous cell carcinoma is not well understood. We investigated how abrogation of E-cadherin-mediated adhesion influenced the behavior and phenotype of squamous cell carcinoma in 3D human tissues. Cell-cell adhesion was disrupted in early-stage epithelial tumor cells (HaCaT-II-4) through expression of a dominant-negative form of E-cadherin (H-2Kd-Ecad). Three-dimensional human tissue constructs harboring either H-2Kd-Ecad-expressing or control II-4 cells (pBabe, H-2Kd-EcadDeltaC25) were cultured at an air-liquid interface for 8 days and transplanted to nude mice; tumor phenotype was analyzed 2 days and 2 and 4 weeks later. H-2Kd-Ecad-expressing tumors demonstrated a switch to a high-grade aggressive tumor phenotype characterized by poorly differentiated tumor cells that infiltrated throughout the stroma. This high-grade carcinoma revealed elevated cell proliferation in a random pattern, loss of keratin 1 and diffuse deposition of laminin 5 gamma2 chain. When II-4 cell variants were seeded into type I collagen gels as an in vitro assay for cell migration, we found that only E-cadherin-deficient cells detached, migrated as single cells and expressed N-cadherin. Function-blocking studies demonstrated that this migration was matrix metalloproteinase-dependent, as GM-6001 and TIMP-2, but not TIMP-1, could block migration. Gene expression profiles revealed that E-cadherin-deficient II-4 cells demonstrated increased expression of proteases and cell-cell and cell-matrix proteins. These findings showed that loss of E-cadherin-mediated adhesion plays a causal role in the transition from low- to high-grade squamous cell carcinomas and that the absence of E-cadherin is an important prognostic marker in the progression of this disease.

Topics: Animals; Cadherins; Carcinoma, Squamous Cell; Cell Adhesion; Cell Movement; Cell Proliferation; Disease Progression; Humans; Keratin-1; Keratins; Laminin; Male; Matrix Metalloproteinases; Mice; Mice, Nude; Neoplasm Invasiveness; Oligonucleotide Array Sequence Analysis; Phenotype; Prognosis; Skin Neoplasms; Tissue Culture Techniques

In this study, the expression patterns of Galectin-3 (Gal-3) and the frequency of infiltrating CD1a positive dendritic cells (DCs) were determined in 82 cases of vulvar tissues, consisting of normal squamous epithelia (NE, N = 10), vulvar condylomas (VC, N = 24), high grade vulvar intraepithelial neoplasias (HG-VIN, N = 26) of common type, and invasive keratinizing squamous cell carcinomas (SCC, N = 22) by a standard immunohistochemical method using monoclonal antibodies to investigate their differential expression in vulvar squamous dysplasia and infiltrating carcinomas with an emphasis on neoplastic transformation and progression. Gal-3 expression was cytoplasmic, nuclear or membranous in NE, VCs, and HG-VINs, with negative or weak and occasionally moderate reactivities. In SCCs, exclusively cytoplasmic staining patterns with moderate or strong reactivity in 59% of cases were observed (p < 0.0001, chi-square test); Gal-3 expression was not related with stage, grade, and recurrence. The frequency of CD1a positive DCs increased from NE and VCs to highest numbers in HG-VINs, was lowest in SCCs (p < 0.0001, ANOVA), and was not related with stage and grade, but with recurrence in SCCs (p = 0,048, t-test). This study indicates that qualitative and quantitative changes of Gal-3 immunoexpression and infiltration by CD1a positive DCs in vulvar NE, VCs, and HG-VIN lesions, respectively, compared with SCCs play a role in the development of an infiltrative phenotype, and may provide adjunctive criteria in the diagnosis of invasion of vulvar squamous epithelia.

Topics: Adult; Aged; Aged, 80 and over; Antigens, CD1; Biomarkers, Tumor; Carcinoma in Situ; Carcinoma, Squamous Cell; Condylomata Acuminata; Dendritic Cells; Female; Galectin 3; Humans; Immunohistochemistry; Keratinocytes; Keratins; Middle Aged; Neoplasm Invasiveness; Phenotype; Vulva; Vulvar Neoplasms

Intermediary filaments are involved in cell motility and cancer progression. In a variety of organs, the expression of distinct intermediary filaments are associated with patient prognosis. In this study, we seeked to define the prognostic potential of cytokeratin and vimentin expression patterns in squamous cell carcinomas (SCC's) of the oral cavity.. 308 patients with histologically proven and surgically treated squamous cell carcinomas of the oral cavity were investigated for the immunohistochemical expression of a variety of intermediary filaments including high- and low-molecular weight cytokeratins (Ck's), such as Ck 5/6, Ck 8/18, Ck 1, CK 10, Ck 14, Ck 19 and vimentin, using the tissue microarray technique. Correlations between clinical features and the expression of Cytokeratins and vimentin were evaluated statistically by Kaplan-Meier curves and multivariate Cox regression analysis.. The expression of Ck 8/18 and Ck 19 were overall significantly correlated with a poor clinical prognosis (Ck 8/18 p = 0.04; Ck19 p < 0.01). These findings could also be reproduced for Ck 8/18 in primary nodal-negative SCC's and held true in multivariate-analysis. No significant correlation with patient prognosis could be found for the expression of the other cytokeratins and for vimentin.. The expression of Ck 8/18 in SCC's of the oral cavity is an independent prognostic marker and indicates a decreased overall and progression free survival. These results provide an extended knowledge about the role of intermediary filament expression patterns in SCC's.

Topics: Adult; Aged; Aged, 80 and over; Biomarkers, Tumor; Carcinoma, Squamous Cell; Female; Gene Expression Profiling; Humans; Immunohistochemistry; Keratins; Male; Middle Aged; Mouth Neoplasms; Prognosis; Survival Analysis

As both mesotheliomas and squamous carcinomas can present a wide variety of morphological patterns, they can on occasion be confused. Recently, some groups of investigators have called attention to the difficulties that sometimes exist in distinguishing between these malignancies and the need to define a panel of markers that can assist in reaching the correct diagnosis. The aim of the present study is to compare the value of the various immunohistochemical markers currently available for the diagnosis of mesothelioma and squamous carcinoma of the lung. A total of 30 epithelioid pleural mesotheliomas exhibiting a solid or predominantly solid pattern, and 30 nonkeratinizing squamous carcinomas of the lung were investigated for the expression of the following markers: podoplanin, calretinin, mesothelin, WT1, keratin 5/6, keratin 7, p63, carcinoembryonic antigen (CEA), MOC-31, Ber-EP4, B72.3, BG-8 (Lewis(y)), leu-M1 (CD15), and thyroid transcription factor-1 (TTF-1). All 30 (100%) of the mesotheliomas reacted for calretinin, mesothelin and keratin 7, 93% each for podoplanin, WT1 and keratin 5/6, 13% for Ber-EP4, 7% each for p63, MOC-31 and BG-8, and 0% for B72.3, CEA, leu-M1 and TTF-1. All 30 (100%) of the squamous carcinomas were positive for p63 and keratin 5/6, 97% for MOC-31, 87% for Ber-EP4, 80% for BG-8, 77% for CEA, 57% for keratin 7, 40% for calretinin and B72.3, 30% for leu-M1, 27% for mesothelin, 15% for podoplanin, and 0% for WT 1 and TTF-1. After analyzing the results, it is concluded that from a practical point-of-view, a combination of two positive mesothelioma markers (WT1 and calretinin or mesothelin) with two negative mesothelioma markers (p63 and MOC-31) would allow the differential diagnosis to be established between epithelioid mesotheliomas and squamous carcinomas of the lung in nearly all instances.

Topics: Biomarkers, Tumor; Calbindin 2; Carcinoma, Squamous Cell; Diagnosis, Differential; Epithelioid Cells; GPI-Linked Proteins; Humans; Immunohistochemistry; Keratin-5; Keratin-6; Keratins; Lung Neoplasms; Membrane Glycoproteins; Mesothelin; Mesothelioma; S100 Calcium Binding Protein G; WT1 Proteins

To investigate the incidence of central nodal necrosis (CNN) in the cervical lymph nodes of patients with oral squamous cell carcinoma (SCC) and the factors that influence the formation of CNN.. Lymph nodes shown as CNN on computed tomography (CT) films in 107 lymph nodes from 27 patients with oral SCC were selected. Lymph nodes with CNN on CT films were compared with the pathological findings of lymph nodes on specimens. We compared many kinds of factors influencing the formation of CNN, including the differentiated type, with the incidence of CNN.. Significant relationships were found between the incidence of CNN in metastatic lymph nodes and the presence of well-differentiated SCC and the presence of keratinization in tumour cells.. The results indicated that if a patient had SCC with low-grade differentiation, CNN in small lymph nodes would be difficult to detect on CT scan. Therefore, noting changes in lymph node density in the absence of CNN on CT scans is necessary in case the primary tumour is low-grade SCC.

Topics: Adult; Aged; Aged, 80 and over; Carcinoma, Squamous Cell; Female; Humans; Keratins; Lymph Nodes; Lymphatic Metastasis; Male; Middle Aged; Mouth Neoplasms; Neck; Neck Dissection; Necrosis; Neoplasm Staging; Tomography, X-Ray Computed

Adenoid squamous cell carcinoma (ASCC) is an uncommon but well-recognized variant of squamous cell carcinoma that was first described by Lever in 1947. ASCC has been reported to originate in the sun-exposed skin of the head and neck and in other sites. An additional case of ASCC is reported here. The patient was a 64-year-old Japanese woman who requested examination of a reddish lesion on the left floor of the mouth. The biopsy material was diagnosed as squamous cell carcinoma. Clinical examination showed a well-circumscribed, 20 x 10 mm-sized lesion, which was categorized as cT2cN0cm 0. Tumor resection was therefore performed. Histologically, most parts of the lesion were conventional squamous cell carcinoma in situ, but the invasive part consisted of ASCC with gland-like or reticular appearance. The latter part was negative for mucin staining. Immunohistochemically, this lesion was positive for pancytokeratin, high-molecular-weight keratin, cytokeratin (CK) 7/8, CK19, E-cadherin and p53, but negative for vimentin, CK20, and S-100 protein. The Ki-67 labeling index was 50.3% in the ASCC part and 34.5% in the carcinoma in situ part. These findings and a review of the literature indicate that a gland-like feature of ASCC is associated with the loss of cell adhesion in the center of the cancer nests, and it can be confirmed simply by mucin staining to be neither an adenosquamous carcinoma nor ductal involvement of conventional squamous cell carcinoma.

Topics: Cadherins; Carcinoma, Adenosquamous; Carcinoma, Mucoepidermoid; Carcinoma, Squamous Cell; Cell Adhesion; Cell Proliferation; Diagnosis, Differential; Female; Humans; Immunohistochemistry; Keratins; Middle Aged; Mouth Neoplasms; Mucins; Tumor Suppressor Protein p53

Lymphoepithelioma-like carcinoma of the skin (LELCs) is a rare cutaneous neoplasm with histologic features resembling lymphoepitheliomatous tumors of the nasopharynx. The association of lymphoepitheliomas with Epstein-Barr Virus (EBV) at some extracutaneous sites is well documented. In contrast, the presence of EBV in LELCs has never been shown in either Caucasians or Asian patients. We present the first case of LELCs in a Tunisian patient, a 78-year-old woman who presented with a nodule of the right cheek of 2 months' duration. The patient underwent surgical excision and there was no evidence of local recurrence 6 months later. Histologically, the entire dermis was occupied by lobules composed of atypical epithelial cells surrounded by a dense lymphoplasmacytic infiltrate. Immunohistochemical examination showed that the epithelial tumor cells were positive for cytokeratin and epithelial membrane antigen. In situ hybridization investigations for the presence of EBV-encoded RNA showed negative results. Our findings suggest that LELCs is not related to EBV among North African patients.

Topics: Aged; Biomarkers, Tumor; Carcinoma, Squamous Cell; Diagnosis, Differential; Disease-Free Survival; Epstein-Barr Virus Infections; Female; Humans; Keratins; Mucin-1; Skin Neoplasms

The p16 and retinoblastoma (Rb) gene products are part of the retinoblastoma pathway controlling the G1-S transition of the cell cycle. Few studies on the expression of p16 and retinoblastoma proteins in oral cavity squamous carcinomas have been conducted.. To correlate the expression of p16 and retinoblastoma proteins to clinicopathological characteristics in these tumours.. 45 patients with resected oral cavity squamous carcinoma were selected, for whom this was the initial treatment and who were followed up for 5 years or until death. Immunohistochemical stains with antibodies to the Rb and p16 gene products were carried out on paraffin wax-embedded tissue. Data on clinicopathological features such as tumour differentiation, nodal status, stage and survival outcome were collected.. Retinoblastoma expression was seen in 39 of 45 (87%) patients and p16 expression in 6 of 45 (13%) patients. A significant inverse correlation was observed between retinoblastoma and p16 expression as nearly all retinoblastoma negative cases were p16 positive, and vice versa. When examined for clinicopathological correlates, it was found that all 39 tumours that expressed retinoblastoma displayed marked keratinisation and were of low-moderate histological grade. Conversely, five of the six tumours that expressed p16 were found to be poorly differentiated, with minimal keratin expression.. Salient relationships were seen between expression of retinoblastoma and p16 and keratinisation. A marked loss of keratin production was evident in the tumours that expressed p16. Tumours expressing retinoblastoma were seen to exhibit more widespread keratinisation. In addition, an inverse staining pattern was found for retinoblastoma and p16 as retinoblastoma-expressing tumours were nearly universally p16 negative and vice versa. No correlation of expression of either p16 or retinoblastoma was found with survival or stage. A link between the histologically observable morphology and expression of cell cycle regulatory protein with the expression of p16 and retinoblastoma has been suggested with keratinisation and differentiation of status.

Topics: Adult; Aged; Aged, 80 and over; Biomarkers, Tumor; Carcinoma, Squamous Cell; Cell Differentiation; Cyclin-Dependent Kinase Inhibitor p16; Female; Follow-Up Studies; Humans; Keratins; Male; Middle Aged; Mouth Neoplasms; Neoplasm Proteins; Neoplasm Staging; Retinoblastoma Protein; Survival Analysis

A clinicopathologic study of 108 cases of high-grade urothelial carcinomas of the renal pelvis is presented. Of the 108 tumors, 44 (40%) showed unusual morphologic features, including micropapillary areas (four cases), lymphoepithelioma-like carcinoma (two cases), sarcomatoid carcinoma (eight cases, including pseudoangiosarcomatous type), squamous differentiation and squamous cell carcinoma (15 cases), clear cells (two cases), glandular differentiation (two cases), rhabdoid, signet-ring or plasmacytoid cells (four cases), pseudosarcomatous stromal changes (four cases) and intratubular extension into the renal pelvis (three cases). Pathological staging was available in 62 patients; of these, 46 cases (74%) were in high stage (pT2-pT4) and 16 (26%) were in low stage (pTis, pTa, pT1). Clinical follow-up ranging from 1 to 256 months (median: 50 months) was available in 42 patients; of these, 26 (61%) died of tumor with a median survival of 31 months. The patients who did not die of their tumors showed only minimal or focal infiltration of the renal parenchyma by urothelial carcinoma, whereas those who died of their tumors showed massive infiltration of the kidney by the tumor. High-grade urothelial carcinomas of the renal pelvis can show a broad spectrum of histologic features similar to those seen in the urinary bladder. Our results support the finding that, unlike urothelial carcinomas of the bladder, the majority of primary urothelial carcinomas of the renal pelvis are of high histologic grade and present in advanced stages. Our study further highlights the fact that, in the renal pelvis, urothelial carcinomas show a tendency to frequently display unusual morphologic features and metaplastic phenomena. The importance of recognizing these morphologic variants of urothelial carcinoma in the renal pelvis is to avoid confusion with other conditions. The possibility of a high-grade urothelial carcinoma should always be considered in the evaluation of a tumor displaying unusual morphologic features in the renal pelvis, and attention to proper sampling as well as the use of immunohistochemical stains will be of importance to arrive at the correct diagnosis.

Topics: Adult; Aged; Aged, 80 and over; Carcinoma, Renal Cell; Carcinoma, Squamous Cell; Carcinoma, Transitional Cell; Diagnosis, Differential; Female; Humans; Immunohistochemistry; In Situ Hybridization; Keratin-7; Keratins; Kidney Neoplasms; Kidney Pelvis; Male; Middle Aged; RNA, Viral; Urinary Bladder Neoplasms

p63 has been recently reported to be expressed in sarcomatoid/metaplastic carcinoma of the breast, in addition to its role as a myoepithelial marker. A large series of 34 metaplastic carcinomas, including cases with pure epithelial component (squamous cell and adenosquamous carcinomas), biphasic tumours with carcinomatous and sarcomatoid components and monophasic tumours with only spindle cell component, were evaluated for p63 expression with respect to the different cellular components.. All of the metaplastic carcinomas were assessed for p63 and conventional epithelial and mesenchymal markers of AE1/3, CAM5.2 and vimentin by immunohistochemistry.. All of the different categories of metaplastic carcinomas showed similar clinico-pathological features (patient age, tumour size, nuclear grade, mitotic activity, lymph node status and hormonal receptor status). For metaplastic carcinoma with epithelial component only, p63 was only expressed in the squamous cell component, but not the adenocarcinoma component. Eight of the 10 tumours were positive for p63. For the tumours with sarcomatoid component, either singly or together with carcinomatous component, p63 was positive in 14 of 24 cases. Pure sarcomas and carcinomas were all negative for p63 staining by immunohistochemistry, thus rendering p63 staining highly specific for diagnosing metaplastic carcinoma.. Using p63 for diagnosis of metaplastic carcinoma gives a sensitivity of 65%, a specificity of 96%, a positive predictive value of 96%, and a negative predictive value of 66% and an accuracy of 78%. p63 may be used as an adjunct marker in the diagnosis of metaplastic carcinoma.

Topics: Adult; Aged; Anion Exchange Protein 1, Erythrocyte; Antiporters; Biomarkers; Biomarkers, Tumor; Breast Neoplasms; Carcinoma, Adenosquamous; Carcinoma, Squamous Cell; DNA-Binding Proteins; Female; Humans; Immunohistochemistry; Keratins; Middle Aged; Sarcoma; Sensitivity and Specificity; Trans-Activators; Transcription Factors; Tumor Suppressor Proteins; Vimentin

To explore possible range of gene expression profiles in head and neck squamous cell carcinomas (HNSCC) and pairwised normal controls from Sudanese (n = 72) and Norwegian (n = 45) patients using a 15K cDNA microarray and to correlate the findings with clinicopathologic variables.. Samples from Sudan were grouped according to anatomic location/patients' habit of toombak (snuff) use, and 37 pools of 2 to 11 tumors matched to 37 pools of their normal controls from the same patients, respectively, were prepared. For Norway, eight pools of 3 to 11 tumors matched to eight pools of their normal controls from the same patients, respectively, were prepared according to anatomic location. Pools (n = 45) were hybridized to microarrays. For controls, 33 of the pools were hybridized against Human Reference RNA. Scanned array images were recorded, and data analysis was done in groups. For verification, results for selected genes were analyzed using quantitative real-time PCR/immunohistochemistry.. We identified 136 genes from Sudan and 154 from Norway as differentially expressed between tumors and controls. Changes of the genes found were confirmed in >70% of the pools by hybridization against Reference RNA. Seventy-three genes and three main pathways (signal transduction, cell communication, and ligand-receptor interaction) were of relevance to the HNSCCs from both countries. Hierarchical clustering of the 73 genes identified subclasses of mixed tumors from the two populations, two independent subgroups for Norwegian tumors by their anatomic sites, and five subgroups for Sudanese tumors by their toombak habits. Quantitative real-time PCR/immunohistochemistry validated the microarray-based data.. Differences in gene expression between tumor and nontumor tissues were identified in HNSCCs. Analysis of the two population groups revealed a common set of 73 genes within three main biological pathways. This indicates that the development of HNSCCs is mediated by similar biological pathways regardless of differences related to race, ethnicity, lifestyle, and/or exposure to environmental carcinogens. Of particular interest, however, was the valuable association of gene expression signature found with toombak use and anatomic site of the tumors.

Topics: Aged; Antigens, Nuclear; Black People; Carcinoma, Squamous Cell; Chemotactic Factors; Cluster Analysis; DNA-Binding Proteins; Female; Fibronectins; Gene Expression Profiling; Gene Expression Regulation, Neoplastic; Head and Neck Neoplasms; Humans; Immunohistochemistry; Keratins; Ku Autoantigen; Life Style; Male; Middle Aged; Norway; RNA, Messenger; S100 Proteins; Sudan; White People

The central type and peripheral type squamous cell carcinoma (SCC) of the lung have different clinicopathological characteristics, but, little is known about their biological characteristics. We investigated differences between the properties and phenotypes of peripheral-type (P-type) and central-type (C-type) SCC by performing an immunohistochemical analysis of each type by tissue microarray analysis with a large panel of antibodies. To examine strictly, we selected 20 P-type SCCs that were pathological stage T1 and limited to more peripherally than the fifth bronchial bifurcation, and 21 C-type SCCs that were pathological stage T1 and limited to a lobar bronchus. The results of the clinicopathological study showed that the patients with P-type SCC were significantly older than the patients with C-type SCC and that squamous metaplasia was predominant in C-type SCC than in P-type SCC. The 36 antibodies revealed different expression patterns of cytokeratin 7 (CK 7) and cytokeratin 19 (CK 19) between C-type and P-type SCC. CK 7 expression was more predominant in P-type SCC than in C-type SCC, and CK 19 expression was more predominant in C-type SCC than in P-type SCC. These results suggest that C-type and P-type SCC have different clinicopathological and biological features.

Topics: Adult; Aged; Biomarkers, Tumor; Carcinoma, Squamous Cell; Female; Humans; Keratin-7; Keratins; Lung Neoplasms; Male; Middle Aged; Neoplasm Proteins; Tissue Array Analysis

We have recently shown that HPV-positive tonsillar carcinoma in young patients exhibits nonkeratinizing basaloid morphology and a characteristic immunophenotype. The purpose of this study was to review a large number of cases of oropharyngeal carcinomas, in all age groups, and to identify tumors with nonkeratinizing morphology. Using polymerase chain reaction (PCR) the prevalence and type of HPV DNA was determined in representative cases and in a control group of conventional keratinizing squamous cell carcinomas. The tumors were further characterized with a panel of immunohistochemical stains. A total of 235 carcinomas were reviewed; 141 of the tonsils and 94 in the base of tongue. Ninety (36%) of the tonsillar and 30 (32%) of the base of tongue carcinomas were nonkeratinizing (NKCa) with basal cell features; the rest were classical keratinizing squamous cell carcinomas (KSCC). HPV DNA, particularly type 16, was identified in 10 (100%) of 10 of NKCA and in only 2 (20%) of 10 of KSCC (P = .0014). NKCas were strongly reactive to p16 antibodies while KSCC showed weak and focal reactivity. Higher Ki67 and lower p53 staining scores were observed in NKCa as compared to KSCC. It is concluded that NKCa of the tonsils and base of tongue is a distinct subtype of squamous cell carcinoma of the head and neck with high prevalence of HPV DNA and a characteristic immunophenotype.

Topics: Carcinoma, Squamous Cell; Case-Control Studies; DNA, Viral; Female; Histocytochemistry; Humans; Immunophenotyping; Keratins; Ki-67 Antigen; Male; Middle Aged; Oropharyngeal Neoplasms; Palatine Tonsil; Papillomaviridae; Papillomavirus Infections; Phenotype; Polymerase Chain Reaction; Sequence Analysis, DNA; Tongue Neoplasms; Tumor Suppressor Protein p53

Salivary gland lymphoepithelial carcinomas (LECs) are associated with Epstein-Barr virus (EBV) in endemic areas, whereas sporadic cases are usually EBV negative. We have studied two EBV-associated LECs from Caucasian patients for their EBV gene expression profile and their immunophenotype. Tumour cells of case 1 showed expression of EBNA1 only, corresponding to an EBV latency type I. Tumour cells of this case expressed various basal and glandular cytokeratins. In case 2, the LEC was accompanied by a low-grade spindle cell lesion with an immunophenotype of myoepithelial cells, whereas the high-grade tumour expressed cytokeratin (Ck) 8 only. In case 2, the high-grade tumour showed an EBV lantency II pattern with expression of EBNA1, LMP1 and LMP2A (latency II). The spindle cell lesion of this case was also EBV-infected and showed low levels of EBNA1 and LMP1 expression, while LMP2A was not detectable. The detection of EBV in both components of case 2 together with immunophenotypic evidence of transition between both components supports the notion that at least some LECs arise through a low-grade myoepithelial intermediate. Expression of LMP2A may be of therapeutic interest because it may make such cases amenable to immunotherapy with EBV-specific cytotoxic T cells.

Topics: Carcinoma, Squamous Cell; Epstein-Barr Virus Infections; Epstein-Barr Virus Nuclear Antigens; Female; Gene Expression; Gene Expression Profiling; Herpesvirus 4, Human; Humans; Immunophenotyping; In Situ Hybridization; Keratins; Male; Middle Aged; Salivary Gland Neoplasms; Tumor Virus Infections; Viral Matrix Proteins; Viral Proteins

A 93-year-old woman developed a mass on her right lower eyelid that was present for more than 6 months but underwent rapid expansion during several weeks prior to her ophthalmological evaluation. Examination revealed an approximately 1.8 cm in diameter, fleshy, fungating growth involving more than 60% of the right lower eyelid. Excisional biopsy disclosed a neoplasm arising from the epidermis composed of adjoining basal cell and signet-ring squamous cell carcinoma, without a transition zone. The cells comprising the basal and squamous cell carcinomas were distinct immunophenotypically, with only the basal cell carcinoma reacting with Ber-EP4 and CAM 5.2 antibodies. To our knowledge, this case represents the first example of a collision tumor composed of basal cell and signet-ring squamous cell carcinoma.

Topics: Aged, 80 and over; Biomarkers; Biomarkers, Tumor; Carcinoma, Basal Cell; Carcinoma, Signet Ring Cell; Carcinoma, Squamous Cell; Eyelid Neoplasms; Female; Humans; Keratins; Neoplasms, Multiple Primary; Treatment Outcome

Lysyl oxidase initiates the enzymatic stage of collagen and elastin cross-linking. Among five isoforms comprising the lysyl oxidase family, LOX is the better studied. LOX is associated to an antitumor activity in ras-transformed fibroblasts, and its expression is down-regulated in many carcinomas. The aim of this work was to shed light on LOX functions within the epidermis by studying its expression in human basal and squamous cell carcinomas and analyzing the effect of its enzymatic activity inhibition and protein absence on human keratinocytes behavior in a skin equivalent. In both carcinomas, LOX expression by epidermal tumor cells was lacking, while it was up-regulated around invading tumor cells in association with the stromal reaction. Lysyl oxidase activity inhibition using beta-aminoproprionitrile in a skin equivalent model prepared with both primary human keratinocytes and HaCaT cell line affected keratin 10 and filaggrin expression and disorganized the collagen network and the basement membrane. In spite of all these changes, no invasion phenotype was observed. Modelization of the invasive phenotype was only noticed in the skin equivalent developed with LOX antisense HaCaT cell line, where the protein LOX is specifically absent. Our results clearly indicate that lysyl oxidase enzymatic activity is essential not only for the integrity maintenance of the dermis but also for the homeostasis of the epidermis. Moreover, LOX protein plays a role in the skin carcinomas and invasion but not through its enzymatic activity.

Topics: Aminopropionitrile; Carcinoma, Basal Cell; Carcinoma, Squamous Cell; Cells, Cultured; Collagen; Dermis; Fibroblasts; Filaggrin Proteins; Humans; Intermediate Filament Proteins; Keratin-10; Keratinocytes; Keratins; Models, Biological; Neoplasm Invasiveness; Phenotype; Protein-Lysine 6-Oxidase; Skin Neoplasms

Screening of head and neck carcinoma patients with the proteomics-based AMIDA technology yielded a set of tumour-associated antigens, including the intermediate filament protein cytokeratin 8 (CK8). The expression pattern and specificity of CK8 was compared with those of the established markers pan-cytokeratins and CK13, and with that of the proliferation marker Ki67. Expression of CK8 correlated positively with malignancies of the head and neck areas. CK8 was not expressed in healthy epithelium, except for some rare cases of cells of the basal layer and laryngeal tissue. In contrast, the vast majority of head and neck squamous cell carcinomas and metastases strongly expressed CK8. Interestingly, CK8 de novo expression correlated with dysplastic areas of oral leukoplakic lesions, while hyperplastic leukoplakia remained CK8-negative but strongly panCK and CK13 positive. Thus, CK8 is an attractive marker molecule for a differentiated diagnosis of leukoplakia and head and neck carcinomas, which possesses notedly improved specificity as compared with panCK and CK13.

Topics: Biomarkers, Tumor; Carcinoma, Squamous Cell; Cell Transformation, Neoplastic; Head and Neck Neoplasms; Humans; Immunohistochemistry; Keratins; Ki-67 Antigen; Leukoplakia, Oral

An adult sooty mangabey (Cercocebus atys) with a solid mass arising from the skin of the dorsolateral cervical area was presented to the veterinary clinical staff. Grossly, the mass was firm, elongated, ulcerated at the tip, and measured 2.7 x 2.0 x 2.3 cm. It was surgically excised and then submitted for histopathologic evaluation. On histopathology, this tumor was composed of irregular masses and cords of neoplastic squamous epithelial cells that invaded the dermis and subcutis, often undergoing keratinization and forming numerous keratin pearls. On the basis of these histologic findings, the mass was diagnosed as a squamous cell carcinoma. Additional tests, including hematologic evaluations and radiographic views of the abdominal, thoracic, and cervical areas, were normal. Sections of the tumor were analyzed by electron microscopy and showed no evidence of viral particles. To the authors' knowledge, this is the first reported case of a spontaneous cutaneous squamous cell carcinoma in a sooty mangabey.

Topics: Animals; Animals, Laboratory; Carcinoma, Squamous Cell; Cercocebus atys; Histocytochemistry; Keratins; Male; Microscopy, Electron, Transmission; Monkey Diseases; Neck; Radiography; Skin Neoplasms

A 64 year old man presented with progressive impairment of right sided cranial nerves. Chronic immunosuppression for renal transplantation had resulted in multiple squamous cell carcinomata of the head and neck. Magnetic resonance imaging and subsequent right facial nerve biopsy confirmed perineural spread of a squamous cell carcinoma as the cause of the multiple cranial neuropathies.

Topics: Carcinoma, Squamous Cell; Facial Nerve Diseases; Head and Neck Neoplasms; Humans; Keratins; Magnetic Resonance Imaging; Male; Middle Aged

Esophageal cancers are predominantly carcinomas, which are-due to their origin from the epithelial lining-visible by endoluminal view. We report in this study about the rare case of an esophageal squamous cell cancer with an unusual, entirely intramural growth pattern. The diagnosis could only be established postoperatively, because all preoperative biopsies had failed to demonstrate the tumor. The entirely intramural growth pattern of esophageal squamous cell cancer is an exceedingly rare variant, with only one previously reported case. Nevertheless, clinicians, radiologists, and pathologists should be aware of the potential existence of this condition, especially when clinical and imaging results suggest a malignant tumor that cannot be proven on biopsies. Surgical exploration must be considered under these circumstances.

Topics: Biomarkers, Tumor; Carcinoma, Squamous Cell; Cell Count; Disease-Free Survival; Esophageal Neoplasms; Humans; Immunohistochemistry; Keratins; Male; Middle Aged; Treatment Outcome

We previously showed that the EP2 knockout mice were resistant to chemically induced skin carcinogenesis. The purpose of this study was to investigate the role of the overexpression of the EP2 receptor in mouse skin carcinogenesis. To determine the effect of overexpression of EP2, we used EP2 transgenic (TG) mice and wild-type (WT) mice in a DMBA (7,12-dimethylbenz[alpha]anthracene)/TPA (12-O-tetradecanoylphorbol-13-acetate) two-stage carcinogenesis protocol. EP2 TG mice developed significantly more tumors compared with WT mice. Overexpression of the EP2 receptor increased TPA-induced keratinocyte proliferation both in vivo and in vitro. In addition, the epidermis of EP2 TG mice 48 h after topical TPA treatment was significantly thicker compared to that of WT mice. EP2 TG mice showed significantly increased cyclic adenosine monophosphate levels in the epidermis after prostaglandin E2 (PGE2) treatment. The inflammatory response to TPA was increased in EP2 TG mice, as demonstrated by an increased number of macrophages in the dermis. Tumors and 7 x TPA-treated and DMBA-TPA-treated (6 weeks) skins from EP2 TG mice produced more blood vessels than those of WT mice as determined by CD-31 immunostaining. Vascular endothelial growth factor (VEGF) protein expression was significantly increased in squamous cell carcinoma (SCC) samples from EP2 TG mice compared that of WT mice. There was, however, no difference in the number of apoptotic cells in tumors from WT and EP2 TG mice. Together, our results suggest that the overexpression of the EP2 receptor plays a significant role in the protumorigenic action of PGE2 in mouse skin.

Topics: Animals; Animals, Newborn; Bromodeoxyuridine; Carcinoma, Squamous Cell; Cattle; Cell Culture Techniques; Cell Proliferation; Female; Humans; Hyperplasia; Inflammation; Keratinocytes; Keratins; Mice; Mice, Transgenic; Neovascularization, Pathologic; Polymerase Chain Reaction; Receptors, Prostaglandin E; Receptors, Prostaglandin E, EP2 Subtype; Skin Neoplasms; Tetradecanoylphorbol Acetate; Up-Regulation

The aim of the present study was to evaluate the occult lymph node carcinomatous diffusion in head and neck squamous cell carcinoma (HNSCC). A total of 1328 lymph nodes from 31 patients treated between 2004 and 2005 were prospectively evaluated by routine haematoxylin-eosin-safran (HES) staining, immunohistochemistry (IHC) and real-time Taqman reverse-transcriptase polymerase chain reaction (real-time RT-PCR) assay. Amplification of cytokeratin 19 (CK19) mRNA transcripts using real-time RT-PCR was used to quantify cervical micrometastatic burden. The cervical lymph node metastatic rates determined by routine HES staining and real-time RT-PCR assay were 16.3 and 36.0%, respectively (P<0.0001). A potential change in the nodal status was observed in 13 (42.0%) of the 31 patients and an atypical pattern of lymphatic spread was identified in four patients (12.9%). Moreover, CK19 mRNA expression values in histologically positive lymph nodes were significantly higher than those observed in histologically negative lymph nodes (P<0.0001). These results indicate that real-time RT-PCR assay for the detection of CK19 mRNA is a sensitive and reliable method for the detection of carcinomatous cells in lymph nodes. This type of method could be used to reassess lymph node status according to occult lymphatic spread in patients with HNSCC.

Topics: Adult; Aged; Carcinoma, Squamous Cell; Female; Head and Neck Neoplasms; Humans; Immunohistochemistry; Keratins; Lymph Node Excision; Lymph Nodes; Lymphatic Metastasis; Male; Middle Aged; Neoplasm Staging; Prospective Studies; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Sensitivity and Specificity

The main goal of sentinel lymph node (SLN) detection in head and neck squamous cell carcinomas is to limit neck dissections to pN+ cases only. However, intraoperative + diagnosis cannot be routinely done using the current gold standard, serial step sectioning with immunohistochemistry. Real-time quantitative reverse transcription-PCR (RT-PCR) is potentially compatible with intraoperative use, proving highly sensitive in detecting molecular markers. This study postoperatively assessed the accuracy of quantitative RT-PCR in staging patients from their SLN.. A combined analysis on the same SLN by serial step sectioning with immunohistochemistry and quantitative RT-PCR targeting cytokeratins 5, 14, and 17 was done in 18 consecutive patients with oral or oropharyngeal squamous cell carcinoma and 10 control subjects.. From 71 lymph nodes examined, mRNA levels (KRT) were linked to metastasis size for the three cytokeratins studied (Pearson correlation coefficient, r = 0.89, 0.73, and 0.77 for KRT 5, 14, and 17 respectively; P < 0.05). Histopathology-positive SLNs (macro- and micrometastases) showed higher mRNA values than negative SLNs for KRT 17 (P < 10(-4)) and KRT 14 (P < 10(-2)). KRT 5 showed nonsignificant results. KRT 17 seemed to be the most accurate marker for the diagnosis of micrometastases of a size >450 mum. Smaller micrometastases and isolated tumor cells did not provide results above the background level. Receiver operating characteristic curve analysis for KRT 17 identified a cutoff value where patient staging reached 100% specificity and sensitivity for macro- and micrometastases.. Quantitative RT-PCR for SLN staging in cN(0) patients with oral and oropharyngeal squamous cell carcinoma seems to be a promising approach.

Topics: Adult; Aged; Carcinoma, Squamous Cell; Humans; Immunohistochemistry; Keratin-14; Keratin-5; Keratins; Lymph Nodes; Lymphatic Metastasis; Middle Aged; Mouth Neoplasms; Neoplasm Staging; Oropharyngeal Neoplasms; Reproducibility of Results; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Sensitivity and Specificity; Sentinel Lymph Node Biopsy

Adequate brushing of oral mucosa is important for accurate human papillomavirus (HPV) detection in potentially malignant (oral leukoplakia [OL], oral lichen planus [OLP]) and malignant (oral squamous cell carcinoma [OSCC]) lesions. Since various factors may limit the adequacy of oral brushing and, consequently, the accuracy of HPV detection, modified sampling procedures should be evaluated for their effect on HPV frequency and/or types detected.. To compare the HPV frequency in samples obtained by brushing the lesion site with the frequency in samples obtained by brushing an apparently normal adjacent site. The correlation between HPV frequency and keratinization of the site affected by the lesion, as well as sociodemographic variables (age, sex, smoking and drinking habits), was also examined.. HPV DNA was detected in brushing samples from 50 patients with OL, 49 with OLP, and 17 with OSCC. Polymerase chain reaction (PCR) amplification was performed by MY09/MY11 and GP05+/GP06+ primers; the HPV type was identified by DNA sequencing and a reverse hybridization (line probe) assay. Data were analyzed by the Z test, the Fisher's exact test, the chi-square test, odds ratio (OR), and a logistic regression model.. HPV DNA was detected in 22% of samples from lesion sites and in 16% of samples from adjacent sites (p = 0.22) in patients with OL, in 24.5% and 22.4% of samples from lesion and adjacent sites, respectively, in patients with OLP (p = 0.40), and in 35.3% and 41.2% of samples from lesion and adjacent sites, respectively, in patients with OSCC (p = 0.36). Lesions adjacent to HPV-positive normal sites had an increased rate of HPV detection (OR = 30; 95% CI 9.57, 94.1). HPV-18 was the most frequent genotype, followed by HPV-6, -16, -33, and -53. HPV prevalence was reduced in lesions at keratinized sites (14.5%) compared with non-keratinized sites (34.4%; p = 0.007; OR = 0.32; 95% CI 0.13, 0.81).. In patients with OL, OLP, or OSCC, a high prevalence of HPV infection was shown in apparently normal sites adjacent to lesion sites infected by HPV. The lower HPV frequency in lesions at keratinized sites suggests that HPV detection by lesion brushing is affected by keratinization. The keratinized epithelium may be less susceptible to HPV infection or, alternatively, the highly proliferative activity in non-keratinized sites may predispose to HPV infection.. Results from this study indicate that taking samples from normal sites adjacent to oral lesions may be of value in HPV detection, particularly when the lesions are located at keratinized sites. This sampling procedure may allow more accurate diagnosis of HPV infection compared with sampling only the lesion site, and may also represent a reliable method to investigate the biological characteristics of HPV infection and related oral carcinogenesis.

Topics: Alphapapillomavirus; Carcinoma, Squamous Cell; DNA, Viral; Female; Humans; Keratins; Lichen Planus, Oral; Male; Middle Aged; Mouth Mucosa; Mouth Neoplasms; Papillomavirus Infections

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

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

The membrane serine protease matriptase is required for epidermal barrier function, hair formation, and thymocyte development in mice, and dysregulated matriptase expression causes epidermal squamous cell carcinoma. To elucidate the specific functions of matriptase in normal and aberrant epidermal differentiation, we used enzymatic gene trapping combined with immunohistochemical, ultrastructural, and barrier function assays to delineate the spatio-temporal expression and function of matriptase in mouse keratinized tissue development, homeostasis, and malignant transformation. In the interfollicular epidermis, matriptase expression was restricted to postmitotic transitional layer keratinocytes undergoing terminal differentiation. Matriptase was also expressed in keratinizing oral epithelium, where it was required for oral barrier function, and in thymic epithelium. In all three tissues, matriptase colocalized with profilaggrin. In staged embryos, the onset of epidermal matriptase expression coincided with that of profilaggrin expression and acquisition of the epidermal barrier. In marked contrast to stratifying keritinized epithelium, matripase expression commenced already in undifferentiated and rapidly proliferating profilaggrin-negative matrix cells and displayed hair growth cycle-dependent expression. Exposure of the epidermis to carcinogens led to the gradual appearance of matriptase in a keratin-5-positive proliferative cell compartment during malignant progression. Combined with previous studies, these data suggest that matriptase has diverging functions in the genesis of stratified keratinized epithelium, hair follicles, and squamous cell carcinoma.

Topics: Animals; Animals, Newborn; beta-Galactosidase; Biomarkers, Tumor; Carcinogens; Carcinoma, Squamous Cell; Cell Differentiation; Cell Line; Cell Proliferation; Embryo, Mammalian; Epidermis; Epithelium; Filaggrin Proteins; Hair; Hair Follicle; Immunohistochemistry; Intermediate Filament Proteins; Keratin-5; Keratins; Mice; Mice, Transgenic; Serine Endopeptidases; Stem Cells; Thymus Gland

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

Immunodetection of GLUT1, p63 and phospho-histone H1 in invasive head and neck squamous carcinoma: correlation of immunohistochemical staining patterns with keratinizationAims : To examine invasive head and neck squamous carcinomas for expression of GLUT1, a glucose transporter and marker of increased glucose uptake, glycolytic metabolism and response to tissue hypoxia; p63, a p53 homologue that is a marker of the undifferentiated proliferative basaloid phenotype; and phospho-histone H1, a marker of activation of the cell cycle-promoting cyclin-dependent kinases 1 and 2. Methods : Routinely processed slides from 34 invasive squamous carcinomas, including 25 with intraepithelial components, were immunostained with anti-GLUT1 (Chemicon), anti-p63 (4A4, Santa Cruz), and antiphospho-histone H1 (monoclonal 12D11). Results : In keratinizing carcinomas, all three markers were most commonly immunodetected peripherally, with loss of expression in central keratinized zones. In contrast, in non-keratinizing carcinomas, p63 and phospho-histone H1 expression was most commonly observed throughout tumour nests and anti-GLUT1 stained in a pattern suggestive of hypoxia-induced expression ('antistromal' staining), in which cells at the tumour-stromal interface were GLUT1- and cells in central, perinecrotic zones showed progressive induction of GLUT1. Intraepithelial components also displayed basal and 'antibasal' GLUT1 staining patterns, homologous to the pro- and antistromal patterns in invasive carcinoma; basal patterns in intraepithelial lesions appeared to be more predictive of keratinizing invasive carcinoma and antibasal intraepithelial staining more predictive of non-keratinizing poorly differentiated carcinomas. Conclusions : Keratinizing and non-keratinizing squamous carcinomas differ in expression patterns of GLUT1, p63 and phospho-histone H1. In the former, all three markers were typically suppressed in conjunction with keratinization; in the latter, GLUT1 expression was more likely to occur in a hypoxia-inducible pattern and expression of p63 and phospho-histone H1 was unsuppressed. GLUT1 expression patterns in intraepithelial lesions may be predictive of the differentiation status of the associated invasive carcinoma.

Topics: Biomarkers, Tumor; Carcinoma, Squamous Cell; Disease Progression; DNA-Binding Proteins; Glucose Transporter Type 1; Head and Neck Neoplasms; Histones; Humans; Immunohistochemistry; Keratins; Neoplasm Invasiveness; Phosphoproteins; Phosphorylation; Trans-Activators; Transcription Factors; Tumor Suppressor Proteins

Topics: Carcinoma, Basal Cell; Carcinoma, Basosquamous; Carcinoma, Squamous Cell; Diagnosis, Differential; Humans; Immunohistochemistry; Keratin-1; Keratin-14; Keratin-7; Keratins

To investigate the frequency of micrometastasis in levels lII - IV of clinical negative neck (cN0) in patients with squamous cell carcinoma (SCC) of oral tongue, and to discuss the management of cervical lymph node for cN0 tongue SCC.. A total of 471 cervical lymph nodes derived from 25 patients with cN0 tongue SCC, including 263 lymph nodes in level III and 208 lymph nodes in level IV, were included in this study. All lymph nodes were re-examined by anti-cytokeratin (CK) immunohistochemical staining combined with semi-serial section per 500 microm.. Among the 25 cases, seven patients were confirmed harboring metastasis in 11 lymph nodes of level III, and no positive lymph node in level IV was detected by routine hematoxylin-eosin (HE) staining. 11 positive lymph nodes in level IIl, which confirmed by HE staining, were also detected by immunohistochemical staining with CK combined with semiserial section. Among the 460 cervical lymph nodes in which HE staining did not show metastasis, only one lymph node in level III harboring a 2.0 mm x 1.5 mm micrometastasis was detected by immunohistochemical staining with CK, and no positive lymph node in level IV was detected by immunohistochemical staining with CK.. The frequency of occult metastasis in level IV was very low, so it seemed unnecessary to dissect level IV for all patients with cN0 tongue SCC.

Topics: Adult; Aged; Carcinoma, Squamous Cell; Female; Humans; Keratins; Lymph Nodes; Lymphatic Metastasis; Male; Middle Aged; Neck; Neoplasm Micrometastasis; Tongue; Tongue Neoplasms

To establish a hepatic metastatic subline of nasopharyngeal carcinoma (NPC) cell line.. NPC cells metastatic to the liver were isolated from nude mice and the invasion and metastatic ability of the cells was observed in vivo and in vitro.. The invasion and metastasis activity of 5-8F-H3B-EGFP (an in vivo isolate with enhanced liver metastatic behaviors) were enhanced obviously in comparison with the parent cell line 5-8F-EGFP. This subline may be useful for cloning genes related to liver metastasis of NPC.

Topics: Animals; Carcinoma, Squamous Cell; Cell Line, Tumor; Cell Proliferation; Cell Survival; Disease Models, Animal; Female; Green Fluorescent Proteins; Humans; Keratins; Liver Neoplasms, Experimental; Male; Mice; Mice, Inbred BALB C; Mice, Nude; Nasopharyngeal Neoplasms; Neoplasm Metastasis; Neoplasm Transplantation

Esophageal cancer remains a highly lethal malignancy for which the genetic and proteomic events are poorly understood. Studies have reported dysregulated proteins in esophageal carcinoma; however, the magnitude of these changes remains largely uncharacterized. Little is known about alterations early in the neoplastic pathway. Using multiplex tissue immunoblotting, we quantified the expression of seven proteins in esophageal carcinogenesis. Regions of normal, dysplasia, and invasive carcinoma of the squamous esophagus in six patients were characterized. Pan-cytokeratin (CK) was essentially unchanged across the transition (0.96 in dysplasia and 0.69 in tumor). Expression levels of annexin 1, CK-4, and CK-14 were all decreased in dysplasia and tumor compared with normal (reference, 1.00): annexin 1, 0.30 in dysplasia and 0.15 in tumor; CK-4, 0.20 in dysplasia and 0.16 in tumor; and CK-14, 0.54 in dysplasia and 0.40 in tumor. Expression of two proteins was increased in dysplasia and tumor versus normal: cyclooxygenase-2, 1.35 in dysplasia and 2.32 in tumor and p53, 1.29 in dysplasia and 2.37 in tumor. Secreted protein, acidic and rich in cysteine, which is expressed in the adjacent stroma, was 1.56-fold higher in stroma underlying dysplasia and 6.20-fold increased in dysplastic stroma surrounding invasive tumor. These findings suggest that changes in protein expression can be detected during the transition to dysplasia and may be useful biomarkers.

Topics: Biomarkers, Tumor; Carcinoma, Squamous Cell; Disease Progression; Esophageal Neoplasms; Esophagus; Gene Expression Regulation, Neoplastic; Humans; Immunoblotting; Keratins; Molecular Diagnostic Techniques; Neoplasm Invasiveness; Osteonectin; Pilot Projects; Precancerous Conditions; Proteome; Tumor Suppressor Protein p53

The study was performed by using a number of eight cases of cervical carcinomas suiting to basaloid carcinomas and spindle cell carcinomas under the circumstances of usual histopathological staining. Immunohistochemically we used anticytokeratin monoclonal antibody (AE1/AE3) to confirm the epithelial differentiation and also PCNA to evaluate the cell proliferation rate. Tumor positiveness for AE1/AE3 cytokeratin cocktail confirmed its epithelial nature. Immunoexpression for PCNA indicated a high index of cell proliferation for all the cases with a more increased value for the basaloid carcinomas.

Topics: Adult; Antibodies, Monoclonal; Carcinoma, Squamous Cell; Female; Humans; Immunohistochemistry; Keratins; Middle Aged; Proliferating Cell Nuclear Antigen; Uterine Cervical Neoplasms

A 10-year-old, female, pot-bellied pig (Sus scrofa) experienced a 3-month history of reduced appetite, dysphagia, and weight loss. Clinical examination revealed a mass in the left part of the oral cavity extending from the hard to the soft palate. At necropsy, a firm, white, poorly demarcated ulcerated mass at the left hard and soft palate with metastases to the left retropharyngeal lymph node and the lung was observed. Additional findings included a uterine adenocarcinoma, a hepatocellular adenoma, and nodular hyperplasias in spleen and adrenal glands. Histologically, the poorly demarcated, infiltrative growing oral mass consisted of islands, cords, and single epithelial cells with moderate squamous differentiation. Cells were strongly positive for cytokeratin by immunohistochemistry. Similar cells were found in the left retropharyngeal lymph node and the lung. The present findings represent the first report of a metastasizing oral squamous cell carcinoma in a pig.

Topics: Animals; Carcinoma, Squamous Cell; Fatal Outcome; Female; Immunohistochemistry; Keratins; Mouth Neoplasms; Neoplasm Metastasis; Sus scrofa; Swine; Swine Diseases

The genetic bases underlying esophageal tumorigenesis are poorly understood. Our previous studies have shown that coordinated deletion of the Smad4 and PTEN genes results in accelerated hair loss and skin tumor formation in mice. Herein, we exemplify that the concomitant inactivation of Smad4 and PTEN accelerates spontaneous forestomach carcinogenesis at complete penetrance during the first 2 months of age. All of the forestomach tumors were invasive squamous cell carcinomas (SCCs), which recapitulated the natural history and pathologic features of human esophageal SCCs. A small population of the SCC lesions was accompanied by adenocarcinomas at the adjacent submucosa region in the double mutant mice. The rapid progression of forestomach tumor formation in the Smad4 and PTEN double knockout mice corresponded to a dramatic increase in esophageal and forestomach epithelial proliferation. The decreased expression of p27, p21, and p16 together with the overexpression of cyclin D1 contributed cooperatively to the accelerated forestomach tumorigenesis in the double mutant mice. Our results point strongly to the crucial relevance of synergy between Smad4 and PTEN to suppress forestomach tumorigenesis through the cooperative induction of cell cycle inhibitors.

Topics: Animals; Carcinoma, Squamous Cell; Cell Growth Processes; Cell Transformation, Neoplastic; Cyclin D; Cyclins; Down-Regulation; Esophageal Neoplasms; Gene Expression Regulation, Neoplastic; Genes, Tumor Suppressor; Keratins; Mice; Mice, Knockout; Mice, Transgenic; Mutation; Proto-Oncogene Proteins c-akt; PTEN Phosphohydrolase; Smad4 Protein; Stomach Neoplasms

Spindle cell squamous carcinoma (SCSC) is a rare and peculiar biphasic malignant neoplasm that occurs mainly in the upper aerodigestive tract. It consists of sarcomatoid proliferation of pleomorphic spindle-shaped cells and squamous cell carcinoma.. Here, we established a SCSC cell line from a tumour arisen in gingiva. We characterized the feature of a SCSC cell line by immunohistochemistry. To know the biological feature, we examined the cell growth, invasiveness and epithelial-mesenchymal transition markers of a SCSC cell line in comparison with oral squamous cell carcinoma (OSCC) cell lines.. By immunohistochemical analyses, the primary tumour expressed cytokeratin and vimentin, indicating carcinosarcoma-like characters. This tumour also showed overexpression of p53 protein. Cultured SCSC cells resulted in bypass of crisis and maintenance over passage 100. The established SCSC cell line was spindle-shaped and showed identical immunohistochemical characters to those of primary tumour cells. Similar to the primary tumour, the cell line showed p53 overexpression and had p53 mutation at codon 132: AAG (lys)-->AAT (asp). The SCSC cell line grew slower than two other OSCC cell lines (MSCC-1 and HSC-2), whereas SCSC cells had remarkable invasiveness in comparison with these cell lines. Moreover, SCSC cells expressed wnt-5a and vimentin mRNA at high levels, but did not express E-cadherin mRNA. This expression pattern of the markers was similar to that of mesenchymal cells, not of epithelial cells.. In the present study, we newly established a SCSC cell line with strong invasiveness. This is the first report on the establishment of SCSC cell line. The SCSC cell line can be a useful cell model for the study to know the cytodifferentiation and nature of SCSC.

Topics: Aged; Biomarkers, Tumor; Cadherins; Carcinoma, Squamous Cell; Cell Line, Tumor; Gingival Neoplasms; Humans; Keratins; Male; Peptide Fragments; Tumor Suppressor Protein p53; Vimentin

To analyze the lymphatic distribution of metastatic carcinomatous cells in cervical lymph nodes in head and neck squamous cell carcinoma (HNSCC).. We retrospectively reviewed 119 patients treated in our hospital for HNSCC (1999-2004). Topography of the neck dissection specimens was prospectively classified according to the classification of Robbins. The 4000 lymph nodes were analyzed by optical microscopy using hematoxylin-eosin-safran (HES) staining. In cases of negative results in level II, cytokeratin (AE1/AE3) immunodetection was performed.. Metastases were visualized using HES in 6.4% of lymph nodes for oral cavity, and 4.7% of oropharyngeal, 4.4% of hypopharyngeal, and 1.3% of endolaryngeal cancers. The highest incidence of nodal metastasis was observed in level IIa (P < 0.01). In eight patients (6.7%) with lymph node metastases, level II was spared. In these patients, all 134 nodes histologically negative on HES were confirmed to be negative by IHC.. Level IIa is the main level involved in regional metastases of HNSCC, regardless of the primary site of cancer. However, in eight (6.7%) patients, level II was spared, as confirmed by IHC. In these cases, level II did not represent the first step of drainage from the tumor. The sentinel lymph node technique in HNSCC is discussed in light of these results.

Topics: Adult; Aged; Aged, 80 and over; Carcinoma, Squamous Cell; Coloring Agents; Female; Fluorescent Dyes; Head and Neck Neoplasms; Humans; Keratins; Laryngeal Neoplasms; Lymph Nodes; Lymphatic Metastasis; Male; Middle Aged; Mouth Neoplasms; Neck; Neck Dissection; Neoplasm Staging; Pharyngeal Neoplasms; Prospective Studies; Retrospective Studies; Sentinel Lymph Node Biopsy

Primary small cell carcinoma of esophagus (SCC) is a rare disease but has more aggressive behavior than esophageal squamous cell carcinoma (SQC). The distinction of SCC from SQC is very important therapeutically. Few systematic studies of immunohistochemical analysis to differentiate primary esophageal SCC with concomitant SQC, and adjacent normal esophageal epithelium have been reported. The objective of this study is to know the immunohistochemical markers in distinguishing SCC from SQC of esophagus. We studied 6 cases of primary esophageal SCC histologically and immunohistochemically using 15 different antibodies including a cytokeratin (CK) panel and neuroendocrine markers. Pure SCCs were identified in 2 of the 6 cases (33.3%), and the remaining 4 cases (66.7%) were found to exhibit combined SCC with an SQC component. Among the combined types, in situ SQC was observed in all 4 cases (100.0%) and invasive SQC was observed in 3 cases (75.0%). Among the normal esophageal epithelia specimens (n=7), CK14 expression was seen 6 out of 7 (85.7%) specimens and CKAE1/3 in 5 out of 7 (71.4%) specimens. CD56 was more frequently expressed among the SCC specimens (4/6; 66.7%) than among the SQC specimens (0/4; 0%; p = 0.07). The expression of p53 protein in SCC (4/6; 66.7%) and SQC (3/4; 75.0%) specimens was significantly more frequent than in normal esophageal epithelium (0/7; 0%; p = 0.02 each). Neurone-specific enolase (NSE), synaptophysin, and CKAE1/3 were expressed in 83.3%, 66.7%, and 66.7% of the SCC cases (n=6), respectively. NSE expression was significantly more frequent in SCC specimens (5/6; 83.3%) (p = 0.02) than in normal esophageal epithelium (0/7; 0%; p = 0.02). However, the frequencies of NSE expression in SCC (5/6; 83.3%) and SQC (2/4; 50%) were not significantly different. All of the SQC specimens (n=4) expressed CK14 and CKAE1/3. The CK14 expression was significantly more frequent in SQC specimens (4/4; 100.0%) than in (p = 0.04) SCC specimens (1/6; 16.6%; p = 0.04). These findings suggest that the CK14 and CD56 may be useful markers for differentiating SQC from SCC and vice versa. The p53 may also be useful to differentiate normal esophageal epithelium from SCC or SQC tissue.

Topics: Carcinoma, Small Cell; Carcinoma, Squamous Cell; CD56 Antigen; Diagnosis, Differential; Epithelium; Esophageal Neoplasms; Humans; Immunochemistry; Keratins

To evaluate the performance of 18F-FDG three-head tomography with coincidence imaging and serum tumor marker assays in identifying lung lesions in 104 patients with abnormal findings on chest X-ray or computer tomography.. A prospective evaluation of 18F-FDG coincidence imaging and the measurement of 3 serum markers for lung cancer ( carcinoembryonic antigen, CYFRA21-1 and neuron specific enolase) were performed within one week in 104 inpatients with suspected lung malignancy. All images were analyzed visually. It was considered positive for malignancy if the 18F-FDG uptake was increased relative to that in the adjacent lung tissue, and was focal. The serum tumor marker test was considered positive for malignancy if the serum level of at least one marker was elevated.. 66 patients were proven to have lung cancer by pathology, and 38 patients had benign lung diseases. The sensitivity, specificity, accuracy of 18F-FDG coincidence imaging and serum tumor markers in assessing lung cancers were 80. 0% , 77. 2% , 77. 9% and 56. 0% , 60. 9%, 64. 4% , respectively. 18F-FDG coincidence images in assessing lung lesions showed significantly higher sensitivity, specificity and accuracy than serum tumor markers. Four patients with lung cancer had negative findings on 18F-FDG coincidence images but showed positive serum markers.. 18F-FDG coincidence imaging is a powerful tool for evaluating patients with lung lesions suggestive of malignancy. Although the determination of serum marker levels is less accurate than 18F-FDG coincidence imaging, the combination of a positive 18F-FDG coincidence result and positive tumor markers may be helpful in improving the diagnosis of lung cancers.

Topics: Adult; Aged; Aged, 80 and over; Antigens, Neoplasm; Biomarkers, Tumor; Carcinoembryonic Antigen; Carcinoma, Small Cell; Carcinoma, Squamous Cell; Female; Fluorodeoxyglucose F18; Humans; Keratin-19; Keratins; Lung Neoplasms; Male; Middle Aged; Phosphopyruvate Hydratase; Plasma Cell Granuloma, Pulmonary; Positron-Emission Tomography; Prospective Studies; Radiopharmaceuticals; Sensitivity and Specificity; Tuberculosis, Pulmonary

The identification of a reliable circulating tumor marker in squamous cell carcinoma of the head and neck (SCCHN) could assist in diagnosis and monitoring response to therapy.. The aim of this study was to investigate the effectiveness of the serum tumor markers CYFRA 21-1, TPA-M, SCCA, and CEA.. Serum levels of CYFRA 21-1, TPA-M, SCCA, and CEA were measured in 136 patients with a histologically proven SCCHN before and after treatment and in 125 healthy subjects, as controls. We evaluated the sensitivity and specificity of these tumor markers and to correlate their levels with tumor staging, grading, or performance status.. The study showed that none of the above markers presented satisfactory specificity and sensitivity in early diagnosis. In comparison with the other markers, TPA-M was the most effective of all markers and indicated a positive correlation with the grade of differentiation and nodal status. A remarkable correlation between high levels of TPA-M and CYFRA 21-1 in advanced stages (III, IV) of cancer has been shown.. All the tumor markers that were studied have significant limitations in the early diagnosis of cancer, but TPA-M and CYFRA 21-1 may have a role in monitoring the success of therapy and follow up of patients with SCCHN.

Topics: Aged; Antigens, Neoplasm; Biomarkers, Tumor; Carcinoembryonic Antigen; Carcinoma, Squamous Cell; Female; Head and Neck Neoplasms; Humans; Keratin-19; Keratins; Male; Middle Aged; Neoplasm Staging; Prospective Studies; Sensitivity and Specificity; Serpins; Tissue Polypeptide Antigen

Lymph node micrometastases in patients with squamous cell carcinoma of the larynx found node-negative by conventional histology may be discovered by immunohistochemistry, particularly by using mono- and policlonal antibodies which are reactive with epithelial cells. Then tumors classified as pN0 by routine methods may be reclassified more correctly as pN1. Authors investigated the incidence of micrometastases in the neck dissection specimens originally staged as pN0 from 22 patients with laryngeal cancer treated surgically at ENT Department Medical University of Lodz between 1998-1999 according to: the survival, using immunostaining with panel of mono- and policlonal antibodies to cytokeratins CK1, CK4, CK5, CK6, CK8, CK10, CK13 and CK18. The relationship between micro-metastases and clinical features of primary tumor and lymph nodes has been discussed.

Topics: Aged; Aged, 80 and over; Antigens, Neoplasm; Biomarkers, Tumor; Carcinoma, Squamous Cell; Female; Humans; Immunohistochemistry; Keratins; Laryngeal Neoplasms; Lymph Node Excision; Lymph Nodes; Lymphatic Metastasis; Male; Middle Aged; Neoplasm Staging; Prognosis; Survival Rate

Accurate morphologic distinction between small cell carcinoma and poorly differentiated squamous cell carcinoma has critical therapeutic significance, but can be limited by crush artifact, tumor necrosis, limited tumor representation, and overlapping morphologic features. We evaluated a panel of antibodies for their efficacy in distinguishing between these neoplasms. Formalin-fixed paraffin-embedded tissue sections of small cell carcinomas and poorly differentiated squamous cell carcinomas underwent immunohistochemical staining with antibodies to thyroid transcription factor-1, p63, high molecular weight keratin, and p16(INK4A). Of 28 small cell carcinomas, 26 (93%) small cell carcinomas showed diffuse moderate or strong staining for thyroid transcription factor-1 with no staining for high molecular weight keratin and p63. In contrast, 27/28 (96%) poorly differentiated squamous cell carcinomas manifested opposite immunoreactivities, with diffuse moderate or strong staining for high molecular weight keratin and p63, and no or minimal staining for thyroid transcription factor-1. In two additional cases originally interpreted as small cell carcinoma, high molecular weight keratin highlighted small numbers of neoplastic large cells, leading to reclassification as combined small cell and non-small cell carcinomas. p16(INK4A) expression varied widely in poorly differentiated squamous cell carcinomas, but was consistently moderate or strong and diffuse in small cell carcinomas, and proved helpful in the two thyroid transcription factor-1-negative small cell carcinomas. This study demonstrates that a panel consisting of antibodies to thyroid transcription factor-1, p63, high molecular weight keratin, and p16(INK4A) is highly effective for distinguishing between small cell carcinoma and poorly differentiated squamous cell carcinoma. This panel also facilitates diagnosis of combined small cell and non-small cell carcinomas.

Topics: Carcinoma, Small Cell; Carcinoma, Squamous Cell; Cell Differentiation; Cyclin-Dependent Kinase Inhibitor p16; Diagnosis, Differential; DNA-Binding Proteins; Genes, Tumor Suppressor; Humans; Immunohistochemistry; Keratins; Lung Neoplasms; Nuclear Proteins; Phosphoproteins; Thyroid Nuclear Factor 1; Trans-Activators; Transcription Factors; Tumor Suppressor Proteins

We investigated the relationship between cell growth and differentiation and COX-2 expression in oral squamous cell carcinoma (SCC) in vitro and in vivo. Treatment of SCC25 oral squamous carcinoma cells with sodium butyrate (SB) at 0.5-5 mM or all-trans retinoic acid (ATRA) at 3-300 microM inhibited cell growth and induced apoptosis in a dose-dependent manner with concomittant increases in expression of keratin 13, p21WAF1/Cip1 and p27Kip1 and decreases in expression of COX-2. These effects were more pronounced with SB than with ATRA. Injection of SB or ATRA near SCC25-derived tumors in nude mice resulted in inhibition of growth and elevation of differentiation of the tumor accompanied by marked keratinization and increased expression of keratin 13 and decreased expression of COX-2. These results show that the differentiation-inducing agents, particularly SB, suppress growth of oral squamous carcinoma cells through apoptosis and induce cell differentiation possibly through mechanisms involving COX-2, p27Kip1 and/or p21WAF1/Cip1 in vitro and in vivo.

Topics: Animals; Apoptosis; Blotting, Western; Butyrates; Carcinoma, Squamous Cell; Cell Cycle Proteins; Cell Differentiation; Cell Line, Tumor; Cell Proliferation; Cyclin-Dependent Kinase Inhibitor p21; Cyclin-Dependent Kinase Inhibitor p27; Cyclooxygenase 2; DNA Primers; Female; Gene Expression Regulation, Neoplastic; Head and Neck Neoplasms; Humans; Immunohistochemistry; Isobutyrates; Keratins; Membrane Proteins; Mice; Mice, Inbred BALB C; Mice, Nude; Mouth Neoplasms; Prostaglandin-Endoperoxide Synthases; Reverse Transcriptase Polymerase Chain Reaction; RNA; Time Factors; Tretinoin; Tumor Suppressor Proteins

Nodal involvement is one of the most significant prognostic factors in squamous cell carcinoma (SCC) of the vulva. We conducted a retrospective analysis of 31 women with histologically node-negative SCC from a population-based cohort of Grampian women. Median follow-up was 42 months after radical vulvectomy with groin node dissection. In total, 13 women (42%) were found to have micrometastases on immunohistochemistry. The risk of recurrence was almost 20-fold higher in those with micrometastases compared to those without (hazard ratio=19.6 (95% CI 2.3-171).

Topics: Adult; Aged; Aged, 80 and over; Carcinoma, Squamous Cell; Female; Humans; Immunohistochemistry; Keratins; Lymphatic Metastasis; Middle Aged; Neoplasm Recurrence, Local; Prognosis; Retrospective Studies; Vulvar Neoplasms

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

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

In head and neck cancers, the presence of cervical lymph node metastasis is an important determinant of outcome. Many attempts have been made to predict cervical lymph node metastasis, but the accuracy of currently available techniques remains inadequate. We used fuzzy inference to predict cervical lymph node metastasis retrospectively in 75 patients with squamous cell carcinoma of the tongue and prospectively in 23 patients. Our model was based on three variables: tumor size, keratinization, and mode of invasion. The accuracy of fuzzy inference for the prediction of cervical lymph node metastasis in the 75 patients studied retrospectively was 86.7%, the sensitivity was 70.8%, and the specificity was 94.1%. In the 23 patients studied prospectively, the accuracy was 91.3%, the sensitivity was 50.0%, and the specificity was 95.2%. The accuracy obtained in this European series of patients was similar to that previously obtained in Japanese patients. We conclude that fuzzy inference may be a useful method for predicting cervical lymph node metastasis. Its high specificity is likely to reduce the number of unnecessary neck dissections. However, the current level sensitivity is inadequate for routine clinical use. Therefore, other predictors of lymph node metastasis should be identified to refine the current model.

Topics: Carcinoma, Squamous Cell; Europe; Follow-Up Studies; Forecasting; Fuzzy Logic; Humans; Keratins; Lymphatic Metastasis; Neck; Neoplasm Invasiveness; Prospective Studies; Retrospective Studies; Sensitivity and Specificity; Tongue Neoplasms; Treatment Outcome

Topics: Biomarkers, Tumor; Carcinoma, Squamous Cell; Cell Transformation, Neoplastic; Epithelial Cells; Female; Humans; Keratins; Uterine Cervical Dysplasia; Uterine Cervical Neoplasms

This study characterizes the morphologic features and the endogenous fluorescence in the stratified squamous epithelia of the 7,12-dimethylbenz(a)anthracene-treated hamster cheek pouch model of carcinogenesis using multiphoton laser scanning microscopy (MPLSM). MPLSM allows high-resolution, three-dimensional image data to be collected deeper within thick tissue samples with reduced phototoxicity compared with single-photon imaging. Three-dimensional image stacks of normal (n = 13), precancerous (dysplasia, n = 12; carcinoma in situ, n = 9) and cancerous tissue [nonpapillary squamous cell carcinoma (SCC), n = 10, and papillary SCC, n = 7] sites in the hamster cheek pouch were collected in viable, unsectioned tissue biopsies at a two-photon excitation wavelength of 780 nm. Five features were quantified from the MPLSM images. These included nuclear density versus depth, keratin layer thickness, epithelial thickness, and the fluorescence per voxel in the keratin and epithelial layers. Statistically significant differences in all five features were found between normal and both precancerous and cancerous tissues. The only exception to this was a lack of statistically significant differences in the keratin fluorescence between normal tissues and papillary SCCs. Statistically significant differences were also observed in the epithelial thickness of dysplasia and carcinoma in situ, and in the keratin layer thickness of dysplasia and SCCs (both nonpapillary and papillary). This work clearly shows that three-dimensional images from MPLSM of endogenous tissue fluorescence can effectively distinguish between normal, precancerous, and cancerous epithelial tissues. This study provides the groundwork for further exploration into the application of multiphoton fluorescence endoscopy in a clinical setting.

Topics: 9,10-Dimethyl-1,2-benzanthracene; Animals; Carcinogens; Carcinoma in Situ; Carcinoma, Squamous Cell; Cheek; Cricetinae; Epithelial Cells; Fluorescence; Keratins; Male; Mesocricetus; Microscopy, Confocal; Microscopy, Fluorescence, Multiphoton; Mouth Neoplasms; Precancerous Conditions

The incidence of skin cancer is increased in transplant recipients. UV radiation, papillomaviruses, and immunosuppression participate in the pathogenesis of these tumors. In addition, donor cells may leave the grafted organ, reach peripheral tissues and either induce immune phenomena or possibly take part in tissue remodeling. Herein, we investigated the possible involvement of donor cells in the development of skin tumors in kidney allograft recipients. We analyzed a series of 48 malignant and benign cutaneous tumors developing in 14 females who had been grafted with a male kidney. The number of male cells was measured on microdissected material by quantitative PCR for Y chromosome. In the samples with high levels of male cells, fluorescent in situ hybridization (FISH) with X and Y probes and/or immuno-FISH with anticytokeratin antibodies were carried out. Male cells were detected in 5/15 squamous cell carcinomas and Bowen disease (range 4-180 copies), 3/5 basal cell carcinomas (91-645), 6/11 actinic keratosis (7-102), 2/4 keratoacanthoma (22-41), and 2/5 benign cutaneous lesions (14-55). In a basal cell carcinoma specimen with a high number of male cells, FISH showed that most cells within the tumoral buds were XY. In this lesion, immuno-FISH showed the presence of XY cytokeratin-positive cells indicating that the tumor nests contained male keratinocytes. In contrast, in other female transplants, male cells present in the tumors were not epithelial. In conclusion, stem cells originating from a grafted kidney may migrate to the skin, differentiate, or fuse as keratinocytes that could, rarely, undergo cancer transformation.

Topics: Bowen's Disease; Carcinoma, Basal Cell; Carcinoma, Squamous Cell; Cell Differentiation; Cell Fusion; Chromosomes, Human, X; Chromosomes, Human, Y; Female; Humans; Immunoenzyme Techniques; In Situ Hybridization, Fluorescence; Karyotyping; Keratinocytes; Keratins; Keratoacanthoma; Keratosis; Kidney Transplantation; Male; Reverse Transcriptase Polymerase Chain Reaction; Skin Diseases; Skin Neoplasms; Stem Cells; Tissue Donors; Transplantation, Homologous

Autofluorescence spectroscopy and Raman spectroscopy have been suggested for lesion diagnostics. We investigate the information contained in autofluorescence and Raman spectra recorded from oral tissue slices of various lesion types. Thirty-seven human oral mucosa lesions were biopsied and freeze-dried. Complete autofluorescence images and spectra were recorded from 20 microm sections. Raman spectra were acquired from the same positions for 12 of the sections. Cluster analysis was applied to find any relationship between spectral shape and lesion type or cell layer. Autofluorescence images showed high intensities for keratin layers and connective tissue, but hardly any for the epithelium. Autofluorescence spectra were centered around 520 nm and did not show specific spectral features. No clustering with regard to lesion type or cell layer was observed. Raman spectra allowed for reliable classification into cell layers, but differences between lesion types were not significant in this study. Autofluorescence spectra of freeze-dried oral mucosa sections did not contain useful information. A more comprehensive study is required for Raman spectra.

Topics: Carcinoma, Squamous Cell; Cluster Analysis; Connective Tissue; Epithelium; Freeze Drying; Humans; Keratins; Mouth Mucosa; Mouth Neoplasms; Spectrometry, Fluorescence; Spectrum Analysis, Raman

Cyclooxygenase 2 (COX-2), an inducible prostaglandin synthase, participates in inflammatory and neoplastic processes. It is expressed by various tumours and contributes to carcinogenesis. Notably, COX-2 inhibitors appear to have tumour suppressor effects and are being evaluated in clinical trials.. To investigate COX-2 expression in nasopharyngeal carcinoma (NPC), a common tumour in parts of Asia, and to discuss potential implications.. Eighty five cases of NPC were reviewed. COX-2 immunohistochemistry and semiquantitative assessment of expression in nasopharyngeal biopsies were performed. Because COX-2 is proangiogenic, tumour microvessel density was also assessed with the use of CD31 immunohistochemistry.. Histologically, 78 NPCs were undifferentiated, six were non-keratinising, and one was keratinising. Thirty nine NPCs had adjacent dysplastic epithelium. COX-2 expression was noted in 60 NPCs, 14 of 39 samples of dysplastic epithelium, and only one of 25 samples of normal epithelium (p < 0.01). Microvessel density was not significantly different between COX-2 positive and COX-2 negative tumours (p = 0.774). Tumour COX-2 positivity was not associated with higher tumour stage (p = 0.423).. COX-2 expression is more frequently seen as nasopharyngeal epithelium progresses from normal to dysplastic to carcinoma. This suggests that COX-2 contributes to the multistep process of NPC carcinogenesis. COX-2 represents a therapeutic target for COX-2 inhibitors, and there is thus a basis for the further investigation of this adjuvant treatment modality for NPC. COX-2 inhibitors are known to potentiate the antitumour effects of radiotherapy, which is the primary treatment for NPC.

Topics: Adult; Aged; Aged, 80 and over; Carcinoma in Situ; Carcinoma, Squamous Cell; Cyclooxygenase 2; Epithelium; Herpesvirus 4, Human; Humans; Immunohistochemistry; Keratins; Membrane Proteins; Microcirculation; Middle Aged; Nasopharyngeal Neoplasms; Neoplasm Staging; Peroxidases; Prostaglandin-Endoperoxide Synthases

Previous studies have suggested that cases of high-grade squamous intraepithelial lesion in conventional smears and in ThinPrep specimens that are frequently misinterpreted as normal have relatively few small and hypochromatic dysplastic cells.. To determine the cytologic differences between conventional Papanicolaou slides of high-grade squamous intraepithelial lesion that perform poorly and those that perform well.. We compared the cytologic features of 22 cases of conventional smears with high-grade squamous intraepithelial lesion that performed poorly in the College of American Pathologists Interlaboratory Comparison Program in Gynecologic Cytology with 45 cases of conventional smears that performed extremely well.. Cases that performed poorly were significantly more likely to have 50 or fewer single dysplastic cells (P = .003) and to have only small dysplastic cells (P = .01). Cases that performed well were also more likely to have more than 500 dysplastic cells (P = .002), to exhibit the presence of large dysplastic cells (P < .001), and to be keratinized (P = .03). Hypochromasia and the number of groups of dysplastic cells were not correlated with performance.. Conventional smears with high-grade squamous intraepithelial lesion with 50 or fewer single dysplastic cells, no large dysplastic cells, and lacking keratinization are highly associated with poor performance in this program.

Topics: Carcinoma, Squamous Cell; Cell Count; Diagnostic Errors; Female; Humans; Keratins; Papanicolaou Test; Pathology, Clinical; Uterine Cervical Dysplasia; Uterine Cervical Neoplasms; Vaginal Smears

Squamous cell carcinoma (SCC) is the most common malignant head and neck tumor and is responsible for more than 90% of head and neck cancers and accounts for 4.5% of all malignant tumors in males and 3.5% in females in South Korea. The purpose of this study was to investigate the correlation of suggested clinico-pathological prognostic factors such as gender, age, T score (T number in TNM), clinical stage, proliferation, invasion index, and lymph node metastasis to the survival of SCC patients in Korea. Furthermore, cytokeratin (CK), carcinoembryonic antigen (CEA), and recently documented apoptosis related protein, survivin, were analyzed by RT-PCR. In 113 patients, survival curves were estimated by the Kaplan-Meier method and nominal or numeric variable influence on survival was studied by Univariate and Multivariate Regression analysis (Cox proportional hazards model). Univariate analysis demonstrated that gender and age factor had no significant effect on survival rate. T score, on the other hand, significantly influenced survival and univariate analysis demonstrated that Stage 4 group had a significantly lower survival rate than the other stage groups but differentiation and invasion index factors had no significant effect on survival rate. Using a 50% cut-off point, patients with lower PCNA scores showed no survival advantages over those with higher PCNA scores but lymph node metastasis was a significant survival predictor in univariate analysis. In addition, lymph node CK and survivin mRNA expression have significant effects on OSCC patient survival rate. This means that prognostic value can be amplified by coincident analysis of T score, pathologically confirmed lymph node metastasis, and lymph node CK or survivin mRNA expression. Multivariate analysis using Cox's proportional hazards model, clinical TNM stage and lymph node survivin mRNA expression were independent OSCC prognostic factors, which support cancer staging based on the TNM as a powerful prognostic variable and lymph node survivin expression might provide predictive information for OSCC patient survival.

Topics: Adolescent; Adult; Age Factors; Aged; Carcinoembryonic Antigen; Carcinoma, Squamous Cell; Cell Differentiation; Female; Humans; Inhibitor of Apoptosis Proteins; Keratins; Lymphatic Metastasis; Male; Microtubule-Associated Proteins; Middle Aged; Mouth Neoplasms; Neoplasm Invasiveness; Neoplasm Proteins; Neoplasm Staging; Prognosis; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Sex Factors; Survival Analysis; Survivin

Although many histopathologic factors in squamous cell carcinoma of the tongue predict the prognosis, the major predictive factors have not been identified clearly. This study analyzed the prognostic value of the histologic grade at the deep invasive front of tongue squamous cell carcinoma.. The clinicopathologic features of 124 consecutive patients seen between January 1985 and December 1999 with previously untreated squamous cell carcinoma of the tongue were reviewed. Their mean age was 58.5 years (range: 23-90) and the male-female ratio was 1.8: 1 (79 men and 45 women). There were 41, 40, 30, and 13 cases at stage I to stage IV, respectively. The clinicopathologic factors, especially the histologic grade at the deep invasive front (invasive front grade, IFG), were analyzed to determine factors predicting prognosis.. The 5-year disease-free survival rate of the patients treated with curative aim only was 66.7%. Clinicopathologic factors significantly associated with the prognosis were T classification, tumor size, stage classification, tumor depth, macroscopic appearance, cervical lymph node metastasis (nodal metastasis), microvascular invasion, and IFG. In a multivariate analysis, patients with tumor depth >/=4 mm, IFG >/=8 points, and nodal metastasis had a reduced disease-free survival and IFG >/=11 points had a predictive value for nodal metastasis (odds ratio: 7.34; P = 0.0019).. This study found that a high IFG malignancy score had a high prognostic value for squamous cell carcinoma of the tongue.

Topics: Adult; Aged; Aged, 80 and over; Carcinoma, Squamous Cell; Cell Nucleus; Disease-Free Survival; Female; Forecasting; Humans; Keratins; Lymphatic Metastasis; Male; Microcirculation; Middle Aged; Neoplasm Invasiveness; Neoplasm Staging; Polymorphism, Genetic; Prognosis; Retrospective Studies; Tongue Neoplasms

Acantholytic carcinoma is a subtype of squamous carcinoma, characterized by tubular and alveolar formations as a consequence of the acantholysis. We report a case of vulvar squamous acantholytic carcinoma (VSAC) in a 69-year-old woman, who was admitted to our institution for vulvar pruritus and the presence of a large, bilateral, exophytic, and ulcerated lesion, measuring 7 x 8 cm. The patient had never received vulvar or pelvic radiation therapy. Pathological examination with an immunohistochemical study showed features of VSAC and high p16 protein expression. Molecular study by polymerase chain reaction amplification of DNA tumor revealed a weakly positive signal for human papillomavirus. In conclusion, our case, which is the first case of VSAC with polymerase chain reaction analysis and immunohistochemical expression of p16 protein, suggested that this neoplasm could be related to human papillomavirus infection.

Topics: Acantholysis; Aged; Carcinoma, Squamous Cell; Cyclin-Dependent Kinase Inhibitor p16; DNA, Viral; Female; Humans; Immunohistochemistry; Keratin-14; Keratins; Papillomaviridae; Papillomavirus Infections; Polymerase Chain Reaction; Tumor Virus Infections; Vimentin; Vulvar Neoplasms

To identify differentially expressed genes during the development of oral malignancy, differential display, northern blotting, reverse transcription-polymerase chain reaction (RT-PCR) and immunohistochemical analyses were undertaken using oral squamous cell carcinoma (OSCC) and leukoplakia tissues. Significantly higher levels of keratin (Ker)-14 and -17 mRNAs, combined with lower levels of Ker-4, Ker-13 and transglutaminase 3 (TG-3) transcripts, were observed in OSCC and severely dysplastic tissues, whereas this expression profile was reversed in hyperplasia and in mild to moderate dysplasia. The expression of Ker-4 and Ker-13 was elevated in density-arrested OSCC cell lines (Ca9-22, HSC-2, -3 and -4) but the expression of Ker-17 mRNA was elevated in these cells, regardless of the growth conditions. In addition, Ker-4 and Ker-13 proteins were predominantly expressed in moderate dysplasia and hyperplasia, whereas Ker-17 was markedly expressed in OSCC tissues. The expression patterns of these genes could therefore be an important determinant of the manifestation of oral malignancy.

Topics: Adult; Aged; Aged, 80 and over; Calcium-Binding Proteins; Carcinoma, Squamous Cell; Disease Progression; Female; Gene Expression Regulation, Neoplastic; Humans; Hyperplasia; Immunoenzyme Techniques; Keratin-14; Keratins; Leukoplakia, Oral; Male; Middle Aged; Mouth Neoplasms; Neoplasm Proteins; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; RNA, Neoplasm; Transglutaminases; Tumor Cells, Cultured

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

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

The aim of this study was immunolabeling oncoproteins Ck14, p53, p21 and Bcl-2 in order to evaluate their expression in premalignant and malignant stomatological lesions in oral epithelial, and to compare this expression with exfoliative cytology alterations in the same patients. It was studied biopsies and cytologies of 13 subjects with oral lichen planus, with or without Human Papilloma Virus (HPV), leukoplakia and squamous cell carcinoma clinically diagnosed and confirmed by anatomopathological studies. The oral lichen planus lesion presented binuclei orange cells; and in leukoplakia lesions only orange stained was observed; meanwhile koilocytes, inflammatory cells, enlarge nuclear volume and pathogenic microorganisms were observed in the HPV infections and squamous cells carcinoma (SCC). The Ck14, p53, p21 and Bcl-2 proteins were found modified in the leukoplakia, oral lichen planus and cancer. Cytological alterations and positive immunolabeling or over-expression of Ck14 cytokeratine in the upper epithelial stratus should be indicator of malignant transformations as doing subsequence exams.

Topics: Adult; Aged; Carcinoma, Squamous Cell; Case-Control Studies; Cytodiagnosis; Female; Humans; Immunohistochemistry; Keratins; Leukoplakia, Oral; Lichen Planus, Oral; Male; Middle Aged; Mouth Mucosa; Mouth Neoplasms; Neoplasm Proteins; Papillomaviridae; Prognosis; Proto-Oncogene Proteins c-bcl-2; Proto-Oncogene Proteins p21(ras); Tumor Suppressor Protein p53

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

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

Malignant bone tumors with epithelial differentiation are extremely rare. Only one case of primary malignant bone tumor with distinct squamous cell carcinoma and chondrosarcoma has ever been reported. Reported herein is a case of primary malignant bone tumor with distinct squamous cell carcinoma and chondrosarcoma, so-called carcinosarcoma of bone, arising in the femur of a 53-year-old man. The tumor was located within the femur and was diagnosed by curettage as a well-differentiated chondrosarcoma. No primary tumor was detected in any other organ. Within a few months the tumor had rapidly grown toward the soft tissue, and hemipelvectomy was performed. Examination of the surgical specimen revealed that the tumor was mainly composed of undifferentiated spindle sarcoma cells with scattered foci of chondrosarcoma and of squamous cell carcinoma with keratin pearl formation. The patient died approximately 6 months postoperatively. At autopsy multiple metastases were detected in the heart, both lungs, muscles, and lymph nodes. Interestingly, the chondrosarcoma and squamous cell carcinoma components were observed in several metastatic foci. The tumors in both the previously reported case and the present case contained components of chondrosarcoma and squamous cell carcinoma with keratin pearl formation, and this combination of histological features may be a unique characteristic of carcinosarcoma of bone.

Topics: Bone Neoplasms; Carcinoma, Squamous Cell; Chondrosarcoma; Fatal Outcome; Humans; Immunohistochemistry; Keratins; Male; Middle Aged; S100 Proteins; Vimentin

Osteopontin (OPN) is a secreted integrin-binding glycophosphoprotein that may have a role in head and neck squamous cell carcinoma (SCC). To evaluate the clinical significance of OPN in esophageal squamous cell carcinoma (ESCC), we compared plasma OPN levels with those of common tumor markers.. Preoperative plasma OPN levels were measured by enzyme immunoassay in 103 ESCC patients. Serum SCC antigen, Cyfra 21-1, and carcinoembryonic antigen (CEA) levels were also measured routinely at admission by radioimmunoassay.. Plasma OPN levels ranged from 82.8 to 1,980 ng/ml. High OPN level was associated with lymph node metastasis (p = 0.05), but not with tumor histology or depth of invasion. The overall survival of the patients with high OPN levels was worse than that of those with low OPN levels (p = 0.02). SCC antigen and Cyfra 21-1 levels were associated with the depth of tumor invasion, the tumor diameter, lymph node metastasis, and the overall survival, but CEA was not associated with these clinicopathological factors. Combined evaluation of OPN plus Cyfra 21-1 or OPN plus SCC antigen was useful as an independent prognostic indicator.. Measurement of the plasma OPN level, as well as serum SCC antigen and Cyfra 21-1, may help to predict the progression of ESCC.

Topics: Aged; Antigens, Neoplasm; Biomarkers, Tumor; Carcinoma, Squamous Cell; Disease Progression; Esophageal Neoplasms; Female; Humans; Keratin-19; Keratins; Male; Middle Aged; Multivariate Analysis; Osteopontin; Predictive Value of Tests; Prognosis; Proportional Hazards Models; Serpins; Sialoglycoproteins; Survival Analysis

In early stage vulvar carcinoma patients, there is at trend towards individualized treatment in order to reduce morbidity and sequela following inguinal lymph node dissection. However, recurrences in the groin are almost always fatal. In the present study, we address the occult lymph node metastases in vulvar squamous cell carcinoma patients by using serial sectioning and immunostaining of lymph nodes in a larger series of vulvar carcinoma patients and relate the findings to clinical follow-up data.. From 75 vulvar squamous cell carcinoma patients staged surgical FIGO I-III, 421 lymph nodes found negative at the hematoxylin & eosin (H&E) routine investigation were scrutinized. From formalin-fixed and paraffin-embedded tissues, sections were cut with 150 mum interval and stained with H&E and cytokeratin AE1/AE3. Two classes were used to describe the amount of tumor cells: <100 cells and >100 cells.. Positive cytokeratin AE1/AE3 staining was found in 25/421 (6%) of the lymph nodes. Occult lymph node metastases were found in 17/75 (23%) of the patients. Correlation was found between lymph node metastasis and site of recurrence (P = 0.01). Twenty-eight percent of the patients had relapse.. The present study underlines the importance of serial sectioning and immunostaining of lymph nodes in the search for micrometastases in vulvar carcinoma patients. However, the results of the present study do not suggest a more thorough examination of non-sentinel lymph nodes in vulvar carcinoma patients where the sentinel lymph nodes are thoroughly examined.

Topics: Adult; Aged; Aged, 80 and over; Carcinoma, Squamous Cell; Eosine Yellowish-(YS); Female; Hematoxylin; Humans; Keratins; Lymph Nodes; Lymphatic Metastasis; Middle Aged; Neoplasm Staging; Retrospective Studies; Staining and Labeling; Vulvar Neoplasms

Cysteine-dependent aspartate-specific proteases (caspases) are the cellular executors of apoptosis. Caspase-14 is the most divergent member of the family of mammalian caspases and displays a variety of unique characteristics. It is expressed in a limited number of tissues and has the shortest amino acid sequence within the caspase protein family. During induction of apoptosis, it is not processed, whereas terminal differentiation in skin leads to cleavage of caspase-14. Here we show that 40% of lung squamous cell carcinomas, 22% of breast cancers, and about 80% of cervical carcinomas express caspase-14. Immunohistochemistry reveals that caspase-14 is localized in areas of ongoing differentiation close to necrotic sites but is not strictly associated with the differentiation markers keratin-1/-10. Caspase-14 is neither mutated nor alternatively spliced in the tumors analyzed. Furthermore, caspase-14 is not processed into a small and large subunit, a process critical for the proteolytic activation of known effector caspases. We conclude that conditions exist in tumors leading to re-expression of this normally silent gene.

Topics: Alternative Splicing; Animals; Apoptosis; Blotting, Western; Carcinoma, Squamous Cell; Caspase 14; Caspases; Cell Differentiation; Cell Line, Tumor; DNA Primers; DNA, Complementary; Gene Expression Regulation, Neoplastic; Gene Silencing; Humans; Immunohistochemistry; Keratin-1; Keratin-10; Keratins; Microscopy, Fluorescence; Mutation; Necrosis; Neoplasms, Glandular and Epithelial; Polymerase Chain Reaction; Skin Neoplasms; Tissue Distribution

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

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

These results indicate that extensive, multiple cervical micrometastases occurred from an early stage in patients with T2N0 tongue cancer. The presence of micrometastases suggests the necessity of preventive neck dissection for Level I-IV nodes as a radical treatment.. Cervical lymph node metastases occur with a relatively high frequency in patients with T2N0 squamous cell carcinoma of the tongue, and control of the metastases greatly influences the prognosis of patients. In this study, micrometastases in the cervical lymph nodes were investigated to clarify the necessity and required extent of preventive neck dissection.. We investigated micrometastases in 24 subjects who had previously been diagnosed with T2N0 tongue cancer. We performed immunostaining with anti-cytokeratin antibody cocktail AE1/AE3 of sections of 401 paraffin-embedded lymph nodes obtained from these patients.. Micrometastases were observed in 14 patients (58%) and were most abundant in Level II nodes (n=11; 46%). Micrometastases were observed in the Level IV nodes of 3 patients (13%), and upstaging to pN2b occurred in 7 patients (29%).

Topics: Adult; Aged; Antibodies, Monoclonal; Carcinoma, Squamous Cell; Coloring Agents; Female; Humans; Immunoenzyme Techniques; Immunohistochemistry; Keratins; Lymph Node Excision; Lymph Nodes; Lymphatic Metastasis; Male; Middle Aged; Neck; Neoplasm Staging; Prognosis; Tongue Neoplasms

Zinc deficiency in rats enhances esophageal cell proliferation, causes alteration in gene expression, and promotes esophageal carcinogenesis. Zinc replenishment rapidly induces apoptosis in the esophageal epithelium thereby reversing cell proliferation and carcinogenesis. To identify zinc-responsive genes responsible for these divergent effects, we did oligonucleotide array-based gene expression profiling analyses in the precancerous zinc-deficient esophagus and in zinc-replenished esophagi after treatment with intragastric zinc compared with zinc-sufficient esophagi. Thirty-three genes (21 up-regulated and 12 down-regulated) showed a > or = 2-fold change in expression in the hyperplastic zinc-deficient versus zinc-sufficient esophageal epithelia. Expression of genes involved in cell division, survival, adhesion, and tumorigenesis were markedly changed. The zinc-sensitive gene metallothionein-1 (MT-1 was up-regulated 7-fold, the opposite of results for small intestine and liver under zinc-deficient conditions. Keratin 14 (KRT14, a biomarker in esophageal tumorigenesis), carbonic anhydrase II (CAII, a regulator of acid-base homeostasis), and cyclin B were up-regulated >4-fold. Immunohistochemistry showed that metallothionein and keratin 14 proteins were overexpressed in zinc-deficient esophagus, as well as in lingual and esophageal squamous cell carcinoma from carcinogen-treated rats, emphasizing their roles in carcinogenesis. Calponin 1 (CNN1, an actin cross-linking regulator) was down-regulated 0.2-fold. Within hours after oral zinc treatment, the abnormal expression of 29 of 33 genes returned to near zinc-sufficient levels, accompanied by reversal of the precancerous phenotype. Thus, we have identified new molecular markers in precancerous esophagus and showed their restoration by zinc replenishment, providing insights into the interaction between zinc and gene expression in esophageal cancer development and prevention.

Topics: 4-Nitroquinoline-1-oxide; Animals; Carcinoma, Squamous Cell; Esophageal Neoplasms; Gene Expression Regulation, Neoplastic; Immunohistochemistry; Keratin-14; Keratins; Male; Metallothionein; Precancerous Conditions; Rats; Reverse Transcriptase Polymerase Chain Reaction; Up-Regulation; Zinc

Micrometastases (MM) and occult tumor cell deposits (OTCD) in pelvic tissue may cause recurrences, and immunohistochemistry may improve their detection. We used cytokeratine-immunohistochemistry to investigate 263 pelvic lymph nodes and parametrial tissue for MM and OTCD obtained from eight squamous cell carcinomas (maximum tumor size: 2.5 cm). These patients were treated with radical abdominal hysterectomy (Piver type III) with complete tumor resection without receiving any adjuvant therapy. The mean count of resected pelvic lymph nodes was 32.9 (range 24-47). All lymph nodes were completely embedded, and three step sections were performed for routine histopathologic evaluation. Three patients developed pelvic side wall and five central tumor recurrences within a median time of 25.9 (range 8-55) months. On immunohistochemistry, only one case (12.5%) showed OTCD in a venule in the parametrial tissue. In patients with small cervical carcinomas (< 2.5 cm in largest dimension), OTCD can only rarely be detected by immunohistochemistry after careful handling of resected lymph nodes using step sectioning for routine histologic examination and complete processing of parametrial pelvic tissue. Therefore, tumor recurrence in those patients appears to be due to occult residual tumor cells that were not resected during the classical Wertheim-Meigs-procedure or that were disseminated during the surgical procedure and persisted in situ.

Topics: Adult; Carcinoma, Squamous Cell; Female; Humans; Immunohistochemistry; Keratins; Lymphatic Metastasis; Middle Aged; Neoplasm Recurrence, Local; Pelvis; Pilot Projects; Uterine Cervical Neoplasms

Cancer cells produce parathyroid hormone-related protein (PTHrP) in the early phase of malignancy development, before hypercalcemia occurs. The relationship between PTHrP and the clinicopathologic features of oral squamous cell carcinoma is poorly understood. We studied 60 patients (43 men, 17 women; mean age, 64.8 +/- 11.2 years) with primary oral squamous cell carcinoma, from whom pretreatment biopsy specimens were obtained. We examined the relationship among immunohistochemical PTHrP expression, serum PTHrP levels, clinical characteristics of the tumor, and histopathologic aspects of the tumor. The mean calcium concentration for the 60 patients was 9.1 +/- 0.4 mg/dl. No patients had laboratory evidence of hypercalcemia before treatment. Six patients had serum levels of C-terminal (C)-PTHrP higher than the normal level of 55.3 pmol/l. There were no significant differences in serum C-PTHrP levels according to TNM stages. Abundant positive immunoreactivity for anti-PTHrP (1-34) antibody was recognized diffusely in the whole cytoplasm of many tumor cells. Anti-PTHrP (38-64) antibody staining tended to localize as small granules in the cytoplasm, especially close to the nuclear periphery. There was no correlation between the serum C-PTHrP concentration and the intensity of either immunostain. The intensity of PTHrP was proportionally related to the degree of differentiation or extent of keratinization (P < 0.05) and the histologic malignancy grade of the tumor (P < 0.05), when using antibody against PTHrP (1-34), but not when using antibody against PTHrP (38-64). Serum C-PTHrP levels did not correlate with the intensity of cellular PTHrP expression and characteristics of the tumor at the initial patient visit. The fragment that includes PTHrP (1-34) may be involved in the differentiation of oral squamous cell carcinoma. The differences between immunoreactivities may have been due to differing tissue malignancies and the use of different antibodies. The results suggest the need for caution when interpreting immunoreactivities of PTHrP in malignancies.

Topics: Antibodies, Monoclonal; Biopsy; Calcium; Carcinoma, Squamous Cell; Cell Differentiation; Cell Nucleus; Cytoplasm; Cytoplasmic Granules; Female; Humans; Immunohistochemistry; Keratins; Male; Middle Aged; Mouth Neoplasms; Neoplasm Proteins; Neoplasm Staging; Parathyroid Hormone; Parathyroid Hormone-Related Protein; Peptide Fragments

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

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

A null mutation in one copy of the Atp2a2 or ATP2A2 gene, encoding sarco(endo)plasmic reticulum Ca2+-ATPase isoform 2 (SERCA2), leads to squamous cell tumors in mice and to Darier disease in humans, a skin disorder that also involves keratinocytes. Here, we examined the time course and genetic mechanisms of tumor development in the mutant animals. Atp2a2+/- mice overexpressed keratins associated with keratinocyte hyperactivation in normal forestomachs as early as 2 months of age. By the age of 5 to 7 months, 22% of mutants had developed papillomas of the forestomach, and 89% of mutants older than 14 months had developed squamous cell papillomas and/or carcinomas, with a preponderance of the latter. Tumors occurred in regions that had keratinized epithelium and were subjected to repeated mechanical irritation. The genetic mechanism of tumorigenesis did not involve loss of heterozygosity, as tumor cells analyzed by laser capture microdissection contained the wild-type Atp2a2 allele. Furthermore, immunoblot and immunohistochemical analysis showed that tumor keratinocytes expressed the SERCA2 protein. Mutations were not observed in the ras proto-oncogenes; however, expression of wild-type ras was up-regulated, with particularly high levels of K-ras. Loss of the p53 tumor suppressor gene occurred in a single massive tumor, whereas other tumors had increased levels of p53 protein but no mutations in the p53 gene. These findings show that SERCA2 haploinsufficiency predisposes mice to tumor development via a novel mode of cancer susceptibility involving a global change in the tumorigenic potential of keratinized epithelium in Atp2a2+/- mice.

Topics: Alleles; Animals; Calcium-Transporting ATPases; Carcinoma, Squamous Cell; Genes, p53; Genes, ras; Genetic Predisposition to Disease; Humans; Keratinocytes; Keratins; Loss of Heterozygosity; Male; Mice; Sarcoplasmic Reticulum Calcium-Transporting ATPases; Stomach Neoplasms; Tumor Suppressor Protein p53

Protein kinase C epsilon (PKCepsilon) overexpressing transgenic (PKCepsilon Tg) mice develop papilloma-independent squamous cell carcinomas (SCC) elicited by 7,12-dimethylbenz[a]anthracene (DMBA) tumor initiation and 12-O-tetradecanoylphorbol-13-acetate (TPA) tumor promotion. We examined whether epidermal cell turnover kinetics was altered during the development of SCC in PKCepsilon Tg mice. Dorsal skin samples were fixed for histological examination. A single application of TPA resulted in extensive infiltration of polymorphonuclear neutrophils (PMNs) into the epidermis at 24 h after TPA treatment in PKCepsilon Tg mice while wild-type (WT) mouse skin showed focal infiltration by PMNs. Complete epidermal necrosis was observed at 48 h in PKCepsilon Tg mice only; at 72 h, epidermal cell regeneration beginning from hair follicles was observed in PKCepsilon Tg mice. Since the first TPA treatment to DMBA-initiated PKCepsilon Tg mouse skin led to epidermal destruction analogous to skin abrasion, we propose the papilloma-independent phenotype may be explained by death of initiated interfollicular cells originally destined to become papillomas. Epidermal destruction did not occur after multiple doses of TPA, presumably reflecting adaptation of epidermis to chronic TPA treatment. Prolonged hyperplasia in the hair follicle may result in the early neoplastic lesions originally described by Jansen et al. (2001) by expanding initiated cells in the hair follicles resulting in the subsequent development of SCC.

Topics: 9,10-Dimethyl-1,2-benzanthracene; Animals; Carcinoma, Squamous Cell; Cell Death; Cell Differentiation; Cell Proliferation; Chemotaxis, Leukocyte; Cocarcinogenesis; Disease Models, Animal; Epidermis; Female; Hair Follicle; Hyperplasia; Keratin-10; Keratinocytes; Keratins; Mice; Mice, Transgenic; Neutrophils; Phenotype; Precancerous Conditions; Protein Kinase C-epsilon; Skin; Skin Neoplasms; Tetradecanoylphorbol Acetate; Time Factors

The human epidermal growth factor receptor (EGFR) is reportedly overexpressed in 15-20% of breast carcinomas. EGFR overexpression is associated with reduced survival and is inversely correlated with expression of estrogen receptor (ER). This study assessed EGFR expression in breast carcinomas with squamous differentiation. The immunohistochemical (IHC) expression of EGFR was evaluated in 39 breast carcinomas with squamous differentiation (30 pure squamous, 6 adenosquamous, 3 carcinosarcomas) by use of the pharmDx assay (clone 2-18C9, DakoCytomation). Cases were considered positive if at least 10% of the cells showed 1+ positivity in the squamous component. Squamous differentiation was confirmed with IHC for CK5-6 (clone D5/16B4, DakoCytomation). ER, PR, and HER2 status as well as clinical information regarding treatment and outcome were correlated. As a control, a tissue microarray comprising 280 lymph node positive breast carcinomas was evaluated with the same EGFR assay. The 39 patients ranged in age from 33 to 77 years (mean 52). The tumors measured 1.3-30 cm (mean 4.8). Sentinel or full axillary lymph node dissection was performed in 28 patients. Fourteen patients had positive lymph nodes. At the time of initial diagnosis, 3 patients had distant metastasis. Follow-up was available for 16 patients (mean 45 months). Disease-free survival at 3 years was 70%. Among the 39 tumors 87% (34) were positive for EGFR (p<0.0001). Sixty-nine percent (27 of 39) showed >50% 2+ EGFR staining. EGFR-positive tumor cells (showing squamous morphology) were also found in 1 bone, 1 lung, and 8 of 11 lymph node metastases available for evaluation. All 11 lymph nodes showed squamous differentiation. All but 1 of the EGFR+ tumors examined were ER and PR negative. Six EGFR-positive tumors were HER2 positive. No statistically significant differences in HER2 status, size, lymph node status and disease-free survival were observed between EGFR+ and EGFR- cases, but the number of EGFR-negative tumors was quite small. Nine of 280 (3%) of lymph node-positive invasive carcinomas on the tissue microarray were EGFR+; review of the initial diagnostic slides failed to reveal squamous features in all but 1 of the 9 EGFR+ tumors. Breast carcinomas with squamous differentiation are a distinct subgroup of breast tumors with a very high frequency of EGFR positivity. Breast carcinomas of this type would be ideal candidates for a trial with EGFR inhibitors.

Topics: Adult; Aged; Bone Neoplasms; Breast Neoplasms; Carcinoma, Adenosquamous; Carcinoma, Squamous Cell; Carcinosarcoma; Cell Differentiation; ErbB Receptors; Follow-Up Studies; Humans; Immunohistochemistry; Keratins; Lung Neoplasms; Lymph Nodes; Lymphatic Metastasis; Middle Aged; Neoplasm Staging; Receptor, ErbB-2; Receptors, Estrogen

We have previously reported that significantly higher levels of Keratin 14 (Ker-14) was observed in oral squamous cell carcinoma (OSCC) and severely dysplastic tissues, whereas this expression was reversed in hyperplasia and in mild to moderate dysplasia. In this study, the mechanism of Keratin 14 activation in oral squamous cell carcinoma (OSCC) cell lines (HSC-2, HSC-3 and Ca9-22) was investigated. Reporter analysis demonstrated that an upstream region (-1759/-1629) accounted for efficient promoter activity. Furthermore, electromobility sift and supershift assay demonstrated that interactions of the SP-1/SP-3 complex at the elements resided in -1737/-1702 and -1680/-1652 and may be essential for this activation in OSCC cells.

Topics: Binding Sites; Carcinoma, Squamous Cell; Cell Line, Tumor; Electrophoretic Mobility Shift Assay; Gene Expression Regulation, Neoplastic; Humans; Keratin-14; Keratins; Luciferases; Molecular Sequence Data; Mouth Neoplasms; Mutation; Oligonucleotide Probes; Promoter Regions, Genetic; Protein Binding; Recombinant Fusion Proteins; Regulatory Sequences, Nucleic Acid; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Sp1 Transcription Factor; Sp3 Transcription Factor; Transcription, Genetic; Transfection

We performed a prospective study to determine the cutoff value and the prognostic value of Cyfra 21-1, a serum tumor marker, in head and neck squamous cell carcinoma (HNSCC).. The serum concentration of Cyfra 21-1 was measured in a group of 300 patients (group 1) with HNSCC, in a control group of 71 healthy subjects (group 2), and in a group of 73 patients with a nonmalignant tumor or inflammatory disease (group 3). The concentrations were compared between the various groups and subgroups; the cutoff value was calculated with a receiver operating characteristic curve. Furthermore, the serum concentrations of Cyfra 21-1 before treatment in the group of 300 patients were compared with the stage of the disease and with the evolution of the overall survival rate and the disease-free survival rate. Finally, to determine whether Cyfra 21-1 is an independent prognostic factor, we compared the concentrations, by a Cox model, with the classic prognostic factors of HNSCC.. At the cutoff value of 1 ng/mL, the specificity was 94% and the sensitivity was 72%. The serum concentrations of Cyfra 21-1 were statistically correlated with the stage of the disease. The overall survival rate and the disease-free survival rate were lower in patients with high serum concentrations, and these differences were statistically significant (p < .001). The Cox model allows us to conclude that Cyfra 21-1 is a prognostic marker that is independent of other classic prognostic factors.. Cyfra 21-1 is an interesting tumor marker that could be proposed for the early detection of HNSCC with a cutoff value of 1 ng/mL. Furthermore, Cyfra 21-1 can be considered an independent prognostic marker.

Topics: Antigens, Neoplasm; Biomarkers, Tumor; Carcinoma, Squamous Cell; Disease-Free Survival; Female; Head and Neck Neoplasms; Humans; Hypopharyngeal Neoplasms; Keratin-19; Keratins; Laryngeal Neoplasms; Male; Middle Aged; Multivariate Analysis; Oropharyngeal Neoplasms; Prognosis; ROC Curve; Sensitivity and Specificity

To validate lymphatic mapping combined with sentinel lymph node biopsy as a staging procedure, and to evaluate the possible clinical implications of added oblique lymphoscintigraphy and/or tomography and test the intra- and interobserver reproducibility of lymphoscintigraphy.. Forty patients (17 F and 23 M, aged 32-90) with 24 T1 and 16 T2 squamous cell carcinoma of the oral cavity. Planar lymphoscintigraphy, emission and transmission tomography were performed. Detection and excision of the sentinel nodes were guided by a gamma probe. The sentinel nodes were step-sectioning and stained with hematoxylin and eosin and cytokeratin (CK 1). Histology and follow-up were used as "gold standard". Tumor location, number of sentinel lymph nodes, metastasis, and recurrences were registered. Two observers evaluated the lymphoscintigraphic images to assess the inter-rater agreement.. Eleven (28%) patients were upstaged. The sentinel lymph node identification rate was 97.5%. Sentinel lymph node biopsy significantly differentiated between patients with or without lymph node metastasis (P = 0.001). Lymphatic mapping revealed 124 hotspots and 144 hot lymph nodes were removed by sentinel lymph node biopsy. Three patients developed a lymph node recurrence close to the primary tumor site during follow-up. Added oblique lymphoscintigraphic images and/or tomography revealed extra hotspots in 15/40 (38%) patients. In 4/40 (10%), extra contralateral hotspots were detected.. Sentinel lymph node biopsy upstaged 28% of the patients. Sentinel lymph nodes close to the primary tumor were difficult to find. Added oblique planar images and/or tomographic images revealed extra clinical relevant hotspots in 38% of patients. Reproducibility proved excellent.

Topics: Adult; Aged; Aged, 80 and over; Carcinoma, Squamous Cell; Coloring Agents; Female; Follow-Up Studies; Humans; Keratins; Lymph Nodes; Lymphatic Metastasis; Male; Middle Aged; Mouth Neoplasms; Neoplasm Recurrence, Local; Neoplasm Staging; Observer Variation; Radiology, Interventional; Radiopharmaceuticals; Reproducibility of Results; Rhenium; Sentinel Lymph Node Biopsy; Technetium Compounds; Tomography, Emission-Computed, Single-Photon

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

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

According to the recent reports analyses of characteristic of neoplasm's invasion is one of the most reliable methods of estimation the progress of the changes of tumor and prediction the outcome in patients with laryngeal cancer. Depth and mode of invasion are features which are able to assess the dynamics of the tumor growth quite precisely. In this study it was presented direct relation between morphological features of tumor front as a depth and mode of carcinoma's growth and the probability of micrometastases. The authors have analysed 22 cases of patients who were operated on the laryngeal squamous cell carcinoma in ENT Department Medical University of Lodz in the period of 1998-1999. Features of the TFG and its dependence on lymph node micrometastases, considered in immunohistochemistry with using of panel of cytokeratins (CKs) were analysed. Our study showed that feature such as depth and mode of invasion is very useful in prediction of micrometastases in patients with laryngeal squamous cell carcinoma.

Topics: Aged; Aged, 80 and over; Antigens, Neoplasm; Carcinoma, Squamous Cell; Female; Gene Expression Regulation, Neoplastic; Humans; Immunohistochemistry; Keratins; Laryngeal Neoplasms; Lymph Nodes; Lymphatic Metastasis; Male; Middle Aged; Neoplasm Invasiveness; Predictive Value of Tests; Prognosis; Retrospective Studies

In patients treated surgically due to neoplasm, in lymph nodes can be presented micrometastases, focuses 1-2 mm of carcinoma's cells. Lymph node micrometastases in patients with squamous cell carcinoma of the larynx found node-negative by conventional histology may be discovered by immunohistochemistry, particularly by using antibodies which are reactive with epithelial cells eg. cytokeratin antigens. Then tumors classified as pN0 by routine methods could be reclassified more correctly as pN1. Authors investigated the incidence of micrometastases in the neck dissection specimens originally staged as pN0 from 22 patients with laryngeal cancer treated surgically at ENT Department Medical University of Lodz between 1998-1999, according to the survival, using immunostaining with panel of polyclonal antibodies to cytokeratins. The relationship between micrometastases and clinical (pre- and intraoperative) features of lymph nodes were estimated.

Topics: Aged; Aged, 80 and over; Antigens, Neoplasm; Carcinoma, Squamous Cell; Female; Gene Expression Regulation, Neoplastic; Humans; Immunohistochemistry; Keratins; Laryngeal Neoplasms; Lymph Nodes; Lymphatic Metastasis; Male; Middle Aged; Predictive Value of Tests; Prognosis; Retrospective Studies

We report the case of an 85-year-old man who presented with an enlarging tumor on the right temple. Histologically, spindle-shaped cells were proliferating continuously within well-differentiated squamous cell carcinoma that was immunohistochemically negative for vimentin and alpha-smooth muscle actin (ASMA) but positive for cytokeratin (AE1/3). These spindle-shaped cells expressed vimentin and ASMA but not cytokeratin (AE1/3). Intermediate cells with round nuclei and small amounts of cytoplasm displayed slight expression of vimentin, ASMA, and cytokeratin. This case illustrated spindle cell squamous cell carcinoma with mesenchymal metaplasia of malignant epithelial cells.

Topics: Actins; Aged, 80 and over; Carcinoma, Squamous Cell; Head and Neck Neoplasms; Humans; Immunohistochemistry; Keratins; Male; Mesoderm; Skin Neoplasms; Vimentin

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

Despite innumerous both therapeutic and histopathologic studies that have been performed no morphologic markers are currently available in order to predict the outcome in patients with laryngeal cancer. According to the recent reports tumor front grading (TFG) is one of the most reliable methods of estimation of the progress of the changes in the peripheral part of tumor. TFG seems to be one of the technics, which is able to assess the dynamics of the tumor growth quite precisely. In this study it was presented direct relation between morphological features of tumor front and the probability of micrometastases. The authors have analysed 22 cases of patients who were operated on the laryngeal squamous cell carcinoma in ENT Department Medical University of Lódź in the period of 1998-1999. Features of the TFG and its dependence on lymph node micrometastases, considered in immunohistochemistry with using of panel of cytokeratins (CKs) were analysed. Our study showed that feature such as TFG is very useful in prediction of micrometastases in patients with laryngeal squamous cell carcinoma. The statistical analysis showed significant correlation between TFG score and mode of invasion and depth of invasion. The presented study emphasizes that it is necessary to extend the traditional histopathological diagnosis by TFG, which might influence decisions regarding therapeutic management and could eventually lead to more appropriate and individualized therapy.

Topics: Aged; Aged, 80 and over; Antigens; Carcinoma, Squamous Cell; Female; Humans; Immunohistochemistry; Keratins; Laryngeal Neoplasms; Lymph Nodes; Lymphatic Metastasis; Male; Middle Aged; Neoplasm Staging; Neoplasms, Second Primary; Prognosis

To establish a rabbit tumor cell line and to characterize its biological parameters.. VX2 tumor tissue was used for the primary culture in vitro. After 40 passages, the cell morphology, CK expression (immunohistochemical staining), cell cycle, karyotype and tumorigenecity in rabbits and nude mice were investigated.. The newly established cell line VX2 was maintained in continuous culture for over 70 passages in 10 months. Morphologically, VX2 cells were polygonal to short spindled. Tonal fibril and tight junction were found under the electron microscope. CK was positive. The cell cycle analysis showed 69.3% in G1 phase, 5.6% in G2 phase and 25.1% in S phase. The population doubling time was 34.5 hours. The chromosomal analysis showed a hypotriploidy with a median chromosome number of 58 approximately 62. The tumorigenecity in rabbits and nude mice were both 100%.. The established VX2 cell line derived from rabbit squamous carcinoma could serve as a model system for experimental oncology in the rabbit.

Topics: Animals; Carcinoma, Squamous Cell; Cell Cycle; Cell Line, Tumor; Keratins; Mice; Mice, Inbred BALB C; Mice, Nude; Neoplasm Transplantation; Polyploidy; Rabbits

Topics: Adenolymphoma; Carcinoma, Squamous Cell; Cell Transformation, Neoplastic; Humans; Keratins; Ki-67 Antigen; Male; Metaplasia; Middle Aged; Parotid Neoplasms

In the last decades, a number of clinicopathologic subtypes of squamous cell carcinoma (SCC) of the skin, ranging from highly aggressive tumors with a tendency to recur and metastasize to neoplasms with a favorable prognosis, have been described. SCCs arising from the wall of hair follicles have been briefly mentioned by some authors but never reported in a series.. Cases of SCC arising from the wall of hair follicles were collected from the files of two large German Centers for Dermatopathology and analyzed clinicopathologically and immunohistochemically.. Sixteen cases of SCC developing in hair follicles were found among more than 7000 cases of cutaneous SCC reviewed. In most cases, tumors arose on sun-damaged skin of the face of elderly persons. There was a male predominance (11/5). The most common clinical diagnosis was basal cell carcinoma (BCC). Microscopically, tumors developed in the upper part of hair follicles without or with focal involvement of the overlying epidermis at the border with the involved follicle. Immunohistochemically, tumors were positive for cytokeratin and negative for a battery of immunomarkers, including antibodies against the most common carcinogenic human papillomaviruses (HPV) of the skin. Most tumors were excised by simple excision. In two cases, a recurrence was noted after incomplete excision. No further recurrences or metastasis have been noted after a follow-up period ranging from 11 months to 12 years.. SCC of the hair follicle represents a poorly recognized but distinctive subset of SCC of the skin that should be considered in the differential diagnosis of other cutaneous epithelial tumors. The term follicular SCC (FSCC) is proposed for this neoplasm.

Topics: Aged; Aged, 80 and over; Biomarkers, Tumor; Carcinoma, Basal Cell; Carcinoma, Squamous Cell; Female; Hair Follicle; Humans; Immunoenzyme Techniques; Keratins; Male; Middle Aged; Neoplasm Recurrence, Local; Skin Neoplasms

Lymphoepithelial carcinoma is a relatively common malignancy in the nasopharyngeal region, but it rarely occurs at other sites. We report a lymphoepithelial carcinoma in the pancreas of a 65-year-old male patient operated on for a gastric stump carcinoma 7 years previously. The solitary tumor in the pancreas presented as a circumscribed lesion and measured 5.5 cm in diameter. The tumor was densely infiltrated by lymphocytes, and the neoplastic cells fulfilled all criteria for a lymphoepithelial carcinoma. Several peripancreatic lymph node metastases were observed. Marked reactivity for Epstein-Barr virus (EBV) early RNA (EBER) was detected in the majority of tumor cells using in situ hybridization. Nuclear EBER signals were also detected in the previously operated gastric stump adenocarcinoma, which also exhibited focal lymphocytic infiltration but otherwise displayed a histology different from lymphoepithelial carcinoma and did not show local recurrence. Even though an unusually late metastasis of the gastric carcinoma cannot be ruled out, we favor the hypothesis that this patient developed an EBV-related pancreatic lymphoepithelial carcinoma as a second primary tumor, based on the considerable delay of this tumor manifestation, the unusual site, the pathologic presentation, the exclusively peripancreatic nodal spread, and the different histology of the lesion.

Topics: Aged; Carcinoma, Squamous Cell; Epstein-Barr Virus Infections; Herpesvirus 4, Human; Humans; Immunohistochemistry; In Situ Hybridization; Keratins; Male; Pancreas; Pancreatic Neoplasms; RNA, Viral

The presence or absence of metastatic disease in cervical lymph nodes is the single most important determinant of therapy and prognosis for patients with head and neck squamous cell carcinoma (HNSCC). However, histologic examination fails to detect metastatic disease in a subset of neck dissection specimens. The accuracy of neck staging may be improved by the use of molecular techniques. Cytokeratins 5, 14, and 20 may be appropriate markers for HNSCC because they are expressed in HNSCC but not in lymphatic tissue.. To test the sensitivity of detection of cytokeratin 5, 14, and 20 messenger RNA by quantitative reverse transcription polymerase chain reaction (RT-PCR), full-length coding DNA sequences were cloned and transcribed. The expression of cytokeratin 5, 14, and 20 messenger RNA was quantified in 4 HNSCC cell lines and 11 tumors. A cell culture lymph node model was created.. As few as 32 molecules of cytokeratin 14 could be detected using quantitative RT-PCR. Cytokeratins 5 and 14 were easily detected in all 4 HNSCC cell lines and almost all tumors. Cytokeratin 20 was not a useful marker, as expression was absent or significantly reduced in cell lines and tumors. In the lymph node model, cytokeratin 14 quantitative RT-PCR was able to detect 1 cancer cell in a background of 10 million lymphatic cells.. Quantitative RT-PCR detection of cytokeratin 5 or 14 is a sensitive new molecular technique that may be used for detection of cervical micrometastases in head and neck cancer.

Topics: Biomarkers, Tumor; Carcinoma, Squamous Cell; Head and Neck Neoplasms; Humans; Keratins; Lymphatic Metastasis; Molecular Probes; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Sensitivity and Specificity; Tumor Cells, Cultured

Squamous cell carcinoma of the oral cavity is one of the most common human neoplasms, and prevention of these carcinomas requires a better understanding of the carcinogenesis process and a model system in which cancer chemoprevention agents can be tested. We have developed a mouse model using the carcinogen 4-nitroquinoline 1-oxide (4-NQO) in the drinking water to induce tumorigenesis in the mouse oral cavity.. 4-NQO was delivered by tongue painting or drinking water to two mouse strains, CBA and C57Bl/6. The incidences of oral cavity carcinogenesis were then compared. In addition, we examined the expression of some of the molecular markers associated with the process of human oral cavity and esophageal carcinogenesis, such as keratin (K) 1, K14, p16, and epidermal growth factor receptor, by immunohistochemistry.. After treatment with 4-NQO in the drinking water, massive tumors were observed on the tongues of both CBA and C57Bl/6 female mice. Pathological analyses indicated that flat squamous dysplasias, exophytic papillary squamous tumors (papillomas), and invasive squamous cell carcinomas were present. Immunohistochemistry analyses showed that 4-NQO changed the expression patterns of the intermediate filament proteins K14 and K1. K14 was expressed in the epithelial suprabasal layers, in addition to the basal layer, in tongues from carcinogen-treated animals. In contrast, control animals expressed K14 only in the basal layer. Moreover, we observed more bromodeoxyuridine staining in the tongue epithelia of 4-NQO-treated mice. Reduced expression of the cell cycle inhibitor, p16, was observed, whereas 4-NQO treatment caused an increase in epidermal growth factor receptor expression in the mouse tongues. Interestingly, similar features of carcinogenesis, including multiple, large (up to 0.5 cm) exophytic papillary squamous tumors and invasive squamous cell carcinomas, increased bromodeoxyuridine staining, and increased K14 expression, were also observed in the esophagi of 4-NQO-treated mice. However, no tumors were observed in the remainder of digestive tract (including the forestomach, intestine, and colon) or in the lungs or livers of 4-NQO-treated mice. These results indicate that this murine 4-NQO-induced oral and esophageal carcinogenesis model simulates many aspects of human oral cavity and esophageal carcinogenesis.. The availability of this mouse model should permit analysis of oral cavity and esophageal cancer development in various mutant and transgenic mouse strains. This model will also allow testing of cancer chemopreventive drugs in various transgenic mouse strains.

Topics: 4-Nitroquinoline-1-oxide; Animals; Bromodeoxyuridine; Carcinogens; Carcinoma, Papillary; Carcinoma, Squamous Cell; Cyclin-Dependent Kinase Inhibitor p16; Disease Models, Animal; ErbB Receptors; Esophageal Neoplasms; Female; Immunoenzyme Techniques; Keratin-14; Keratins; Mice; Mice, Inbred C57BL; Mice, Inbred CBA; Mouth Neoplasms; Neoplasm Invasiveness; Tongue Neoplasms

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

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

Topics: Carcinoma, Squamous Cell; Diagnosis, Differential; Humans; Immunohistochemistry; Keratins; Keratoacanthoma; Protein Precursors; Skin Neoplasms

Mucoepidermoid carcinomas (MECs) are the most common malignant tumor of the salivary glands; however, the histogenesis of MECs has been still controversial. This study was undertaken to investigate the histogenesis of MECs by the examination of their collagen gel-based coculture tissue and transplanted tumors.. Two cell lines from a primary and a metastatic MECs were established and characterized by the mutational analysis of the p53 gene and in vivo tumorigenicity in athymic nude mice. Collagen gel-based organotypic cocultures were performed, and the ultrastructural and immunohistochemical findings were examined.. Two cell lines demonstrated p53 point mutation at the same codon. A metastatic cell line of MEC showed in vivo tumorigenicity. Transplanted tumors and the collagen gel-based culture tissues showed poorly differentiated squamous cell carcinomas devoid of mucous cell differentiation; however, they disclosed the differentiation of myoepithelial cells.. MECs appear to be centered on the squamous cell differentiation, and the specific differentiation of myoepithelial or mucous cells seems to be modulated by the property of microenvironment.

Topics: 3T3 Cells; Actins; Adult; Animals; Carcinoma, Mucoepidermoid; Carcinoma, Squamous Cell; Cell Differentiation; Cell Line, Tumor; Coculture Techniques; Codon; Collagen; Culture Media; Epithelial Cells; Genes, p53; Humans; Keratins; Lymphatic Metastasis; Male; Mice; Mice, Inbred BALB C; Mice, Nude; Muscle, Smooth; Neoplasm Transplantation; Point Mutation; Tongue Neoplasms

There has been no report on useful immunohistological markers for epithelioid sarcoma (ES) so far. The purpose of this study is to evaluate the positivity and specificity of CA125 as a marker for the correct diagnosis of ES.. This study was performed in 11 patients with ES (nine men and two women; distal type: 10 cases; proximal type: one case), 78 patients with other soft tissue tumors and nine with benign granulomas. The other soft tissue tumors consisted of six synovial sarcomas, six clear cell sarcomas, eight leiomyosarcomas, six rhabdomyosarcomas, five malignant peripheral nerve sheath tumors, ten malignant fibrous histiocytomas, 17 desmoid tumors, 14 liposarcomas, six squamous cell carcinomas (cutaneous SCC of the distal extremities), two rheumatoid nodules and seven foreign body granulomas. Immunohistochemical analysis for CA125 was performed for these 89 soft tissue tumors and nine granulomas using a labeled streptavidin biotin method. Immunohistochemical analysis of epithelial membrane antigen, cytokeratin, carcinoembrionic antigen, vimentin and CD34 was performed only for the 11 ES patients.. CA125 was strongly expressed in 10 out of the 11 ES patients. EMA, cytokeratin and vimentin were also positive in all the cases. CEA was positive in two of the 11 patients. Immunohistochemical study in six ES patients showed expression of CD 34. The other 78 soft tissue tumors and nine granulomas did not express CA125.. This study clearly revealed the specificity and positivity of CA125 in ES. These data indicate that CA125 may be a useful tumor marker for diagnosing ES.

Topics: Adolescent; Adult; Antibodies, Monoclonal; Antigens, CD34; Biomarkers, Tumor; CA-125 Antigen; Carcinoembryonic Antigen; Carcinoma, Squamous Cell; Female; Granuloma; Humans; Immunohistochemistry; Keratins; Male; Middle Aged; Mucin-1; Rhabdomyosarcoma; Sarcoma; Sarcoma, Clear Cell; Sarcoma, Synovial; Sensitivity and Specificity; Soft Tissue Neoplasms

Several candidate tumor markers for cervical neoplasia have been identified. Among those are keratin markers, whose precise implications in the diagnosis are still under debate. In the present study, we aimed to clarify the usefulness of studying the expression of keratins 8, 10, 13, and 17 for diagnostic purposes in human cervix carcinomas. Forty-four invasive squamous carcinomas, 10 cervical intraepithelial neoplasia grade III (CIN III), and 10 reference cervix were examined immunohistochemically with monoclonal antibodies. Expression of keratins in reference exocervix, CIN III, and invasive carcinomas was as follows: keratin 8--0, 44.4%, and 57.1%, respectively; keratin 10-77.8%, 40%, and 19%, respectively; keratin 13--100%, 22.2%, and 25%, respectively; keratin 17-0, 40%, and 73.2%, respectively. In invasive carcinomas, expression of keratin 10 was significantly associated with keratinizing carcinomas. In conclusion, we observed that expression of keratins 8 and 17 and loss of keratins 10 and 13 are good markers of malignant transformation in human cervix. Keratin expression patterns, namely expression of keratin 10, can be useful for subtyping and grading squamous cell carcinomas of the cervix.

Topics: Biomarkers, Tumor; Carcinoma, Squamous Cell; Female; Humans; Immunohistochemistry; Keratins; Sensitivity and Specificity; Uterine Cervical Dysplasia; Uterine Cervical Neoplasms

We describe AMIDA (autoantibody-mediated identification of antigens), a novel target identification technology based on the immunoprecipitation of disease-specific antigens by autologous serum antibodies followed by two-dimensional electrophoretic separation, and their identification via mass spectrometry. Twenty-seven potential carcinoma antigens were identified including proteins of hitherto unknown function. Validation of one of the identified antigens, cytokeratin 8, revealed its de novo expression in hyperplastic tissue, gradual overexpression with increasing malignancy, and ectopic localization on the cell surface. Furthermore, a strong prevalence of CK8-specific antibodies occurred in the serum of cancer patients already at early disease stages. In situ hybridization for one marker of unknown function, KIAA1273/TOB3, demonstrated its strong overexpression in head and neck carcinomas, thus making it a likely tumor antigen candidate. Eventually, AMIDA could foster significant improvements for the diagnosis and therapy of human diseases eliciting a humoral immune response, and allows for the rapid identification of new target molecules.

Topics: Allergy and Immunology; Antibodies; Antibody Formation; Antigens, Neoplasm; Carcinoma, Squamous Cell; Cell Line, Tumor; Cell Separation; Electrophoresis, Gel, Two-Dimensional; Flow Cytometry; Humans; Immunohistochemistry; In Situ Hybridization; Keratins; Mass Spectrometry; Microscopy, Fluorescence; Precipitin Tests; Proteomics; Tumor Cells, Cultured

Immunostaining depending on antigen-antibody specificity is the commonest approach for determining the localization of specific antigens in tissue sections. This procedure is applicable not only with frozen or specially fixed samples, but also has proved reliable with formalin-fixed paraffin-embedded tissue sections through improvement of antigen-retrieval. Immunostaining is thus firmly established as a tool for diagnostic pathology and in our institute multiple antibodies are applied for 13-15% of the cases examined, as well as H and E staining. With the standard approach, approximately 3 h is necessary from the beginning of deparaffinization till covering sections with the Envision system. We utilized intermittent microwave irradiation for 10 min during hybridization with primary and secondary antibodies in a special moist-chamber, to achieve all immunostaining steps within 1 h in 178 primary antibodies frequently used for diagnostic pathology. According to our 5 years experience, such microwave irradiation not only obtained significant specific staining for enhancing the specificity of antigen-antibody reactions, but also inhibited nonspecific binding. We present herein the details of the methodology and recommendations for its application with particular primary antibodies. This method can contribute to savings in time and energy, allowing pathologists to rapidly obtain diagnostic information.

Topics: Antibodies, Monoclonal; Carcinoma, Squamous Cell; Gastrointestinal Stromal Tumors; Hospitals, University; Humans; Immunohistochemistry; Japan; Keratin-5; Keratins; Microwaves; Proto-Oncogene Proteins c-kit; Reproducibility of Results; Schools, Medical; Staining and Labeling; Time Factors

Despite histologically negative lymph nodes, approximately 15% of patients with early-stage cervical cancer will develop recurrence. Micrometastases have been shown to be important in staging and treatment of breast cancers and melanoma and have been identified by polymerase chain reaction analysis in cervical cancers. This study sought to estimate the frequency of micrometastases identified by immunohistochemistry in histologically negative lymph nodes and compare this to other known risk factors for recurrence of cervical cancer.. Early-stage (stages IA2, IB1, and IB2) cervical cancer patients of all histologic subtypes were identified from the surgical logs of the Los Angeles County-University of Southern California Medical Center for the period 1994-2000. One hundred thirty-two patients had histologically negative lymph nodes. Immunohistochemical assay was performed on 3,106 lymph nodes by using antibodies against cytokeratins AE-1 and CAM 5.2 in combination according to standard protocols. The stained nodes were then evaluated for the presence of micrometastases and compared against the respective clinicopathologic information in each case.. Micrometastases were detected in 19 of 132 (15%, 95% confidence interval [CI] 9%, 22%) patients, found in 29 of the 3,106 (0.9%) lymph nodes evaluated. Vascular space invasion was seen in 50 of 132 cases (38%, 95% CI 30%, 47%) and in 8 of 19 (42%, 95% CI 21%, 66%) cases with micrometastases. Surgical margins of the resected specimen were negative in 120 of 132 cases (91%, 95% CI 84%, 95%) and in 16 of 19 (84%, 95%CI 60%, 96%) of those cases with micrometastases. Micrometastases were seen most frequently in pelvic lymph nodes (25 of 29, 86%). Patients with more than 20 lymph nodes removed were more likely to demonstrate metastasis (P <.001). There was no statistically significant association between micrometastasis and vascular space invasion or tumor volume.. Micrometastases are identifiable in histologically negative lymph nodes in 15% (95% CI 9%, 22%) of early-stage cancer patients, a frequency which approximates the recurrence rate for patients with negative nodes. In this series, patients with greater numbers of lymph nodes analyzed were more likely to have lymph node micrometastasis identified. There appears to be no relationship between tumor volume and the identification of micrometastases. Although micrometastases can be identified in histologically negative lymph nodes, their presence is not strongly associated with other known factors of cervical cancer recurrence. Further research is needed to determine whether the presence of lymph node micrometastases is associated with an unfavorable prognosis.. II-3

Topics: Adult; Biomarkers; California; Carcinoma, Squamous Cell; Female; Hispanic or Latino; Humans; Immunohistochemistry; Keratins; Lymph Nodes; Lymphatic Metastasis; Neoplasm Staging; Pelvis; Prognosis; Uterine Cervical Neoplasms

In the K14-HPV16 transgenic mouse model of human papillomavirus (HPV)-associated squamous cell cancers, HPV16 E6 and E7 oncogenes and E1 and E2 regulatory genes are driven by the K14 keratinocyte-specific promoter. HPV transcription varies within the different layers of the epithelium. The correlation between HPV transcription patterns and disease pathogenesis is not well understood. Understanding these patterns is critical to designing and testing new HPV-specific therapeutic strategies. We examined HPV gene expression in homogenous populations of cells microdissected from the stratum basale, stratum spinosum, and stratum corneum of lesions from the transgenic mice using PALM microlaser technology. RNA extracted from each cell layer was subjected to two-step gene-specific RT-PCR and real-time quantitative nested PCR. To ensure specific amplification of spliced transcripts, the primers used for real-time nested PCR spanned the splice sites. High levels of E2 were detected in the basal and supra-basal layers of hyperplastic and dysplastic lesions. E7 and E6* levels increased significantly over time in stratum basale and stratum spinosum. E6** was expressed at much lower levels. We showed that the transgenic mice express correctly spliced E2 transcripts and are suitable as a preclinical model to test a therapeutic strategy using transcriptional regulation by the E2 protein.

Topics: Animals; Carcinoma, Squamous Cell; Computer Systems; Disease Models, Animal; Dissection; DNA-Binding Proteins; Epidermis; Genes, Viral; Humans; Keratin-14; Keratins; Lasers; Mice; Mice, Transgenic; Micromanipulation; Oncogene Proteins, Viral; Papillomaviridae; Papillomavirus E7 Proteins; Papillomavirus Infections; Polymerase Chain Reaction; Promoter Regions, Genetic; Repressor Proteins; Skin Neoplasms; Transcription, Genetic; Transgenes

The diagnostic sensitivity and specificity of tumor markers in head and neck cancers is not satisfactory. It is a stimulus for search of other biochemical indicators, among others determinations of acute phase proteins, helpful in head and neck cancers diagnostics and prognosis. In a group of 33 patients with squamous cell carcinoma of the pharynx and larynx (T1-4 N0-3 M0) CYFRA 21-1, SCC-Ag and acute phase proteins such as prealbumin, albumin, alpha-1 acid glycoprotein, alpha-1 antytrypsin, transferrin, ceruloplasmin and C-reactive protein (CRP) determinations were performed before radiotherapy. Significantly greater area under ROC curve for CYFRA 21-1 than for SCC-Ag was found. In T3-4 group, significantly lower albumin and higher AAG and CRP concentrations in comparison with T1-2 patients were observed. Multivariate analysis revealed that apart from tumor stage, elevated concentrations of SCC-Ag and/or CRP are independent unfavorable prognostic factors.

Topics: Acute-Phase Proteins; Antigens, Neoplasm; Biomarkers, Tumor; Carcinoma, Squamous Cell; Humans; Keratin-19; Keratins; Laryngeal Neoplasms; Multivariate Analysis; Pharyngeal Neoplasms; Prognosis; ROC Curve; Sensitivity and Specificity; Serpins; Time Factors; Treatment Outcome

This study examines differences between cultures of normal human oral epithelial cells and two squamous cell carcinoma cell lines (SCC15 and SCC25) in the expression of structural proteins, adhesion molecules, plasma membrane lipid composition, and intercellular junctions. Based on immunocytochemistry, most normal cell cultures appeared to express more E-cadherin, integrin beta-1, cytokeratin (CK) 14, CK19, and involucrin than SCC cultures. By Western blot analysis, normal cultures expressing high levels of E-cadherin also expressed high levels of involucrin and low levels of CK19. Both SCC cultures demonstrated lower expression of E-cadherin and involucrin, whereas only SCC15 cells showed high levels of CK19. Expression of beta-catenin, an E-cadherin associated protein with potential oncogene function, did not vary among normal and SCC cells. Proportions of saturated fatty acids quantified by thin layer chromatography were higher in the normal cell cultures, than in both SCC cell lines. No morphological differences were evident by transmission electron microscopy (TEM) between normal and SCC cell-cell intercellular junctions. Although no quantitation was attempted, observation suggested that normal cells form more intercellular junctions (TEM observation) and larger intercellular bridges (SEM observation) compared to both SCC cell lines. Of the factors examined, main variations between cultures of normal oral epithelium and the two SCC cell lines examined include the expression of structural and adhesion proteins, lipid composition, and intercellular junctions. The extent of the differences varies according to the stage of terminal differentiation demonstrated by the normal cell cultures.

Topics: Biomarkers, Tumor; Blotting, Western; Cadherins; Carcinoma, Squamous Cell; Cell Differentiation; Cell Line, Tumor; Cells, Cultured; Fatty Acids; Gingiva; Humans; Immunohistochemistry; Integrin beta1; Keratinocytes; Keratins; Microscopy, Electron; Mouth Neoplasms; Protein Precursors

A squamous cell carcinoma (SCC) with sarcomatous features (so-called carcinosarcoma) of stomach is reported in a 72-year-old man. The gastric submucosal tumor (12 x 11 x 6 cm) consisted of carcinoma cells and sarcomatous spindle cells, which were immunohistochemically recognized to contain high molecular weight cytokeratin. These histological and immunohistochemical results indicated that carcinoma cells and spindle tumor cells had cytokeratin similar to that of stratified squamous epithelium. These features were consistent with so-called carcinosarcoma of esophagus. A combined type of tumor consisting of polypoid and shallow ulcerative lesions (5.5 cm in diameter) was demonstrated by the biopsy to have SCC on the polypoid surface area. Therefore, the gastric tumor was thought to have metastasized from the esophageal tumor. The quick-freezing and deep-etching (QF-DE) method demonstrated that many spindle tumor cells in the gastric tumor had abundant intermediate filaments, which were evenly distributed in more peripheral cytoplasm along the cell membrane. This feature was similar to that of the control SCC. Intramembranous protein particles in the cell membrane of the tumor cells were markedly decreased as compared with those of control SCC. These ultrastructures by QF-DE method could be used for the pathological diagnosis of so-called carcinosarcomas of esophagus.

Topics: Aged; Carcinoma, Squamous Cell; Carcinosarcoma; Esophageal Neoplasms; Freeze Etching; Humans; Keratins; Male; Microscopy, Electron; Stomach Neoplasms

An approach for isolation of cell surface, nucleic acid binding proteins is described. This approach relies on affinity modification of the proteins of living cells with reactive oligonucleotides bearing a haptenic group. Covalently modified proteins were isolated by hapten-specific affinity chromatography with subsequent SDS-PAGE. Isolated 68-kDa proteins responsible for the binding of oligonucleotides were MS/MS sequenced and identified as keratin K1, keratin K10, keratin K2e, and albumin.

Topics: Carcinoma, Squamous Cell; Cell Line, Tumor; Chromatography, Affinity; DNA-Binding Proteins; Electrophoresis, Polyacrylamide Gel; Haptens; Humans; Keratin-10; Keratin-2; Keratins; Mass Spectrometry; Molecular Weight; Neoplasms, Squamous Cell; Oligodeoxyribonucleotides; Sequence Analysis, Protein; Serum Albumin

The cytokeratin (CK) pair 8 and 18 is normally expressed in all simple epithelia. This pair is not normally seen in stratified epithelial cells. Squamous cell carcinomas derived from stratified epithelia show anomalous expression of this CK pair. It is not known whether CKs 8 and 18 in any way contribute to the malignant phenotype of these cells. We used an immortalised, nontransformed human foetal buccal mucosa (FBM) cell line that expresses significantly higher amounts of CK18 compared to CK8. FBM cells were transfected with the full-length CK8 gene to study the role of CKs 8 and 18 in malignant transformation. Clones with higher expression of CK8 compared to untransfected FBM cells were studied for changes in their phenotypic characteristics. Immunofluorescence studies using antibodies to CKs 8 and 18 revealed well-decorated filaments throughout the cytoplasm in CK8 gene-transfected cells vs. untransfected FBM cells. Transmission images showed that FBM cells were isolated while transfected cells were in groups of well-spread cells with cellular projections. Transfected cells were independent of growth supplement requirements and showed anchorage-independent growth in soft agar assay and significantly reduced doubling time compared to nontransfected FBM cells. DNA flow-cytometric studies revealed increased DNA content and prolonged S phase in transfected clones vs. FBM cells. Injection of cells s.c. obtained from soft agar colonies developed from 2 of the clones resulted in tumour formation at the site of injection. In both cases, lung metastasis was also seen. Thus, in conclusion, it appears that increased expression of CK8 in some way changes the phenotypic characteristics of stratified epithelial cells, resulting in malignant transformation.

Topics: Animals; Carcinoma, Squamous Cell; Cell Cycle; Cell Division; Cell Line; Cell Transformation, Neoplastic; DNA; Epithelial Cells; Flow Cytometry; Fluorescent Antibody Technique; Gene Expression Regulation, Neoplastic; Humans; Keratins; Mice; Mice, Nude; Mouth Mucosa; Mouth Neoplasms; Neoplasms, Experimental; Phenotype; Transfection; Transplantation, Heterologous

The mechanisms employed by human papillomaviruses (HPVs) to control the replication of the viral genome and the expression of the viral genes are extremely complex and further complicated by the fact that the viral life cycle is intricately tied to the differentiation program of its host epithelial tissue. Indeed, HPV-induced immortalization of keratinocytes and disruption of the normal cytokeratin (CK) expression pattern progress pari passu during the stepwise process that preludes to squamous cell carcinoma. In our study, we have analyzed the interaction occurring between HPV type 16 E7 mRNA and the intermediate cytokeratin filaments 7 and 19 and report data in favor of a possible association between HPV16 E7 protein level and CK19.

Topics: Carcinoma, Squamous Cell; Female; Gene Expression Profiling; Gene Expression Regulation, Neoplastic; Humans; Keratin-7; Keratinocytes; Keratins; Oncogene Proteins, Viral; Papillomaviridae; Papillomavirus E7 Proteins; RNA, Messenger; Transcription Factors; Uterine Cervical Neoplasms; Zinc Fingers

Head and neck squamous cell cancer (HNSCC) requires precise characterization of their biological properties to better stratify treatment approaches. Some biological features of tumor cells are related to altered glycosylation of their surface. This study characterized alpha2,3/6-N-acetylneuraminic acid (NeuNAc) expression in adult squamous epithelia of primary and metastatic HNSCC in relation to expression of well established differentiation markers, such as cytokeratins. The expression of NeuNAc was assessed by plant lectins: Maackia amurensis agglutinin type 2 (MAA) and Sambucus nigra agglutinin (SNA) specific for alpha2,3NeuNAc and alpha2,6NeuNAc, respectively. Double labeling studies at the single-cell level were performed to compare alpha2,3/6NeuNAc linkage with expression of intermediate filaments. In studied normal adult epithelia, predominantly basal expression of alpha2,6NeuNAc and suprabasal expression of alpha2,3NeuNAc was seen, showing their differentiation-dependent linkage. The cells with markers of terminal differentiation (i.e. CK10+ alpha2,3NeuNAc+ alpha2,6NeuNAc-) prevailed in HNSCC, with increasing proportion from differentiation grade G1 to G3. High proportions of cytokeratin pCK37+ carcinoma cells occurred in all studied tumors and were accompanied by a hypersialylated phenotype (i.e. alpha2,3 NeuNAc+ alpha2,6NeuNAc+) not generally seen in non-transformed epithelia. It is hypothesized that these cells could be the pool for tumor spreading in the organism. Monitoring HNSCC using multiparameter phenotype analysis can produce new data important for the understanding of the biological behavior of HNSCC, and useful for the treatment rationalization.

Topics: Biotinylation; Carcinoma, Squamous Cell; Cell Differentiation; Cell Nucleus; Epithelium; Head and Neck Neoplasms; Humans; Keratins; Larynx; Lymphatic Metastasis; Mouth Mucosa; N-Acetylneuraminic Acid; Phenotype; Plant Lectins; Tissue Distribution; Tongue

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

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

A 54-year-old man was admitted to our hospital because of dyspnea. Radiographic examination showed an anterior mediastinal mass and pericardial effusion. Serum calcium and parathyroid hormone-related protein (PTHrP) levels were elevated, and serum CYFRA 21-1 level was extremely high. Results of percutaneous needle biopsy under computed tomography guidance led to a diagnosis of moderately differentiated squamous cell carcinoma. Immunohistological staining showed the tumor cells to be positive for PTHrP and cytokeratin monoclonal antibodies. Postmortem findings were considered to indicate thymic carcinoma. Thymic carcinoma is rare, but our case indicates that thymic squamous cell carcinoma can be identified in terms of paraneoplastic hypercalcemia.

Topics: Antigens, Neoplasm; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Biopsy; Carcinoma, Squamous Cell; Cisplatin; Cyclophosphamide; Diphosphonates; Doxorubicin; Fatal Outcome; Humans; Keratin-19; Keratins; Male; Mediastinum; Middle Aged; Pamidronate; Parathyroid Hormone-Related Protein; Thymus Neoplasms; Vincristine

In this study, we examined the distribution of heparanase protein in 75 esophageal squamous cell carcinomas by immunohistochemistry and analyzed the relationship between heparanase expression and clinicopathological characteristics. In situ hybridization showed that the mRNA expression pattern of heparanase was similar to that of the protein, suggesting that increased expression of the heparanase protein at the invasive front was caused by an increase of heparanase mRNA in tumor cells. Heparanase expression correlated significantly with depth of tumor invasion, lymph node metastasis, tumor node metastasis (TNM) stage and lymphatic invasion. Overexpression of heparanase in esophageal cancers was also associated with poor survival. In addition to its localization in the cytoplasm and cell membrane, heparanase was also identified in the nuclei of normal epithelial and tumor cells by immunohistochemistry. Furthermore, nuclear heparanase was detected in nuclear extract of cancer cell lines by Western blot and immunohistochemistry. Examination of the role of nuclear heparanase in cell proliferation and differentiation by double immunostaining for proliferating cell nuclear antigen (PCNA) and cytokeratin 10 (CK10) showed significant relationship between nuclear heparanase expression and differentiation (heparanase vs CK10), but not for proliferative state of esophageal cancer cells (heparanase vs PCNA). Our results suggest that cytoplasmic heparanase appears to be a useful prognostic marker in patients with esophageal cancer and that nuclear heparanase protein may play a role in differentiation. Inhibition of heparanase activity may be effective in the control of esophageal tumor invasion and metastasis.

Topics: Adult; Aged; Biomarkers, Tumor; Blotting, Western; Carcinoma, Squamous Cell; Cell Differentiation; Cell Division; Cell Line, Tumor; Cell Transformation, Neoplastic; Esophageal Neoplasms; Female; Fluorescent Antibody Technique, Indirect; Glucuronidase; Humans; Immunoenzyme Techniques; In Situ Hybridization; Keratins; Male; Middle Aged; Prognosis; Proliferating Cell Nuclear Antigen; RNA, Messenger; Survival Rate

Mouse models for cancer represent powerful tools to analyze the causal role of genetic alterations in cancer development. We have developed a novel mouse model that allows the focal activation of mutations in stratified epithelia. Using this system, we demonstrate that activation of an oncogenic K-rasG12D allele in the oral cavity of the mouse induces oral tumor formation. The lesions that develop in these mice are classified as benign squamous papillomas. Interestingly, these tumors exhibit changes in the expression pattern of keratins similar to those observed in human premalignant oral tumors, which are reflective of early stages of tumorigenesis. These results demonstrate a causal role for oncogenic K-ras in oral tumor development. The inducible nature of this model also makes it an ideal system to study cooperative interactions between mutations in oncogenes and/or tumor suppressor genes that are similar to those observed in human tumors. To our knowledge, this is the first reported inducible mouse model for oral cancer.

Topics: Animals; Blotting, Western; Carcinoma, Squamous Cell; Epithelial Cells; Fluorescent Antibody Technique; Gene Expression Regulation, Neoplastic; Genes, ras; Keratins; Mice; Mice, Knockout; Mouth Neoplasms; Mutation; Oncogene Protein p21(ras); Papilloma; Polymorphism, Restriction Fragment Length; Precancerous Conditions; Reverse Transcriptase Polymerase Chain Reaction

We analyzed clinical, morphological and immunohistochemical features in 5 cases of sarcomatoid or spindle cell squamous cell carcinoma of the penis.. The clinical and pathological files of all patients with penile carcinoma treated at our hospital between 1956 and 2002 were reviewed. Cases diagnosed as sarcomatoid squamous cell cancer were selected.. Five of 341 patients (1.4%) had sarcomatoid penile carcinoma. Tumor stage was T2N0 in 2 patients, T2N2 in 2 and T4N3 in 1. In all patients partial or total penectomy was eventually performed. Three patients underwent bilateral inguinal lymphadenectomy. Four of 5 patients had distant metastatic disease and died within 1 year after diagnosis. One patient had exclusive hematogenous spread without lymph node involvement. Foci of distant metastatic tumor sites were the lung, skin, bone, pericardium and pleura. In 4 patients the diagnosis was based on the expression of keratin filaments in a predominantly spindle cell penile tumor or by the identification of carcinomatous and sarcomatoid areas on hematoxylin and eosin stained slides of the primary tumor. In 1 case a squamous component in a lymph node metastasis rendered the keratin negative spindle cell primary tumor sarcomatoid squamous cell carcinoma.. Sarcomatoid squamous cell carcinoma of the penis is a subtype of squamous cell carcinoma with a poor prognosis often associated with wide hematogeneous spread. It is a rare malignancy that is often difficult to diagnose, requiring additional immunohistochemical stains.

Topics: Aged; Carcinoma, Squamous Cell; Humans; Immunohistochemistry; Keratins; Lymphatic Metastasis; Male; Middle Aged; Penile Neoplasms; Sarcoma

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

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

To better detect occult cervical metastases.. RNA from 153 cervical lymph nodes was analyzed for the presence of squamous cell carcinoma using quantitative cytokeratin (CK) 14 real-time reverse transcription polymerase chain reaction (RT-PCR). Detection of CK RNA in pathologically negative nodes was further analyzed by semi-step sectioning and CK immunohistochemistry. Subjects Thirteen consecutive patients with head and neck squamons cell carcinoma (HNSCC) presenting to the Department of Otolaryngology/Head and Neck Surgery of the University of North Carolina at Chapel Hill for neck dissection.. Cytokeratin detection was deemed nonspecific if expressed at fewer than 50 molecules of CK 14 RNA per nanogram total RNA. Of 35 HNSCCs, 33 expressed CK 14 RNA, and 15 lymph nodes with routine pathologically positive metastasis were also positive for CK 14 RNA. Four lymph nodes that were pathologically negative nodes were positive for CK 14 RT-PCR, with 2 containing metastases detected by semi-step sectioning.. Cytokeratin 14 RT-PCR is very sensitive for detecting micrometastasis in lymph nodes that are negative by routine pathological examination, with a relatively high false-positive rate. Quantitative CK 14 RT-PCR could be used to identify nodes negative for tumor by standard pathological analysis that should be examined by step sectioning and CK immunohistochemistry. Identification of micrometastases in patients with HNSCC will allow for appropriate and aggressive treatment of patients with metastatic disease.

Topics: Biomarkers, Tumor; Carcinoma, Squamous Cell; False Positive Reactions; Female; Head and Neck Neoplasms; Humans; Keratins; Lymph Node Excision; Lymphatic Metastasis; Molecular Diagnostic Techniques; Neck Dissection; Neoplasm Staging; North Carolina; Prospective Studies; Reverse Transcriptase Polymerase Chain Reaction; RNA, Neoplasm; Sensitivity and Specificity; Uterine Cervical Neoplasms; Women's Health

Clinical outcome of patients with head and neck squamous cell carcinoma (SCCHN) depends on several risk factors like the presence of locoregional lymph node or distant metastases, stage, localisation and histologic differentiation of the tumour. Circulating tumour cells in the bone marrow indicate a poor prognosis for patients with various kinds of malignoma. The present study examines the clinical relevance of occult tumour cells in patients suffering from SCCHN.. Bone marrow aspirates of 176 patients suffering from SCCHN were obtained prior to surgery and stained for the presence of disseminated tumour cells. Antibodies for cytokeratin 19 were used for immunohistochemical detection with APAAP on cytospin slides. Within a clinical follow-up protocol over a period of 60 months, the prognostic relevance of several clinicopathological parameters and occult tumour cells was evaluated.. Single CK19-expressing tumour cells could be detected in the bone marrow of 30.7% of the patients. There is a significant correlation between occult tumour cells in the bone marrow and relapse. Uni- and multivariate analysis of all clinical data showed the metastases in the locoregional lymph system and detection of disseminated tumour cells in the bone marrow to be statistically highly significant for clinical prognosis.. The detection of minimal residual disease underlines the understanding of SCCHN as a systemic disease. Further examination of such cells will lead to a better understanding of the tumour biology, as well as to improvement of diagnostic and therapeutic strategies.

Topics: Biomarkers, Tumor; Biopsy, Needle; Bone Marrow; Carcinoma, Squamous Cell; Follow-Up Studies; Humans; Immunoenzyme Techniques; Keratins; Lymphatic Metastasis; Neoplasm Recurrence, Local; Neoplasm Staging; Neoplasm, Residual; Neoplastic Cells, Circulating; Otorhinolaryngologic Neoplasms; Prognosis; Statistics as Topic

This study investigates the potential value of the nuclear matrix protein NMP179 as a marker of abnormal squamous cells in ThinPrep slides. Forty-six cervical scrapes were collected as cell suspensions and ThinPrep slides were prepared. They were double-immunostained for NMP179 and Cytokeratin 18 (CK18), an endocervical cell marker. The method of analysis adopted for the study was designed to distinguish the abnormal squamous cells from benign epithelial cell so that the percentages of abnormal squamous cells that expressed the marker could accurately be determined. Initially, an attempt was made to identify benign and abnormal cells in the ThinPrep slides on the basis of their morphology and immunostaining patterns. Discrimination between the various types of epithelial cells was incomplete using this approach and a more precise method of discrimination between the different epithelial cell types was carried out using a combination of double immunostaining (NMP179 and CK18) and morphometry using nuclear area and nuclear cytoplasmic ratios. Once the different epithelial cell types had been identified, the specificity and sensitivity of NMP179 were determined. The optimal sensitivity (89.9%) was achieved at the N/C ratio 0.36; however, the specificity of NMP179 was very low for all N/C ratios and ranged from 38.8% to 42.2%.

Topics: Biomarkers, Tumor; Carcinoma, Squamous Cell; Female; Humans; Immunohistochemistry; Keratins; Nuclear Matrix-Associated Proteins; Sensitivity and Specificity; Uterine Cervical Dysplasia; Uterine Cervical Neoplasms; Vaginal Smears

DNA microarrays are powerful tools for exploring gene expression and predicting disease state. However, since the number of variables (genes) typically exceeds the number of samples (tissue specimens), many potentially spurious genes may be selected for a predictor function. Principle component analysis (PCA) can greatly reduce the high-dimensional microarray data space while retaining most of the inherent variability. We propose a methodology that uses PCA to identify a predictor vector between two mutually exclusive and collectively exhaustive classes. By projecting the training set upon this vector a distribution of projections can be computed for each class. A log-likelihood ratio is then calculated for class membership. We used this methodology to classify 48 biopsy specimens as either oral squamous cell carcinoma or normal oral mucosa using oligonucleotide microarrays. The system was trained using a set of half the samples, and correctly predicted the membership of the other half. The three most highly positively and three most highly negative predictive genes were all keratins that are known markers of squamous cell carcinoma.

Topics: Biopsy; Carcinoma, Squamous Cell; Gene Expression Profiling; Genetic Markers; Humans; Keratins; Linear Models; Mouth Mucosa; Mouth Neoplasms; Oligonucleotide Array Sequence Analysis; Principal Component Analysis; RNA, Messenger

Our study was designed to find out the rate and the characteristics of micrometastasis in cervical lymph nodes using immunohistochemical staining.. From 69 patients, 1710 lymph nodes negative for metastasis on hematoxylin-eosin stain, were examined. Immunohistochemical stain was performed using pan-cytokeratin AE1/AE3 antibody.. In 13 cases, occult lymph node metastasis was detected by immunohistochemical method. On retrospective review of the hematoxylin-eosin stain by the pathologist, lymph node metastasis was detected in 4 of 13 patients.. Because the immunohistochemical method enhanced the detection rate of occult micrometastasis in cervical lymph nodes of head and neck squamous cell carcinoma patients, it may be recommended for routine diagnostic use in patient with negative for a lymph node metastasis on routine hematoxylin-eosin stain.

Topics: Adult; Aged; Carcinoma, Squamous Cell; Female; Head and Neck Neoplasms; Humans; Immunohistochemistry; Keratins; Lymph Node Excision; Lymphatic Metastasis; Male; Middle Aged; Neoplasm Staging; Retrospective Studies

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

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

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

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

Squamous cell carcinoma (SCC) is the most common form of oral malignancy and is often preceded by premalignant lesions, some of which are more likely to progress to carcinoma than others. In this study, a panel of monoclonal antibodies (AE1/AE3, cytokeratin [CK] 14, Ki-67 and p53) is applied to 10 cases of human oral tissue in each of six categories to establish staining patterns indicative of which lesions are more likely to progress to malignancy. The six tissue categories are normal tissue; abnormal benign lesions; mild, moderate and severe dysplasia; and SCC. A statistical analysis of Ki-67 and p53 immunoexpression is performed. The results showed that AE1/AE3 and CK 14 expression was reduced as a late event in oral carcinogenesis, particularly in poorly differentiated SCC. Expression of Ki-67 and p53 proved to be a weak but statistically significant predictor of malignant progression in oral tissue.

Topics: Antibodies, Monoclonal; Biomarkers, Tumor; Carcinoma, Squamous Cell; Gene Expression Regulation, Neoplastic; Humans; Immunohistochemistry; Keratins; Ki-67 Antigen; Mouth Neoplasms; Neoplasm Proteins; Precancerous Conditions; Tumor Suppressor Protein p53

Topics: Carcinoma, Squamous Cell; Herpesvirus 4, Human; Humans; Immunohistochemistry; Keratins; Parotid Neoplasms

Only 10 cases of lymphoepithelioma-like carcinoma of the breast have been reported in the literature. This report adds one more case to the published literature. A 62-year-old woman presented with a mass in her left breast on physical examination. The mammographic images showed a 3.0 cm, poorly defined mass in the upper outer quadrant. A biopsy was recommended. The gross specimen consisted of a 5 cm portion of breast parenchyma with no discrete tumor. On microscopic examination, the tumor was composed of sheets of epithelioid cells arranged as single cells or in cords partially obscured by a dense lymphocytic infiltrate. The epitheliod cells extensively expressed cytokeratin stain, but did not express E-cadherin. The lymphoid cells expressed L26 stain in the germinal centers, and CD3 stain in the T lymphocytes surrounding the germinal centers and in between tumor cells. In situ hybridization showed no evidence of Epstein-Barr virus infection in the tumor cells. An overall review of 11 cases shows that the disease is usually seen in older patients. In situ and invasive lobular component was reported in 36% of the cases. Eight of 11 were negative for E-cadherin, 36% were estrogen receptor-positive, 18% were progesterone receptor-positive, and all of them were HER2/neu negative. None of the reported cases have been associated with Epstein-Barr virus infection. Only two of the cases showed lymph node metastasis, and long-term follow-up in one of them showed good prognosis. In summary, lymphoepithelioma-like carcinoma of the breast is a tumor with a good prognosis that should be considered as a possible diagnosis in breast tumors with an intense lymphocytic infiltrate.

Topics: Biomarkers, Tumor; Breast Neoplasms; Carcinoma, Squamous Cell; CD3 Complex; Diagnosis, Differential; Epithelioid Cells; Female; Humans; Keratins; Lymphoma; Middle Aged

To assess cytokeratin-17 (CK17) as an immunohistochemical marker for squamous cell carcinoma of the larynx, we stained 63 tissue samples from 63 consecutive patients who were believed or suspected to have squamous cell carcinoma of the larynx for CK17 and analyzed them by computerized histomorphometry. The mean staining intensity for CK17 was significantly stronger (p < .01) in cancerous cells, dysplasia, and normal epithelium proximal to the tumor than in distal normal epithelium and polyps. The percentage of stained area, within samples taken from a single patient, was significantly higher in malignancy and dysplasia as compared to distal normal epithelium and in malignancy as compared to dysplasia and proximal normal epithelium (p < .001). The integrated optical density was significantly higher in the malignant epithelium, dysplasia, polyps, and proximal normal epithelium than in distal normal epithelium (p < .0001). We conclude that CK17 is a highly sensitive and specific immunohistochemical marker for premalignant and malignant transformation in the larynx. Further investigation is warranted in order to assess the role of CK17 in determining safe resection borders.

Topics: Aged; Biomarkers, Tumor; Carcinoma, Squamous Cell; Cell Transformation, Neoplastic; Female; Humans; Immunohistochemistry; Keratins; Laryngeal Neoplasms; Male; Middle Aged; Neoplasm Proteins; ROC Curve; Sensitivity and Specificity

The most frequent consideration in the clinical and histologic differential diagnosis of keratoacanthoma is squamous cell carcinoma. In the present study, cytokeratin 10 expression and proliferation rate as measured by Ki-67 expression were compared between 50 clinically and histologically diagnosed keratoacanthomas and 50 squamous cell carcinomas. Tissue sections from the skin were immunohistochemically stained with anti-cytokeratin 10 and anti-Ki-67 monoclonal antibodies. The distribution of cytokeratin 10 expression and proliferative cell count were analyzed. Study results showed higher cytokeratin 10 expression in keratoacanthomas than in squamous cell carcinomas and different distribution of staining in the two entities. The analysis of cytokeratin 10 expression showed a much wider range of values and statistically higher median (p<0.001) in keratoacanthomas than in squamous cell carcinomas. Additionally, the proliferation index of keratinocytes as measured by Ki-67 expression was significantly higher in squamous cell carcinomas than in keratoacanthomas (p<0.01). These results may prove helpful in histologic differentiation of these disorders.

Topics: Carcinoma, Squamous Cell; Diagnosis, Differential; Humans; Keratins; Keratoacanthoma; Ki-67 Antigen; Skin Neoplasms

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

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

To investigate the relationship of vascular endothelial growth factor C (VEGF-C) and induced nitride oxide synthesizase (iNOS) expression in lymph node micrometastasis of oral squamous cell carcinoma.. Samples were obtained from 47 cases of oral squamous cell carcinoma and 15 cases with normal oral mucosa, VEGF-C and iNOS mRNA expression were detected by RT-PCR method. Lymph node micrometastasis of 10 normal lymph nodes and 355 lymph nodes from 47 cases of oral squamous cell carcinoma was detected with immunohistochemical reaction in cytokeratin antibody.. The percentages in tumors with higher expression were 57.4% for VEGF-C, 68.1% for iNOS (P < 0.05). They were significantly higher than that of normal groups. Significant positive relationship was found between VEGF-C and iNOS (P < 0.01). The positive rate of cytokeratin (CK) was 48.9%. Significant positive relationship was found between VEGF-C and CK, iNOS and CK (P < 0.01). The expression rates of CK in positive group of VEGF-C and iNOS were 63.0%, 65.6% respectively, and were significant higher than negative groups.. Expression of VEGF-C and iNOS in lymph node micrometastasis of oral squamous cell carcinoma is significant related.

Topics: Carcinoma, Squamous Cell; Humans; Keratins; Lymphatic Metastasis; Mouth Neoplasms; Neoplasm Micrometastasis; Nitric Oxide Synthase Type II; Vascular Endothelial Growth Factor C

We investigated the value of some tumor markers in the diagnosis and treatment follow-up of squamous cell carcinoma of the head and neck.. Ferritin, lipid-associated sialic acid (LSA), carcinoembryonic antigen (CEA), squamous cell carcinoma (SCC) antigen and CYFRA 21-1 levels were determined in 28 patients with squamous cell carcinoma and in a control group of 20 patients with benign lesions of the head and neck. The measurements were made before treatment and in the first and third months of treatment.. The sensitivity rates were as follows: 10.7% for ferritin, 89.3% for LSA, 21.4% for CEA, 42.9% for SCC antigen, and 14.3% for CYFRA 21-1. The specificity was 100% for all the markers. The sensitivity increased to 96.4% when CEA and LSA were used in combination. Declines in the levels after treatment were significant for ferritin, CEA, SCC antigen, and LSA. No significant relationship was found between the marker levels and lymph node metastasis, stage, and histologic differentiation of the tumors. Only ferritin and LSA levels were correlated with tumor size. Squamous cell carcinoma antigen was the only marker that manifested high levels in patients who developed locoregional recurrence and/or mortality.. Of the markers studied, LSA, CEA and SCC antigen may be of value in the evaluation of squamous cell carcinoma of the head and neck. Sensitivity and specificity rates may increase when they are used in combination.

Topics: Adult; Aged; Antigens, Neoplasm; Biomarkers, Tumor; Carcinoembryonic Antigen; Carcinoma, Squamous Cell; Case-Control Studies; Female; Ferritins; Head and Neck Neoplasms; Humans; Keratin-19; Keratins; Lipids; Male; Middle Aged; N-Acetylneuraminic Acid; Predictive Value of Tests; Sensitivity and Specificity; Serpins

The value of histological grading was examined with emphasis on reliability of assessment in 102 cases of intraoral squamous cell carcinoma from Northern Ireland with known outcome.. Two pathologists independently graded the invasive tumour front blinded to the stage and outcome.. Intraobserver agreement was acceptable but interobserver agreement was not satisfactory. The degree of keratinisation was assessed most consistently while nuclear polymorphism was the least reliable feature. Multivariate survival analysis showed that the total grading score was associated with overall survival while the pattern of tumour invasion was the most valuable feature in estimating regional lymph node involvement. The number of positive lymph nodes was strongly associated with regional relapse, while the treatment modality and status of the surgical margins correlated with local relapse.. Grading of selected features in OSCC is reliable and can facilitate treatment planning.

Topics: Adult; Aged; Aged, 80 and over; Carcinoma, Squamous Cell; Female; Humans; Keratins; Lymphatic Metastasis; Male; Middle Aged; Mitotic Index; Mouth Neoplasms; Neoplasm Invasiveness; Neoplasm Staging; Observer Variation; Polymorphism, Genetic; Prognosis; Proportional Hazards Models; Reproducibility of Results; Survival Analysis

We report a surgical case of liver tumor, 40 x 35 mm in size, with squamous cell carcinoma (SCC) and hepatocellular carcinoma (HCC) components in a 60-year-old Japanese man with steatohepatitis. Most of the SCC component showed typical intercellular bridge and keratinization, while most of the HCC components showed a thick trabecular pattern with mild to moderate nuclear atypia. Both components transit each other without undifferentiated foci; however, a small foci showing glandular structure was intermediated. No cyst formation was found in the liver. The primary site of the squamous cell carcinoma was not detected in general clinical and radiological examination. Immunohistochemical analysis revealed that part of the HCC components neighboring the SCC showed patchy and weak expression of cytokeratin 7. There are several possibilities for the origin of squamous cell carcinoma in this case: marked squamous metaplastic change of cholangiocarcinoma and/or HCC, and carcinoma originating from pleuripotential stem cells. Irregular fatty changes, scattered giant mitochondria and acellular fibrosis with bridging were seen in the liver; however, this patient had no episode of hepatitis-associated viral infection. This is an interesting case of combined hepatocellular and cholangiocarcinoma with marked SCC components arising in a non-cirrhotic fibrotic liver.

Topics: Bile Duct Neoplasms; Bile Ducts, Intrahepatic; Biomarkers, Tumor; Carcinoma, Hepatocellular; Carcinoma, Squamous Cell; Cholangiocarcinoma; Humans; Immunohistochemistry; Keratin-7; Keratins; Liver Cirrhosis; Liver Neoplasms; Male; Middle Aged; Neoplasms, Multiple Primary; Stem Cells

To test laser scanning cytometry (LSC) for the analysis of ploidy in squamous cell carcinoma of the hypopharynx (SCCH) and to develop a routine application for minimal samples such as fine needle aspirate biopsies (FNABs).. From 11 individuals 30 FNABs of primary tumors (n=11) and lymphatic metastases of SCCH (n=11) and non-metastatic lymph nodes (n=8) are analyzed by LSC. This microscope based instrument scans the cells after immobilization on a glass slide and after double staining of cytokeratin and DNA. The location of each cell is stored with the fluorescence data. Therefore the morphology of every cell can be documented by re-staining with H & E; and re-localization on the slide. Additionally, aliquots are Feulgen-stained for image cytometry in 8 specimens.. The diploid reference peak is identified taking leukocytes as internal standard. The DNA-index of the carcinoma cells ranges from 0.4 to 3.8. Comparison with image cytometry shows good correlation (r=0.89).. LSC provides a reliable and objective way to determine the ploidy of SCCH pre-operatively. Colour figures can be viewed on http://www.esacp.org/acp/2003/25-2/gerstner.htm.

Topics: Biopsy; Biopsy, Fine-Needle; Carcinoma, Squamous Cell; Cell Separation; Eosinophils; Flow Cytometry; Humans; Hypopharyngeal Neoplasms; Keratins; Leukocytes; Lymph Nodes; Lymphatic Metastasis; Microscopy, Confocal; Ploidies; Rosaniline Dyes

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

The aim of this study was to determine the occult lymph node metastasis rates with immunoperoxidase staining for cytokeratin in supraglottic larynx cancers and to assess our approach to the neck.. Twenty-two patients who had squamous cell carcinoma in the supraglottic region and no histopathologic metastasis in the neck who had their cancer detected with the use of hematoxylin-eosin were included in the study. All of the specimens were reevaluated with the use of immunoperoxidase staining for cytokeratin.. Micrometastatic disease (pN1) has been detected in 3 patients (13.61%) in whom no metastasis was detected with routine histopathologic examination.. Results suggest that the occult metastasis rates are higher than those detected with routine hematoxylin-eosin staining. However, because it is accepted that neck dissection alone has adequate therapeutic efficiency in pN1 patients, the detected 13.61% rate of micrometastases has not changed our treatment plan in the neck.

Topics: Carcinoma, Squamous Cell; Eosine Yellowish-(YS); Fluorescent Dyes; Glottis; Hematoxylin; Humans; Immunoenzyme Techniques; Keratins; Laryngeal Neoplasms; Lymph Node Excision; Lymphatic Metastasis

This paper attempts to evaluate the clinical usefulness of CYFRA 21-1 as a serum tumour marker in patients with head and neck squamous cell carcinoma (HNSCC). The serum concentration of CYFRA 21-1 was measured utilizing a new electrochemiluminescent immunoassay (ECLIA) in 142 patients with HNSCC before and after treatment, 68 patients with benign tumours of the head and neck, and 50 healthy controls. Serum levels of CYFRA 21-1 in patients with HNSCC were significantly higher than those of benign tumours and healthy controls (p < 0.001). The diagnostic sensitivity and specificity of CYFRA 21-1 for HNSCC were 62 per cent and 100 per cent, respectively. The positive rates of CYFRA 21-1 increased with progression of HNSCC, serum CYFRA 21-1 levels were related to the tumour stage expressed by primary tumour (T) and nodal status (N) (p < 0.001), but not related to patient age, gender, smoking and drinking habit, or histopathological grade (p > 0.05). Post-treatment levels of CYFRA 21-1 in HNSCC decreased significantly (p < 0.001). Among 38 patients with clinical or radiological evidence of a recurrence during follow-up, 78.9 per cent (30 of 38) showed an increase in CYFRA 21-1. The analytical ECLIA performance for serum CYFRA 21-1 provides a new means of clinical assessment for HNSCC. The results of ECLIA suggest that the serum marker CYFRA 21-1 is valuable not only for diagnosis but also for close monitoring of patients with HNSCC.

Topics: Adult; Antigens, Neoplasm; Biomarkers, Tumor; Carcinoma, Squamous Cell; Female; Head and Neck Neoplasms; Humans; Immunoassay; Keratin-19; Keratins; Luminescent Measurements; Male; Middle Aged

The correlation between TNM classification and histological scores of malignancy, and the correlation of these parameters with the prognosis was evaluated in 16 cases of squamous cell carcinoma of the tongue. The cases were selected from the files of "Dr. Luiz Antônio" Cancer Hospital, Natal, RN, Brazil. After analysis of the patients' records, the data concerning TNM classification and prognosis (in a 5-year-follow-up) were obtained. All cases were classified according to the histological malignancy grading system proposed by Anneroth et al. [Scand Dent Res 1987;95:229-249]. There was no correlation (r = 0.3083) between TNM classification and histological scores of malignancy. There was significant correlation (r = 0.7206) between TNM classification and prognosis, but there was no correlation between the histological scores of malignancy and the prognosis. It was concluded that TNM classification is an important prognostic indicator of squamous cell carcinoma of the tongue.

Topics: Adult; Aged; Aged, 80 and over; Carcinoma, Squamous Cell; Cell Nucleus; Disease-Free Survival; Female; Follow-Up Studies; Humans; Keratins; Lymph; Male; Middle Aged; Mitosis; Neoplasm Invasiveness; Neoplasm Recurrence, Local; Neoplasm Staging; Plasma Cells; Prognosis; Retrospective Studies; Statistics, Nonparametric; Tongue Neoplasms

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

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

Enhancing factor (EF), a growth factor modulator, is the mouse homologue of human secretory group II phospholipase A(2). EF exhibits growth-promoting activity in vitro, in the presence of epidermal growth factor, and also brings about phenotypic transformation of normal cells. In order to ascertain the role of EF in vivo, a human keratin-14 promoter was used to drive the expression of EF ectopically to squamous epithelial cells. The founder mouse and its progeny showed abnormal whiskers and a scaly, beaded tail. In these mice, keratinization pattern of the epidermis was disturbed and parakeratosis and acanthosis were noted. The transgenic mice, TgK14-EF, expressed EF in the suprabasal layers of tail epidermis as well as in the epithelial cells of hair follicle and sebaceous glands of skin. Expression of EF along with hyperplasia was also observed in other squamous epithelia such as buccal mucosa, tongue and oesophagus. TgK14-EF mice homozygous for the transgene showed delayed and scanty hair growth although the mice were healthy and fertile. The hemizygous TgK14-EF mice were sensitive to a two-stage chemical carcinogenesis and developed a higher number of papillomas than their normal littermates over the course of the experiment. The conversion rate of papilloma to carcinoma was two fold higher in the transgenic mice.

Topics: 9,10-Dimethyl-1,2-benzanthracene; Abnormalities, Multiple; Animals; Carcinogens; Carcinoma, Squamous Cell; Epidermis; Fibrosarcoma; Genetic Predisposition to Disease; Genotype; Group II Phospholipases A2; Humans; Keratins; Mice; Mice, Transgenic; Neoplasms, Basal Cell; Papilloma; Phenotype; Phospholipases A; Promoter Regions, Genetic; Recombinant Fusion Proteins; Skin; Skin Neoplasms; Tail; Tetradecanoylphorbol Acetate; Transgenes; Vibrissae

CYFRA 21-1 has been reported as a useful tumor marker for esophageal carcinoma, but little information was reported about the clinicopathologic importance of CYFRA 21-1. The aim of this study was to analyze the clinicopathologic and prognostic significance of preoperative CYFRA 21-1 in patients with esophageal squamous cell carcinoma.. The CYFRA 21-1 levels were measured before surgery by enzyme-linked immunosorbent assays in 157 patients with primary esophageal squamous cell carcinomas using 3.5 ng/mL as the upper limit of normal. All patients underwent radical surgical procedures without any preoperative therapy. The association between the clinicopathologic factors assessed and the CYFRA 21-1 level was determined. The CYFRA 21-1 values were monitored after surgery in 45 available patients. The prognostic values were determined by multivariate analysis using Cox's proportional hazards model.. Thirty-one of the 157 patients (19.7%) had high CYFRA 21-1 levels (> or =3.5 ng/mL). CYFRA 21-1 levels were significantly increased in patients with large tumors (> or =40 mm, p = 0.009), deep tumors (T2-T4, p = 0.003), and node-positive tumors (p = 0.003). CYFRA 21-1 levels significantly decreased after surgery (p < 0.001). A high CYFRA 21-1 level before surgery was an independent prognostic factor for survival (p = 0.043).. A high CYFRA 21-1 level is associated with tumor progression and poor survival in patients with esophageal squamous cell carcinoma.

Topics: Adult; Aged; Aged, 80 and over; Antigens, Neoplasm; Biomarkers, Tumor; Carcinoma, Squamous Cell; Disease Progression; Enzyme-Linked Immunosorbent Assay; Esophageal Neoplasms; Female; Humans; Keratin-19; Keratins; Male; Middle Aged; Predictive Value of Tests; Prognosis; Proportional Hazards Models; Statistics, Nonparametric

The frequency of amyloid deposits associated with squamous cell carcinoma (SCC) and dysplasia in the oral cavity, pharynx and larynx was examined. In addition, the origin of amyloid proteins by immunohistochemical staining with a panel of anticytokeratin monoclonal antibodies was investigated. Amyloid deposits were found in eight of 73 (11.0%) SCC and one of seven (14.3%) dysplasias in the oral cavity, in eight of 22 (36.4%) SCC and zero of two (0%) dysplasias in the pharynx, and in 22 of 37 (59.5%) SCC and four of 10 (40.0%) dysplasias in the larynx. Eight of 12 different cytokeratin (CK) antibodies reacted with these deposits: 34 beta E12 (CK1, -5, -10, -14) reacted with amyloid deposits in 19 of 19 cases (100%), LL002 (CK14) in eight of 18 cases (44.4%), MNF116 (CK5, -6, -8, -17) in eight of 19 cases (42.1%), D5/16B4 (CK5, -6) in five of 18 cases (27.8%), DE-K10 (CK10) in four of 17 cases (23.5%), RCK108 (CK19) in three of 18 cases (16.7%), 34 beta B4 (CK1) in three of 19 cases (15.8%) and AE8 (CK13) in two of 17 cases (11.8%). These antibodies always reacted with the cytoplasm of squamous cell lesions. Amyloid deposits in two cases contained a CK5 and CK14 pair, and in another two cases they contained both a CK5 and CK14 pair, and a CK1 and CK10 pair. Anti-CK antibodies, including OV-TL12/30 (CK7), c-51 (CK8), DC10 (CK18) and IT-Ks20.8 (CK20) did not react with the amyloid deposits. We conclude that the amyloid deposits associated with SCC or dysplasia in the oral cavity, pharynx or larynx were derived from CK of cancer cells and that some amyloid deposits might be assembled by two or more different CK.

Topics: Adult; Aged; Aged, 80 and over; Amyloid; Amyloidosis; Biomarkers, Tumor; Carcinoma, Squamous Cell; Female; Head and Neck Neoplasms; Humans; Immunoenzyme Techniques; Keratins; Laryngeal Neoplasms; Male; Middle Aged; Mouth Neoplasms; Pharyngeal Neoplasms; Precancerous Conditions

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

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

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

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

Tumor promoters such as the phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA) are proinflammatory agents, and their mechanism of action in epithelial carcinogenesis has been linked to the release of IL-1 alpha and the induction of chronic inflammation in skin. To test the role of IL-1 alpha and inflammation in models of cutaneous carcinogenesis, we used our previously described FVB/N transgenic mice overexpressing 17-kDa IL-1 alpha in the epidermis under the keratin 14 (K14) promoter. Strikingly, the K14/IL-1 alpha mice were completely resistant to papilloma and carcinoma formation induced by a two-stage DMBA/TPA protocol, while littermate controls developed both tumor types. K14/IL-1 alpha mice crossed with the highly sensitive TG.AC mice, constitutively expressing mutant Ha-Ras, also failed to develop papillomas or carcinomas. When the K14/IL-1 alpha transgene was bred onto a recombinase-activating gene-2-deficient background, the resistance persisted, indicating that innate, but not acquired, mechanisms may be involved in the resistance to the initiation/promotion model. As an alternative approach, a complete carcinogenesis protocol using repetitive application of DMBA alone was applied. Surprisingly, although the IL-1 alpha mice still did not develop papillomas, they did develop carcinomas de novo at an accelerated rate compared with controls. We conclude that constitutive IL-1 alpha expression rendered FVB mice completely resistant to carcinomas that required evolution from prior papillomas, but facilitated carcinomas that did not evolve from papillomas, as in the complete carcinogenesis protocol. Thus, the role of IL-1 alpha and, by extension that of other proinflammatory factors, in epithelial carcinogenesis are more complex than previously appreciated. These mice may provide a mechanism to investigate the validity of these models of human skin tumorigenesis.

Topics: 9,10-Dimethyl-1,2-benzanthracene; Animals; Carcinogens; Carcinoma, Squamous Cell; Cell Transformation, Neoplastic; DNA-Binding Proteins; Epidermis; Female; Humans; Immunity, Innate; Interleukin-1; Keratin-14; Keratins; Mice; Mice, Inbred C57BL; Mice, Knockout; Mice, Transgenic; Nuclear Proteins; Papilloma; Skin Neoplasms; Tetradecanoylphorbol Acetate; Transgenes

The incidence of occult nodal metastases associated with head and neck squamous cell carcinoma (HNSCC) and the clinical significance of nodal micrometastases by cytokeratin immunohistochemical analysis are examined.. In all, 1012 lymph nodes from 50 patients treated between 1992 and 2001 at the University of Colorado Health Sciences Center (Denver, CO) were evaluated retrospectively for micrometastases.. Serial sectioning in 5-to 6-microm interval specimens stained either with hematoxylin and eosin (H&E) or immunostaining for cytokeratins using the monoclonal antibody cocktail AE1/AE3 was performed in 21 N0, 11 N1, and 14 N2 patient cases. Cases that showed scattered cells with suspect staining qualities but without morphological features consistent with HNSCC were further evaluated by epithelial membrane antigen (EMA) immunohistochemical analysis.. H&E-stained and cytokeratin-stained sections revealed occult nodal micrometastases in 3.8% of N0 and 5% of N1 cases. Overall, 26 micrometastases were identified in N0 and N1 patients, causing 29% of N0 patients and 45% of N1 patients to be upstaged. Cytokeratin immunostaining detected micrometastases in eight cases that were negative on H&E serial sectioning. Serial sectioning by H&E alone identified three additional micrometastases. Negative EMA immunostaining confirmed the absence of malignant cells in lymph node sections that were equivocal on cytokeratin staining.. The use of serial sectioning with H&E and cytokeratin immunohistochemical analysis increases the detection of micrometastases that are often elusive by routine processing in patients with HNSCC. Improved methods of detecting micrometastases may provide a basis for improved planning of postoperative therapy for patients already at risk for tumor recurrence.

Topics: Antibodies, Monoclonal; Carcinoma, Squamous Cell; Culture Techniques; Head and Neck Neoplasms; Humans; Immunohistochemistry; Keratins; Mucin-1; Neoplasm Metastasis; Neoplasm Staging; Spinal Neoplasms

We report here that human esophageal keratinocyte stem cells are characterized by the expression of the low-affinity neurotrophin receptor p75(NTR) and differentially expressed cell adhesion molecules, the beta1 and beta4 integrins. The candidate stem cells could be fractionated from keratinocytes as a minor cell subset by means of immunocytochemical cell sorting based on the different levels of expression of these cell surface molecules. Flow cytometric analysis revealed that this minor cell subset retained a relatively slow-cycling phenotype in vitro. These cells expressed low levels of involucrin and cytokeratin 13, indicating that the p75(NTR)-positive cell subset is immature relative to the other predominant subpopulations coexpressing beta1 integrin at higher levels. The p75(NTR)-positive cell subset was crucial for achieving longevity and the greatest output of keratinocytes comprising all distinguishable subpopulations in vitro. This process was associated with self-renewal and self-amplification of the p75(NTR)-positive cell subset. These findings strongly implicate p75(NTR) as a stem cell marker, which will be valuable for prospectively investigating stem cell regulation in association with different biological processes including neoplastic transformation of regenerative epithelia.

Topics: Blotting, Western; Carcinoma, Squamous Cell; Cell Adhesion; Cell Cycle; Cell Division; Cell Membrane; Cell Transformation, Neoplastic; Epithelial Cells; Epithelium; Esophagus; Flow Cytometry; Humans; Immunohistochemistry; Integrin beta1; Integrin beta4; Keratinocytes; Keratins; Neoplasms; Phenotype; Propidium; Protein Precursors; Receptor, Nerve Growth Factor; Receptors, Nerve Growth Factor; Reverse Transcriptase Polymerase Chain Reaction; Stem Cells; Subcellular Fractions; Time Factors

Squamous cell carcinoma (SCC) is the most frequent malignant tumor of the upper aerodigestive tract. Cell lines of these tumors facilitate the investigation of various tumor biological parameters. This study was conducted to compare molecular biologic characteristics between cell lines and fresh tumor tissue.. In seven SCC-derived cell lines, cytokeratin 5/6 and cytokeratin 19 expression, DNA content, chromosome aberrations and tumorigenicity were assessed in nude rats. Unbalanced numerical and structural chromosomal aberrations were investigated by comparative genomic hybridization (CGH), and results were compared to those obtained in fresh tumor tissues of the same patients.. All cell lines expressed cytokeratins 5/6 and 19, indicating their epidermoid origin. Tumor growth after transplantation into nude rats occurred in five of seven cell lines. Routine histology and immunohistochemical examinations confirmed SCC. Aneuploidy was detected in all cell lines, with a 2c deviation index ranging from 1.9 through 9.5 and a 5c exceeding rate ranging from 2.6 through 36.7%. The most frequent chromosomal aberrations in cell lines were overrepresentations of chromosomal material on chromosomes 15q, 7p (5 cases each), 3q, 5p (4 cases each), and 11q and 17q (3 cases each) and losses of chromosomal material on chromosomes 3p, 18q (3 cases each), and 19p and 7q (2 cases each). Comparing these results to CGH analysis of fresh tumor tissue from the same patients, overrepresentations of chromosomal material on 10q, 20q and 21q, along with loss of chromosomal material on 4q was detected more frequently in primary tumors, whereas overrepresentations on 7p and loss of chromosomal material on 7q were more frequently detected in cell lines. Nevertheless, there was a high degree of similarity of chromosomal alterations in cell lines and corresponding fresh tumor tissue.. The data suggest a high degree of genetic similarity between tumor cells of cell lines and the tumors from which they were derived. Therefore, these cell lines can serve as an accurate model to investigate cell biology of SCC in vitro.

Topics: Animals; Biopsy; Carcinoma, Squamous Cell; Chromosome Aberrations; Chromosome Mapping; DNA, Neoplasm; Head and Neck Neoplasms; Humans; Immunohistochemistry; Keratins; Nucleic Acid Hybridization; Papillomaviridae; Polymerase Chain Reaction; Rats; Rats, Nude; Transplantation, Heterologous; Tumor Cells, Cultured

Although the histopathologic differential diagnosis of pagetoid neoplasms is broad, unique histopathologic identifiers and clinical correlation can often identify the process. However, in the case of mammary Paget's disease (MPD) or extramammary Paget's disease (EPD) without an obvious underlying malignancy, distinction from pagetoid squamous cell carcinoma in situ (PSCCIS) can be challenging. Our goal was to better define the immunohistochemical staining patterns of these three entities in the hope of determining distinctive staining patterns.. We evaluated nine cases of PSCCIS, five cases of MPD, and 10 cases of EPD with the immunohistochemical antibodies CAM 5.2 and CK 5/6. In addition, only PSCCIS was stained with CK 7, as the staining patterns of CK 7 in MPD and EPD are well known from prior studies.. CAM 5.2 diffusely stained all cases of MPD and EPD and failed to stain any case of PSCCIS. Furthermore, CK 7 only focally stained two of the 10 cases of PSCCIS. CK 5/6 was difficult to interpret due to the high functional background staining of the normal keratinocytes in the epidermis.. Based on these results, our data supports the use of CAM 5.2 and CK 7 immunoperoxidase markers in differentiating between difficult cases of PSCCIS and MPD or EPD. An antibody panel consisting of S-100, CAM 5.2, and CK 7 will aid in the accurate diagnosis of almost all pagetoid neoplasms of the breast or genital skin.

Topics: Adult; Aged; Aged, 80 and over; Biomarkers, Tumor; Carcinoma in Situ; Carcinoma, Squamous Cell; Female; Fluorescent Antibody Technique, Indirect; Humans; Immunoenzyme Techniques; Keratinocytes; Keratins; Male; Middle Aged; Paget Disease, Extramammary; Skin Neoplasms

This study was conducted to assess the feasibility of the sentinel lymph node procedure in patients with epidermoid carcinoma of the anal canal.. Between February 2001 and November 2002, 14 patients with epidermoid carcinoma of the anal canal and no clinical evidence of inguinal involvement were prospectively enrolled in the study. The sentinel lymph node procedure consisted of a combination of preoperative lymphoscintigraphy with technetium 99m dextran 500 injected around the tumor and intraoperative detection of the sentinel node with a gamma probe. Patent blue V dye was also injected at the periphery of the tumor to facilitate direct identification of the blue-stained lymph node. After removal, the sentinel node was studied by hematoxylin and eosin staining and immunohistochemistry for pancytokeratins (antigen A1 and A3).. Detection and removal of sentinel lymph nodes was possible in all patients. There was no correlation between tumor size and pattern of lymphatic drainage to the groin. Tumors located in the midline of the anal canal gave rise to bilateral sentinel nodes in eight of nine cases. In total, 23 sentinel lymph nodes were removed. One patient (7.1 percent) had a node identified as positive for metastatic carcinoma on immunohistochemical staining. Surgical complications were minimal.. The standardized technique was safe and highly effective in sampling inguinal sentinel lymph nodes in carcinoma of the anal canal. It also proved to be useful as an instrument to detect micrometastatic deposits in clinically normal nodes. Our early results suggest the sentinel lymph node procedure may have a role in guiding a more selective approach for patients with anal cancer. Additional studies in a larger patient population to determine the sensitivity and specificity of this method are warranted.

Topics: Aged; Antigens, Neoplasm; Anus Neoplasms; Carcinoma, Squamous Cell; Feasibility Studies; Female; Humans; Immunohistochemistry; Keratins; Male; Middle Aged; Prospective Studies; Radionuclide Imaging; Sentinel Lymph Node Biopsy

Cytokeratins (CK) are the epithelia specific intermediate filament proteins. We have shown consistent non-expression of CK-5 protein in human oral pre-cancer and cancer, in earlier studies. To investigate whether non-expression of CK-5 protein is the result of transcriptional or translational block and to evaluate the possibility if CK-5 non-expression can be used as a marker for early diagnosis of tobacco related oral cancer, RT-PCR using CK-5 specific primers was conducted. Out of 36 precancerous lesions and 29 squamous cell carcinomas (SCC) of buccal mucosa (BM) samples studied, 11 and 13 samples respectively of precancer and SCC did not show CK-5 product in RT-PCR. Down regulation of CK-5 mRNA expression was also observed in some samples. Thus, in conclusion, our results have shown that CK-5 non-expression is the result of transcriptional block. We proposed CK-5 non-expression as a potential marker for the early diagnosis of tobacco related oral cancer.

Topics: Carcinoma, Squamous Cell; Case-Control Studies; Cheek; Gene Expression Regulation; Genetic Markers; Humans; Keratins; Leukoplakia, Oral; Mouth Neoplasms; Reverse Transcriptase Polymerase Chain Reaction; Tobacco Use Disorder; Tobacco, Smokeless; Transcription, Genetic

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

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

This study was designed to help establish the most appropriate samples and tests to detect disseminated tumor cells (DTCs) for head and neck cancer patients.. Samples of bone marrow (BM) and central venous blood (CVB), collected preoperatively, and BM and peripheral venous blood, collected 3 months transcription postoperatively, were screened for the presence of DTCs using immunocytochemistry (ICC) with a pan-cytokeratin antibody and E48 reverse transcriptase-PCR. The molecular approach was also applied to intraoperative CVB.. The concordance between the molecular and ICC tests applied to preoperative samples, measured by Cohen's kappa, was not uniformly good, which likely reflected sampling errors, heterogeneity of E48 antigen expression, or stochastic effects. However, testing samples of BM and CVB preoperatively with the molecular or ICC approaches gave results that predicted disease-free survival and distant-metastases-free survival. Application of a single preoperative test predicted development of distant metastases, and the prediction could be improved by combining information derived from testing both CVB and BM. Applying two tests to the same sample of blood or BM served to validate the findings from a single assay but did not improve the prediction. Testing the intraoperative sample of CVB was also a sensitive predictor of distant metastases, but testing BM or blood 3 months postsurgery was not useful.. These findings suggest that detection of DTCs pre- or intraoperatively indicates a high risk of local and distant recurrence and reduced survival in head and neck cancer.

Topics: Bone Marrow; Bone Marrow Cells; Carcinoma, Squamous Cell; Cell Adhesion Molecules; Glycoproteins; GPI-Linked Proteins; Head and Neck Neoplasms; Humans; Immunoenzyme Techniques; Keratins; Neoplastic Cells, Circulating; Reverse Transcriptase Polymerase Chain Reaction; Risk Factors; Survival Rate; Treatment Failure; Tumor Cells, Cultured; Veins

A new sensitive method for the detection of skin cancer micrometastases in lymph nodes is based on amplification of keratin 19 (K19) mRNA by reverse transcriptase-polymerase chain reaction (RT-PCR).. To compare results of RT-PCR with those of histological examination in terms of the detection rate of skin cancer micrometastases.. Twenty-six lymph nodes obtained from 13 patients with squamous cell carcinoma (SCC), eccrine porocarcinoma and Paget's disease were investigated by histological examination (haematoxylin and eosin sections) and RT-PCR. RT-PCR was performed on extracted RNA by using K19 primer pairs. RT-PCR products were visualized by ethidium bromide staining and confirmed by non-radioactive hybridization with K19-specific probes.. All of 10 histologically positive lymph nodes yielded the expected 460-bp band. Of the 16 histologically negative lymph nodes, one (6%) was found by RT-PCR to express K19 mRNA, indicating the presence of micrometastases which could not be detected by histological examination. A serial dilution study using RNA extracted from SCC cells mixed with RNA extracted from normal lymph node cells showed a detection sensitivity of K19 RT-PCR of 10-5 micro g cancer cell RNA in 1 micro g lymph node RNA. Nested RT-PCR showed a detection sensitivity of one tumour cell in 106 lymphocytes.. These results demonstrate the usefulness of K19 RT-PCR for the detection of skin cancer micrometastases in lymph nodes.

Topics: Biomarkers, Tumor; Carcinoma, Squamous Cell; Humans; Keratins; Lymphatic Metastasis; Neoplasm Proteins; Polymerase Chain Reaction; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; RNA, Neoplasm; Sensitivity and Specificity; Skin Neoplasms

The interaction of surface proteins from A431 cells and cellular extracts with nucleic acids was investigated using affinity modification with 32P-labeled reactive oligonucleotide derivatives. Proteins with molecular weights of 68, 46, 38, and 28 kD as well as several low molecular weight proteins capable of binding to nucleic acids were found on the surface of intact cells. It was demonstrated that a protein with molecular weight of 68 kD is exposed at the cell surface, since the treatment of cells with trypsin results in the cleavage of this protein. Disruption of the integrity of the cell membrane (scrapping, treatment with trypsin, or permeabilization of the cell membrane with streptolysin O or saponin) disrupts the interaction of the reactive oligonucleotides with the cell surface proteins. Affinity modification of the cytosolic and membrane-cytosolic cell fractions with labeled oligonucleotides results in the modification of a large number of proteins, where proteins with molecular weights of 68, 46, 38, and 28 kD can be found as minor components. Surface oligonucleotide-binding proteins with molecular weight of ~68 kD were isolated by affinity chromatography after the modification of intact A431 cells with a reactive oligonucleotide derivative. The isolated surface oligonucleotide-binding proteins from A431 cells were sequenced, and one of the proteins was identified as keratin K1.

Topics: Animals; Base Sequence; Carcinoma, Squamous Cell; Cell Line, Tumor; Cell Membrane; Chromatography, Affinity; Cytoskeletal Proteins; Electrophoresis, Polyacrylamide Gel; Fluorescein-5-isothiocyanate; Humans; Keratins; Membrane Proteins; Nucleic Acids; Oligonucleotides; Protein Binding; Rabbits

Serologic tumor markers are actually a valuable tool for diagnosis, management and follow up in some cancer types. The concentrations of Cyfra 21.1, SCC and TPS has been analysed in several groups of head and neck tumors, but exclusively in larynx there are no studies concerning this subject.. The purpose of the present study was to assess the expression of serum fragments of cytokeratins (CK's) 18/19, and squamous cell carcinoma antigen (SCCA) in a same group of patients with squamous cell carcinoma of larynx, and correlate the results with tumor localisation, T, stage, histology, presence of regional metastasis, and smoking habits.. Forty six patients treated at the Department of Otorhinolaryngology, Porto Center of the Portuguese Institute of Oncology were enrolled in the study. Blood samples were obtained before treatment, and determinations effectuated using standard commercial available kits.. Although serum concentrations of Cyfra 21.1, TPS and SCC were not significantly elevated in patients with laryngeal cancer, more expressive levels namely for TPS were observed in advanced supraglotic and metastasis tumors independent of the differentiation degree.

Topics: Antigens, Neoplasm; Carcinoma, Squamous Cell; Female; Humans; Keratin-19; Keratins; Laryngeal Neoplasms; Male; Middle Aged; Peptides; Serpins

Topics: Antigens, Neoplasm; Biomarkers, Tumor; Carcinoma, Squamous Cell; Head and Neck Neoplasms; Humans; Immunoassay; Keratin-19; Keratins; Luminescent Measurements

We report two patients with keratoacanthoma, simple in one and multiple in the other, displaying typical histological features except for intravascular spread. Although this spread points to malignancy, it did not allow to rule out the diagnosis of keratoacanthoma. These aggressive histological features, as well as perineural invasion, are not linked to malignant clinical course, according to the literature. Intravascular spread suggests that keratoancanthoma could be considered as a peculiar form of well differentiated squamous cell carcinoma. Comparison between clinical and pathological observations should lead to more specific diagnosis.

Topics: Adult; Aged; Carcinoma, Squamous Cell; Female; Humans; Keratins; Keratoacanthoma; Male; Neoplasm Invasiveness; Skin Neoplasms; Treatment Outcome

The correct diagnosis of high-grade mucoepidermoid (MEC), which is composed of solid islands of intermediate and squamous cells, may be challenging, due to its similarity to other tumours, mainly with squamous cell carcinoma (SCC). The present report employed immunohistochemical technique against different cytokeratins (CKs), in order to differentiate these two entities. : Six high-grade MEC and six SCC of the parotid region, retrieved from the files of both Oral Pathology Department of the School of Dentistry of University of São Paulo and Pathology Department of A.C. Camargo Hospital, were submitted immunohistochemical technique against Cks 7,8, 10, 13, 14 and 19. : High-grade MEC was positive for Cks 7, 8, 13, 14 and 19. The cases of SCC showed strong positivity for CK14, and CK10 was present only in focal areas. Our results highlight the use of CKs (especially CK14) to differentiate high-grade MEC and SCC.

Topics: Adult; Aged; Aged, 80 and over; Biomarkers, Tumor; Carcinoma, Mucoepidermoid; Carcinoma, Squamous Cell; Diagnosis, Differential; Female; Humans; Immunoenzyme Techniques; Keratins; Male; Middle Aged; Neoplasm Proteins; Parotid Neoplasms

Abdominal para-aortic lymph node (APAL) dissection of esophageal cancer is not widely accepted. The aim of this article is to propose the indications for APAL dissection in esophageal cancer patients from the viewpoint of micrometastases.. To evaluate the value of APAL dissection in patients with esophageal cancer, the status of APAL metastases and recurrence in 230 patients with esophageal squamous cell carcinoma (1989 to 1998) was examined retrospectively. On the basis of our findings, 16 patients received a prophylactic APAL dissection from January 1999 to March 2001. Micrometastases in the dissected lymph nodes were examined using cytokeratin staining and reverse transcription-polymerase chain reaction of squamous cell carcinoma antigen messenger RNA.. Among the 230 patients who had esophageal squamous cell carcinoma, 21 had APAL metastases (including micrometastases) or APAL recurrence. Among the 21 patients with APAL metastases and recurrence, 20 (95.2%) had metastases (including micrometastases) in perigastric lymph nodes (paracardial and lesser curvature nodes). Among 51 patients with lower thoracic esophageal carcinoma, 13 (25.5%) had APAL metastases or recurrence. On the basis of these results, prophylactic APAL dissection was performed in patients with lower thoracic esophageal cancer who were suspected of perigastric lymph node metastases during operations. APAL metastases (including micrometastases) were detected in 6 (38%) of these patients, and 2 patients with APAL micrometastases survived without recurrence. However, 7 patients had hematogenic recurrence after the operation.. Our results suggested that the indications for APAL dissection were limited. Patients with lower thoracic esophageal cancer who are suspected to have perigastric lymph node metastasis and APAL micrometastases may be considered for APAL dissection.

Topics: Adult; Aged; Antigens, Neoplasm; Aorta, Abdominal; Carcinoma, Squamous Cell; Esophageal Neoplasms; Female; Humans; Immunohistochemistry; Keratins; Lymph Node Excision; Lymphatic Metastasis; Male; Middle Aged; Prospective Studies; Retrospective Studies; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Serpins

The establishment of esophageal cancer cell lines can facilitate the search for molecular mechanisms underlying its pathogenesis. Two novel human esophageal squamous cell carcinoma (ESCC) cell lines, HKESC-2 and HKESC-3, were established from a moderately differentiated ESCC of a 46-year-old Chinese woman and a well-differentiated ESCC of a 74-year-old Chinese man, both from Hong Kong. The pathological characteristics (morphological, immunohistochemical, and electron microscopic studies), tumorigenicity in nude mice, cytogenetic features, and DNA ploidy of the two cell lines were investigated. The two cell lines have been maintained in vitro for more than 17 months and passaged over 85 times for HKESC-2 and 58 times for HKESC-3. Both grew as monolayers, with a doubling time of 24 hours for HKESC-2 and 48 h for HKESC-3. Their squamous epithelial nature was authenticated by their strong immunopositivity with the anti-cytokeratin antibodies and the ultrastructural demonstration of tonofilaments and desmosomes. They are tumorigenic in nude mice and had DNA aneuploidy. G-banding cytogenetic analysis showed hyperdiploidy in HKESC-2 and near-tetraploidy in HKESC-3. Frequent breakpoints were noted at 1p22, 1p32, and 9q34 in HKESC-2 and at 1p31, 3p25, 3p14, 6q16, 6q21, 8p21, 9q34, 13q32, and 17q25 in HKESC-3. Comparative genomic hybridization analysis found that chromosomal gains were at 3q24-qter, 5q21-qter, 8q11-qter, 13q21-q31, 17q11-qter, 19, 22q22 for HKESC-2 and at 3q13-qter, 5p, 6p, 9q21-qter, 10q21-q22, 12q15-pter, 14q24-qter, 16, 17q24-qter, 20 for HKESC-3. Chromosomal losses were at 3p13-pter, 18q12-qter for HKESC-3. These two newly established cell lines will be useful tools in the study of the molecular pathogenesis and biological behavior of ESCC cells and for testing new therapeutic reagents for ESCC in the future.

Topics: Aged; Aneuploidy; Animals; Asian People; Carcinoma, Squamous Cell; Cell Division; Chromosomes, Human; Esophageal Neoplasms; Female; Hong Kong; Humans; Karyotyping; Keratins; Male; Mice; Mice, Inbred BALB C; Mice, Nude; Middle Aged; Neoplasm Proteins; Neoplasm Transplantation; Nucleic Acid Hybridization; Transplantation, Heterologous; Tumor Cells, Cultured

Carcinomas that arise in a proliferating trichilemmal cyst (PTC) have been described under a variety of names. Monoclonal antibodies (mAbs) indicating follicular differentiation have become available and were used here in two rare tumors with uncommon biologic behavior. To further elucidate the histogenesis of carcinomas arising in a PTC, mAbs to hair follicle stem cells and to hair follicle differentiation-specific cytokeratins (mAbs to cytokeratin [CK] 7, CK8, CK18, and CK19 as well as mAbs to CD8/CK15 and CD34) were studied on paraffin-embedded sections of two cases of carcinoma arising in a PTC, one anaplastic carcinoma, and one poorly differentiated squamous cell carcinoma (SCC). For comparison, concurrent PTCs and trichilemmal cysts as well as four SCCs from controls were studied. The anaplastic carcinoma showed expression of CK7, indicating a fetal hair root phenotype, and expression of CD34, indicating trichilemmal differentiation. In contrast, the poorly differentiated SCCs as well as the control SCCs stained negative for most of the mAbs applied. Expression of fetal and trichilemmal hair follicle phenotypes suggests differentiation from hair stem cells and might explain differences in biologic behavior.

Topics: Aged; Biomarkers; Carcinoma, Squamous Cell; Cell Division; Epidermal Cyst; Female; Hair Diseases; Hair Follicle; Humans; Keratins; Phenotype; Scalp; Skin Neoplasms

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

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

Susceptibility to tumor development varies among individuals in the human population. This variability can also be found among different strains of mice, particularly in the mouse skin chemical carcinogenesis model. The genetic mechanisms underlying mouse skin tumor susceptibility are not fully understood. The SENCAR stock has been found to be the most sensitive mice for skin carcinogenesis studies; however, little is known about the genes underlying tumor susceptibility, particularly, those involved in tumor progression. Experiments with the SSIN/Sprd mice, an inbred strain derived from the outbred SENCAR stock, suggested that papilloma development, tumor promotion, and their conversion into squamous cell carcinomas (SCCs), progression, are regulated by different genes. In the highly sensitive SSIN/Sprd mice, papillomas rarely progress to SCC. Using crosses between the outbred SENCAR and the SSIN/Sprd mice, we previously determined that papilloma progression in the SENCAR stock could be controlled by at least one autosomal dominant gene. However, the outbred nature of the SENCAR stock precluded us from extending those findings. More recently, another inbred strain was developed from the outbred SENCAR stock, the SENCARB/Pt. These mice have similar tumor promotion sensitivity to the SSIN/Sprd but in contrast, have high papilloma progression susceptibility, similar to the outbred original stock. In the present study, we generated F(1), F(2), and backcross hybrids between the SSIN/Sprd and SENCARB/Pt mice to determine a possible model for tumor progression susceptibility and to map the putative tumor susceptibility genes. Our tumor data suggests that papilloma progression susceptibility in the SENCAR mouse skin model could be genetically determined by one susceptibility gene. Our preliminary linkage analysis failed to identify one strong susceptibility locus to confirm this but provided some evidence for at least one possible susceptibility locus in mouse chromosome 14.

Topics: Animals; Carcinoma, Squamous Cell; Chimera; Chromosome Mapping; Chromosomes; Crosses, Genetic; Disease Progression; Genetic Linkage; Genetic Markers; Genetic Predisposition to Disease; Incidence; Keratins; Mice; Mice, Inbred SENCAR; Papilloma; Skin Neoplasms

Primary squamous-cell carcinoma (SCC) of the thyroid gland is extremely rare. We had an opportunity to treat two such cases recently. Two elderly females presented with left lobe thyroid swelling that had a history of long-standing goiter. Fine-needle aspiration (FNA) of the thyroid nodule was done in both cases. FNA cytology showed an thyroid abscess in the first, and a Hürthle-cell neoplasm in the second case. Histopathologic diagnosis was a well-differentiated squamous-cell carcinoma with an adjacent area of lymphocytic thyroiditis in the first case, and a moderately differentiated squamous-cell carcinoma in association with a Hürthle-cell adenoma in the second case. Serial sections of the excised gland ruled out any other associated thyroid malignancy. Immunostaining for pan-cytokeratin, thyroglobulin, and calcitonin were performed. The tumor, comprising polygonal and spindle cells, showed positive staining for cytokeratin and thyroglobulin; however, calcitonin did not stain any structures. Exhaustive clinical, endoscopic, and radiological examinations, i.e., X-ray of the chest, contrast-enhanced computer tomography (CECT) of the neck and chest, and ENT checkup in both cases did not reveal any primary site of squamous-cell carcinoma as the likely source of the metastases, or any contiguous spread from neighboring structures. Both patients had ipsilateral nodal metastases, and both succumbed to the disease within 6 mo of histological diagnosis. The interesting observation in both cases was thyroglobulin positivity, indicating a follicular epithelial cell origin of the SCC.

Topics: Adult; Biopsy, Needle; Carcinoma, Squamous Cell; Fatal Outcome; Female; Humans; Immunohistochemistry; Keratins; Lymph Nodes; Lymphatic Metastasis; Middle Aged; Thyroglobulin; Thyroid Neoplasms

In the literature, few studies based on clinical and histological evaluation analyze skin structural changes after transplantation to the oral cavity. Ten patients affected by squamous cell carcinoma of the oral cavity who were reconstructed with a free forearm flap were included in the current study to analyze skin alterations. The authors performed a histological and ultrastructural evaluation of skin samples from the free forearm flap before transplantation and 18 months after intraoral reconstruction. They analyzed cytokeratin and involucrin distribution, which represent markers of maturation and differentiation of epithelia. The aim of this study was to demonstrate whether skin "mucosalization" occurs. They found that the skin undergoes some morphological changes induced by the intraoral environment. Cytokeratin and involucrin distribution is mostly unchanged. This aspect is in favor of skin structure preservation. Thus, they found that "mucosalization" of the skin is not evident after 18 months.

Topics: Aged; Carcinoma, Squamous Cell; Female; Humans; Immunohistochemistry; Keratins; Male; Microscopy, Electron, Scanning; Middle Aged; Mouth; Mouth Neoplasms; Protein Precursors; Skin; Skin Transplantation; Surgical Flaps

Finding tumor markers for disease progression, and especially development of distant metastases, is desirable for patients with squamous cell carcinoma of the head and neck (SCCHN). Elevated serum levels of Cyfra 21-1 (cytokeratin fraction 21-1) have been frequently associated with disease progression in patients with lung cancer. In SCCHN, Cyfra 21-1 has not been established as a routine tumor marker yet, probably due to difficulties in finding the appropriate cut-off for the serum level. The aim of this study was to investigate whether assessment of changes in serum Cyfra 21-1 over time can predict distant metastases in patients with SCCHN, without attempting to establish an arbitrary cut-off for abnormal levels.. Cyfra 21-1 serum levels of 25 patients with SCCHN and distant metastases were evaluated by means of an ELISA test kit.. There was a wide range of Cyfra 21-1 serum levels at the time of primary diagnosis, without correlation with tumor size, lymph node status, time to recurrence, or presence of distant metastases. All patients had a clear increase of Cyfra 21-1 levels which preceded the appearance of distant metastases clinically.. Due to the wide range of Cyfra 21-1 levels at the time of primary tumor diagnosis, Cyfra-21-1 is neither a suitable screening marker for SCCHN, nor for diagnosis of distant metastases at the time of initial diagnosis of the tumor, but is of evident prognostic value for follow-up, especially for early detection of distant metastases.

Topics: Antigens, Neoplasm; Biomarkers, Tumor; Carcinoma, Squamous Cell; Disease Progression; Enzyme-Linked Immunosorbent Assay; Follow-Up Studies; Head and Neck Neoplasms; Humans; Keratin-19; Keratins; Lymph Nodes; Neoplasm Metastasis; Neoplasm Recurrence, Local; Neoplasm Staging; Pharyngeal Neoplasms; Prognosis

Carcinoembryonic antigen (CEA), squamous cell carcinoma antigen (SCC-Ag), and CYFRA 21-1 are the most useful markers for non-small cell lung cancer (NSCLC), but neuron-specific enolase (NSE) is a tumor maker of choice for SCLC. The determination of NSE in NSCLC could allow selection of patients with neuroendocrine features. NSCLC patients whose tumors have neuroendocrine properties may be more responsive to chemotherapy; however, these tumors have been reported to be more aggressive. Tumor markers are not suitable for diagnosis; their principal applications are in monitoring of therapy and prognosis.. Tumor markers were measured in 200 untreated patients with squamous cell lung cancer (SQC) and a reference group (n = 220; 124 healthy persons and 96 patients with nonmalignant lung disease). CEA and SCC-Ag were measured by microparticle enzyme immunoassays on Abbott AxSYM and IMx analyzers. CYFRA 21-1 and NSE were measured by electrochemiluminescence immunoassays on the Roche Elecsys 2010.. CEA, SCC-Ag, CYFRA 21-1, and NSE were increased above the cutoffs in 26%, 32%, 67%, and 28% of tested patients, respectively. The area under the ROC curve for CYFRA 21-1 was higher than those for CEA, SCC-Ag, and NSE (SQC vs controls). CYFRA 21-1 and CEA were significantly higher in advanced SQC than in early stages of disease (P <0.0001 and P <0.0004, respectively). In multivariate analysis of survival, CYFRA 21-1 was an independent but nonspecific prognostic factor in the operable group of SQC patients, whereas NSE was an independent prognostic factor in the advanced stages of disease.. CYFRA 21-1 is an independent prognostic factor in earlier stages and NSE in the advanced stages of SQC.

Topics: Antigens, Neoplasm; Biomarkers, Tumor; Carcinoembryonic Antigen; Carcinoma, Squamous Cell; Female; Humans; Keratin-19; Keratins; Lung Neoplasms; Male; Neoplasm Staging; Phosphopyruvate Hydratase; ROC Curve; Sensitivity and Specificity; Serpins; Survival Rate

Primary squamous cell carcinoma of the endometrium (PSCCE) is an exceedingly rare tumor. Rarely are cytological criteria discussed. We report our experience in the cytological diagnosis of a case. A postmenopausal, 64-yr-old woman suffered from pyometria. An endometrial Pap smear displayed some malignant squamous cells. Curettage of the cervix and the uterine cavity only recovered some fragments of atypical squamous epithelium whose origin could not be precisely identified. A hysterectomy with bilateral adnexectomy was decided upon. Pathological study evidenced a primary squamous cell carcinoma in the uterine cavity while the cervix was tumor-free and the lymph nodes were devoid of metastases (pT1, pN0, pM0). The patient died 46 mo PO with multiple pulmonary and renal metastases. The histological feature of PSCCE is identical to that of any tumor of a similar nature, whatever the site, especially the cervix. Confirmation of the primary endometrial nature is only possible on the hysterectomy specimen.

Topics: Carcinoma, Squamous Cell; Dilatation and Curettage; Endometrial Neoplasms; Fatal Outcome; Female; Humans; Hysterectomy; Immunohistochemistry; Keratins; Kidney Neoplasms; Lung Neoplasms; Lymphatic Metastasis; Middle Aged; Mucin-1; Papanicolaou Test; Vaginal Smears

The prognostic significance of intratumour microvessel density (IMD) and haemoglobin (Hb) level was studied in 152 (FIGO stage IB-IIIB) cervical cancer patients before radiotherapy. Patients' age and tumour stage, grade and degree of keratinization were also studied. IMD measurement expressed as the mean vessel count per 1 mm2 was performed on formalin-fixed, paraffin-embedded tumour biopsies stained with anti-factor VIII antibody (DAKO Ltd.) using immunohistochemistry and the vascular hot-spot technique. The median age of patients was 55 years (29-80). Median values for IMD and Hb level were: 142.5 (range 56.3-476.6) vessels/mm2 and 129 (range 81-160) gil, respectively. The median time of follow-up was 26 months, with a range of 2-145 months. Tumour stage (p = 0.7009), grade (p = 0.6660) and degree of keratinization (0.2669) were not significant in the Kaplan-Meier univariate analysis. However, patients' age > 50 years (p = 0.0079). high vascularity (IMD > 190.0 vessels/mm2, minimal cut-off point, p = 0.0503) and Hb concentration > 116 g/l (p = 0.0213) were favourable prognostic factors for cervical cancer treated with radiotherapy. In the Cox multivariate analysis only higher vascularity (IMD > 190/mm2 and Hb concentration > 116 g/l were favourable prognostic factors in terms of patients' survival. However, when a Cox analysis was done separately for keratinizing and non-keratinizing tumours, it was found that higher vascularity was significant only for keratinizing, and higher Hb level only for non-keratinizing cancers.

Topics: Adult; Aged; Aged, 80 and over; Anemia; Capillaries; Carcinoma, Squamous Cell; Female; Follow-Up Studies; Hemoglobins; Humans; Keratins; Life Tables; Middle Aged; Neoplasm Proteins; Neoplasm Staging; Neovascularization, Pathologic; Prognosis; Proportional Hazards Models; Survival Analysis; Treatment Outcome; Uterine Cervical Neoplasms

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

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

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

This study was designed to characterize the expression profiles of nine bladder cancer cell lines (T24, J82, 5637, HT1376, RT4, SCaBER, TCCSUP, UMUC-3, and HT1197) using cDNA microarrays (8976 genes and expressed sequence tags). Novel targets involved in bladder cancer progression of potential clinical relevance were validated by immunohistochemistry using tissue microarrays of primary bladder tumors (n = 193 cases). Hierarchical clustering classified uroepithelial cells based on their histopathogenesis and cell cycle alterations. Keratin 10 and caveolin-1 transcripts were more abundant in tumor cells from squamous and invasive origin. Their combined expression was shown to stratify bladder tumors and define squamous differentiation. To assess the robustness of the clustering analysis, a bootstrap resampling technique was used. This grouped tumor cell lines based on their biological properties, including cell cycle and cell adhesion features. E-cadherin, zyxin, and moesin were identified as genes differentially expressed in these clusters and related to the p53, RB, and INK4A status of the cell lines. Loss of these adhesion molecules was associated with stage and grade in primary tumors (P < 0.05), and moesin expression was also associated with survival (P = 0.01). Deregulation of cell cycle and apoptotic pathways, such as mutations or altered expression of p53, pRB, and INK4A (p16), is necessary for uroepithelial transformation. However, it appears that deregulation of cell adhesion is a common event associated with tumor progression in uroepithelial neoplasms.

Topics: Biomarkers, Tumor; Cadherins; Carcinoma, Squamous Cell; Carcinoma, Transitional Cell; Caveolin 1; Caveolins; Cell Differentiation; Cluster Analysis; Cytoskeletal Proteins; Gene Expression Profiling; Glycoproteins; Humans; Keratin-10; Keratins; Metalloproteins; Microfilament Proteins; Monte Carlo Method; Neoplasm Staging; Oligonucleotide Array Sequence Analysis; Retinoblastoma Protein; Tumor Cells, Cultured; Tumor Suppressor Protein p53; Urinary Bladder Neoplasms; Zyxin

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

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

Certain tumors of the esophagus that display both sarcomatous and carcinomatous features have long been recognized. The nomenclature, classification, and histogenesis remain controversial and the microscopic differential diagnosis from other esophageal malignancies can be challenging, particularly in small biopsies. In this paper, we review the literature of carcinosarcoma and present two cases of esophageal carcinosarcoma, describing their salient histologic, immunohistochemical, and ultrastructural features. Also, we assess the expression of MDM2 and CDK4 in the carcinomatous and sarcomatous compartments of our cases and we compare them with the expression of these oncogenes in selected cases of esophageal squamous cell carcinoma with prominent stromal reaction. In both of our cases, identification of some epithelial ultrastructural and immunohistochemical features in cells of otherwise sarcomatous phenotype lends support to the common epithelial origin of these neoplasms. Moreover, positive staining for MDM2 and CDK4 in our cases with equally strong reactions in both carcinomatous and sarcomatous elements provides evidence of a role for these molecules in the pathogenesis of carcinosarcoma. In contrast, in cases of squamous cell carcinoma with prominent stromal reaction only the epithelial cells stained strongly for MDM2 and CDK4. These differences in the MDM2 and CDK4 immunohistochemical profile between carcinosarcomas and carcinomas of the esophagus may assist in their differential diagnosis.

Topics: Aged; Carcinoma, Squamous Cell; Carcinosarcoma; Cyclin-Dependent Kinase 4; Cyclin-Dependent Kinases; Esophageal Neoplasms; Female; Humans; Keratins; Middle Aged; Neoplasm Proteins; Nuclear Proteins; Proto-Oncogene Proteins; Proto-Oncogene Proteins c-mdm2

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

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

A tumour-secreted cytokine autocrine motility factor (AMF) induces in vivo invasion and metastasis, and in vitro tumour cell motility by a signal transduction through interaction with its cell surface receptor gp78. In this report, we investigated the characterization of a high-metastatic human oral squamous cell carcinoma (SCC) cell line LMF4 and low-metastatic HSC-3 in comparison with non-metastatic HSC-2 and HSC-4. Morphological and motility analyses revealed LMF4 cells to have the highest motile activity among those cells. However, LMF4 cells shared the similar features with HSC-3: high level secretion of AMF, enhancement of gp78 expression, co-expression of vimentin and cytokeratin, although LMF4 cells showed twice as high motile reactivity as HSC-3. The only difference was that LMF4 had twice as high amount of low-affinity receptor(s) as HSC-3, shown by Scatchard analysis.

Topics: Blotting, Northern; Blotting, Western; Carcinoma, Squamous Cell; Cell Movement; Confidence Intervals; Electrophoresis, Polyacrylamide Gel; Glucose-6-Phosphate Isomerase; Humans; Keratins; Mouth Neoplasms; Neoplasm Invasiveness; Receptors, Autocrine Motility Factor; Receptors, Cytokine; Tumor Cells, Cultured; Ubiquitin-Protein Ligases; Vimentin

To apply a new immunocytochemistry (ICC) assay to peripheral blood samples for micrometastatic circulating tumor cell detection in patients with head and neck squamous cell cancer (HNSCC).. The ICC assay uses established monoclonal antibodies that bind to tumor-associated antigens combined with an enrichment system that uses positive selection with anti-human epithelial antigen (EpCAM antibody) to detect circulating tumor cells.. Eighteen consecutive patients newly diagnosed as having HNSCC are described.. Of the 18 patients, 8 (44%) demonstrated circulating tumor cells using the ICC assay. The numbers of patients positive for circulating tumor cells per stage are as follows: stage I, 1 of 1; stage II, 0 of 2; stage III, 2 of 5; stage IV, 5 of 6; and unknown stage, 0 of 4. The numbers of patients positive for circulating tumor cells per location are as follows: oral cavity, 1 of 2; oropharynx, 3 of 4; glottic area, 3 of 5; supraglottic area, 1 of 3; and unknown primary 0 of 4.. Circulating tumor cells were identified in almost half of the patients using the ICC assay. In a literature review, we were not able to identify previous reports of circulating tumor cell detection in patients with HNSCC from peripheral blood samples using ICC or identify any study that has attempted to quantify circulating tumor cell levels. Although the clinical implications of circulating tumor cells in micrometastatic tumor detection in patients with HNSCC are still unknown, they may be significant. Long-term follow-up may help elucidate the patients in whom conventional treatment may fail and, thus, those who may benefit from different treatment; it may also assist with the detection of recurrence with a simple blood collection.

Topics: Adult; Aged; Carcinoma, Squamous Cell; Female; Head and Neck Neoplasms; Humans; Immunohistochemistry; Keratins; Male; Middle Aged; Neoplastic Cells, Circulating

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

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

It has been previously shown that S100A2 is downregulated in tumor cells. The level of immunohistochemical S100A2 expression was therefore characterized in 424 normal and tumoral (benign and malignant) tissues of various origins, but mostly epithelial (with either glandular, squamous, respiratory or urothelial differentiation). We also investigated whether S100A2 could be co-localized with cytokeratin K14, an intermediate filament protein expressed in basal proliferative keratinocytes. Our data show that S100A2 has a low level of expression in non-epithelial tissue. In epithelial tissue S100A2 expression decreases remarkably in the tumors when compared to the normal specimens, and was correlated with the level of keratin K14. This decrease in S100A2 staining from normal to cancer cases is more pronounced in glandular than in squamous epithelial tissue. In addition, the patterns of S100A2 staining also differ between glandular and squamous tissue. These data suggest distinct functional roles for S100A2 in epithelial tissue of squamous or glandular origins.

Topics: Carcinoma, Squamous Cell; Chemotactic Factors; Cytoplasm; Epithelial Cells; Gene Expression Regulation, Neoplastic; Head and Neck Neoplasms; Humans; Immunohistochemistry; Keratins; Neoplasms, Glandular and Epithelial; Paraffin Embedding; S100 Proteins; Tissue Fixation

The ability of oral squamous cell carcinoma to metastasize to lymph nodes does not always show a relationship with clinical staging. The aim of this study was to attempt to define a trend for predictive histopathologic and/or molecular biomarkers in the development of nodal metastasis by analyzing 2 clinically extreme groups.. Patients with small primary tumors (T1, T2) with lymph node metastasis and patients with large primary tumors (T3, T4) without metastatic disease were identified among 315 consecutive cases of primary oral squamous cell carcinoma. Group comparisons were made with use of a Mann-Whitney test, and associations among the variables were assessed with nonparametric and parametric correlational analyses.. The degree of keratinization was significantly less in primary tumors with lymph node metastasis (P < or = .01). The degree of keratinization was significantly associated with nuclear pleomorphism (P =.02), number of mitoses (P =.02), stage of invasion (P =.002), and p53 expression (P =.04), independent of clinical stage of the tumor. Other microscopic features and immunohistochemical markers did not differ significantly between the groups (P >.05).. These data indicate that there still is no single predictive parameter superior to the degree of keratinization to identify patients at risk for the development of regional metastasis.

Topics: Adult; Aged; Biomarkers; Carcinoma, Squamous Cell; Cell Nucleus; Female; Forecasting; Gene Expression Regulation, Neoplastic; Humans; Immunohistochemistry; Keratins; Lymphatic Metastasis; Male; Middle Aged; Mitosis; Mouth Neoplasms; Neoplasm Invasiveness; Neoplasm Staging; Proliferating Cell Nuclear Antigen; Proto-Oncogene Proteins c-bcl-2; Receptor, ErbB-2; Risk Factors; Statistics as Topic; Statistics, Nonparametric; Tumor Suppressor Protein p53

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

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

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

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

Cytokeratins (CKs) are a subgroup of intermediate filament proteins that take part in forming the cytoskeleton. The epithelial cells in different organs express distinct CKs, and this expression may be modified during malignant transformation. Here we describe the use of reverse transcriptase-polymerase chain reaction followed by Southern blotting to determine the profile of expression of CKs in both normal and malignant laryngeal samples. Thirty-six samples were subjected to histologic examination and classified as 17 squamous cell carcinomas, 3 dysplastic lesions, and 16 normal samples. CK8 and CK19 were expressed in almost all samples, both cancerous and normal, and were therefore used to verify the integrity of RNA. Expression of CK2, CK9, and CK20 was not detected in any of the samples, normal or cancerous. CK15 and CK18 showed low sensitivity for detection of cancer (36.4% and 45.5%, respectively). CK10 showed relatively high sensitivity (91%), but only moderate specificity (69.2%). Only CK17 showed both high sensitivity and specificity (91% and 92.3%, respectively; positive predictive value, 91%). We propose that CK17 may be considered a promising candidate to use as a molecular marker for malignant transformation in laryngeal squamous cell carcinoma.

Topics: Adult; Aged; Aged, 80 and over; Biomarkers, Tumor; Blotting, Southern; Carcinoma, Squamous Cell; Female; Humans; Keratins; Laryngeal Mucosa; Laryngeal Neoplasms; Male; Middle Aged; Reverse Transcriptase Polymerase Chain Reaction

Cyfra 21-1, measuring serum fragments of cytokeratin 19, has been found to be related to tumour stage and tumour size in patients with cervical cancer. It could be a promising marker in squamous lung cancer. We evaluated this new marker with carcinoembryonic antigen, (CEA) and squamous cell carcinoma antigen (SCC-Ag) in the monitoring of 27 patients with head and neck cancer.. The retrospective study group consisted of 27 patients, 17 not suited for surgery and 10 after laser resection. Patients were clinically staged according to the TNM-classification. The mean age of the patients was 53 years (range 37-70 years). Serum levels of each marker were studied in relation to tumour stage and clinical status of the patients during radiotherapy and 6 weeks after the end of the treatment. The clinical performance of the various assays to separate those patients with complete remission from those patients with the presence of tumour was assessed.. Pre-treatment serum Cyfra 21-1, CEA, and SCC-Ag levels were not related to stage of disease and were not found to be predictive of tumour response. The clinical performance of post-treatment serum SCC-Ag levels in predicting the presence of tumour was not better than the Cyfra 21-1 assays.. We could not conclude from this study that Cyfra 21-1 marker is an additional parameter in identifying patients at risk of residual tumour after treatment, recurrent or progressive disease. An elevation of cyfra 21-1 marker was not detectable in 70% of the cases with macroscopic tumour. Therefore, Cyfra 21-1 is not a reliable parameter for the monitoring of patients with head and neck cancer during radiotherapy.

Topics: Adult; Aged; Antigens, Neoplasm; Biomarkers, Tumor; Carcinoembryonic Antigen; Carcinoma, Squamous Cell; Follow-Up Studies; Head and Neck Neoplasms; Humans; Immunoenzyme Techniques; Keratin-19; Keratins; Middle Aged; Radiotherapy Dosage; Retrospective Studies; Risk Factors; Serpins; Time Factors

Cytokeratins (also known as keratins (K)) are members of the family of intermediate filaments and form major components of the mammalian epithelial cell cytoskeleton. Cytokeratins have emerged as reliable cellular markers of oral cancer development and chemoprevention because of their abundance, stability and high antigenicity.. We investigated the effect of aqueous garlic extract on cytokeratin expression during 7,12-dimethylbenz[a]anthracene (DMBA)-induced hamster buccal pouch (HBP) carcinogenesis. Hamsters were divided into four groups of six animals. Animals in group 1 were painted with a 0.5% solution of DMBA in liquid paraffin, on the right buccal pouches, three times a week for 14 weeks. Group 2 animals were painted with DMBA as in group 1 and also received 250 mg/kg body weight aqueous garlic extract orally on alternate days to the DMBA application. Group 3 animals received garlic extract only, as in group 2. Group 4 animals received neither DMBA nor garlic extract and served as the control. The hamsters were killed after an experimental period of 14 weeks.. Cytokeratin expression was studied using human monoclonal antibodies AE1 and AE3, which react with type I and II keratins. In DMBA-induced squamous cell carcinomas, decreased expression of high molecular weight keratins was observed. Administration of garlic extract to animals painted with DMBA suppressed HBP carcinomas and restored normal cytokeratin expression.. The results of the present study suggest that inhibition of HBP carcinogenesis by garlic may be due to its regulatory effects on differentiation, tumour invasiveness, migratory and metastatic potential. We suggest that one of the mechanisms of tumour inhibition by garlic is an influence on cellular differentiation.

Topics: Animals; Antibodies, Monoclonal; Antineoplastic Agents, Phytogenic; Blotting, Western; Carcinoma, Squamous Cell; Cell Differentiation; Cheek; Chemoprevention; Cricetinae; Disulfides; Electrophoresis, Polyacrylamide Gel; Garlic; Humans; Keratins; Male; Mesocricetus; Mouth Neoplasms; Phytotherapy; Random Allocation; Sulfinic Acids

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

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

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

In surgically resected specimens of squamous cell carcinoma (SCC) of the lung from 45 patients, we immunohistochemically examined the expression of 13 subtypes of cytokeratin (CK), the intermediate filament in cytoplasm of epithelial cells. To investigate heterogeneity of CK, its expression was compared among tumor cell nests with or without keratinization and stratification. Furthermore, the relationship between CK expression and Ki-67 labeling index or p53 expression was investigated. The tumor cell nests with keratinization showed the expression of CK1 and CK10 as a central pattern and the expression of CK14 as a peripheral pattern. The nests with stratification showed CK14 expression as a peripheral pattern, whereas those without stratification showed the expression as a diffuse pattern. The tumor cell nests showing stromal invasion with fibrosis in the marginal zone were diffusely positive for CK14. Ki-67 antigen labeling index was significantly higher in the nests where CK14 expression was diffuse or peripheral than in the nests where the expression was focal or negative. In lymph node metastases, the tumor cells often showed CK14 expression, like trabecular nests in the primary carcinoma. These results suggest that CK14 is a parameter of proliferative activity and metastatic potential of SCC of the lung.

Topics: Aged; Aged, 80 and over; Biomarkers, Tumor; Carcinoma, Squamous Cell; Cell Division; Female; Humans; Immunoenzyme Techniques; Keratin-14; Keratins; Ki-67 Antigen; Lung Neoplasms; Lymph Nodes; Lymphatic Metastasis; Male; Middle Aged; Tumor Suppressor Protein p53

In order to investigate the role of Cytokeratin 13(CK13) gene in laryngeal carcinogenesis, we detected the deletion of CK13 gene through LOH analysis indirectly at DNA level using 5 STR primers within and near CK13 gene in 72 cases of laryngeal squamous cell carcinoma, then detected the differential expression between 16 cases of paired normal and cancerous tissue by Northern blot, and performed immunohistochemistry using well characterized monoclonal antibody against CK13 in squamous cell carcinoma of different stages. We found that all of the microsatellite loci exist LOH, and the LOH frequencies were 18.03%, 28.13%, 27.42%, 39.68% and 34.85% at D17S1964E, D17S2092, D17S791, D17S1665 and D17S808 respectively. The LOH+ cases accounted for 77.78% (56/72), and the frequencies of LOH were not related to the type of laryngeal carcinoma and the lymphoid metastasis; but significantly related to the differentiation, P < 0.05. CK13 gene is expressed significantly higher in 16 cases of normal tissues than in paired cancerous tissues, and the immunostain revealed that CK13 was expressed in normal laryngeal squamous cell or high differentiation stage, and its expression decreased or disappeared in poor ones, P < 0.01. CK13 gene might play an important role in the laryngeal carcinogenesis, acting as a novel tumor suppressor gene, and may be relevant to laryngeal squamous cell carcinoma diagnosis and prognosis. Further research will contribute to conform it.

Topics: Carcinoma, Squamous Cell; Chromosomes, Human, Pair 17; DNA, Neoplasm; Gene Expression Regulation, Neoplastic; Humans; Immunohistochemistry; Keratins; Laryngeal Neoplasms; Loss of Heterozygosity; Microsatellite Repeats; Neoplasm Staging

To establish a radioimmunodetection (RAID) system for localization of cervical cancer by labeling 111-indium ((111)In) to a monoclonal antibody against cytokeratin 19 (MAb Cx-99), and detecting it with a hand-held gamma detector in an animal model.. MAb Cx-99 was labeled with 111-Indium by the DTPA chelating method. From the second day to the seventh day after injection of this immunoconjugate into athymic nude mice bearing cervical cancer cell line CC7T xenografts, the biodistribution ratios of tumor and non-tumor radioactivity were detected by a hand-held gamma detector. Data were also correlated with the data detected by the conventional gamma counter.. The labeling efficiency of this (111)In-labeled MAb Cx-99 and (111)In-labeled MOPC was 91.6% and 95.5%, respectively. After injection, the liver, kidney and lung were initially noticed to have high radioactivity, but the localization of tumor/tissue ratios increased progressively as time passed, indicating the effect of delayed detection for distinguishing tumor from non-tumor tissues. Except for the spleen, the range of tumor/tissue ratios was 1.18-32.7 and 1.14-39.35 for the fourth day and the seventh day, respectively. The tumor/spleen ratio remained low until the seventh day after injection, thus indicating that the spleen might have a different excretion rate.. This study indicated the feasibility of a hand-held detection system in the localization of cervical cancer after injection of (111)In-labeled MAb Cx-99. The effect of delayed detection was obvious by the decreasing high bindings in the liver, spleen and kidney, with the applicable detection time being four to seven days after injection.

Topics: Animals; Antibodies, Monoclonal; Carcinoma, Squamous Cell; Female; Humans; Indium Radioisotopes; Keratins; Mice; Mice, Inbred BALB C; Mice, Nude; Predictive Value of Tests; Radioimmunodetection; Sensitivity and Specificity; Transplantation, Heterologous; Tumor Cells, Cultured; Uterine Cervical Neoplasms

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

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

A 26-year-old Hispanic woman complaining of "itching" and "herpetic lesions" on the vulva for 9 months was seen at a university hospital. On physical examination, multiple vulvar masses were noted. Biopsies taken from these lesions showed invasive keratinizing squamous cell carcinoma. The vulvectomy specimen revealed 4 tumor masses, the largest located on the mons pubis. Although the incidence of vulvar intraepithelial neoplasia has increased in recent years, only very few cases of invasive carcinoma have been reported in young women. The tumors that occur at a younger age characteristically have basaloid or warty histology, in contrast to those occurring in older women, which usually are well-differentiated keratinizing carcinomas. We believe this is an unusual case of vulvar squamous cell carcinoma. In addition to our patient's young age, her tumor had a histologic profile usually found in lesions of an elderly woman. The tumor was negative for human papillomavirus by polymerase chain reaction analysis and was positive for p53 by immunohistochemistry.

Topics: Adult; Biopsy; Carcinoma, Squamous Cell; Female; Humans; Immunoenzyme Techniques; Keratins; Lymph Node Excision; Neoplasm Invasiveness; Polymerase Chain Reaction; Tumor Suppressor Protein p53; Vulvar Neoplasms

The term ocular surface squamous neoplasia (OSSN) encompasses conjunctival and corneal intraepithelial neoplasia through to invasive squamous cell carcinoma of the ocular surface. The disease is related to prolonged exposure to solar ultraviolet light and has been proposed as an acquired immune deficiency syndrome-associated tumor. To the authors' knowledge, very few reports describing the cytology of these lesions have been published.. Impression cytology (IC) samples collected from the eyes of patients with a range of ocular surface diseases were available for study. From these, 267 sets of impressions had subsequent histopathology that had been collected within 6 months of the IC, and which indicated the presence of OSSN. The IC from these cases was used to describe the cytomorphology of intraepithelial and invasive OSSN.. Within the intraepithelial group, keratinized dysplastic cells that often were accompanied by hyperkeratosis, syncytial-like groupings, and nonkeratinized dysplastic cells were described. Within the invasive group, cases with significant keratinization and an additional group of cases with little keratinization and sometimes also prominent macronucleoli were described. Keratinized cases were the most numerous in both the intraepithelial and invasive groups. A description also was given of a low number of cases with cytology and also subsequent histopathology indicating the presence of intraepithelial OSSN, in the absence of a clinically detectable lesion.. This detailed description of the cytomorphology of a high number of cases of OSSN with confirmation by histopathology should assist others with little experience of the cytology of these lesions to examine them with increased confidence. Cancer (Cancer Cytopathol)

Topics: Carcinoma in Situ; Carcinoma, Squamous Cell; Conjunctival Neoplasms; Cornea; Cytodiagnosis; Eye Neoplasms; Humans; Keratins; Neoplasm Invasiveness

Epstein-Barr virus (EBV) has been linked to carcinomas of several body sites, especially of the nasopharynx, salivary gland, lung, and stomach. We present five cases of lymphoepithelioma-like cholangiocarcinoma, including one that had been previously reported. Two patients were men and three were women. Their ages ranged from 42 to 66 years. Histologically, all five tumors were composed of variable proportions of undifferentiated epithelial cells and glandular components in a lymphocyte-rich stroma. EBV was detected in all five tumors by in situ hybridization for EBER-1 in both lymphoepithelioma-like carcinoma (LELC) and glandular parts, but not in 36 cases of cholangiocarcinoma without the LELC component. Taken together, these observations indicate that lymphoepithelioma-like cholangiocarcinoma is strongly linked to EBV. The LELC type of cholangiocarcinoma, like LELC of other body sites, may be more common in areas with endemic EBV infection.

Topics: Adult; Aged; Bile Duct Neoplasms; Bile Ducts, Intrahepatic; Carcinoma, Squamous Cell; Cholangiocarcinoma; Epstein-Barr Virus Infections; Female; Herpesvirus 4, Human; Humans; Immunoenzyme Techniques; In Situ Hybridization; Keratins; Male; Middle Aged; RNA, Viral

We assessed the association of vascular endothelial growth factor (VEGF) and nm23 expression with occult micrometastasis in lung cancer. As destination sites for micrometastasis, we scrutinized lymph node (LN) and bone marrow (BM) specimens. For LN, 122 stage I patients who had received curative operations were studied. As regards BM, 203 patients in stage I - IV who underwent operations were registered. Immunohistochemical anti-cytokeratin staining was used to detect microdissemination of cancer cells. The VEGF and the nm23 expression at the primary sites were immunohistochemically studied in 285 cases in total. The percentages of the patients with microdissemination were 28.7% for LN and 42.4% for BM. The outcome for the patients with LN or BM microdissemination was significantly worse than that for patients without it. The increased VEGF and the decreased nm23 expression within primary tumors were significantly associated with LN and BM microdissemination. The results indicate possible value of using these biological markers to predict the risk of systemic micrometastasis in non-small cell lung cancer.

Topics: Adenocarcinoma; Aged; Biomarkers, Tumor; Bone Marrow; Carcinoma, Adenosquamous; Carcinoma, Non-Small-Cell Lung; Carcinoma, Squamous Cell; Endothelial Growth Factors; Female; Humans; Immunohistochemistry; Keratins; Lung Neoplasms; Lymph Nodes; Lymphatic Metastasis; Lymphokines; Male; Middle Aged; Monomeric GTP-Binding Proteins; Neoplasm Metastasis; Neoplasm Staging; NM23 Nucleoside Diphosphate Kinases; Nucleoside-Diphosphate Kinase; Predictive Value of Tests; Sensitivity and Specificity; Transcription Factors; Vascular Endothelial Growth Factor A; Vascular Endothelial Growth Factors

The aim of the study was to investigate the differentiation-specific keratins (K4, K13, K1 and K10) in oral epithelial dysplasia and squamous cell carcinoma (SCC). Alterations in keratin gene expression were determined by in situ hybridization using 35S-labeled riboprobes and immunohistochemistry with monoclonal antibodies. In mild dysplasia, both sets of differentiation keratins were expressed in the same group of cells but in moderate lesions, expression of K4 and K13 was reduced in the presence of enhanced K1 and K10 synthesis. In severe dysplasia, neither mRNAs nor proteins were detected. In tumor islands of well and moderately differentiated SCCs, the K4/K13 complex was co-expressed with K1/K10, but in poorly differentiated carcinomas, differentiation keratins were absent. Consequently, mild oral epithelial dysplasia and well differentiated SCC retain an essentially normal pattern of keratin gene expression and hence epithelial differentiation while in severe dysplasia and poorly differentiated SCC keratin gene expression reflects the gross changes in epithelial differentiation and maturation.

Topics: Carcinoma, Squamous Cell; Cell Differentiation; Cheek; Epithelium; Gene Expression; Humans; Immunohistochemistry; In Situ Hybridization; Keratins; Mouth Mucosa; Mouth Neoplasms; Precancerous Conditions; RNA, Messenger; Staining and Labeling

The purpose of this article is to highlight an unusual form of breast carcinoma and discuss its differential diagnosis. A 50-year-old woman underwent wide local excision of a breast lump. Microscopic examination revealed features of a lymphoepithelioma-like carcinoma. Individual tumor cells were present within an abundant lymphoid stroma. Immunohistochemistry revealed the epithelial nature of the cells and excluded a diagnosis of lymphoma. In addition, surrounding nontumorous breast tissue displayed the histologic features of sclerosing lymphocytic lobulitis or lymphocytic mastopathy. This is the second report of a lymphoepithelioma-like carcinoma of the breast, but to the best of our knowledge, it is the first description of coexistent sclerosing lymphocytic lobulitis.

Topics: Biomarkers, Tumor; Breast; Breast Neoplasms; Carcinoma, Squamous Cell; Diagnosis, Differential; Female; Humans; Keratins; Lymphoma; Mastitis; Middle Aged; Sclerosis

Human beta-defensin(hBD)-2, an antimicrobial peptide, is produced by various epithelial cells. Because hBD-2 expression in the oral epithelium has not been assessed, we investigated its localization in normal oral epithelium and epithelial lesions. hBD-2 expression was studied using immunohistochemistry and in situ hybridization on formalin-fixed, paraffin-embedded tissue sections from 30 cases of squamous cell carcinoma and 6 cases of leukoplakia. Immunostaining for hBD-2 was more intense in hyperkeratinized than in ortho- or non-keratinized epithelium. In contrast, signals for hBD-2 mRNA were frequently stronger in non-keratinized epithelium than in hyper- or ortho-keratinized epithelium. The results suggest that keratinization in oral epithelium plays an important role in the biological function of hBD-2 both at the mRNA level and in the retention of the peptide in the epithelium.

Topics: beta-Defensins; Carcinoma, Squamous Cell; Humans; Immunohistochemistry; In Situ Hybridization; Keratins; Mouth Mucosa; Mouth Neoplasms; RNA, Messenger

Atypical fibroxanthoma can mimic other tumors, particularly spindle cell squamous cell carcinoma and spindle cell or desmoplastic melanoma. We describe a patient with chronic lymphocytic leukemia who developed acantholytic squamous cell carcinoma on the face, which recurred and metastasized to a cervical lymph node. This tumor was at first diagnosed as atypical fibroxanthoma because of its histologic and immunostaining similarity. It showed weak or negative keratin cocktail staining and strong vimentin staining. However, a recurrent tumor was immunostained for high-molecular-weight keratin and showed strong positivity. Aggressive behavior of this squamous cell carcinoma may be due to altered immune response secondary to chronic lymphocytic leukemia.

Topics: Aged; Carcinoma, Squamous Cell; Diagnosis, Differential; Histiocytoma, Benign Fibrous; Humans; Immunohistochemistry; Keratins; Leukemia, Lymphocytic, Chronic, B-Cell; Lymphatic Metastasis; Male; Neoplasm Recurrence, Local; Neoplasms, Multiple Primary; Skin Neoplasms; Vimentin

Keratins have been extensively studied in tissues and cultured keratinocytes but limited information is available on epithelia reconstructed in vitro. The aim of this study was to examine keratin expression in organotypic epithelia with normal (NOK), immortalized (SVpgC2a) and malignant (SqCC/Y1) human buccal cells. Organotypic epithelia were derived from 10 days of culture at the air-liquid interface of collagen gels containing human oral fibroblasts using a standardized serum-free medium. Sections were stained immunohistochemically with selected mono-specific antibodies to a range of keratins. Organotypic epithelia showed sharp differences in keratin expression and distribution. K4/K13, K1/K10, K6/K16 were variably expressed in NOK and SqCC/Y1 but were not detected in SVpgC2a. K5 was expressed in all organotypic epithelia but K14 was absent in SVpgC2a. K7 and K8 showed variable expression while K18 was expressed uniformly in all epithelia. K19 was expressed consistently in NOK and K20 was distributed heterogeneously in SVpgC2a. Overall, organotypic cultures of normal keratinocytes express many of the same keratins as buccal mucosa. Further, the loss of keratins in SVpgC2a and their retention in SqCC/Y1 have several features in common with the respective keratin profile of oral epithelial dysplasia and well-differentiated oral squamous cell carcinoma. Although qualitative and quantitative differences exist compared to keratin expression in vivo, these cell lines in organotypic culture may serve in studies of the multi-step progression of oral cancer.

Topics: Carcinoma, Squamous Cell; Case-Control Studies; Epithelial Cells; Fibroblasts; Humans; Keratinocytes; Keratins; Mouth Mucosa; Mouth Neoplasms; Tumor Cells, Cultured; Up-Regulation

Although numerous studies have shown that nm23-H1 gene product expression is inversely related to metastatic potential in some cancers, the expression in lymph nodes has not been studied in detail. An analysis of nm23-H1 gene product expression in mediastinal lymph nodes from lung cancer patients is reported.. One hundred and thirty-four, randomly selected lymph nodes (63 with positive pathological lymph node status) from 39 surgically treated lung cancer patients were examined. Expression of nm23-H1 gene product was determined using specific monoclonal antibodies. Metastatic cancer cells were highlighted using anti-cytokeratin antibody.. Expression of nm23-H1 gene product in patients with less and more than 50% nodes-positive was 12/23 (52.2%) and 15/16 (93.8%) cases, respectively. Immunohistochemical studies with cytokeratin revealed micrometastasis in 6/39 (15.4%) patients and 9/71 (12.7%) nodes previously reported as cancer negative. Expression of nm23-H1 gene product in micrometastasis and metastasis-positive nodes was 5/9 (55.6%) and 55/63 (87.3%), respectively. We also found nm23-H1 gene product expression in germinal center cells. However, we found no relationship between expression of nm23-H1 gene product in germinal center cells and extent of metastasis.. Our study demonstrates a positive relationship between expression of nm23-H1 gene product and extent of metastasis in mediastinal lymph nodes from lung cancer patients. Our data for normal germinal center cells suggests that nm23-H1 gene product expression does not play a specific biological role in suppressing tumor metastasis in lung cancer.

Topics: Adenocarcinoma; Carcinoma, Squamous Cell; Humans; Immunohistochemistry; Keratins; Lung Neoplasms; Lymph Nodes; Lymphatic Metastasis; Mediastinum; Monomeric GTP-Binding Proteins; NM23 Nucleoside Diphosphate Kinases; Nucleoside-Diphosphate Kinase; Transcription Factors

The definition of biological markers for oropharynx and larynx cancer is essential to predict their clinical behavior. Since cellular glycans play an important role in biological information transfer, we have employed an endogenous lectin, galectin-3, to examine in primary squamous carcinomas, lymph node metastases, and physiological squamous epithelia whether glycans recognized by this lectin are altered in relation to the state of differentiation. The expression of galectin-3 was concomitantly evaluated by immunohistochemistry using the A1D6 monoclonal antibody. In addition, other antibodies were used for the detection of cytokeratins and desmosomal proteins (desmoplakin-1 and desmoglein). The results show the expression of galectin-3-reactive ligands in moderately/highly differentiated carcinomas only in areas exhibiting a high level of keratinization. Except for one patient out of 14, metastatic cells in lymph nodes expressed no accessible binding sites for galectin-3. No galectin-3-reactivity was detected in the basal cell layer of all studied normal epithelia (which contains the proliferating cells). The suprabasal layers were positive in epidermis and epithelium of tongue and cornea and negative in epithelium of palatine tonsil. The tumor cells expressed galectin-3 with an intensity positively correlated with tumor differentiation. The position of galectin-3-reactive sites colocalized with the two tested desmosomal proteins. However, presence of these proteins was also detected in areas of tumor and suprabasal layers of tonsil epithelium where no binding reactivity for galectin-3 was found. The present study showed that expression of galectin-3-reactive glycoligands is differentiation-dependent in normal as well as malignant squamous cells. Colocalization of galectin-3-reactive sites with desmosomal proteins (desmoplakin-1 and desmoglein) suggests an association of the galectin-3 ligand(s) with the cell surface, pointing to a potential participation of galectin-3 in mediation of intercellular contacts in these tumor types.

Topics: Antigens, Differentiation; Binding Sites; Biomarkers, Tumor; Carcinoma, Squamous Cell; Cell Differentiation; Cytoskeletal Proteins; Desmogleins; Desmoplakins; Epithelial Cells; Fluorescent Antibody Technique, Indirect; Fluorescent Dyes; Galectin 3; Head and Neck Neoplasms; Humans; Keratins; Ligands; Lymphatic Metastasis; Membrane Glycoproteins; Neoplasm Proteins; Neoplasm Staging; Prognosis

The tissue distribution of cytokeratin 14 (CK14) in epithelial neoplasms is not well defined. We have evaluated 435 cases of epithelial neoplasm of various origins with cytokeratin 14 monoclonal antibody with special attention to possible use in differential diagnosis.. Immunohistochemistry (ABC-HRP method) was performed for detection of CK14. We found that the expression of cytokeratin 14 was generally restricted to: (i) the majority of cases of squamous cell carcinoma regardless of origin (67/74) and degree of differentiation; (ii) neoplasms with focal squamous differentiation, including endometrial, and ovarian adenocarcinoma, malignant mesothelioma and transitional cell carcinoma; (iii) thymoma (8/8); (iv) myoepithelial components of salivary gland pleomorphic adenoma (3/4); and (v) oncocytic neoplasms, including thyroid Hurthle cell adenoma (1/1) and salivary gland Warthin's tumour (2/2).. CK14 protein is a useful marker in differential diagnosis of squamous cell carcinomas.

Topics: Carcinoma, Squamous Cell; Diagnosis, Differential; Humans; Immunohistochemistry; Keratin-14; Keratins; Neoplasms, Glandular and Epithelial; Predictive Value of Tests

Topics: Carcinoma, Squamous Cell; Humans; Immunohistochemistry; Keratins; Leukocyte Common Antigens; Male; Middle Aged; Tumor Suppressor Protein p53; Ureteral Neoplasms

Lymphoepithelioma-like carcinoma (LELCA) of the urinary bladder is a rare variant of bladder cancer characterized by a malignant epithelial component densely infiltrated by lymphoid cells. It is characterized by indistinct cytoplasmic borders and a syncytial growth pattern. These neoplasms deserve recognition and attention, chiefly because they may be responsive to chemotherapy. We report on the clinicopathologic features of 13 cases of LELCA recorded since 1981. The chief complaint in all 13 patients was hematuria. Their ages ranged from 58 years to 82 years. All tumors were muscle invasive. A significant lymphocytic reaction was present in all of these tumors. There were three pure LELCA and six predominant LELCA with a concurrent transitional cell carcinoma (TCC). The remainder four cases had a focal LELCA component admixed with TCC. Immunohistochemistry showed LELCA to be reactive against epithelial membrane antigen and several cytokeratins (CKs; AE1/AE3, AE1, AE3, CK7, and CK8). CK20 and CD44v6 stained focally. The lymphocytic component was composed of a mixture of T and B cells intermingled with some dendritic cells and histiocytes. Latent membrane protein 1 (LMP1) immunostaining and in situ hybridization for Epstein-Barr virus were negative in all 13 cases. DNA ploidy of these tumors gave DNA histograms with diploid peaks (n=7) or non-diploid peaks (aneuploid or tetraploid; n=6). All patients with pure and 66% with predominant LELCA were alive, while all patients having focal LELCA died of disease. Our data suggest that pure and predominant LELCA of the bladder appear to be morphologically and clinically different from other bladder (undifferentiated and poorly differentiated conventional TCC) carcinomas and should be recognized as separate clinicopathological variants of TCC with heavy lymphocytic reaction relevant in patient management.

Topics: Aged; Aged, 80 and over; Aneuploidy; Carcinoma, Squamous Cell; Carcinoma, Transitional Cell; DNA, Neoplasm; Female; Humans; Image Cytometry; Immunoenzyme Techniques; Keratins; Male; Middle Aged; Mucin-1; Neoplasms, Multiple Primary; Survival Rate; Urinary Bladder Neoplasms

Spindle cell carcinoma of the breast, a variant of metaplastic carcinoma, includes a wide spectrum of lesions with histomorphologic and nuclear features ranging from overtly malignant to mildly atypical. Spindle cell carcinomas with mildly atypical features may resemble fasciitis, fibromatosis, or myofibroblastic tumors and therefore are often misinterpreted as such. A recent study has suggested that spindle cell carcinomas with a dominant fibromatosis-like phenotype, unlike spindle cell carcinomas in general, have no propensity for distant metastasis and should be termed "tumors" rather than "carcinomas." To investigate the question of fibromatosis-like spindle cell breast carcinoma (FLSpCCs) metastatic potential, we studied cases of FLSpCC seen at the University of Texas M.D. Anderson Cancer Center between 1987 and 2000. Clinical, pathologic, and immunophenotypic features were reviewed, with emphasis on biologic behavior and predictors of clinical outcome. Our series included 24 women who ranged in age from 55 to 85 years (mean 66 years). Tumor size ranged from 1.0 to 5 cm (mean 2.8 cm). Most tumors were grossly well defined but had microscopic infiltrative borders. Tumors showed a dominant fibromatosis-like or myofibroblastic-like growth pattern with prominent collagenization. Inflammatory infiltrate was noted in the majority of tumors. Cytokeratin-positive cells were seen in all cases and usually appeared as cords or sheets of polygonal cells; isolated cytokeratin-positive cells were rare. In most tumors immunoreactivity for smooth muscle actin (SMA) was confined to the cytokeratin-negative cells. In five cases intense co-expression of cytokeratin and SMA was noted. None of the tumors showed immunoreactivity for smooth muscle heavy chain myosin, estrogen receptors, progesterone receptors, or HER-2/neu. Ki-67 expression was noted in fewer than 5% of tumor cells. Treatment consisted of local excision (seven cases) or modified radical mastectomy (13 cases). Treatment was unknown in four cases. In patients who underwent axillary nodal dissection, no lymph node metastases were found. Two of the six patients who underwent local excision developed local recurrence. Two patients who underwent modified radical mastectomy developed lung metastases within 2 years after the initial diagnosis. The metastatic tumors were histologically similar to the primary tumors. Our findings indicate that FLSpCCs have the potential for local recurrence and distant metastasis an

Topics: Actins; Adult; Aged; Aged, 80 and over; Biomarkers, Tumor; Breast Neoplasms; Carcinoma, Squamous Cell; Female; Fibroma; Humans; Immunoenzyme Techniques; Keratins; Lung Neoplasms; Middle Aged; Neoplasm Recurrence, Local

To study the morphological and immunohistochemical characteristics of spindle cell squamous carcinoma of the oesophagus, in order better to understand the histogenesis of this tumour.. In this study we analysed the morphological and immunohistochemical characteristics of 17 cases of spindle cell squamous carcinoma of the oesophagus. Most tumours were polypoid, but tumours with an ulcerated and infiltrative pattern were also observed. Histologically, most tumours were of superficial type, with a characteristic morphological aspect consisting of two types of tumour cells, i.e. differentiated squamous cells, and spindle cells with transition zones between the two components. On immunohistochemistry, the squamous cells were positive for cytokeratin and the spindle cells showed variable expression of cytokeratin, vimentin and smooth muscle actin. p53 protein was over-expressed in 10 cases, both tumour cell types showing strong nuclear positivity. In most tumours, E-cadherin was expressed in the squamous cells and absent in the spindle cells.. The similar pattern of p53 protein expression in the two tumour cell types of spindle cell squamous carcinoma of the oesophagus suggests their common origin. The change in adhesion molecule expression with loss of E-cadherin expression may be associated with the acquisition of spindle cell morphology by the squamous tumour cells.

Topics: Actins; Adult; Aged; Cadherins; Carcinoma, Squamous Cell; Clone Cells; Esophageal Neoplasms; Female; Humans; Immunohistochemistry; Keratins; Male; Middle Aged; Muscle, Smooth; Tumor Suppressor Protein p53; Vimentin

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

Primary squamous cell carcinoma of the thyroid gland is uncommon. This study aims to identify the clinicopathological features and the pattern of expression of cytokeratins and oncoproteins in this tumour.. Histological slides from Chinese patients with thyroid cancer treated in our institution from 1980 to 1999 were reviewed. Patients with primary squamous cell carcinoma of the thyroid were identified and their clinical records were analysed. The expression of cytokeratins (CKs), p53 and p21 in these cases were also studied by an immunohistochemical method. Four women (mean age 71 years) with squamous cell carcinoma of thyroid were found. The main presenting features were signs and symptoms of airway obstruction in three patients and neck swelling in one. The tumours were located at the right lobe (n=2), left lobe (n=1) or in both lobes of the thyroid (n=1). One patient died shortly after admission and the other three died within 4 months after thyroidectomy. The p53 protein was positive in 50% (2/4) of the tumours and p53+ tumours were poorly differentiated. The tumours were negative for p21. CK19 was expressed in all the tumours while CK7 expression was noted in 3/4 of the tumours. One carcinoma showed focal positivity to CK18. The tumours were negative for CKs 1, 4, 6, 10/13 and 20. The pattern of cytokeratin expression in squamous cell carcinoma of the thyroid gland was different from carcinoma showing thymus-like differentiation (CASTLE) of the thyroid gland and oesophageal squamous cell carcinoma.. Squamous cell carcinoma of the thyroid has aggressive clinical behaviour and characteristic CK expression pattern. p53 over-expression in these tumours was associated with tumour differentiation.

Topics: Aged; Aged, 80 and over; Carcinoma, Squamous Cell; Cyclin-Dependent Kinase Inhibitor p21; Cyclins; Female; Humans; Immunohistochemistry; Keratins; Middle Aged; Thyroid Neoplasms; Tumor Suppressor Protein p53

Few studies have investigated the presence of lymph node micrometastases (MM) in the cervical region of patients with esophageal squamous cell cancer. The present study examines the presence of cervical MM and attempts to determine a way to predict the occurrence and site of such micrometastases. A total of 2203 cervical lymph nodes and 118 mediastinal recurrent nerve nodes obtained from 86 patients with esophageal carcinoma were examined immunohistochemically using cytokeratins. Cervical lymph nodes and mediastinal recurrent nerve nodes metastases were detected histologically in 33 and 41 of the 86 patients respectively. Cervical lymph node and mediastinal recurrent nerve node MM were immunohistochemically detected in 16 (18.6%) and 6 (7.0%) patients respectively. Of these 16 patients with cervical MM, seven were found to have lymph node metastases in different cervical regions, whereas cervical MM only were detected in nine patients. Among the former group of patients, five were diagnosed by ultrasound examination as having cervical lymph node metastases. Mediastinal recurrent nerve node metastases and MM correlated with the presence of cervical MM in all but one patient. Cervical lymph node metastasis, including micrometastasis, can be predicted by preoperative ultrasonography and the routine histologic examination of mediastinal recurrent nerve nodes.

Topics: Adult; Aged; Carcinoma, Squamous Cell; Esophageal Neoplasms; Female; Humans; Immunohistochemistry; Keratins; Lymph Node Excision; Lymph Nodes; Lymphatic Metastasis; Male; Middle Aged; Neck

Basaloid carcinoma (BC) and large-cell neuroendocrine carcinoma (LCNEC) are 2 recently recognized variants of large-cell lung carcinomas that may overlap in their morphology, and are discriminated by expression of neuroendocrine markers in LCNEC. Because thyroid transcription factor 1 (TTF-1) is expressed in lung adenocarcinomas but not in squamous cell carcinomas (SCC), and 34betaE12 recognizes a set of high-molecular-weight cytokeratins characteristic of basal stem cells, we hypothesized that these 2 markers could help in distinguishing BC from LCNEC. Immunostaining for TTF-1 was detected in 40.9% of pure LCNEC but in no BC or basaloid variant of SCC. In contrast, immunoreactivity for 34betaE12 was shown in all BC and basaloid variant of SCC but in only 1 LCNEC. Bouin fixation was less efficient than formalin in the immunodetection of both markers for its well-known deleterious effect on antigen preservation. Specificity of TTF-1 for LCNEC (100%) and that of 34betaE12 for BC (98.3%) exceeded that of NE markers for distinction of these 2 entities. These data show that TTF-1 and 34betaE12, in association with specific neuroendocrine markers, represent a useful panel of antibodies in differentiating carcinomas presenting with a solid pattern, palisading, or pseudorosettes, the expression of TTF-1 excluding the diagnosis of BC, and staining with 34betaE12 excluding pure LCNEC.

Topics: Carcinoma, Large Cell; Carcinoma, Neuroendocrine; Carcinoma, Squamous Cell; Carcinoma, Transitional Cell; Humans; Immunoenzyme Techniques; Keratins; Lung Neoplasms; Nuclear Proteins; Retrospective Studies; Sensitivity and Specificity; Thyroid Nuclear Factor 1; Transcription Factors

Topics: Aged; Carcinoma, Squamous Cell; Cystectomy; Cystoscopy; Diagnosis, Differential; Female; Humans; Immunohistochemistry; Keratins; Urinary Bladder Neoplasms

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

The distinction of a primary lung carcinoma from a metastatic lesion is important, because the treatment and prognosis differ for patients with these malignancies. Such a distinction can be difficult because of overlapping cytologic features. It has been shown that antibodies to thyroid transcription factor 1 (TTF-1) and PE-10 are fairly specific markers for primary lung tumors in histologic specimens. TTF-1 regulates the expression of surfactant protein production, and PE-10 is a monoclonal antibody against components of human surfactant proteins. The combination of cytokeratin 7 (CK7) and cytokeratin 20 (CK20) immunoprofiling has been helpful in the identification of the primary site of origin of lung tumors.. In the current study, the authors evaluated the utility of TTF-1 and PE-10 immunostaining and also compared the staining with expression of CK7 and CK20 in the discrimination between primary lung tumors and metastatic lesions in 55 specimens from fine-needle aspiration (FNA) biopsies of the lung. Formalin fixed, paraffin embedded cell blocks from 35 primary lung tumors (16 adenocarcinomas, 8 squamous cell carcinomas, 6 large cell undifferentiated carcinomas, and 5 small cell carcinomas) and 20 metastatic carcinomas (6 breast lesions, 6 colon lesions, 3 urinary bladder lesions, 2 kidney lesions, 1 biliary tract lesion, 1 endometrial lesion, and 1 thyroid lesion) were immunostained with monoclonal antibodies to TTF-1, PE-10, CK7, and CK 20. Positive immunostaining for CK7, CK20, and PE-10 was based on cytoplasmic staining, whereas TTF-1 positive staining was based on nuclear staining of the neoplastic cells.. Positive immunostaining with TTF-1 and PE-10 was noted in six primary lung tumors (17%). One metastatic lesion (5%) and two metastatic lesions (10%) were positive for TTF-1 and PE-10, respectively. The CK7 positive/CK20 negative immunophenotype was noted in 30 primary lung tumors (86%) and in 11 metastatic lesions (55%). The CK7 negative/CK20 negative immunophenotype was seen in four metastatic lesions and in the remaining five primary lung tumors. The CK7 negative/CK20 positive and CK7 positive/CK20 positive immunophenotypes were seen in two and three metastatic lesions, respectively, but in none of the primary lung tumors. When a CK7 positive/CK20 negative adenocarcinoma also demonstrated either TTF-1 positive or PE-10 positive staining, it was likely that the adenocarcinoma was of pulmonary origin (P < 0.035; Fisher exact test). The specificity of such a combination for discriminating between primary and metastatic adenocarcinomas was 94%.. The results suggest that TTF-1, PE-10, or CK7/CK20 alone did not distinguish reliably between primary pulmonary tumors carcinomas and metastatic neoplasms of the lung in FNA biopsy specimens because of low sensitivity and specificity. The use of a panel of antibodies that includes CK7/CK20, TTF-1, and PE-10 may be helpful in discriminating between primary and metastatic adenocarcinomas of the lung. An adenocarcinoma is likely a primary lung tumor when it is of the CK7 positive/CK20 negative phenotype and demonstrates either TTF-1 positive or PE-10 positive staining.

Topics: Adenocarcinoma; Biomarkers, Tumor; Biopsy, Needle; Carcinoma, Large Cell; Carcinoma, Small Cell; Carcinoma, Squamous Cell; Humans; Immunohistochemistry; Intermediate Filament Proteins; Keratin-20; Keratin-7; Keratins; Lung Neoplasms; Neoplasm Metastasis; Nuclear Proteins; Predictive Value of Tests; Pulmonary Surfactants; Sensitivity and Specificity; Thyroid Gland; Thyroid Nuclear Factor 1; Transcription Factors

To explore the biological features of basaloid squamous cell carcinoma (BSC) of the esophagus.. Cytokeratins (CK4, CK18 and CK19), epithelial membrane antigen (EMA), carcino embryo antigen (CEA), alpha-smooth muscle antigen (alpha-SMA), S-100, laminin (LN), collagen IV (Col-IV), neural-specific enolase (NSE), proliferating cell nuclear antigen (PCNA) and p53 antibodies were used to detect the corresponding antigen expression in 8 cases of BSC with ABC immunohistochemical methods.. Two kinds of BSC cell components have different responses to the above antibodies. For basaloid cells (BCs), 7 cases were positive for CK19, and were negative for the other 4 epithelial antibodies CK4, CK18, CEA and EMA. BCs of 4 cases were positive to the muscular antibodies alpha-SMA and S-100, and the hyaline degeneration in the tumor nests was positive for LN and Col-IV. BCs had a high index of PCNA, with an average level of 54%. For squamous cells (SCs), 7 cases were positive for the epithelial antigen CK4, CEA and EMA, but were negative for CK19, alpha-SMA and S-100. The index of PCNA of SC was low, with an average level of 25%.. BSC of the esophagus is a high-malignancy tumor which is of multi-oriented differentiation. BCs represent basal cells which have the tendency of myoepithelial differentiation and have strong proliferation ability, whereas SCs represent typical squamous cell differentiation.

Topics: Carcinoembryonic Antigen; Carcinoma, Basal Cell; Carcinoma, Squamous Cell; Esophageal Neoplasms; Humans; Immunohistochemistry; Keratins; Mucin-1; Proliferating Cell Nuclear Antigen; S100 Proteins

Topics: Aged; Carcinoma, Papillary; Carcinoma, Squamous Cell; Carcinoma, Transitional Cell; Cell Differentiation; Diagnosis, Differential; Female; Humans; Immunohistochemistry; Keratin-7; Keratins; Vaginal Neoplasms

Topics: Bile Duct Neoplasms; Bile Ducts, Intrahepatic; Carcinoma, Squamous Cell; Cholangiocarcinoma; Diagnosis, Differential; Epstein-Barr Virus Infections; Germinoma; Herpesvirus 4, Human; Humans; Immunohistochemistry; Keratins; Lymphoma; Male; Melanoma; Middle Aged; Mucin-1; Skin Neoplasms

The purpose of this study is to report an unusual variant of cervical squamous cell carcinoma, not associated with either human papillomavirus infection or antecedent squamous intraepithelial lesions. Five women had a diagnosis of invasive cervical cancer discovered at hysterectomy performed for prolapse (two cases), leiomyoma (one case), or a vaginal fistula (two cases). The women ranged in age from 47 to 78 years (mean 59 years). Four of the five had a history of normal Papanicolaou (Pap) smears; the other had a Pap smear diagnosis of atypical squamous cells of undetermined significance (ASCUS). All had large cervical tumors (two with parametrial involvement and one with vaginal involvement) that showed extensive keratin formation, an inverted pattern of growth, and, except for one case, minimal cytologic atypia. There was extensive hyperkeratosis and parakeratosis adjacent to each tumor; none had evidence of squamous intraepithelial lesion. Human papillomavirus testing by polymerase chain reaction in situ hybridization and reverse-transcribed polymerase chain reaction in situ was negative in each case, compared with a detection rate of 107 of 108 (99%) for squamous intraepithelial lesion-associated cervical squamous cell and adenocarcinomas. Two of the women died of extensive local recurrence; two other women were recently diagnosed. We conclude that highly differentiated keratinizing squamous cell carcinoma of the cervix is a rare entity not associated with human papillomavirus infection or squamous intraepithelial lesion and thus difficult to detect on routine cervical cancer screening.

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

We sought to determine the critical diameter of a peripheral non-small cell lung cancer tumor less than which no evidence of nodal micrometastasis is present.. Samples of 3081 lymph nodes from 181 patients with stage I peripheral lung cancer (155 with adenocarcinoma and 26 with squamous cell carcinoma) who had undergone complete resection with systematic lymphadenectomy were used in the study. In the samples immunohistochemical staining for cytokeratin was performed. The expression of vascular endothelial growth factor (VEGF) at primary sites was also immunohistochemically assessed.. Nodal micrometastasis was detected in 44 patients. The mean tumor sizes were 2.2 +/- 1.3 cm (range, 1.0-7.0 cm) in nodal micrometastasis-positive adenocarcinoma, 2.1 +/- 0.9 cm (range, 0.5-6.0 cm) in nodal micrometastasis-negative adenocarcinoma, 4.8 +/- 2.3 cm (range, 2.2-10.0 cm) in nodal micrometastasis-positive squamous cell carcinoma, and 3.2 +/- 2.1 cm (range, 0-9.0 cm) in nodal micrometastasis-negative squamous cell carcinoma. The tumor size in the nodal micrometastasis-positive group tended to be greater than that in the nodal micrometastasis-negative group in squamous cell carcinomas, but there was no significant difference in adenocarcinomas. Nodal micrometastasis was not found in patients with squamous cell carcinoma of 2.0 cm or less in diameter. However, nodal micrometastasis was found in 20% (19/95) of the patients with adenocarcinoma of 1.1 to 2.0 cm in diameter and even in 4 of 11 patients with adenocarcinoma of 1.0 cm or less. Among the patients with nodal micrometastasis, survival of patients with vascular endothelial growth factor overexpression was worse than that of patients without it. The survival of patients with nodal micrometastasis without vascular endothelial growth factor overexpression was comparable with that of patients without nodal micrometastasis.. A limited surgical intervention without lymphadenectomy is validated for squamous cell carcinoma of 2.0 cm or less without pleural involvement. In adenocarcinoma the tumor size itself is not a reliable guide for nodal micrometastasis status. In patients with nodal micrometastasis with vascular endothelial growth factor overexpression, the risk of systemic disease should be considered.

Topics: Adenocarcinoma; Carcinoma, Non-Small-Cell Lung; Carcinoma, Squamous Cell; Endothelial Growth Factors; Female; Follow-Up Studies; Humans; Keratins; Lung Neoplasms; Lymph Node Excision; Lymph Nodes; Lymphatic Metastasis; Lymphokines; Male; Middle Aged; Protein Isoforms; Time Factors; Vascular Endothelial Growth Factor A; Vascular Endothelial Growth Factors

Cyfra 21-1 is a useful marker in lung cancer. The only tumor marker used at the present time in oesophageal squamous cell carcinoma (OSCC) is SCC (squamous cell carcinoma). In this study we evaluated the pre-treatment sensitivity and specificity of these two markers in this setting. Cyfra 21-1 and SCC were determined by radio-immunoassay on 76 patients having OSCC. Staging was done according to the UICC 1978 classification based on endoscopy, baryum enema and CT scan. The sensitivity of Cyfra 21-1 is better at the 1.5 ng/ml level (54%) than at the usual reported level of 3.6 ng/ml (26%). The best level for sensitivity of SCC is 1.5 ng/ml. At these levels, sensitivity of Cyfra 21-1 and SCC for advanced stages (T3 or M1) are respectively 72% and 50%. The specificity of Cyfra 21-1 and SCC for stages T1 or T2 are respectively 53% and 73%. The combination of these two markers increase sensitivity at 64% for all stages and at 89% for advanced stages (T3 or M1) and is a significant prognostic factor for survival. This study confirms the value of Cyfra 21-1 in OSCC at the normal level of 1.5 ng/ml. The combination with SC improves the results. We now need to evaluate the role of these two markers in the follow up of oesophageal carcinoma.

Topics: Aged; Antigens, Neoplasm; Biomarkers, Tumor; Carcinoma, Squamous Cell; Diagnosis, Differential; Esophageal Neoplasms; Female; Humans; Keratin-19; Keratins; Male; Middle Aged; Neoplasm Staging; Sensitivity and Specificity; Serpins

p63 is a p53-related DNA-binding protein that helps regulate differentiation and proliferation in epithelial progenitor cells. Its expression has never been evaluated in the human gastrointestinal tract. The aim of this study was to evaluate the expression of p63 in the esophagus and related metaplastic and neoplastic disorders to gain insight into the pathogenesis of these processes. Of particular interest was the expression of p63 in Barrett esophagus (BE) and in BE-associated multilayered epithelium. Multilayered epithelium has been postulated to represent an early precursor to the development of BE primarily because it shares morphologic and immunophenotypic features of both squamous and columnar epithelium, and has been shown prospectively to be highly associated with BE. Routinely processed mucosal biopsy or resection specimens that contained normal esophageal squamous epithelium (n = 20), squamous dysplasia (n = 4), squamous cell carcinoma (n = 7), BE (n = 10), BE-associated multilayered epithelium (n = 13), esophageal mucosal gland ducts (n = 10), BE-associated dysplasia (n = 12), and BE-associated adenocarcinoma (n = 7) were immunostained for p63 to determine the extent and location of staining. p63 staining was compared with the staining patterns observed for p53, Ki 67 (proliferation marker), and cytokeratins (CKs) 13 (squamous marker), 14 (basal squamous marker), 8/18 (columnar marker), and 19 (basal/columnar marker). Expression of p63 messenger RNA (mRNA) isoforms was also analyzed by reverse-transcription polymerase chain reaction of freshly isolated tissues. In the normal esophagus, p63 was expressed in the basal and suprabasal layers of the squamous epithelium and in basal cells that line the mucosal gland ducts but was negative in all other epithelia of the gastrointestinal tract, including the stomach, small intestine, and colon. Similarly, p63 was not expressed in BE, but it, was present in the basal layer of multilayered epithelium in 9 of 13 cases (69%). p63-positive cells in multilayered epithelium and in the mucosal gland duct epithelium were positive for CK8/18 (100%) and CK13 (67% and 30%, respectively) and negative for CK14 (0%), in contrast to p63-positive cells in squamous epithelium, which were positive for CK14 and CK13 (100%) but negative for CK8/18. In neoplastic tissues, p63 was diffusely expressed in all cases of esophageal squamous cell dysplasia and carcinoma but was negative in all cases of esophageal and colorectal ad

Topics: Adenocarcinoma; Barrett Esophagus; Carcinoma, Squamous Cell; Digestive System; DNA-Binding Proteins; Epithelium; Esophageal Diseases; Esophageal Neoplasms; Esophagus; Genes, Tumor Suppressor; Humans; Immunohistochemistry; Keratins; Ki-67 Antigen; Membrane Proteins; Metaplasia; Phosphoproteins; Protein Isoforms; Retrospective Studies; RNA, Messenger; Trans-Activators; Transcription Factors; Transcription, Genetic; Tumor Suppressor Protein p53; Tumor Suppressor Proteins

Cutaneous spindle cell squamous cell carcinoma (SSCC) is a challenging diagnosis since it may be difficult to distinguish from spindle cell melanoma, leiomyosarcoma and atypical fibroxanthoma. Furthermore, it may be difficult to demonstrate epithelial differentiation by a traditional immunohistochemical panel. We performed an expanded immunohistochemical evaluation of ultrastructurally documented SSCC to assess its utility in diagnosing this entity.. We identified 16 cases of SSCC that were composed predominantly of spindle-shaped cells and with ultrastructural evidence of epithelial differentiation (i.e. at least rudimentary cell junctions). Immunohistochemical analysis using antibodies to a variety of cytokeratins (AE1/3, K903, CK5/6) and S-100 protein was performed. The extent of immunostaining was graded on a scale of 0 to 4+ (0: no staining; 1+: < or =25%; 2+: 26-50%; 3+: 51-75%; 4+: >75%).. Of the 16 cases, 6 expressed AE1/3 (38%), 8 expressed K903 (50%) and 11 (69%) expressed CK5/6. Six cases were positive for all three CK markers and two cases were positive for both K903 and CK5/6 but negative for AE1/3. Three cases (19%) stained for CK5/6 without any staining for AE1/3 or K903. Five cases (31%) were negative for all epithelial markers. The extent of CK5/6 staining was either similar to or greater than K903 staining in 7 of 8 cases that stained with both markers. All 16 cases were negative for S-100 protein.. Including CK5/6 in the initial battery of immunostains performed on a cutaneous spindle cell neoplasm can help demonstrate epithelial differentiation in SSCC, even in the absence of AE1/3 or K903 staining. However, some cases of cutaneous SSCC can only be confirmed ultrastructurally, as up to one-third may not show evidence of epithelial differentiation using an expanded immunohistochemical panel.

Topics: Carcinoma, Squamous Cell; Humans; Immunohistochemistry; Keratin-5; Keratins; Predictive Value of Tests; Skin Neoplasms

To facilitate the differential diagnosis of poorly differentiated metastatic carcinomas of unknown primary site, we evaluated p63 and cytokeratin (CK) 5/6 as immunohistochemical markers for squamous cell carcinomas. The study cases were as follows: squamous cell carcinoma of the lungs, head/neck, esophagus, cervix uteri, or anal canal, 73; non-squamous cell carcinomas of various primary sites, 141; and urothelial carcinoma, 20. We also tested 14 malignant mesotheliomas. Immunoreactivity for p63 was as follows: squamous cell carcinomas, 59 (81%); urothelial carcinoma, 14 (70%), most often with diffuse staining patterns; non-squamous cell carcinomas, 20 (14.2%), resulting in a specificity of 0.86 of p63 for squamous cell carcinomas. Coexpression of p63 and CK5/6 had a sensitivity of 0.77 and a specificity of 0.96 for squamous cell carcinomas. Increasing the minimal criterion of positive immunostaining for both markers to more than 50% of immunoreactive tumor cells resulted in a specificity of 0.99, although the sensitivity diminished to 0.66. All malignant mesotheliomas were negative for p63. Our data suggest that positive immunostaining for both p63 and CK5/6 in poorly differentiated metastatic carcinomas is highly predictive of a primary tumor of squamous epithelial origin.

Topics: Biomarkers, Tumor; Carcinoma, Squamous Cell; Diagnosis, Differential; DNA-Binding Proteins; Female; Genes, Tumor Suppressor; Humans; Immunoenzyme Techniques; Keratin-5; Keratins; Male; Membrane Proteins; Neoplasms, Unknown Primary; Phosphoproteins; Reproducibility of Results; Sensitivity and Specificity; Trans-Activators; Transcription Factors; Tumor Suppressor Proteins

Carcinomas of the anus are subdivided into those of the anal canal and those of the anal margin. It has been postulated that the various types of tumours of the anal canal represent a spectrum of differentiation rather than tumours of a separate origin. We compared the expression of Pan-cadherin, cytokeratins (CKs) 5/6, 7, 13, 18 and 19, p53 and MIB-1 in 17 cases of carcinoma of the anal canal and 5 cases of carcinoma of the anal margin. Expression of Pan-cadherin was decreased in 70% of carcinomas of the anal canal but preserved in all five carcinomas of the anal margin. Most of the carcinomas of the anal canal expressed all of the CKs studied. Carcinomas of the anal margin showed expression of CK 5/6 and CK 13, whereas CK7, CK18 and CK19 were rarely expressed. Loss of expression of CK 18 and 19, but not CK 7, is a marker of dedifferentiation in anal canal carcinoma. Of the carcinomas of the anal canal and anal margin, 46% and 80%, respectively, expressed p53. The immunhistochemical findings support the opinion that the various subtypes of carcinoma of the anal canal represent variants in differentiation of squamous cell carcinomas of the anal canal. They confirm the separate histogenetic origin of tumours from the anal canal and anal margin.

Topics: Adult; Aged; Aged, 80 and over; Antigens, Nuclear; Anus Neoplasms; Biomarkers, Tumor; Cadherins; Carcinoma, Squamous Cell; Cell Nucleus; Female; Humans; Keratins; Ki-67 Antigen; Male; Middle Aged; Mitotic Index; Neoplasm Recurrence, Local; Nuclear Proteins; Tumor Suppressor Protein p53

Metaplastic carcinoma is a very rare breast neoplasm that is often confused with benign and others malignant entities on both clinical and conventional histopathologic basis. Three cases of metaplastic carcinoma of breast are presented. The difficulties found on fine needle aspiration cytology and the limitations of this procedure are discussed as well the main features of this tumor.

Topics: Adult; Aged; Biopsy, Needle; Breast Neoplasms; Carcinoma, Ductal, Breast; Carcinoma, Squamous Cell; Cell Differentiation; Diagnosis, Differential; Female; Humans; Keratins; Metaplasia; Middle Aged

We examined the prevalence, patterns, and clinical significance of nodal micrometastases in patients with esophageal cancer.. Cervical, mediastinal, and abdominal lymph nodes systematically removed from 37 patients without conventional histologic evidence of lymph node metastasis from esophageal squamous cell carcinoma were immunohistochemically examined to detect cells that were stained for cytokeratins by the monoclonal antibody cocktail AE1/AE3. Postoperative care and survival were compared in cases with and without such micrometastases.. Nodal micrometastases were found in 14 of 37 patients (38%). Among these patients, 9, 7, and 4 had micrometastases to abdominal, mediastinal, and cervical lymph nodes, respectively. Postoperative tumor recurrence was significantly more frequent in patients with micrometastases (50%) than in those without (9%, P = .008). Overall and relapse-free survival in the former group was significantly worse than in the latter group (P = .042 and P = .002, respectively). Nodal micrometastases had an independent prognostic importance for relapse-free survival as determined by multivariate analysis.. Metastatic tumor cells are frequently present in lymph nodes, even in patients without histologic evidence of nodal metastasis from esophageal cancer. Nodal micrometastases indicates a poorer prognosis after a curative esophagectomy procedure in histologically node-negative cases.

Topics: Aged; Carcinoma, Squamous Cell; Esophageal Neoplasms; Female; Humans; Immunohistochemistry; Keratins; Lymph Node Excision; Lymph Nodes; Lymphatic Metastasis; Male; Middle Aged; Neoplasm Recurrence, Local; Prognosis; Survival Analysis

Pigmented squamous cell carcinomas have been reported in the oral and ocular mucosae, but rarely in the skin. We present a case of pigmented squamous cell carcinoma of the forehead and review the current English literature. Pigmented squamous cell carcinoma can be confused with pigmented basal cell carcinomas and melanoma, especially those melanomas associated with pseudoepitheliomatous hyperplasia and should be included in the differential diagnosis of atypical pigmented lesions.

Topics: Carcinoma, Squamous Cell; Cell Differentiation; Diagnosis, Differential; Forehead; Humans; Keratins; Male; Melanins; Melanocytes; Melanoma; Melanosis; Middle Aged; Skin Neoplasms

In the normal stratified squamous epithelium of the esophagus, only the third to the fifth layers of cells express the cyclin-dependent kinase inhibitor p21WAF1/CIP1 (p21). Using immunohistochemical staining, we examined the topological distribution of cells expressing p21, p53, Ki67, and cytokeratin 10 (CK10), a differentiation marker of esophageal squamous cell carcinoma (SCC), in 25 superficial SCCs and 72 dysplastic lesions of the esophagus. Image analysis of p21, p53, and Ki67 expression was also performed in 48 dysplastic lesions. In superficial SCCs, although Ki67- and p53-expressing cells were mainly distributed in the deep layers of tumors despite tumor differentiation, the distribution of p21 correlated with tumor differentiation. In dysplastic lesions, p53- and Ki67-coexpressing cells tended to locate in the same layers and expand in the lower layers of epithelium with the progression of dysplasia. p21-expressing cells shifted to the upper layers of the epithelium with the progression of dysplasia. However, this change was heterogeneous; in some lesions, p21-expressing cells were confined to the superficial layers of atypical cells (confined type), whereas in others, p21-overexpressing cells were scattered among atypical cells (scattered type). CK10 expression was observed in 25% of dysplastic lesions, and the frequency of CK10 expression was significantly higher in the scattered than in the confined type. Our results suggest that esophageal squamous dysplasia represents the earliest pathological process in esophageal squamous carcinogenesis. Our results also suggest that differentiation of esophageal SCC is determined at the stage of dysplasia, and that p21 plays a critical role in the differentiation process.

Topics: Adult; Aged; Biomarkers, Tumor; Carcinoma, Squamous Cell; Cyclin-Dependent Kinase Inhibitor p21; Cyclins; Enzyme Inhibitors; Epithelium; Esophageal Neoplasms; Esophagus; Female; Humans; Keratin-10; Keratins; Male; Middle Aged; Precancerous Conditions; Tumor Suppressor Protein p53

To discover unique genes specific for squamous cell carcinoma of the head and neck for eventual development as tumor markers and vaccine candidates.. Molecular biological analysis of fresh-frozen head and neck squamous cell cancer (HNSCC).. A subtractive library was made from two HNSCC and six normal tissues using a polymerase chain reaction (PCR)-based approach. Genes from this library were PCR amplified and placed on a microarray glass slide. RNA was prepared or obtained from 16 fresh-frozen HNSCC and 22 normal tissue sources. Fluorescent probes were made from the polyA+ RNA derived from the tumor and normal tissues. The probes were hybridized to the glass slides and excited by a tuneable laser. One hundred seven of the genes showing the highest differential fluorescence value between tumor and normal tissue were identified by sequence analysis.. Thirteen independent genes were found to be overexpressed in tumor tissues. Of these, nine were previously known: keratins K6 and K16, laminin-5, plakophilin-1, matrix metalloproteinase-2 (MMP), vascular endothelial growth factor, connexin 26, 14-3-3 sigma, and CaN19. The level of polyA+ RNA of these genes in the tumors was significantly different from the levels in normal tissue (P < .05). Four previously unidentified genes were also discovered to have increased expression in tumor tissue. Comparing the total tumor group (n = 16) to the normal group (n = 22), only one of these genes showed significant overexpression.. We report the identification of nine known genes that are significantly overexpressed in HNSCC as compared to normal tissue using subtractive and microarray technology. In addition, we present four previously unidentified genes that are overexpressed in a subset of tumors. These genes will be developed as tumor markers and vaccine candidates.

Topics: 14-3-3 Proteins; Adolescent; Adult; Aged; Biomarkers, Tumor; Cancer Vaccines; Carcinoma, Squamous Cell; Cell Adhesion Molecules; Chemotactic Factors; Connexin 26; Connexins; DNA Probes; DNA, Complementary; Endothelial Growth Factors; Gene Expression Regulation, Neoplastic; Gene Library; Head and Neck Neoplasms; Humans; In Situ Hybridization, Fluorescence; Kalinin; Keratins; Lasers; Lymphokines; Matrix Metalloproteinase 2; Middle Aged; Molecular Biology; Plakophilins; Polymerase Chain Reaction; Proteins; RNA, Messenger; RNA, Neoplasm; S100 Proteins; Sequence Analysis, DNA; Tyrosine 3-Monooxygenase; Vascular Endothelial Growth Factor A; Vascular Endothelial Growth Factors

Expression of glycan determinants for in situ binding is the prerequisite for a productive protein (lectin)-carbohydrate recognition. Labeled tissue lectins as tools are preferable to plant lectins to assess this parameter, because plant and animal lectins with identical saccharide specification can well differ in their profiles of oligosaccharide binding pattern. Due to their relevance in growth control and matrix adhesion the family of galectins (galactoside-binding metal ion independent animal lectins) is receiving increasing utilization in human biology. Employing biotinylated galectin-1 and galectin-3 we studied the expression of binding sites for these galectins in normal human squamous epithelium and human carcinomas from the oropharyngeal region and larynx in relation to the expression of LP-34+ cytokeratins by the procedure of double labeling. Tissue sites accessible for galectin-1 were located in all layers of normal epithelium and in tumor cells. In contrast, galectin-3 binding was suprabasal in the normal epithelium and in tumor cells exhibiting signs of keratinization. These results reveal differences in the localization of accessible sites for the two galectins. Relating to cell development galectin-3 appeared to display affinity to areas with increased extent of differentiation.

Topics: Antigens, Differentiation; Carcinoma, Squamous Cell; Cell Differentiation; Fluorescent Antibody Technique, Indirect; Galactosides; Galectin 1; Galectin 3; Hemagglutinins; Humans; Keratins; Laryngeal Neoplasms; Lectins; Oropharyngeal Neoplasms

We examined differences in the 2-year survival rate in bronchogenic squamous cell carcinoma patients with normal serum levels of both cytokeratin 19 fragment (CYFRA 21-1) and squamous cell carcinoma-related antigen (SCC) (NL group, n=15), patients with only increased SCC levels (SCC+ group, n=14), patients with only increased CYFRA 21-1 levels (CYFRA+ group, n=14), and patients with elevated levels of both CYFRA 21-1 and SCC (EL group, n=65). The 2-year survival rates for the CYFRA+ and the EL group were lower than those for the SCC+ group and the NL group (0 and 12.9% vs. 66.7 and 85.6%, log rank: p<0.0001, Wilcoxon: p<0.0001). However, there were no differences between the rate for the SCC+ and the NL group and between that for the CYFRA+ and the EL group. Serum carcinoembryonic antigen (CEA) levels increased in the patients with the elevated CYFRA 21-1 levels. This results suggest that there may be some differences between squamous cell carcinoma patients with increased CYFRA 21-1 levels and those with normal levels and that it is CYFRA 21-1 levels, not SCC levels, that relate to the prognosis.

Topics: Aged; Aged, 80 and over; Antigens, Neoplasm; Biomarkers, Tumor; Carcinoembryonic Antigen; Carcinoma, Bronchogenic; Carcinoma, Squamous Cell; Female; Humans; Keratin-19; Keratins; Lung Neoplasms; Male; Middle Aged; Predictive Value of Tests; Probability; Prognosis; Survival Rate; Time Factors

We report a case of cutaneous malignant melanoma associated with extensive pseudoepitheliomatous hyperplasia. Pseudoepitheliomatous hyperplasia may mimic squamous cell carcinoma and may complicate the diagnosis of cutaneous melanoma. This diagnostic pitfall is important to both recognize and be cognizant of, so as to avoid diagnostic errors. The observation of the pseudoepitheliomatous hyperplasia, in this case with an extensive proliferation of eccrine ducts, provides further evidence that cutaneous pseudoepitheliomatous hyperplasia arises within the eccrine apparatus.

Topics: Aged; Aged, 80 and over; Biomarkers, Tumor; Carcinoembryonic Antigen; Carcinoma, Squamous Cell; Diagnosis, Differential; Eccrine Glands; Epithelial Cells; Humans; Hyperplasia; Immunoenzyme Techniques; Keratins; Male; Melanoma; Skin; Skin Neoplasms

Mucous cells in the respiratory tract contribute to the maintenance of the normal epithelial cell population via mechanisms of cell proliferation and differentiation. Mucous cell hyperplasia often occurs as a basic response to injury in the tracheobronchial epithelium. These cells are also thought to be involved in the histogenesis of epidermoid metaplasia. A typical biochemical feature of these cells is mucus secretion. Aberrant glycosylation or under-glycosylation of mucins is well known in cancer; however, the specific role played by mucin genes is at present unclear. To provide information regarding the expression of these genes in squamous metaplasia and squamous cell carcinoma, we analyzed and compared the expression of MUC1-MUC7 genes by in situ hybridization in control respiratory mucosa and lesions associated with neoplasia (hyperplasia, metaplasia and dysplasia) and squamous cell carcinomas. MUC4 was expressed independently of mucus secretion since it was expressed weakly by basal cells and probably by ciliated cells as well as collecting ducts, epidermoid metaplasia with complete squamous cell differentiation, and most of epidermoid carcinomas even well differentiated and keratinized. In squamous metaplasia and dysplasia, MUC4 gene expression was diffuse and less intense than in normal epithelium. MUC5AC was overexpressed in dysplasia as well as in mucous cell and basal cell hyperplasia and undetectable when squamous differentiation was achieved.

Topics: Biomarkers, Tumor; Bronchi; Carcinoma, Squamous Cell; Epithelium; Gene Expression; Histocytochemistry; Humans; Hyperplasia; In Situ Hybridization; Keratins; Mucin 5AC; Mucin-1; Mucin-2; Mucin-4; Mucin-5B; Mucins; Mucous Membrane; Respiratory System; RNA, Messenger; Salivary Proteins and Peptides

The aim of this study was to determine whether lymph node metastases or prognosis can be predicted by initial serum Cyfra 21-1, tissue polypeptide antigen (TPA), and squamous cell carcinoma antigen (SCC-Ag) levels in squamous cell cervical cancer.. Pretreatment serum levels of 92 patients were correlated with clinicopathologic parameters and prognostic data. The clinical performance of the tests was evaluated by their receiver operating characteristic curves. The prognostic power of the variables was assessed using Cox regression analysis.. Serum levels of each marker were significantly related to tumor stage, size, and depth of infiltration. The clinical performance of each marker in predicting lymph node metastases or parametrial involvement was poor. In the stepwise Cox regression analysis, regarding patients with early stage cervical cancer (stage Ib/IIa, n = 63), tumor size (P = 0.0005) was the only independent prognostic factor for disease-free interval. Lymph node status (P = 0.0014), tumor size (P = 0.004), and parametrial involvement (P = 0.025) were independent risk factors for survival. Considering all patients with stages Ia through IVb disease, tumor size (P = 0.0001) and TPA level (P = 0. 026) were independent risk factors for disease-free interval, whereas tumor size (P = 0.0001) and parametrial involvement (P = 0. 0002) were risk factors for survival.. Pretreatment Cyfra 21-1, TPA, and SCC-Ag levels were strongly related to tumor burden, but insufficiently reliable for identifying patients at risk of the presence of lymph node metastases or parametrial involvement. Serum levels of each marker showed no independent prognostic value in early stage cervical cancer.

Topics: Adult; Aged; Antigens, Neoplasm; Biomarkers, Tumor; Carcinoma, Squamous Cell; Female; Humans; Keratin-19; Keratins; Lymphatic Metastasis; Middle Aged; Neoplasm Staging; Predictive Value of Tests; Prognosis; Prospective Studies; Risk Assessment; Serpins; Tissue Polypeptide Antigen; Uterine Cervical Neoplasms

Two human tongue squamous cell carcinoma cell lines, SQUU-A and SQUU-B, were established from the same patient. Cervical lymph node metastasis was detected in the mice orthotopically implanted with SQUU-B (86.7%, 13/15), but not in those with SQUU-A (0/13). Histologically, SQUU-B showed invasive growth and intravasation in the tongue, whereas SQUU-A simply demonstrated expansive growth without intravasation. By Western blot analysis, nonmetastatic clone SQUU-A expressed cytokeratin (CK)13/4, 14, 16/6, 18/8, and 19, whereas a high metastatic clone SQUU-B expressed CK18/8 and 19. The reverse transcription-polymerase chain reaction technique showed that CK13/4 mRNA was expressed in both cell lines, but CK14 and 16 mRNA was expressed only in SQUU-A. CK13 was immunohistochemically expressed in both SQUU-A and SQUU-B transplanted into the tongues of nude mice; CK14 and 16 were detected in SQUU-A of the tongues, but not in SQUU-B. As seen in SQUU-B cell line, SQUU-B of the cervical lymph node metastasis did not exhibit CK13, 14, or 16. These results suggest that the loss or down-regulation of CK13, 14, or 16 is related to the invasive and metastatic ability of cancer. The cytoskeletal system is thus considered to be closely related to the malignant phenotype.

Topics: Animals; Carcinogenicity Tests; Carcinoma, Squamous Cell; Female; Humans; Keratins; Mice; Mice, Inbred BALB C; Neoplasm Invasiveness; Neoplasm Transplantation; Tongue Neoplasms; Tumor Cells, Cultured

A unique series of epidermal cell lines representing different stages of malignant transformation were spontaneously derived from a single adult immunosuppressed individual. Four keratinocyte lines (PM1-4) established from forehead skin are here compared with 4 squamous cell carcinoma (SCC) lines (MET1-4) derived respectively from a primary cutaneous tumour, two local recurrences and a distant metastasis of invasive SCC. Despite altered growth properties, the PM lines retained many features of normal keratinocytes including keratin phenotype, differentiation capacity and non-tumorigenicity in athymic mice. In contrast, from early passage, the MET lines displayed markedly reduced growth requirements, abnormal differentiation, aberrant K18 expression and tumorigenicity in athymic mice. The abnormal keratin profile of individual MET lines closely reflected the keratin phenotype of the tumour of origin. Although unusual HPV types were identified in the original tissue, there was no evidence of persistent virus within any cell line and it appears that HPV is not critical for maintenance of the immortal phenotype. The PM lines were distinctly different from invasive SCC lines and are likely to be useful for studies of mutations important early in neoplastic progression. The SCC series represent primary, recurrent and metastatic carcinoma. Availability of such a series from the same individual will facilitate genetic analysis of the malignant process.

Topics: Adaptation, Physiological; Adult; Animals; Carcinogenicity Tests; Carcinoma, Squamous Cell; Cell Differentiation; Cell Division; Cell Line; Cell Transformation, Neoplastic; Epidermis; Face; Humans; Keratinocytes; Keratins; Male; Mice; Mice, Nude; Neoplasm Staging; Neoplasm Transplantation; Papillomaviridae; Skin Neoplasms

The ets family of transcription factors comprises many members which contribute to diverse cellular functions that vary depending upon the cell- and tissue-type context. Recently, different groups have identified a novel member of the ets family that is epithelial-specific. Variably called ESE-1, ERT, jen, ESX, this gene is designated currently as ELF3. In order to understand transcriptional regulatory mechanisms mediated by ELF3, we investigated its effect on the human keratin 4 gene promoter based upon the role of keratin 4 in early differentiation of the esophageal squamous epithelium. Interestingly, ELF3 suppressed basal keratin 4 promoter activity in both esophageal and cervical epithelial cancer cell lines, a novel result, while simultaneously activating the late-differentiation linked SPRR2A promoter. Furthermore, serial deletion constructs of the keratin 4 promoter continued to be suppressed by ELF3, a phenomenon that was only partially rescued by ELF3 ets domain mutants, but completely abrogated by deletion of the ELF3 pointed domain. These results suggest that ELF3 may have dual functions in the transcriptional regulation of genes involved in squamous epithelial differentiation. One of these functions may not be exclusively mediated through DNA binding in the context of transcriptional suppression of the keratin 4 promoter.

Topics: Amino Acid Sequence; Carcinoma, Squamous Cell; Cell Differentiation; DNA-Binding Proteins; Epithelial Cells; Esophageal Neoplasms; HeLa Cells; Humans; Keratins; Molecular Sequence Data; Mutation; Proto-Oncogene Proteins; Proto-Oncogene Proteins c-ets; Transcription Factors; Tumor Cells, Cultured

A 32-year-old woman underwent a suction curettage for missed abortion. The initial serum human chorionic gonadotropin (beta-hCG) level was 40 IU/ml. The histologic examination of the uterine curettage specimen showed scant strips of a poorly differentiated malignant neoplasm and no chorionic villi. The tumor showed strong immunoreactivity for cytokeratin (AE1/AE3) and beta-hCG but no reactivity for human placental lactogen. The combination of histologic appearance, beta-hCG immunoreactivity, and elevation of serum beta-hCG raised a strong suspicion for epithelioid trophoblastic tumor (ETT). Postcurettage serial serum beta-hCG levels remained in the range of 20 to 45 micrograms/ml. Computerized tomographic scan showed a 1.0-cm circumscribed mass in the upper endocervix. A radical hysterectomy and pelvic lymphadenectomy were performed. Gross examination of the hysterectomy specimen likewise showed a well-circumscribed mass in the upper endocervix. Histologic examination revealed an undifferentiated carcinoma accompanied by intense lymphoplasmacytic infiltrate. A final diagnosis of lymphoepithelioma-like carcinoma (LELC) was rendered. LELC with elevated serum beta-hCG level and immunoreactivity to beta-hCG should be distinguished from ETT in a small endocervical curettage sample.

Topics: Abortion, Missed; Adult; Carcinoma, Squamous Cell; Chorionic Gonadotropin, beta Subunit, Human; Diagnosis, Differential; Female; Humans; Hysterectomy; Keratins; Lymphocytes; Necrosis; Placental Lactogen; Plasma Cells; Pregnancy; Trophoblastic Neoplasms; Uterine Cervical Neoplasms

The use and limitations of fine-needle aspiration (FNA) of lesions of the parotid gland are known, but those of nonparotid lesions of the head have been described only sporadically. We conducted this study to evaluate the utility of FNA and to analyze the causes of diagnostic discrepancies for these lesions. A total of 6,898 FNAs of different sites was performed at our institutions between January 1991-August 1998, and 214 (3.1%) of the cases were FNAs of nonparotid lesions of the head. The most common diagnosis of nonparotid lesions was squamous-cell carcinoma, in 22% (n = 48), and the most common site aspirated was the scalp, in 34% (n = 73). Lipomas and keratinous cysts comprised 5% (n = 9) of the total. A statistical analysis was conducted on 98 paired cytology and histology (n = 83) and cytology and flow cytometry (n = 15) specimens (70 malignant and 28 benign). FNA recognized the malignant and benign nature of the lesion in 60 and 26 cases, respectively with 86% sensitivity 93% specificity and 88% accuracy. Causes of false-negative FNA diagnoses (n = 10) included sampling error (n = 6), bloody smears with scant cellularity (n = 3), and bland cytomorphology (n = 1). Florid granulation tissue and a mucocele of the tongue accounted for the two false-positive cases. We conclude that FNA is an effective tool for triage of surgery candidates with nonparotid lesions of the head. Adequate samples with sufficient cellularity are required for avoiding false-negative diagnoses. Occasionally, tissue biopsy is needed for diagnosis of equivocal cases.

Topics: Adult; Aged; Aged, 80 and over; Biopsy, Needle; Carcinoma, Squamous Cell; Epidermal Cyst; Evaluation Studies as Topic; Female; Head and Neck Neoplasms; Humans; Keratins; Lipoma; Male; Middle Aged; Multiple Myeloma; Scalp; Sensitivity and Specificity

The telomere and the telomerase in human esophageal cancer are not yet completely understood. The regulatory mechanism of telomerase activity and telomere dynamics has drawn considerable attention. It is generally assumed that when telomerase has been activated, no further telomere shortening should ensue; however, a much more complex pattern of telomere dynamics may exist in telomerase-positive cancer cells. A novel human esophageal cancer cell line (KAN-ES) was established and characterized. Using KAN-ES and its serially passaged subclones up to the 55th generation, we determined the alteration of telomere length (TRF), telomerase activity (TA), telomerase RNA expression (hTR), population doubling time, karyotype, and cytokeratin 14 expression during the process of establishing a cancer cell line. We found that the TRF was maintained between 4.0 and 5.0 kb during the serial passages, despite sustained high TA (assessed by an in vitro TRAP assay). No close relationships were found among TRF, TA, and hTR expression. TA and telomere dynamics were not associated with cellular growth ability and differentiation. However, the number of population doublings showed significant correlations with both the TA and doubling times. In conclusion, these dissociations between telomere dynamics and TA support the existence of additional controls on TRF in cancer cells. KAN-ES and its restored subclones should prove a valuable resource for esophageal cancer research.

Topics: Biomarkers, Tumor; Carcinoma, Squamous Cell; Cell Division; Cell Transformation, Neoplastic; Esophageal Neoplasms; Gene Expression Regulation, Neoplastic; Humans; Keratins; Male; Middle Aged; RNA, Messenger; Telomerase; Telomere; Tumor Cells, Cultured

Phenotypic changes resembling an epithelial-to-mesenchymal transition often occur as epithelial cells become tumorigenic. Two proteins that have been implicated in this process are vimentin and N-cadherin. In this study, we sought to establish a link between expression of vimentin and N-cadherin as oral squamous epithelial cells undergo a morphologic change resembling an epithelial-to-mesenchymal transition. We found that N-cadherin and vimentin did not influence the expression of one another.

Topics: Animals; Cadherins; Carcinoma, Squamous Cell; Cell Adhesion; Clone Cells; Humans; Keratins; Laryngeal Neoplasms; Mice; Phenotype; Recombinant Proteins; Transfection; Tumor Cells, Cultured; Vimentin

The reactions of a number of epithelial skin tumours in dogs to a panel of monoclonal antibodies against different human cytokeratins (CKs) were examined immunohistochemically, the purpose being to detect a specific CK profile. CK 6 was present in all epithelial skin tumours with the exception of pilomatrixoma. CK 14 was found in basal cell-derived neoplasias and in sebaceous and perianal gland tumours. CK 10/11 was restricted to spinous cell-derived tumours and CK 8/18 was limited to sweat gland tumours.

Topics: Animals; Carcinoma, Basal Cell; Carcinoma, Squamous Cell; Dog Diseases; Dogs; Humans; Immunohistochemistry; Keratins; Skin; Skin Neoplasms

A cutaneous melanocytoma-acanthoma in a 2-year-old female German Shepherd Dog was characterized by the presence of two populations of neoplastic cells: epithelial and melanocytic. The epithelial component consisted of nests of well-differentiated stratified squamous epithelium closely associated with neoplastic melanocytes. The epithelial cells immunoreacted with both monoclonal and polyclonal anti-cytokeratin antibodies, and immunoreaction to S-100 protein and vimentin was observed in the melanocytic cells. This rare pigmented skin neoplasm of the dog apparently has a benign behavior.

Topics: Animals; Carcinoma, Squamous Cell; Dog Diseases; Dogs; Female; Keratins; Neoplasms, Glandular and Epithelial; Nevus, Blue; Skin Neoplasms

Topics: Adult; Biopsy, Needle; Carcinoma, Squamous Cell; Female; Herpesviridae Infections; Herpesvirus 4, Human; Humans; Immunoenzyme Techniques; In Situ Hybridization; Keratins; Ribosomal Proteins; RNA-Binding Proteins; RNA, Viral; Salivary Gland Neoplasms

Serum pyridinoline cross-linked carboxy-terminal telopeptide of type I collagen (ICTP) is a metabolite of type I collagen comprising 90% or more of organic substances in bone. Its usefulness as a marker of bone metastasis from malignant tumors is expected.. We measured ICTP to evaluate its clinical usefulness for diagnosis of bone metastasis in 140 patients with lung cancer. For comparison, serum carcinoembryonic antigen (CEA), cytokeratin 19 fragment (CYFRA 21-1), gastrin-releasing peptide precursor (ProGRP), alkaline phosphatase and calcium were simultaneously measured. ICTP was measured by double-antibody radioimmunoassay.. ICTP was significantly higher in patients with bone metastasis from lung cancer than in the group without bone metastasis, patients with other pulmonary diseases or healthy control subjects and showed excellent sensitivity and specificity, indicating that this marker is highly useful for complementary diagnosis of bone metastasis from lung cancer. Moreover, the survival duration was significantly shorter in the ICTP-positive group than in the ICTP-negative group, suggesting that ICTP can be a prognostic factor in lung cancer.. It is suggested that measurement of ICTP is worthwhile as a serological diagnostic method of bone metastasis from lung cancer. Moreover, since repeated measurements are possible, this measure was considered very helpful in complementary diagnosis of bone metastasis and also as a standard to determine the timing of examinations such as bone scintigraphy.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Alkaline Phosphatase; Antigens, Neoplasm; Biomarkers; Biomarkers, Tumor; Bone Neoplasms; Calcium; Carcinoembryonic Antigen; Carcinoma, Large Cell; Carcinoma, Small Cell; Carcinoma, Squamous Cell; Collagen; Collagen Type I; Female; Gastrointestinal Hormones; Humans; Keratin-19; Keratins; Lung; Lung Diseases; Lung Neoplasms; Male; Middle Aged; Peptide Fragments; Peptides; Prognosis; Recombinant Proteins; Sensitivity and Specificity; Survival Rate

Sixty patients with squamous cell carcinoma (SCC) of the lung, including 25 cases with recurrence and 35 cases without recurrence 1 year after operation, were enrolled in this study. The serial serum levels of cytokeratin fragment 19 (CYFRA 21-1) and SCC antigen were measured before operation and 1 week, 1 month, 3 months, 6 months, 9 months, and 12 months after operation for early detection of recurrence. The results revealed that 1) mean serum values of CYFRA 21-1 were significantly higher at early and any times after operation in 25 patients with recurrent SCC when compared with 35 patients without recurrent SCC; and 2) mean serum values of SCC antigen were significantly higher until 9 and 12 months after operation, in 25 patients with recurrent SCC when compared with 35 patients without recurrent SCC. We conclude that CYFRA 21-1 is a better marker than SCC antigen for early prediction of SCC recurrence in the lung.

Topics: Aged; Antigens, Neoplasm; Biomarkers, Tumor; Carcinoma, Squamous Cell; Female; Humans; Immunoradiometric Assay; Keratin-19; Keratins; Lung Neoplasms; Male; Middle Aged; Neoplasm Recurrence, Local; Postoperative Period; Serpins

A fragment of cytokeratin 19, referred to as CYFRA 21-1, is abundant in the serum of many patients with malignant tumors and is recognized as one of the established tumor markers, especially for non-small-cell lung cancer. In this study, the clinical usefulness of CYFRA 21-1 was investigated in cervical cancer patients treated with radiation therapy with reference to squamous-cell-carcinoma-related antigen (SCC-Ag), a common tumor marker of cervical squamous cell carcinoma.. The serum levels of CYFRA 21-1 and SCC-Ag of 50 patients with squamous cell carcinoma of the uterine cervix were measured before and after radiation therapy.. CYFRA 21-1 was positive in 52% of the patients. The incidence increased with the stage of the cancer, and post-treatment increases were a sign of disease progression. During radiation, serum levels of CYFRA 21-1 decreased significantly and reflected the radiation effect well. In addition, CYFRA 21-1 was negative in all patients without distant metastasis at the end of radiation therapy. Compared with SCC-Ag, patients were less often positive for CYFRA 21-1, but there was a statistically positive correlation between the two markers (correlation matrix=0.69).. CYFRA 21-1 can be used in monitoring the outcome of patients with squamous cell carcinoma of the uterine cervix. It may be particularly useful for patients without SCC-Ag.

Topics: Adult; Aged; Aged, 80 and over; Antigens, Neoplasm; Biomarkers, Tumor; Carcinoma, Squamous Cell; Female; Humans; Keratin-19; Keratins; Middle Aged; Neoplasm Staging; Predictive Value of Tests; Radiotherapy Dosage; Uterine Cervical Neoplasms

The detection of epithelial cells in bone marrow, blood or lymph nodes indicates a disseminatory potential of solid tumours. 225 patients with squamous cell carcinoma of the oesophagus were prospectively studied. Prior to any therapy, cytokeratin-positive (CK) cells in bone marrow were immunocytochemically detected in 75 patients with the monoclonal anti-epithelial-cell antibody A45-B/B3 and correlated with established histopathologic and patient-specific prognosis factors. The prognosis factors were assessed by multivariate analysis. Twenty-nine of 75 (38.7%) patients with oesophageal cancer showed CK-positive cells in bone marrow. The analyses of the mean and median overall survival time showed a significant difference between patients with and without epithelial cells in bone marrow (P < 0.001). Multivariate analysis in the total patient population and in patients with curative resection of the primary tumour confirmed the curative resection rate and the bone marrow status as the strongest independent prognostic factors, besides the T-category. The detection of epithelial cells in bone marrow of oesophageal cancer patients is a substantial prognostic factor proved by multivariate analysis and is helpful for exact preoperative staging, as well as monitoring of neoadjuvant therapy.

Topics: Adult; Aged; Aged, 80 and over; Antimetabolites, Antineoplastic; Biomarkers, Tumor; Bone Marrow; Bone Marrow Examination; Carcinoma, Squamous Cell; Chemotherapy, Adjuvant; Combined Modality Therapy; Epithelial Cells; Esophageal Neoplasms; Esophagectomy; Female; Fluorouracil; Humans; Keratins; Lymphatic Metastasis; Male; Middle Aged; Multivariate Analysis; Neoplasm Metastasis; Neoplasm Proteins; Neoplasm Recurrence, Local; Neoplasm Staging; Neoplastic Stem Cells; Prognosis; Prospective Studies; Radiotherapy, Adjuvant; Survival Analysis; Treatment Outcome

A rare case of carcinoma characterized by extensive chondroid elements at a site of primary esophageal and metastatic lesion is reported. The patient was a 67-year-old man complaining of dysphagia due to an ulcerative lesion at the lower middle esophagus. He underwent irradiation treatment prior to surgery. Histologically, the tumor consisted of both carcinomatous and chondroid elements and had invaded deeply into the esophageal wall. The carcinomatous cells had gradually become chondroid cells embedded within an extensive extracellular matrix. In addition, the metastatic lesion showed findings similar to those of the primary lesion. Immunohistochemistry revealed that both carcinomatous and chondroid elements were immunostained with cytokeratin and epithelial membrane antigen, suggesting an epithelial nature to the chondroid cells. Conversely, only chondroid cells were positively stained for S-100 protein. Furthermore, bone morphogenetic proteins (BMP) were positive for chondroid cells and their surrounding carcinomatous cells. Given the apparent transition between carcinomatous and chondroid cells based on microscopy and immunohistochemical findings in the present case, we concluded that the chondroid cells were derived from carcinomatous cells. In addition, our findings suggest that BMP produced by carcinomatous cells lead to chondroid differentiation of the carcinoma cells.

Topics: Aged; Bone Morphogenetic Proteins; Carcinoma, Squamous Cell; Cell Differentiation; Chondrocytes; Esophageal Neoplasms; Humans; Immunohistochemistry; Keratins; Male; Mucin-1; S100 Proteins

Metastases to inguinofemoral lymph nodes in patients with carcinoma of the vulva alter the prognosis and treatment of this disease. Our goal was to determine if immunohistochemical staining could reveal occult metastatic nodal disease not detected with routine hematoxylin and eosin staining. We retrospectively examined a total of 110 lymph nodes from 10 patients who had undergone lymph node dissection and found to have all negative nodes. Paraffin embedded lymph nodes were immunostained with a monoclonal antibody directed against multiple low- and high-molecular weight cytokeratins. Micrometastases were not detected in any lymph nodes examined with immunohistochemistry. All positive and negative controls yielded satisfactory results. It is concluded that immunohistochemistry with cytokeratin antibodies does not provide greater sensitivity than routine hematoxylin and eosin staining for the detection of nodal metastases in vulvar carcinoma.

Topics: Antibodies, Monoclonal; Carcinoma, Squamous Cell; Female; Humans; Immunohistochemistry; Keratins; Lymph Node Excision; Lymph Nodes; Lymphatic Metastasis; Neoplasm Staging; Prognosis; Retrospective Studies; Vulvar Neoplasms

To examine whether cancer cell dissemination results from incisional biopsy, we tried to detect squamous cell carcinoma (SCC) cells in peripheral blood before and after incisional biopsy by means of cytokeratin 19 (CK19) reverse-transcriptase polymerase chain reaction (RT-PCR). The study population consisted of 20 patients with oral SCC; 10 were given incisional biopsies followed by radical excision (the incisional biopsy group), and the remaining 10 were treated by excisional biopsy alone (the excisional biopsy group). Ten non-oral cancer patients with benign oral lesions served as controls. Five-ml blood aspirates collected before and after incision were used for CK19 RT-PCR. Two (20.0%) of 10 patients from the incisional biopsy group were positive for CK19 transcripts in their peripheral blood drained 15 min after incision. In contrast, CK19 transcript was not detected either in the excisional biopsy group or in controls. Surgical invasiveness for oral cancer, including incisional biopsy, causes dissemination of cancer cells into circulation, resulting in increased risk of metastasis.

Topics: Aged; Aged, 80 and over; Biopsy; Carcinoma, Squamous Cell; Case-Control Studies; DNA, Neoplasm; Female; Humans; Keratins; Male; Middle Aged; Mouth Neoplasms; Neoplasm Seeding; Reverse Transcriptase Polymerase Chain Reaction

We investigated by immunocytochemistry the expression of the Ca(2+) binding protein S100A2 in 62 cases of laryngeal squamous-cell carcinoma (SCC). S100A2 was detected in 18/19 (95%) low-grade tumors and in 22/43 (51%) high-grade tumors, which were partially keratinizing. The remaining 21/43 (49%) high-grade tumors were non-keratinizing, anaplastic tumors and clearly S100A2-negative. In normal laryngeal squamous epithelium and in laryngeal SCC, S100A2 expression was strictly associated with that of cytokeratins 14 (P = 0.0002) and 17 (P = 0.0021), suggesting an association of S100A2 expression and cell commitment to squamous differentiation. A correlation was found between S100A2 tumor positivity and longer relapse-free (P = 0.0005) and overall (P = 0.0095) survival.

Topics: Analysis of Variance; Biomarkers, Tumor; Calcium-Binding Proteins; Carcinoma, Squamous Cell; Chemotactic Factors; Humans; Immunohistochemistry; Keratins; Laryngeal Neoplasms; Middle Aged; Neoplasm Recurrence, Local; Neoplasm Staging; Prognosis; S100 Proteins; Survival Analysis

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

Topics: Carcinoma, Squamous Cell; Humans; Keratins; Laryngeal Neoplasms; Neoplasm Staging

The erbB family of receptor tyrosine kinases, which consists of the epidermal growth factor receptor (EGFr/erbB1), erbB2 (neu), erbB3 and erbB4, has been shown to be important for both normal development as well as neoplasia. The expression of rat erbB2 was targeted to the basal layer of mouse epidermis with the bovine keratin 5 promoter. Overexpression of wild type rat erbB2 in the basal layer of epidermis led to alopecia, follicular hyperplasia and sebaceous gland enlargement as well as hyperplasia of the interfollicular epidermis. Spontaneous papillomas, some of which converted to squamous cell carcinomas, arose in homozygous erbB2 transgenic mice as early as 6 weeks of age with >90% incidence by 6 months. Analysis of several proliferation/differentiation markers indicated that erbB2 overexpression led to epidermal hyperproliferation and a possible delay in epidermal differentiation. Transgenic mice were also hypersensitive to the proliferative effects of the skin tumor promoter, 12-0-tetradecanoylphorbol-13-acetate (TPA) and were more sensitive to two-stage carcinogenesis. Elevations in EGFr and erbB2 protein as well as erbB2:EGFr and erbB2:erbB3 heterodimers were observed in skin of the erbB2 transgenic mice. Phosphotyrosine levels of the EGFr, erbB2 and erbB3 proteins were also elevated. These results indicate an important role for erbB2 signaling in epidermal growth, development and neoplasia. Oncogene (2000) 19, 4243 - 4254

Topics: Animals; Carcinogens; Carcinoma, Squamous Cell; Cattle; Cell Differentiation; Cell Division; Cell Transformation, Neoplastic; Cocarcinogenesis; Dimerization; Disease Progression; Epidermis; ErbB Receptors; Female; Gene Expression Regulation; Gene Expression Regulation, Neoplastic; Genes, erbB-2; Genes, ras; Genes, Synthetic; Hyperplasia; Keratins; Male; Mice; Mice, Inbred ICR; Mice, Transgenic; Neoplasm Proteins; Papilloma; Phosphorylation; Promoter Regions, Genetic; Protein Processing, Post-Translational; Rats; Receptor, ErbB-2; Receptor, ErbB-3; Recombinant Fusion Proteins; Signal Transduction; Skin Neoplasms; Tetradecanoylphorbol Acetate; Transgenes

The histologic classification of pulmonary neoplasms can have important implications regarding appropriate management of patients. Although the histologic classification of lung tumors is predominantly based on morphology, ancillary studies such as immunohistochemistry can be used in difficult cases, and the diagnosis of large cell neuroendocrine carcinoma requires confirmation of neuroendocrine differentiation by immunohistochemistry or electron microscopy. We immunostained 142 lung tumors for B72.3, keratin 34betaE12, keratin 7, keratin 14, keratin 17, synaptophysin, and chromogranin to determine the utility of neuroendocrine markers and epithelial markers in the differential diagnosis. Among neuroendocrine carcinomas (small cell carcinoma and large cell neuroendocrine carcinoma), 84% (37 of 44) were chromogranin positive, 64% (21 of 36 small cell, 6 of 6 large cell neuroendocrine) were synaptophysin positive, 5% (2 of 43) were keratin 34betaE12 positive, 9% (4 of 44) were keratin 7 positive, and 5% (2 of 37) of small cell carcinomas and 50% (3 of 6) of large cell neuroendocrine carcinomas were B72.3 positive. Among non-neuroendocrine carcinomas, 5% (5 of 98) were chromogranin positive, 3% (3 of 96) were synaptophysin positive, and 97% (95 of 98) were positive for either keratin 34betaE12 or keratin 7 and 99% (97 of 98) were positive for either keratin 34betaE12, keratin 7 or B72.3. An antibody panel consisting of keratin 7, keratin 34betaE12, chromogranin, and synaptophysin separated 132 of 141 tumors (94%) into distinct groups. We conclude that immunostaining with both neuroendocrine markers and epithelial markers can be useful in the differential diagnosis of lung neoplasms.

Topics: Adenocarcinoma; Adenocarcinoma, Bronchiolo-Alveolar; Biomarkers, Tumor; Carcinoma, Large Cell; Carcinoma, Non-Small-Cell Lung; Carcinoma, Small Cell; Carcinoma, Squamous Cell; Chromogranins; Diagnosis, Differential; Humans; Immunohistochemistry; Keratins; Lung Neoplasms; Pilot Projects; Synaptophysin

During surgical treatment of periodontal disease, enamel matrix derivative (EMD) is topically applied as a substitute for extracellular matrix in order to facilitate regeneration of damaged periodontal tissue. However, the mechanism for EMD action is poorly understood. We have now examined the effects of EMD on the proliferation of oral epithelial (SCC25) cells in vitro. After 3 days of treatments, EMD (25 100 microg/ml) dose-dependently inhibited cell division and concomitantly arrested cell cycle at the G1 phase. Prior to this inhibition, EMD significantly up-regulated p21WAF1/cip1, a cyclin-dependent kinase inhibitor, induced G1-arrest, and inhibited DNA synthesis. In addition, EMD down-regulated expression of cytokeratin-18 (CK18) protein, which was most due to decreased production, but less to increased degradation. However, EMD did not discernibly increase the number of apoptotic cells over 8 days of treatment. These findings indicate (1) that EMD acts as a cytostatic agent, rather than a cytotoxic agent, on epithelial cells, and (2) that this anti-proliferative action is probably due to p21WAF1/cip1-mediated G1-arrest. Furthermore, our in vitro cellular data clearly verify and provide an explanation for the clinical observation that EMD application suppresses the down-growth of junctional epithelium onto dental root surfaces, a process that frequently interferes with the formation of new connective tissue attachments.

Topics: Adolescent; Analysis of Variance; Apoptosis; Carcinoma, Squamous Cell; Cell Differentiation; Cell Division; Cyclin-Dependent Kinase Inhibitor p21; Cyclin-Dependent Kinases; Cyclins; Dental Enamel Proteins; DNA Replication; Enzyme Inhibitors; Epithelial Cells; Fibroblasts; G1 Phase; Gene Expression Regulation; Humans; Keratins; Periodontal Ligament; Statistics, Nonparametric; Tumor Cells, Cultured

While there are reports that CYFRA 21-1 is a useful tumor marker, to our knowledge the clinical utility of this marker to detect recurrences for squamous cell carcinoma of the esophagus has not been addressed.. By immunoradiometric assay, human serum levels of CYFRA 21-1, SCC antigen and CEA were measured in esophageal squamous cell carcinoma patients prior to their initial treatment. Monthly follow-ups of these tumor markers was done after surgery.. The diagnostic sensitivity of CYFRA 21-1 was 43.9% (18 of 41), a value superior to that for SCC antigen (26.8%) and CEA (17.0%) (P < 0.05). The positive rates of CYFRA 21-1 increased with progression of the disease, 22.2% of pTNM Stage 0-IIA and 77.8% of pTNM Stage IIB/III (P = 0.013), whereas SCC antigen and CEA rates were not related to pTNM stage. Among 13 patients with clinical evidence of a recurrence, 76.9% (10 of 13) exhibited an increase in CYFRA 21-1, and this increase was evident before clinical detection of the recurrence in 9 of these 13 patients (69.2%). Consequently, postoperative elevations of serum CYFRA 21-1 levels were indicative of a tumor recurrence 1-13 months before acquisition of clinical and radiological data.. The assay of CYFRA 21-1 is useful not only for diagnosis but also for close monitoring of patients with esophageal squamous cell carcinoma.

Topics: Antigens, Neoplasm; Biomarkers, Tumor; Carcinoma, Squamous Cell; Esophageal Neoplasms; Humans; Keratin-19; Keratins; Neoplasm Recurrence, Local; Predictive Value of Tests; Prognosis; Sensitivity and Specificity

Primary carcinomas of the Waldeyer's ring area are typically nonkeratinizing squamous cell carcinomas (SCC). Their cervical lymph node metastases are not uncommonly cystic and filled with necrotic tumor cells. Some cysts, however, contain clear fluid. During the investigation of SCC producing "fluid-filled" cystic metastases, we evaluated hematoxylin and eosin (H&E) sections of 90 primary SCC for their site of origin. We analyzed the cytokeratin (CK) profile of primary and metastatic carcinoma with special focus on the expression of CK7, a putative marker for ductal differentiation. CK7 was expressed in submucosal minor salivary gland acini and ducts, but not in the squamous surface epithelium of the Waldeyer's ring. CK7 was expressed in 11 primary SCC (8 base of tongue/3 palatine tonsil). The CK7-positive SCC were deep-seated, arose from large excretory ducts of submucosal minor salivary glands, and showed only insignificant surface involvement. They were characterized by a solid infiltrative growth pattern of basaloid cells with focal ductal differentiation. Salivary ducts adjacent to the carcinoma showed extensive intraductal hyperplasia and metaplasia. All CK7-positive carcinomas produced CK7-positive cystic nodal metastases, most of which contained paucicellular fluid. No solid CK7-positive nodal metastases were identified. In summary, a subset of carcinomas occurring in the Waldeyer's ring area appear to arise from large excretory ducts of submucosal minor salivary glands with only limited surface involvement, express CK7, and produce CK7-positive cystic "fluid-filled" nodal metastases. The histomorphology and immunophenotype suggest that these carcinomas represent basaloid SCC arising from excretory ducts of the submucosal minor salivary glands.

Topics: Biomarkers, Tumor; Carcinoma, Squamous Cell; Cysts; Humans; Immunohistochemistry; Keratin-7; Keratins; Lymph Nodes; Lymphatic Metastasis; Neck; Palatine Tonsil; Salivary Ducts; Salivary Glands, Minor; Tongue Neoplasms; Tonsillar Neoplasms

The aim of the study was to assess diagnosis value of tumor markers for differential diagnosis between mesothelioma and other pleural tumors.. Prospective study of 85 patients attending our hospital with malignant pleural effusion. The diagnostic approach involved routine pleurocentesis followed by pleural needle. When precise diagnosis was not achieved, thoracoscopy with pleural biopsies was performed. Carcinoembryonic antigen (CEA), hyaluronic acid, tissue polypeptide antigen and cyfra 21 to 1 were measured in serum and pleural fluid.. By using receiver operating characteristics curves and area under curves, the best diagnostic characteristics were obtained with pleural and serum CEA concentrations. The area under the curve was larger for pleural ACE than for serum ACE. The sensitivity and specificity of a pleural CEA level exceeding 3 ng/mL for ruling out the diagnosis of mesothelioma were 100% and 77%, respectively.. A CEA level above 3 ng/mL in pleural fluid eliminated the diagnosis of mesothelioma, whereas the other markers were not sufficiently discriminant. However, despite a negative predictive value of 100% at a cutoff of 3 ng/mL, CEA assay in pleural fluid only avoids a small number of diagnostic thoracoscopies.

Topics: Adenocarcinoma; Aged; Antigens, Neoplasm; Area Under Curve; Biomarkers, Tumor; Carcinoembryonic Antigen; Carcinoma, Small Cell; Carcinoma, Squamous Cell; Diagnosis, Differential; Female; Humans; Hyaluronic Acid; Keratin-19; Keratins; Lung Neoplasms; Male; Mesothelioma; Middle Aged; Pleural Effusion; Pleural Neoplasms; Prospective Studies; ROC Curve; Sensitivity and Specificity; Tissue Polypeptide Antigen

Topics: alpha Catenin; beta Catenin; Cadherins; Carcinoma, Squamous Cell; Cytoskeletal Proteins; Fatal Outcome; Humans; Immunohistochemistry; Keratins; Male; Maxillary Neoplasms; Middle Aged; Mucin-1; Trans-Activators

Diploid tumour cells regularly continue to progress after the development of aneuploid cell populations in head and neck squamous cell carcinomas. The coexistence of aneuploid clones with their diploid progenitor cells provides a unique opportunity to study the order of appearance of p53 mutation and aneuploidy in the same tumour. Multiparameter flow cytometry was therefore applied to 22 oral squamous cell carcinomas to simultaneously assess cellular DNA content and p53 protein expression on a single-cell basis. Concurrent measurements of cytokeratin expression served to identify tumour cells of epithelial origin. One of 5 diploid and 2 of 17 aneuploid carcinomas were p53-negative. For 15 p53-positive aneuploid tumours, overexpression of p53 protein was identified for the aneuploid clones as well as for coexisting diploid tumour cell populations in 14 cases. On the understanding that coexisting diploid and aneuploid tumour cell populations have a common clonal origin, these results provide evidence that aneuploid tumour clones typically develop from p53-deficient diploid progenitor cells. Loss of wild-type p53 function may therefore contribute to the development of aneuploidy in head and neck cancer.

Topics: Aneuploidy; Carcinoma, Squamous Cell; Cell Transformation, Neoplastic; Clone Cells; Cohort Studies; Diploidy; Disease Progression; DNA, Neoplasm; Flow Cytometry; Genes, p53; Humans; Keratins; Mouth Neoplasms; Neoplasm Proteins; Neoplastic Stem Cells; Pharyngeal Neoplasms; Tumor Suppressor Protein p53

Patients with superficial (mucosal or submucosal) esophageal carcinoma (SEC) have significantly better survival rates than patients with advanced carcinoma. Some patients with advanced esophageal carcinoma have been reported to test positive for serum p53 antibodies (Abs). Because very few patients with superficial carcinoma have been examined, the aim of this study was to evaluate the clinical significance of serum p53-Abs in patients with superficial esophageal squamous cell carcinoma (SESCC).. Thirty-five consecutive patients with SESCC were studied for serum p53-Abs by enzyme-linked immunoabsorbent assay before and after treatment. The clinicopathologic features of p53 seropositive and p53 negative patients were compared. The relation between the presence of serum p53-Abs and p53 immunoreactivity of the resected specimens was examined. Three tumor markers (squamous cell carcinoma antigen [SCC-Ag], CYFRA21-1, and carcinoembryonic antigen [CEA]) were assessed to compare their sensitivities with serum p53-Abs.. Fourteen of 35 patients (40%) were p53 seropositive. Relatively few patients tested positive for the other tumor markers: CEA, 11.4%; SCC-Ag, 14.3%; CYFRA21-1, 5.7%. There were no significant correlations between clinicopathologic features and p53 seropositivity except for tumor location. A strong correlation between p53 immunostaining and the presence of serum p53-Abs was observed (P = 0.003). Of the 14 patients with seropositive results, 12 turned seronegative after resection, and the other 2 experienced disease recurrence.. Surveillance of serum p53-Abs is superior to the three tumor markers for detecting SESCC. This serum marker is also useful for the detection of p53 protein overexpression and for the monitoring of residual tumor cells.

Topics: Aged; Antibodies, Neoplasm; Antigens, Neoplasm; Autoantibodies; Biomarkers, Tumor; Carcinoembryonic Antigen; Carcinoma, Squamous Cell; Enzyme-Linked Immunosorbent Assay; Esophageal Neoplasms; Female; Humans; Keratin-19; Keratins; Male; Middle Aged; Neoplasm Invasiveness; Survival Rate; Tumor Suppressor Protein p53

A small composite esophageal carcinoma measuring 1.5 x 1.4 x 1.0 cm is described. The tumor had a polypoid elevation with a superficial extension. Histologic examination revealed invasion of the submucosal layer and multidirectional differentiation, including neuroendocrine, squamous, ciliated glandular, and sarcomatous components. The neuroendocrine component was strongly positive for chromogranin and formed the bulk of the polypoid tumor. The squamous cell carcinoma exhibited a superficial extension. The adenocarcinoma was located in a small region of the tumor and contained ciliated glandular cells. The spindle cell sarcomatous component, which was positive for alpha-smooth muscle actin and negative for cytokeratin, exhibited no specific mesenchymal differentiation. Each component was found in 60%, 10%, 5%, and 25% of the tumor, respectively. Cases of small composite esophageal carcinoma containing various carcinomatous and sarcomatous components are extremely rare.

Topics: Actins; Adenocarcinoma; Carcinoma, Neuroendocrine; Carcinoma, Squamous Cell; Carcinosarcoma; Cell Differentiation; Chromogranins; Esophageal Neoplasms; Humans; Immunohistochemistry; Keratins; Male; Middle Aged; Muscle, Smooth

The predictive value of lymph node micrometastasis, detected by immunohistochemical or genetic methods, is well appreciated in terms of prognosis. However, a major problem is high false-positive rates, because most methods focus on cytokeratin, which is a component not only of carcinoma but also normal epithelial and nonepithelial cells. Mutant allele-specific amplification (MASA) can detect DNAs derived from cancer cells itself, reportedly with high sensitivity. It was, therefore, used with nested-PCR using p53 or K-ras mutation for analysis of lymph node micrometastasis in non-small cell lung carcinoma (NSCLC) patients in the present study, in comparison with the immunohistochemical method using an anti-cytokeratin reagent for the same samples. Lymph nodes from 31 NSCLC patients with p53 and K-ras mutated tumors (30 and 1, respectively) staged as pathological (p)-T1-4 N0-1 and M0 were examined. Genetic and immunohistochemical methods demonstrated positive reactions in 34 (15%) and 61 (27%) of 229 lymph nodes, respectively (9 cases, 29%, and 24 cases, 77%). The concordance with the two methods was 77%, but 13 (39%) of 34 genetically positive lymph nodes could not be detected by immunohistochemistry (IHC). Of 22 cases with p-N0 disease, 6 (27%) were genetically positive in hilar and/or mediastinal lymph nodes, and 4 (67%) of them died after cancer relapse. In contrast, none of the patients without micrometastasis died of cancer (P < 0.001, log rank analysis). Of the same p-N0 patients, 17 (77%) were positive by IHC, and 4 (24%) of them died of cancer, whereas 5 negative patients did not suffer cancer relapse. Survival did not significantly differ between cases positive and negative (P = 0.246) by IHC. According to the g-N (N factor restaged by a genetic method), patients with g-N1 and g-N2 disease had a shorter survival than those with g-N0 disease (P = 0.042 and P < 0.001, respectively). However, no significant difference was observed with grading by IHC. Thus, detection of micrometastasis in regional lymph nodes with the MASA method, in other words with a carcinoma-specific marker, is of greater prognostic significance for early stage NSCLC patients than immunohistochemical results. This approach should facilitate selection of patients for whom postoperative adjuvant chemotherapy should be performed.

Topics: Adenocarcinoma; Adult; Aged; Alleles; Carcinoma, Squamous Cell; Female; Humans; Immunohistochemistry; Keratins; Lung Neoplasms; Lymph Nodes; Lymphatic Metastasis; Male; Middle Aged; Mutation; Nucleic Acid Amplification Techniques; Polymerase Chain Reaction; Prognosis; Survival Analysis

Keratinization of the ocular surface epithelium is associated with various disorders impairing vision. We immunohistochemically determined whether the ocular surface epithelia express involucrin, and whether its expression pattern may differ in benign vs. malignant disorders. Expression of cytokeratins was also examined to provide further information relative to the epithelial differentiation.. We evaluated 17 specimens; 6 specimens of the normal ocular surface epithelia, 3 specimens from cases of conjunctival intraepithelial neoplasia (CIN), 6 of conjunctival squamous cell carcinoma (SCC) and 2 of conjunctivae from cases of superior limbic keratoconjunctivitis (SLK).. Corneal epithelium exhibited intracellular immunoreactivity for involucrin. Four of the 6 specimens of bulbar conjunctival epithelium showed involucrin immunoreactivity in the perimembranous region, whereas the fornical conjunctiva was negative. Cornified envelope in SLK specimens was positive for involucrin. The CIN showed its immunoreactivity in the perimembranous region in all levels of the hyperproliferative epithelium without keratinization, i.e., similar to the bulbar conjunctiva. The neoplastic cells of well-differentiated SCC showed involucrin in the perimembranous region, and those of moderately- to poorly-differentiated SCC have involucrin in their cytoplasm. The expression pattern of cytokeratins was unrelated to grade of malignancy in ocular SCC.. The epithelia of normal subjects and of CIN expresses involucrin without keratinization. In contrary, the keratinized SLK epithelium markedly expresses involucrin in the cornified envelope. The subcellular immunolocalization of involucrin in the ocular SCC may help in evaluating the differentiation, i.e., malignancy, of neoplastic cells.

Topics: Adult; Aged; Aged, 80 and over; Carcinoma in Situ; Carcinoma, Squamous Cell; Conjunctiva; Conjunctival Diseases; Conjunctival Neoplasms; Epithelium; Eye Proteins; Female; Filaggrin Proteins; Humans; Immunoenzyme Techniques; Intermediate Filament Proteins; Keratins; Keratoconjunctivitis; Male; Middle Aged; Protein Precursors

The aim of this study is to assess the clinical usefulness of serum assays of carcinoembryonic antigen (CEA), squamous cell carcinoma antigen (SCC), and CYFRA 21.1 in the diagnosis of squamous cell lung cancer. Sixty patients with squamous cell, and twenty-four patients with nonsquamous cell histology of nonsmall cell lung cancer were enrolled in this study. Serum CEA, SCC, and CYFRA 21.1 levels were obtained by commercially available kits. Upper cutoff levels were 10 ng/ml, 3.5 ng/ml, and 3.5 ng/ml, respectively. In squamous cell lung cancer, percentages and 95% confidence interval (CI) of the patients with elevated levels were as follows: for CEA 23.3% (13-36), for SCC 20.0% (10-32), and for CYFRA 21.1 85.0% (73-93). The positivity rate of CYFRA 21.1 was more significant than CEA and SCC in both squamous and nonsquamous cell lung cancer. None of the markers were significant in differentiating squamous/nonsquamous histology. Only tumor marker CEA was significantly elevated in metastatic squamous cell lung cancer (p=0.004). A novel tumor marker CYFRA 21.1 can be used as a reliable tumor marker in diagnosing squamous cell lung cancer. In addition, CEA has an important role in determining metastatic disease.

Topics: Adult; Aged; Antigens, Neoplasm; Biomarkers, Tumor; Carcinoembryonic Antigen; Carcinoma, Non-Small-Cell Lung; Carcinoma, Squamous Cell; Confidence Intervals; Female; Humans; Keratin-19; Keratins; Lung Neoplasms; Male; Middle Aged; Neoplasm Staging; Reproducibility of Results; Serpins; Smoking

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

To investigate whether the simple epithelial cytokeratin CK18 and CK19 can be used as a marker of oral precancerous lesions.. Formalin-fixed, paraffin-embedded tissue sections of normal oral mucosa, epithelial hyperplasia, mild epithelial dysplasia, moderate epithelial dysplasia, severe epithelial dysplasia and oral squamous cell carcinomas were stained with a CK18-specific antibody and CK19-specific antibody respectively by LSAB immunohistochemical method. The stained sections were observed under light microscopy. The results were described and analyzed with Rank Sum Test.. CK18 was not detected in normal and abnormal oral tissue sections. But in normal nonkeratinized mucosa, CK19 was detected in the basal cell layer dispersively. In epithelial dysplasia, CK19 was detected in the suprabasal cell layer and the number of CK19-positive cell layers was correlated with the dysplasia degree of epithelia. Furthermore, CK19 was detected in oral squamous cell carcinoma, especially in the poor-differentiated cancer cells.. CK19 expression in suprabasal cell layer of oral mucosa can be used as a candidate marker for diagnosis of oral precancerous lesions and determination of the differentiation level of oral squamous cell carcinoma.

Topics: Biomarkers, Tumor; Carcinoma, Squamous Cell; Humans; In Vitro Techniques; Keratins; Mouth Mucosa; Mouth Neoplasms; Precancerous Conditions

Micrometastases within bone marrow indicate a poor prognosis. We prospectively examined micrometastases in patients undergoing resection of esophagogastric cancers for (1) prevalence in rib marrow; (2) comparative detection rates in rib and iliac crest marrow; (3) responsiveness to neoadjuvant therapy; and (4) viability and tumorigenicity.. In 50 consecutive patients, marrow was obtained before manipulation of the primary tumor. Micrometastatic cells were detected by staining contaminant cytokeratin-18-positive cells. Viability and tumorigenicity were determined by culture and xenograft.. Micrometastases were detected in rib marrow from 88% of patients (44 of 50). When bilateral iliac crest marrow was also obtained, micrometastases were found in 15% (4 of 27) compared with 89% (24 of 27) for ribs (P < 0.001). Detection rates were independent of histological type or nodal status and were similar in patients with and without neoadjuvant therapy. Metastatic cells were cultured from rib marrow of 5 of 7 patients and were tumorigenic in nude mice.. Most patients undergoing resection of esophagogastric malignancies have micrometastases in rib marrow. Detection rates based on iliac crest marrow are underestimates. Hematogenous spread of metastatic cells is independent of histological type or nodal status. The metastatic cells are viable, tumorigenic, and resistant to neoadjuvant therapy.

Topics: Adenocarcinoma; Animals; Bone Marrow; Carcinoma, Squamous Cell; Esophageal Neoplasms; Esophagogastric Junction; Flow Cytometry; Humans; Ilium; Keratins; Mice; Mice, Nude; Neoplasm Metastasis; Neoplasm Staging; Prospective Studies; Ribs; Stomach Neoplasms; Transplantation, Heterologous

Lymph node metastasis is a well known feature of poor prognosis in patients with esophageal adenocarcinoma and squamous cell carcinoma. However, a significant proportion of apparently lymph node negative patients die early of metastatic disease. The aim of this study was to determine the prevalence and prognostic significance of occult lymph node metastasis in patients with esophageal adenocarcinoma and squamous cell carcinoma.. Lymph node sections from esophagectomy specimens of 78 patients with lymph node negative esophageal carcinoma (49 patients with adenocarcinoma and 29 with squamous cell carcinoma) were cut serially, it toto, and immunostained with the cytokeratin antibody AE1/AE3 and evaluated for occult lymph node metastasis. The results were correlated with the clinical and pathologic features and with patient survival.. Fifteen of 49 patients (31%) with adenocarcinoma and 5 of 29 patients (17%) with squamous cell carcinoma had occult lymph node metastasis detected by cytokeratin staining. In the adenocarcinoma patients, the presence of occult lymph node metastasis showed a significant correlation with increasing depth of invasion, but was not associated significantly with any other clinical or pathologic feature. In the squamous cell carcinoma patients, the presence of occult lymph node metastasis did not correlate significantly with any clinical or pathologic parameter, except that patients with occult lymph node metastasis were more likely to have received preoperative chemotherapy or radiation therapy. Occult lymph node metastasis did not correlate with poorer survival rates in patients with either adenocarcinoma (Cox proportional hazards ratio: 1.42; P - 0.46) or squamous cell carcinoma (Cox proportional hazards ratio: 0.86; P = 0.90).. Occult lymph node metastasis is not an independent poor prognostic feature in esophageal adenocarcinoma or squamous cell carcinoma. Therefore, the authors do not recommend extensive lymph node sectioning with keratin immunostaining for prognostication of patients with these malignancies.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Biomarkers, Tumor; Carcinoma, Squamous Cell; Esophageal Neoplasms; Female; Humans; Immunohistochemistry; Keratins; Lymphatic Metastasis; Male; Middle Aged; Prognosis; Proportional Hazards Models

Mucosal oral squamous cell carcinoma (SCC) accounts for 3-5% of all reported cancers, with a 5-year survival rate of approximately 50%. Unfortunately, current detection means are of no value in diagnosing lesions early enough for cure, especially when they recur after resection. Postoperative radiotherapy and/or covering the resection site with reconstructive flaps (regional or free vascularized) often makes early diagnosis an impossible task.. The authors examined the detection and treatment monitoring capacity of two relatively new tumor markers in the serum of SCC patients, comparing their levels with those in patients with other oral/perioral malignancies or benign oral tumors and with disease free, posttreatment SCC patients and healthy controls.. Values of sensitivity, specificity, and positive and negative prediction for Cyfra 21-1 were 96%, 87%, 93%, and 53%, respectively, whereas those for tissue polypeptide specific antigen (TPS) were 69%, 87%, 93%, and 54%, respectively. Approximately 2-3 weeks after resection of the SCC lesion, Cyfra 21-1 and TPS levels were reduced by 47% (P < or = 0.003) and 36% (P < or = 0.041), respectively. Cyfra 21-1 levels in SCC patients were significantly greater than those of healthy patients by 73% (P < or = 0.0001), patients with benign tumors by 74% (P < or = 0.0003), and patients in disease remission by 66% (P < or = 0.0002). Similarly, the TPS levels of SCC patients were significantly greater than those of healthy patients by 59% (P < or = 0.0005), patients with benign tumors by 55% (P < or = 0.0001), and patients in disease remission by 59% (P < or = 0.0001). In two patients, a second, new SCC lesion was diagnosed within the follow-up period, with increased tumor markers noted concomitantly with the diagnosis.. The accumulated data point to the suitability of the clinical usage of these two markers, especially Cyfra 21-1, in the early detection of oral SCC lesions (primary, recurrent, or secondary) as well as for treatment monitoring. These results may open new avenues for the diagnosis and follow-up of these patients and hopefully improve their treatment outcome.

Topics: Adult; Aged; Aged, 80 and over; Antigens, Neoplasm; Biomarkers, Tumor; Carcinoma, Squamous Cell; Diagnosis, Differential; Female; Humans; Jaw Neoplasms; Keratin-19; Keratins; Male; Middle Aged; Mouth Neoplasms; Peptides; Predictive Value of Tests; Sensitivity and Specificity; Time Factors; Treatment Outcome

An experimental study was carried out in hamster tongue cancer induced with 9,10-dimethyl-1,2-benzanthracene (DMBA) to examine the association between the histological features and the incidence of lymph node metastases. Squamous cell carcinoma was induced in 64 of 71 hamsters exposed to DMBA 3 times weekly for a period of 10-24 weeks, and lymph node metastases were found in 8 necks. Various histological variables in the primary lesion were examined, and the mode of invasion, degree of keratinization, and stage of invasion were found to be closely related to the development of neck metastases. We then did a prospective study in 37 human patients with T1-2 tongue cancer, which also showed a close association between the incidence of neck metastases and the histological variables of mode of invasion and degree of keratinization. These experimental and clinical studies suggest that the mode of invasion and degree of keratinization may be risk factors for neck metastases that are independent of T stage, and that the indications for elective neck dissection should be re-evaluated in that light.

Topics: 9,10-Dimethyl-1,2-benzanthracene; Animals; Biopsy; Carcinogens; Carcinoma, Squamous Cell; Cricetinae; Elective Surgical Procedures; Humans; Incidence; Keratins; Lymph Node Excision; Lymphatic Metastasis; Male; Mesocricetus; Neck; Neoplasm Invasiveness; Neoplasm Staging; Prospective Studies; Risk Factors; Tongue Neoplasms

Fas antigen is a cell-surface protein that transduces an apoptotic signal from the cell surface into the cytoplasm. The localization of Fas antigen in human oral squamous cell carcinoma (SCC) was examined by immunohistochemistry using a monospecific polyclonal antibody with a high titre. This antibody, designated as Fas D, was raised against a synthetic polypeptide segment corresponding to a specific extracellular domain of human Fas antigen (aa 104-114). Thirty-eight specimens of oral SCCs were stained with Fas D antibody and 26 (68%) reacted intensely. The specimens were graded as 'well', 'moderately', or 'poorly differentiated', according to the histopathological criteria. Out of 24 cases of the well differentiated tumours examined, 22 had reacted to Fas staining. The tumour cells formed nests that encompassed keratin pearls; staining was confined to cytoplasmic granules of peripheral cells. Among the moderately differentiated tumours, 4 out of 11 cases had reacted to Fas staining. No Fas-positive cells were observed in the poorly differentiated tumours, but only three specimens were examined. The expression of Fas antigen seems to be related to the degree of tumour differentiation.

Topics: Aged; Antibodies; Apoptosis; Carcinoma, Squamous Cell; Cell Differentiation; Cell Membrane; Coloring Agents; Cytoplasm; Cytoplasmic Granules; fas Receptor; Gene Expression Regulation, Neoplastic; Humans; Immunoenzyme Techniques; Immunoglobulin G; Immunohistochemistry; Keratins; Middle Aged; Mouth Neoplasms

We investigated the differences of Fourier transform infrared (FTIR) spectra between oral squamous cell carcinoma (OSCC) and normal gingival epithelium (NGE) or normal subgingival tissue (NST). We used 15 specimens of OSCC which had not been treated before measurement and 10 of NGE or NST. We also used cultured oral squamous cell carcinoma (COSCC) and the tissue (MSCC) which massed for 3 months after the cultured oral squamous cell carcinoma was transplanted into the lower back of a rat. Those tissue spectra were compared with the purified human collagens and human keratin. One half of every tissue specimen was measured with FTIR and the other half was investigated histologically. The differences of FTIR spectra between OSCC and NGE were observed in the bands between 1431 and 1482 cm(-1) and between 1183 and 1274 cm(-1). The shoulder at 1368 cm(-1) tended to disappear in OSCC, and the peaks at 1246 and 1083 cm(-1) found in NGE tended to shift to those at 1242 and 1086 cm(-1) in OSCC, respectively. The infrared spectrum of NST was noticed to be strongly influenced by the presence of collagen. Significant differences were also observed in the second derivative FTIR spectra between OSCC and NGE. Our data suggested that this infrared technique is applicable to clinical diagnostics.

Topics: Adolescent; Adult; Age Factors; Aged; Animals; Carcinoma, Squamous Cell; Cells, Cultured; Collagen; Epithelium; Female; Gingiva; Humans; Keratins; Male; Middle Aged; Mouth Mucosa; Mouth Neoplasms; Rats; Reference Values; Sex Factors; Spectroscopy, Fourier Transform Infrared; Tumor Cells, Cultured

Serum concentrations of Cyfra 21-1, a soluble cytokeratin fragment, were evaluated in 157 healthy patients, 66 patients with benign ear, nose or throat disease, and 102 patients with untreated epidermoid carcinoma of the head and neck. The technique had a sensitivity of 53.9% and specificity of 98.4% for a cutoff value of 1.5 ng/ml. Cyfra 21-1 levels differed significantly with tumor location (p < 0. 005) and tumor stage (p < 0.005), but not with the degree of histological differentiation.

Topics: Antigens, Neoplasm; Biomarkers, Tumor; Carcinoma, Squamous Cell; Head and Neck Neoplasms; Humans; Keratin-19; Keratins; Sensitivity and Specificity

Based on results from evaluation of tissue sections from premalignant lesions of the uterine cervix, the authors examined the hypothesis that immunostaining of Papanicolaou-stained cytologic smears with monoclonal antibodies to keratins 8 and 17 allows detection of cervical intraepithelial neoplasia (CIN) with progressive potential. They also investigated whether detection of these two keratin subtypes could be of help in the analysis of normal and/or poor quality cytology smears.. Sixty-one Papanicolaou-stained smears, representing 25 normal smears, 8 CIN 1, 7 CIN 2, 18 CIN 3, and 3 cervical carcinomas, were stained with CAM 5.2 and E3, which are capable of detecting keratin 8 and 17, respectively. The percentages of immunoreactive normal, metaplastic, dysplastic, and malignant epithelial cells were determined.. In normal cervical smears, keratin 8 was detected in endocervical columnar cells and sporadically in immature squamous metaplastic cells. Keratin 17 was identified in reserve cells and frequently in immature squamous metaplasic cells. In CIN, the number of cases in which keratin 8 was present increased with the severity of the lesion. Keratin 17 was found in the majority of CIN lesions, irrespective of grade. Intensity of immunostaining and number of cells stained per lesion varied and were also not related to the severity of CIN.. The use of the keratin 8 antibody in normal cervical smears enabled the detection of endocervical cells in cases where they were thought to be absent, particularly in cases with severe inflammation. Staining with keratin 17 enabled the identification of reserve cells or immature metaplastic cells, which were often misinterpreted as parabasal cells. The application of antibodies to these subtypes of keratins in cervical cytology can to a certain extent help in the identification of CIN and may in future be tested in automated screening.

Topics: Carcinoma, Squamous Cell; Cervix Uteri; Cytodiagnosis; Diagnosis, Differential; Epithelial Cells; Feasibility Studies; Female; Humans; Immunohistochemistry; Keratin-7; Keratins; Papanicolaou Test; Uterine Cervical Dysplasia; Uterine Cervical Neoplasms; Vaginal Smears

The purpose of this study is to better estimate the true incidence of occult regional metastases associated with stage I and II squamous cell carcinoma of the oral cavity. The clinical and prognostic significance of micrometastatic disease discovered by cytokeratin immunoperoxidase reactivity in the previously pathologically N0 neck is also evaluated.. Forty patients treated between 1985 and 1996 with T1 or T2 squamous cell carcinoma of the lip and oral cavity were studied. All had primary surgical treatment including functional neck dissection. No metastases were demonstrated on hematoxylin and eosin microscopy. All specimens were reexamined with immunoperoxidase staining for cytokeratin.. Five percent of patients had micrometastatic disease. Retrospective analysis of patients with a minimum follow-up of 2 years has failed to show a statistically significant association between a positive cytokeratin analysis and poor locoregional control or overall survival.. Results suggest that the true incidence of occult metastases with carcinoma of the oral cavity is significantly higher than previously documented. However, the prognostic significance of these findings remains unclear.

Topics: Adult; Aged; Carcinoma, Squamous Cell; Female; Head and Neck Neoplasms; Humans; Immunoenzyme Techniques; Incidence; Keratins; Male; Middle Aged; Mouth Neoplasms; Neck Dissection; Neoplasm Staging; Prognosis; Retrospective Studies; Survival Analysis

Primary squamous cell carcinoma of the breast is a rare clinical entity. Two large review series found only five cases out of a total of 8351 breast malignancies. This case report presents a patient with metaplastic, pseudoangiosarcomatous carcinoma or acantholytic variant of a squamous cell carcinoma of the breast. This diagnosis was based on the histological finding of highly atypical, acantholytic squamous cells. Because the tumor stained positive for keratin and negative for factor VIII, the diagnosis of angiosarcoma was ruled out. Although only scattered case reports have been published on this histological variant, these tumors tend to follow an aggressive course.

Topics: Acantholysis; Breast Neoplasms; Carcinoma, Squamous Cell; Female; Humans; Keratins; Middle Aged

The cytokine interferon-beta is a regulator of cell replication and function, including invasion and induction of angiogenesis. The goal of this study was to determine whether the expression of interferon-beta by cells in the epidermis correlated with terminal differentiation. In situ hybridization analysis and immunohistochemical staining of formalin-fixed, paraffin-embedded specimens of normal human and murine epidermis and human and murine skin tumors of epithelial origin revealed that only differentiated, nondividing cells of the epidermis expressed interferon-beta protein. Keratinocyte cultures established from the epidermis of 3 d old mice were maintained under conditions permitting continuous cell division or induction of differentiation. Continuously dividing cells did not produce interferon-beta whereas nondividing differentiated cells expressing keratin 1 did. Growth-arrested, undifferentiated keratinocytes also expressed interferon-beta protein. Neutralizing interferon-beta in the culture medium inhibited differentiation, but the addition of exogenous interferon-beta did not stimulate differentiation. These data indicate that interferon-beta is produced by growth-arrested, terminally differentiated keratinocytes.

Topics: Animals; Antibodies; Calcium; Carcinoma, Squamous Cell; Cell Differentiation; Cell Division; Cells, Cultured; Epidermal Cells; Epidermis; Fluorescent Antibody Technique; Humans; Immunohistochemistry; Interferon-beta; Keratin-14; Keratinocytes; Keratins; Membrane Proteins; Mice; Mice, Inbred BALB C; Mice, Transgenic; Skin Neoplasms; Time Factors

The preventive effects of retinoids on oral carcinogenesis may be related to their ability to modulate the growth and differentiation of human oral squamous epithelial cells. Nuclear retinoid receptors (RAR alpha, beta, and gamma, and RXR alpha, beta, and gamma) may mediate these effects by regulating gene transcription. The removal of serum from the growth medium of two head and neck squamous cell carcinoma lines 1483 and SqCC/Y1 resulted in a decrease in RAR beta mRNA level and concurrent increases in the expression of the keratin K1 and transglutaminase type I (TGase I), which are markers of differentiation of keratinizing squamous epithelial cells. All-trans-retinoic acid (tRA) or 13-cis-RA increased RAR beta and decreased K1 and TGase I mRNA levels in serum-free medium. Transcriptional activation of reporter genes by means of retinoid response elements (RARE and RXRE) indicated that the RXR-RAR pathway predominates over the RXR homodimer pathway in the 1483 cells. Among several synthetic retinoids with preference for binding to specific nuclear retinoid receptors, those that induced RAR beta also suppressed K1. The inverse association between RAR beta expression and K1 and TGase I levels implicates this receptor in suppression of keratinization in oral epithelial cells.

Topics: Biomarkers, Tumor; Carcinoma, Squamous Cell; Cell Differentiation; Cell Division; Collagenases; Dose-Response Relationship, Drug; Gene Expression Regulation, Neoplastic; Head and Neck Neoplasms; Humans; Keratins; Promoter Regions, Genetic; Receptors, Retinoic Acid; Response Elements; Retinoid X Receptors; Retinoids; Transcription Factor AP-1; Transcription Factors; Transcription, Genetic; Transcriptional Activation; Tretinoin; Tumor Cells, Cultured

We report four cases of an unusual cutaneous squamo-melanocytic neoplasm with histological features of malignancy and uncertain biological potential. These tumors developed on the face of middle-aged and older adults. Clinically, a purple-black nodule ranged in size from 3 to 10 mm in maximum diameter. After complete excision, neither recurrence nor metastasis has been observed (mean follow-up time, 3.25 years). Histologically, a discrete dermal nodule surrounded by a fibroblastic stroma was composed of large islands of mitotically active atypical epithelioid cells. The nodule was not connected to the epidermis in three of four cases. Two types of cells were either diffusely admixed or clustered in small groups within the nodule. Small, atypical, epithelioid cells containing finely granular brown pigment, proven to be melanin, constituted the first cell type. The second type consisted of atypical squamoid cells, some with abundant pink cytoplasm, giving rise to squamous pearls. A lentigo maligna was present in one case. The remaining three cases had neither significant intraepidermal melanocytic nor keratinocytic atypia. Immunohistochemical studies indicated that the melanin-containing epithelioid cells expressed S-100 antigens, and the squamoid cells expressed cytokeratins. A small population of tumor cells did not label with either of the antibodies. These four tumors (along with a previously reported, apparently identical tumor arising in the setting of lentigo maligna) represent a unique biphasic dermal neoplasm with histological features of malignancy but, at this time, uncertain biological behavior. Although none have recurred or metastasized, the follow-up time is too short in our estimation to guarantee a benign course. These neoplasms are easily recognized by their characteristic features. Further follow-up evaluations should allow determination of their biologic potential.

Topics: Adult; Aged; Antigens, Neoplasm; Carcinoma, Squamous Cell; Face; Female; Humans; Hutchinson's Melanotic Freckle; Immunohistochemistry; Keratins; Male; Melanoma; Melanoma-Specific Antigens; Middle Aged; Neoplasm Proteins; S100 Proteins; Skin Neoplasms

Topics: Carcinoma, Squamous Cell; Evaluation Studies as Topic; Female; Humans; Immunoenzyme Techniques; Keratins; Uterine Cervical Neoplasms

The present study was designed to clarify the mechanism by which some lung cancer cell lines can produce cytokeratin 19 (CK19) fragment and others cannot. We hypothesized that some lung cancer cell lines which cannot release CK19 express an incomplete sequence of CK19 mRNA. Expression of mRNA was evaluated by RT-PCR using several primer pairs for CK19. CK19 in the culture supernatant was measured by an immuno-radiometric assay. CK19 protein synthesis was evaluated by Western immunoblot and immunohistochemistry. Among 16 lung cancer cell lines, 7 released significant amounts of CK19 in the supernatant. In some cell lines, expression of CK19 mRNA was observed only in some combinations of primers, suggesting that incomplete mRNA was expressed. 3'-RACE analysis detected amplified products of a shorter size compared with normal amplified products in cell lines which expressed incomplete CK19 mRNA, suggesting that 3'-ends of mRNA for CK19 were deleted. Results of Western immunoblot and immuno-histochemical staining using anti-human CK19 monoclonal antibody completely correlated with the results on CK19 levels in culture supernatants as well as with complete expression of mRNA. We conclude that levels of CK19 closely relate to the expression of complete mRNA for CK19.

Topics: Adenocarcinoma; Carcinoma, Small Cell; Carcinoma, Squamous Cell; DNA Primers; Gene Expression Regulation, Neoplastic; Humans; Keratins; Lung Neoplasms; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Transcription, Genetic; Tumor Cells, Cultured

A resected esophagus with numerous heterotopic sebaceous glands was examined in an attempt to determine whether esophageal heterotopic sebaceous glands are the result of a metaplastic process or a congenital anomaly. The present case concerns a 79-year-old Japanese man with numerous esophageal heterotopic sebaceous glands accompanied by superficial esophageal cancer. The resected esophagus possessed numerous heterotopic sebaceous glands, which could be seen clearly as slightly elevated, yellowish lesions. Histological examination of these glands, all of which were located in the lamina propria, revealed lobules of cells that showed characteristic sebaceous differentiation. Bulbous nests of proliferating basal cells showing sebaceous differentiation were occasionally observed in the esophageal epithelium. Of the antibodies against six different keratins used, only anti-keratin 14 labeled both the heterotopic sebaceous glands and the bulbous nests. Acquired metaplastic change of the esophageal epithelium is probably the pathogenetic mechanism involved in these unusual lesions.

Topics: Aged; Carcinoma, Squamous Cell; Choristoma; Esophageal Diseases; Esophageal Neoplasms; Humans; Immunohistochemistry; Keratin-14; Keratins; Male; Metaplasia; Sebaceous Glands

Diagnosis of sebaceous carcinoma of the periorbital region is often delayed. Clinically, this lesion can mimic several inflammatory disorders. Histopathologically, it can mimic either squamous cell or basal cell carcinoma.. To identify an immunohistochemical approach to assist in the diagnosis of periorbital sebaceous carcinoma.. The immunohistochemical profiles of several cases of periorbital sebaceous, basal cell, and squamous cell carcinoma were examined.. Although at least focal epithelial membrane antigen (EMA) staining can effectively distinguish sebaceous carcinoma (10 of 11 were positive) from basal cell carcinoma (1 of 16 were positive), most squamous cell carcinomas examined were also focally EMA positive (11 of 14). However, Cam 5.2 reactivity was seen in most sebaceous carcinomas (8 of 11) but no squamous cell carcinomas (0 of 14). In addition, at least focal BRST-1 reactivity was also seen in most sebaceous carcinomas (7 of 11) but no basal cell carcinomas (0 of 16).. Periorbital sebaceous, basal cell, and squamous cell carcinomas have different immunohistochemical staining profiles; a panel of commonly available antibodies, including anti-EMA, BRST-1, and Cam 5.2, may help distinguish these diseases from each other when that distinction cannot be clearly made by light microscopy alone.

Topics: Adenocarcinoma, Sebaceous; Adult; Aged; Aged, 80 and over; Antigens, Neoplasm; Biomarkers, Tumor; Carcinoma, Basal Cell; Carcinoma, Squamous Cell; Conjunctival Neoplasms; Diagnosis, Differential; Eyelid Neoplasms; Female; Glycoproteins; Humans; Immunoenzyme Techniques; Keratins; Male; Middle Aged; Mucin-1

Squamous cell carcinoma (SCC) of the head and neck is the sixth most frequent cancer worldwide. The survival rate is among the lowest of the major cancers and has not improved significantly in the past two decades. Extensive local invasion and regional lymph node metastasis are, in large part, responsible for the poor clinical outcome of these tumors. Keratin intermediate filaments are the most abundant cytoskeletal proteins in SCCs and regulate the migration of normal and transformed epithelial cells. Previous studies have shown that expression of the 40-kDa keratin K19 is dysregulated in SCCs arising from oral epithelium. Immunohistochemical experiments demonstrated that, while normal epithelium and dysplastic lesions expressed abundant K19 protein, invasive SCCs exhibited a patchy or negative staining pattern. We subsequently determined that K19 expression was consistently downregulated in seven SCC lines compared with normal epithelium. We therefore wanted to determine if K19 downregulation affected the invasive phenotype of these cells. We found that SCC lines which do not express K19 are significantly more invasive in vitro than those which retain expression of this gene. Stable expression of the K19 cDNA in K19 negative cell lines altered cell morphology and intercellular adhesiveness, and significantly decreased the number of cells able to migrate through a reconstituted basement membrane. Reduced invasiveness was not due to decreased metalloproteinase activity in the K19-expressing clones. We conclude that K19 overexpression in oral SCCs decreases their invasive potential by diminishing migratory capability.

Topics: Basement Membrane; Blotting, Western; Carcinoma, Squamous Cell; Cell Adhesion; Cell Line, Transformed; Cell Movement; Coloring Agents; DNA, Complementary; Down-Regulation; Electrophoresis, Polyacrylamide Gel; Epithelial Cells; Fluorescent Antibody Technique; Gene Expression Regulation, Enzymologic; Gene Expression Regulation, Neoplastic; Humans; Immunohistochemistry; Intermediate Filament Proteins; Keratins; Lymphatic Metastasis; Metalloendopeptidases; Mouth Mucosa; Mouth Neoplasms; Neoplasm Invasiveness; Prognosis; Survival Rate; Tumor Cells, Cultured

To determine the clinical efficacy of serum concentration of cytokeratin 19 fragment (CYFRA 21-1), sera from 66 patients with oesophageal squamous cell carcinoma were examined, and 54 surgically resected specimens were immunohistochemically stained for cytokeratin 19 (CK-19). The patients with positive CK-19 staining in the tissues of their carcinomas had significantly higher serum CYFRA 21-1 levels compared with those with negative CK-19 staining. When the cut-off value was defined as 2.0 ng/mL, CYFRA 21-1 had a higher positive ratio than that of either squamous cell carcinoma antigen (SCC-Ag) or carcinoembryonic antigen (CEA). Serum CYFRA 21-1 level increased significantly along with the clinical stages. In addition, serum CYFRA 21-1 level served as a prognostic factor for patients with oesophageal carcinoma after surgery, whilst SSC-Ag and CEA is not connected with the outcome. These findings suggest that the serum CYFRA 21-1 probably originated from the tumour tissue is an important marker for determining the stage and outcome of oesophageal carcinoma.

Topics: Adult; Aged; Antigens, Neoplasm; Biomarkers, Tumor; Carcinoembryonic Antigen; Carcinoma, Squamous Cell; Esophageal Neoplasms; Female; Humans; Immunohistochemistry; Keratin-19; Keratins; Male; Middle Aged; Neoplasm Staging; Prognosis; Retrospective Studies; Serpins

The development of aneuploid clones from diploid progenitor cells is a regular characteristic of head and neck squamous cell carcinoma progression. While the significance of aneuploidy formation for the acquisition of invasive and metastatic behavior is well documented, little is known about the contribution of diploid tumor cells after aneuploid clones have emerged. To distinguish diploid cells of epithelial origin from benign cellular components, we applied multiparameter flow cytometry of DNA content and cytokeratin (CK) expression to 36 primary tumors. Twenty-seven carcinomas accommodated aneuploid cell lines that stained positive for CK. All diploid cell populations obtained from aneuploid carcinomas contained CK-positive subpopulations as did all of nine tumors that consisted exclusively of diploid cells. The proportions of CK-positive diploid cells ranged between 6% and 80%, independent of whether they were achieved from entirely diploid or from aneuploid carcinomas. CK-gated diploid and aneuploid cell populations showed largely identical S-phase fractions. These results emphasize that diploid tumor cells regularly persist after the development of aneuploid clones and significantly contribute to local tumor progression. Despite the presence of diploid epithelial cells in aneuploid primary tumors, exclusively the aneuploid clones of eight corresponding lymph node metastases were CK-positive. This provides further evidence of a largely reduced metastatic potential of diploid tumor cells.

Topics: Aneuploidy; Carcinoma, Squamous Cell; Clone Cells; Diploidy; Disease Progression; Epithelial Cells; Flow Cytometry; Head and Neck Neoplasms; Humans; In Vitro Techniques; Keratins

DNA ploidy and cell-cycle distribution were determined by flow cytometry in fresh tumor tissue of 27 epithelial head and neck carcinomas. Epithelial cells were labeled with a fluorescein-isothiocyanate-conjugated cytokeratin antibody to study the possible influence of contaminating stromal and inflammatory cells on the results of cell-cycle analysis of tumor cells. The patient sample included 26 men and 1 women with a mean age of 60 years. Without cytokeratin gating, 11/27 tumors (40.74%) were aneuploid. After selecting the cytokeratin population, 10 more aneuploid tumors were found that had not been detected when considering the total population. Therefore, aneuploid tumors increased from 40.74% to 77.74%. The remaining 6/27 (22.26%) tumors were diploid. In the tumors that were either aneuploid without cytokeratin gating or diploid, the S-phase and G2M phase were significantly higher after cytokeratin staining, specially in diploid tumors (24.2% versus 10% and 6.8% versus 3.2%, respectively, p < 0.01). Therefore, in head and neck tumors cytokeratin staining optimizes both the determination of DNA ploidy and cell-cycle analysis, which is advantageous for tumor staging and prognosis assessment in these patients.

Topics: Adult; Aged; Antibodies, Monoclonal; Antibodies, Neoplasm; Carcinoma, Squamous Cell; Diploidy; DNA, Neoplasm; Female; Flow Cytometry; Head and Neck Neoplasms; Humans; Interphase; Keratinocytes; Keratins; Male; Middle Aged; Quantitative Trait, Heritable

The serum concentrations of three separate tumor markers, squamous cell carcinoma antigen (SCC Ag), carcinoembryonic antigen (CEA) and Cyfra 21-1 were clinically correlated in 86 randomly selected patients with squamous cell carcinoma involving the head and neck. Positive findings for each tumor marker were totalled and statistically analysed. The upper limits of normal for SCC Ag, CEA and Cyfra 21-1 were set at 1.5, 2.5 and 2.0 ng/ml, respectively. Positivity rates were 20.6% for SCC Ag, 14.0% for CEA and 41.7% for Cyfra 21-1. Elevated Cyfra 21-1 concentrations correlated somewhat with age, whereas elevated CEA levels correlated with the site of tumor involvement. Overall, Cyfra 21-1 appeared to be the most useful marker in head and neck squamous cell carcinoma.

Topics: Aged; Antigens, Neoplasm; Biomarkers, Tumor; Carcinoembryonic Antigen; Carcinoma, Squamous Cell; Female; Head and Neck Neoplasms; Humans; Immunoenzyme Techniques; Keratin-19; Keratins; Male; Middle Aged; Radioimmunoassay; Random Allocation; Serpins

To be informative for chemoprevention, animal models must both closely emulate human disease and possess surrogate endpoint biomarkers that facilitate rapid drug screening. This study elucidated site-specific histopathological and biochemical surrogate endpoint biomarkers of spontaneous epidermal carcinogenesis in K14-HPV16 transgenic mice and demonstrated that the incidence and severity of these markers were decreased by the ornithine decarboxylase (ODC) inhibitor difluoromethylornithine (DFMO). The cumulative incidence of visible epidermal cancers in 127 untreated transgenic mice was 42% by 52 weeks of age, most frequently affecting the chest as flat lesions in association with chronic ulcers, or in the ear as protuberant masses. Microscopic malignancies were detected in 39% of 32-week-old transgenic mice and were found to emerge from precursor lesions that were of two distinct types: dysplastic sessile ear papillomas and hyperproliferative follicular/interfollicular chest dysplasias. ODC activity and tissue polyamine contents were differentially elevated in ear and chest skin during carcinogenesis, such that there was a marked elevation of both parameters of polyamine metabolism as early as 4 weeks of age in the ear, whereas in the chest, polyamine metabolism was increased significantly only in the late stages of neoplastic progression and in epidermal cancers. Administration of 1.0% DFMO in the drinking water from 4 to 32 weeks of age prevented both visible and microscopic malignancies and significantly decreased the incidence of chest and ear precursor lesions. ODC activity and tissue putrescine content were markedly diminished by DFMO chemoprevention in ear skin, whereas there was a more modest decline of these parameters in chest skin. DFMO treatment of transgenic mice from 28 to 32 weeks of age was associated with an absence of ear cancer and a marked regression of dysplastic papillomas. In contrast, the results in chest skin were complex in that the severity of chest precursors diminished, but their incidence was unchanged, and microscopic cancers were still detectable within these lesions. Collectively, this study highlights the utility of multistage epidermal carcinogenesis in K14-HPV16 transgenic mice both for the study of the biology of, and as a screening tool for, novel drugs and chemopreventive regimens.

Topics: Administration, Oral; Animals; Anticarcinogenic Agents; Carcinoma, Squamous Cell; Disease Progression; DNA Replication; Ear; Eflornithine; Epidermis; Gene Expression Regulation; Genes, Viral; Keratin-14; Keratins; Mice; Mice, Transgenic; Neoplasm Proteins; Organ Specificity; Ornithine Decarboxylase Inhibitors; Papilloma; Papillomaviridae; Precancerous Conditions; Putrescine; Skin Diseases; Skin Neoplasms; Thorax; Transgenes

Carcinogenesis involves the accumulation of genetic changes within a single cell. Tumor promotion functions in the initial clonal expansion of an initiated cell but is generally not considered to influence later stages. To investigate whether tumor promotion can influence later stages of carcinogenesis we developed a two-hit 7, 12-dimethylbenz[a]anthracene (D) protocol designed to enrich for keratinocytes that contain at least two D-induced genetic alterations. FVB/N mice were initiated with D and promoted with 12-O-tetradecanoylphorbol-13-acetate (T) or treated with acetone (A) vehicle for 6 weeks. At 7 weeks after the start of promotion, but before visible papilloma development, groups of mice were treated with a second dose of D or A and 1 week later T promotion was resumed. D/T/A/T mice developed 2.8 papillomas/mouse and D/A/D/T mice demonstrated an additive tumor response and developed 5.8 papillomas/mouse. Importantly, D/T/D/T mice developed 12.4 papillomas/mouse, thereby demonstrating a synergistic tumor response compared with D/A/D/T and D/T/A/T mice. D/T/D/T papillomas exhibited increases in suprabasal S phase cells and keratin 13 expression when compared with D/T/A/T papillomas. D/T/D/T mice developed squamous cell carcinomas (SCCs) 10 weeks earlier than D/T/A/T mice and demonstrated a 96% malignancy incidence and 1.71 SCC/mouse compared with D/T/A/T mice, which demonstrated a 28% malignancy incidence and 0.32 SCC/mouse. Greater than 90% of D/T/A/T and D/T/D/T papillomas and SCCs contained mutant Ha-ras, while a normal Ha-ras allele persisted in all cases, indicating that a gene other than the remaining normal allele of Ha-ras was a target gene for the second D hit. These data demonstrate that: (i) promotion between the first and second hits has a profound outcome on carcinogenesis, presumably by increasing the probability that a second hit will occur in a previously initiated cell; (ii) continued promotion after the second hit is required for full expression of malignancy; (iii) the classic initiation-promotion protocol can be extended to a multihit, multistage model.

Topics: 9,10-Dimethyl-1,2-benzanthracene; Acetone; Animals; Carcinogens; Carcinoma, Squamous Cell; Cell Transformation, Neoplastic; Cocarcinogenesis; DNA Mutational Analysis; DNA, Neoplasm; Female; Gene Expression Regulation, Neoplastic; Genes, ras; Keratinocytes; Keratins; Mice; Models, Biological; Neoplasm Proteins; Papilloma; Polymerase Chain Reaction; Polymorphism, Single-Stranded Conformational; S Phase; Skin Neoplasms; Tetradecanoylphorbol Acetate

We explored the hypothesis that the chemotactic migration of carcinoma cells that assemble hemidesmosomes involves the activation of a signaling pathway that releases the alpha6beta4 integrin from these stable adhesion complexes and promotes its association with F-actin in cell protrusions enabling it to function in migration. Squamous carcinoma-derived A431 cells were used because they express alpha6beta4 and migrate in response to EGF stimulation. Using function-blocking antibodies, we show that the alpha6beta4 integrin participates in EGF-stimulated chemotaxis and is required for lamellae formation on laminin-1. At concentrations of EGF that stimulate A431 chemotaxis ( approximately 1 ng/ml), the alpha6beta4 integrin is mobilized from hemidesmosomes as evidenced by indirect immunofluorescence microscopy using mAbs specific for this integrin and hemidesmosomal components and its loss from a cytokeratin fraction obtained by detergent extraction. EGF stimulation also increased the formation of lamellipodia and membrane ruffles that contained alpha6beta4 in association with F-actin. Importantly, we demonstrate that this mobilization of alpha6beta4 from hemidesmosomes and its redistribution to cell protrusions occurs by a mechanism that involves activation of protein kinase C-alpha and that it is associated with the phosphorylation of the beta4 integrin subunit on serine residues. Thus, the chemotactic migration of A431 cells on laminin-1 requires not only the formation of F-actin-rich cell protrusions that mediate alpha6beta4-dependent cell movement but also the disruption of alpha6beta4-containing hemidesmosomes by protein kinase C.

Topics: Actins; Antigens, Surface; Carbazoles; Carcinoma, Squamous Cell; Cell Membrane; Cell Size; Chemotaxis; Desmosomes; Enzyme Activation; Epidermal Growth Factor; ErbB Receptors; Humans; Indoles; Integrin alpha6beta4; Integrins; Keratins; Laminin; Phosphorylation; Phosphoserine; Phosphotyrosine; Protein Kinase C; Pseudopodia; Signal Transduction; Tumor Cells, Cultured

Dissemination of single tumor cells to the bone marrow is a common event in cancer. The clinical significance of cytokeratin-positive cells detected in the bone marrow of cancer patients is still a matter of debate. In gastric cancer, overexpression of the receptor (uPAR or CD87) for the serine protease urokinase-type plasminogen activator (uPA) in disseminated cancer cells indicates shorter survival of cancer patients. A new immunofluorescence approach, applying confocal laser scanning microscopy, is introduced to locate CD87 antigen in cytokeratin-positive tumor cells and to quantify the CD87 antigen by consecutive scanning. At first, cytokeratin 8/18/19-positive carcinoma cells are identified at excitation wavelength 488 nm using monoclonal antibody A45B/B3 to the cytokeratins and goat anti-mouse IgG labeled with the fluorochrome Alexa488. Next, CD87 in tumor cells is identified by chicken antibody HU277 to the uPA-receptor and goat anti-chicken IgY labeled with fluorochrome Alexa568 (excitation wavelength 568 nm) and the fluorescence signal quantified on a single cell basis using fluorescently labeled latex beads as the fluorescence reference. From 16 patients with gastric or esophageal carcinoma, bone marrow aspirates were obtained, stained for cytokeratins and CD87 and then subjected to laser scanning fluorescence microscopy. Three of six gastric cancer patients had tumor cells present in the bone marrow of which 2 stained for CD87. Three of ten esophageal carcinoma patients had tumor cells in the bone marrow, all three samples stained for CD87. CD87-positive tumor cells were also dissected from stained bone marrow aspirates by laser microdissection microscope to allow analysis of single cells at the gene level.

Topics: Adenocarcinoma; Adult; Aged; Bone Marrow Examination; Bone Marrow Neoplasms; Carcinoma, Squamous Cell; Esophageal Neoplasms; Fluorescent Antibody Technique, Indirect; Humans; Immunohistochemistry; Keratins; Microscopy, Confocal; Middle Aged; Plasminogen Activators; Predictive Value of Tests; Receptors, Cell Surface; Receptors, Urokinase Plasminogen Activator; Sensitivity and Specificity; Stomach Neoplasms; Tumor Cells, Cultured

Human chorionic gonadotropin (beta-hCG) has been detected within tissue homogenates, culture fluid, and sera of patients with squamous cell carcinoma of the cervix. Studies regarding in vivo localization of beta-hCG in squamous cell carcinoma of the cervix are scant and conflicting. Cervical samplings (biopsy and/or curettage specimens) of 63 cases of poorly differentiated invasive squamous cell carcinoma of the cervix were initially stained by the immunoperoxidase technique for the presence of beta-hCG and human placental lactogen (hPL). Based on beta-hCG reactivity, patients were divided into beta-hCG-positive and beta-hCG-negative groups. Thirty-three of the 63 (52%) cases showed localization of beta-hCG in tumor cells. Subsequent specimens of patients, who underwent surgical treatment, were likewise examined for beta-hCG reactivity. These surgical specimens showed focal beta-hCG reactivity in the beta-hCG-positive group only. The beta-hCG reactivity was seen in both high-grade SIL (CIN III), invasive squamous cell carcinoma, and its metastases. The focal beta-hCG reactivity was predominantly confined to the peripheral tumor cells at the stromal-epithelial interface in noninvasive and invasive lesions. Intensity of immunostaining was moderate to strong. The beta-hCG staining was observed in different cancer stages and in various age groups. No hPL reactivity was seen in any cases. Poorly differentiated squamous cell carcinoma of uterine cervix showing immunoreactivity for beta-hCG should be distinguished from choriocarcinoma and other trophoblastic tumors.

Topics: Adult; Aged; Carcinoma, Squamous Cell; Chorionic Gonadotropin, beta Subunit, Human; Female; Humans; Immunohistochemistry; Keratins; Middle Aged; Retrospective Studies; Uterine Cervical Neoplasms

It has been reported that cytokeratin 8 (CK8) is expressed in all non-small-cell lung cancers (NSCLC). We hypothesized that antigenic changes of CK8 may occur in some NSCLC cell lines. To prove this, Western immunoblot analysis using anti-human CK8 monoclonal antibodies as well as immunohistological staining of CK8 were performed in NSCLC cell lines. As a result, CK8 which had a higher molecular weight than recombinant CK8 was demonstrated in two of eight NSCLC cell lines. In addition, this CK8 contained antigenic epitopes of CA19-9. This CK8 with higher molecular weight, may have played a role in the process of invasion or metastasis of NSCLC.

Topics: Adenocarcinoma; Animals; Blotting, Western; CA-19-9 Antigen; Carcinoma, Non-Small-Cell Lung; Carcinoma, Squamous Cell; Carrier Proteins; Humans; Immunohistochemistry; Keratins; Lung Neoplasms; Molecular Weight; Neoplasm Proteins; Rabbits; Tumor Cells, Cultured

Salivary duct carcinoma is a highly malignant adenocarcinoma of salivary origin. Its pathologic features are distinct from the other salivary gland tumors and bear a remarkable histologic resemblance to ductal breast carcinoma. The clinical course is rapid and the prognosis is dismal. Aggressive therapy is warranted, including primary tumor resection, cervical neck dissection, and radiotherapy. We present a case of salivary duct carcinoma of parotid origin with a very long-term evolution in clear contrast to its supposed aggressiveness. Tumor cells expressed low- and high-molecular-weight cytokeratins, epithelial membrane antigen, carcinoembryonic antigen, and c-erbB-2 but not estrogen and progesterone receptors, actin, and S-100.

Topics: Aged; Carcinoembryonic Antigen; Carcinoma, Squamous Cell; Humans; Immunoenzyme Techniques; Keratins; Male; Mucin-1; Neck Dissection; Neoplasm Invasiveness; Parotid Neoplasms; Radiotherapy, Adjuvant; Receptor, ErbB-2; Salivary Ducts

Cytokeratin (CK) alterations have been reported in carcinomas from different anatomical sites, and these have been associated with specific aspects of tumour behaviour. In order to assess the relationships between CK modifications and future tumour behaviour, we conducted the present prospective study on 26 squamous cell carcinomas (SCC) of oral and pharyngeal mucosae and corresponding controls. Cytokeratins were investigated using two-dimensional gel electrophoresis and immunofluorescence techniques. All healthy tissues, oral lining and oropharyngeal mucosae, expressed the oesophageal type CKs, including CK 19. Other simple epithelial CKs (7, 8, 17 and 18) were not detected. In carcinomas originating from corresponding sites, expression of oesophageal CKs varied widely from one specimen to another, and simple epithelial keratins were often found. Statistical analysis indicated correlations between CK expression and the clinicopathological data of SCC patients. Small tumour size was strongly associated with the expression of CKs 10 and 19. Interestingly, an absence of lymph node involvement was significantly associated with CK 18 expression. Tumours giving rise to recurrences, metachronous tumours, and distant metastasis were significantly associated with an absence of CK 13. These results suggest that CKs 10, 19, 18 and 13 could be reliable diagnostic and prognostic markers in the assessment of oral and pharyngeal squamous carcinomas.

Topics: Adult; Aged; Biomarkers, Tumor; Carcinoma, Squamous Cell; Case-Control Studies; Chi-Square Distribution; Disease Progression; Electrophoresis, Gel, Two-Dimensional; Female; Fluorescent Antibody Technique, Indirect; Humans; Keratins; Male; Middle Aged; Molecular Weight; Mouth Mucosa; Mouth Neoplasms; Neoplasm Metastasis; Neoplasm Proteins; Neoplasm Recurrence, Local; Pharyngeal Neoplasms; Prognosis; Prospective Studies

We report the first documented case of undifferentiated carcinoma of the renal pelvis with a prominent lymphoid stroma (lymphoepithelioma-like carcinoma [LELC]). LELCs are morphologically identical to nasopharyngeal carcinoma and are rarely seen in the urinary tract, with only isolated cases involving the urinary bladder and ureter. The tumor was composed entirely of large pale staining malignant epithelial cells with ill-defined borders arranged in syncytial sheets separated by mainly reactive lymphocytes, occasional plasma cells and histiocytes. Tumor cells were immunoreactive to cytokeratin and were negative for leukocyte common antigen. Awareness of LELC is important, as it should be distinguished from lymphoma or inflammatory lesions including, xanthogranulomatous pyelonephritis.

Topics: Aged; Carcinoma, Squamous Cell; Female; Humans; Immunohistochemistry; Keratins; Kidney Neoplasms; Kidney Pelvis; Leukocyte Common Antigens; Tomography, X-Ray Computed

Topics: Adenocarcinoma; Carcinoma, Squamous Cell; Female; Humans; Keratins; Uterine Cervical Neoplasms

This study is designed to assess gene expression of squamous cell carcinoma antigen (SCCA) mRNA to detect micrometastases in cervical lymph nodes (LNs) of head and neck cancer. We examined the expression of SCCA mRNA in 12 primary tumors and 212 cervical LNs (101 LNs taken from 8 patients with tongue cancer, 71 from 7 patients with gingival cancer, 19 from 2 patients with laryngeal cancer, 9 from 2 patients with pharyngeal cancer, 7 from 1 patient with cancer of the buccal mucosa, and 5 from 1 patient with cancer of floor of the mouth). Detectability of metastatic LNs by nested and single reverse transcriptase-polymerase chain reaction (RT-PCR) was compared with semiserial sections (hematoxylin-eosin staining and keratin immunostaining). All primary tumors expressed SCCA mRNA. Of 198 histologically metastasis-negative nodes, SCCA mRNA was detected in 37 (18.7%) by nested PCR. Eleven micrometastatic foci in 9 LNs (4.6%) were discovered by semiserial sectioning. This suggests that SCCA mRNA is a promising tumor marker for detecting the micrometastases in cervical LNs of head and neck cancer.

Topics: Antigens, Neoplasm; Biomarkers, Tumor; Biopsy; Carcinoma, Squamous Cell; False Negative Reactions; Gingival Neoplasms; Head and Neck Neoplasms; Humans; Keratins; Laryngeal Neoplasms; Lymphatic Metastasis; Microtomy; Mouth Mucosa; Neck; Neoplasm Proteins; Pharyngeal Neoplasms; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; RNA, Neoplasm; Sensitivity and Specificity; Serpins; Staining and Labeling; Tongue Neoplasms

Recently, cytokeratins (CK) were studied as tumor markers for many carcinomas. In lung cancer they appeared to be useful in distinguishing primary from secondary tumors, in histological typing as well as in evaluating patient's prognosis. However, the results have yet to be conclusive. In this study, expression of CK7, CK10/13, CK18, CK19, CK20 was investigated in a group of 72 surgically resected specimens of lung including 31 adenocarcinomas, 30 squamous cell carcinomas and 11 neuroendocrine carcinomas. Cytokeratin immunophenotypes were analyzed in comparison to histological characteristics of tumors, TNM stages and patients survival.. CK7, CK10/13 and CK18 can be used in distinguishing the lung adenocarcinomas from the lung squamous cell carcinomas: CK7(+), CK10/13(-), CK18(+) for adenocarcinomas; CK7(-), CK10/13(+), CK18(-) for squamous cell carcinomas. Relatively higher CK7 and CK18 immunostaining rates of the squamous cell carcinomas with high keratinization, with high percentage of dead cells and with late stages of disease suggested their prognostic significance but it was not confirmed when comparing different survival groups. Both adenocarcinomas and squamous cell carcinomas were stained strongly with antibody against CK19 (90.3% and 86.7% respectively) but much less with anti-CK20 antibody (9.7% and 3.3% respectively). In general, neuroendocrine tumors of the lung were non-reactive for these cytokeratins except CK18, among them all carcinoid tumors expressed CK18 abundantly.

Topics: Adenocarcinoma; Adult; Aged; Biomarkers, Tumor; Carcinoma, Squamous Cell; Diagnosis, Differential; Female; Humans; Immunohistochemistry; Keratins; Lung Neoplasms; Male; Middle Aged; Molecular Weight; Neuroendocrine Tumors

Patients with solitary rectal ulcer syndrome (SRUS) frequently present with a mass that can be misinterpreted as cancer. In contrast, the occurrence and characteristics of SRUS-like histopathology produced by underlying malignancy have not been reported in detail. We report seven patients whose rectal mass that was induced by infiltrating carcinoma showed only histopathologic changes of SRUS on initial mucosal biopsy specimens. Carcinoma was evident in subsequent specimens after one to five repeat biopsies with delay in diagnosis from 1 week to 18 months in six patients. In one patient, infiltrating carcinoma was suggested on the first biopsy specimen by immunohistochemistry for cytokeratin. Three of the patients had primary rectal adenocarcinoma, two had metastatic carcinoma from stomach or ovary, and two had direct invasion of anal squamous cell carcinoma or prostatic adenocarcinoma. We conclude that the histopathology of SRUS may occasionally represent a characteristic but nonspecific mucosal reactive change to a deeper seated malignancy. The terminology "solitary rectal ulcer syndrome/mucosal prolapse changes" with a cautionary note may be useful for reporting biopsy results to emphasize the possibility of underlying primary or metastatic malignancy in the differential diagnosis.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Biopsy; Carcinoma, Squamous Cell; Diagnosis, Differential; Female; Follow-Up Studies; Humans; Immunohistochemistry; Keratins; Male; Middle Aged; Proctoscopy; Prostate-Specific Antigen; Rectal Diseases; Rectal Neoplasms; Rectal Prolapse; Retrospective Studies; Ulcer

Topics: Carcinoma, Squamous Cell; Humans; Keratins; Male; Middle Aged; Tomography, X-Ray Computed; Urinary Bladder Neoplasms

The bcl-2 proto-oncogene is a known inhibitor of apoptosis; in normal human stratified squamous epithelium, its expression is restricted to the basal cell layer. To investigate the functional role of bcl-2 protein in the process of differentiation of oral keratinocytes, bcl-2 expression vector was transfected into SCC-25 cells, which normally undergo squamous cell differentiation in vitro while expressing specific differentiation markers, e.g., keratin 10/11 and involucrin. In bcl-2 transfected SCC-25 cells, the expression of these differentiation markers was markedly suppressed. The bcl-2 proto-oncogene may play a critical role in opposing the commitment to terminal differentiation and apoptosis of oral keratinocytes.

Topics: Apoptosis; Carcinoma, Squamous Cell; Cell Differentiation; DNA Fragmentation; Down-Regulation; Genes, bcl-2; Humans; Immunoenzyme Techniques; Keratinocytes; Keratins; Mouth Neoplasms; Protein Precursors; Proto-Oncogene Mas; Proto-Oncogene Proteins c-bcl-2; Tumor Cells, Cultured

The purpose was to evaluate the usefulness of serum Cyfra 21.1 assay for the monitoring of patients with uterine cervix cancer.. Pre-treatment sera and complete follow-up of the patients were available for SCC and Cyfra 21.1 for 79 patients Another group of 50 patients was studied to evaluate the specificity, sensitivity, negative or positive predictive values of the markers. The cut-off value for Cyfra 21.1 (1.1 ng/ml) was established by ROC curve analysis.. A positive or negative concordance between SCC and Cyfra 21.1 was observed in 65.8% of the cases. Positive SCC and negative Cyfra 21.1 were found in 22.8% of the sera, while the inverse was observed in 11.4% of the cases. The mean concentrations of SCC and Cyfra 21.1 were correlated to FIGO stages, with Cyfra 21.1 being elevated in 100% of stages III and IV. Cyfra 21.1 was also correlated with the extension of the cancer, and to the presence of metastases. The mean concentrations of both markers were significantly higher in the sera of patients with constant progression (P < or = 0.0019). Analysis of 186 results from 91 patients followed-up with a median of 3.29 years showed a sensitivity of 89.5% for Cyfra 21.1, 75.0% for SCC, and a specificity of 86.4% and 99.1%, respectively. The positive predictive values were 91.9% for Cyfra 21.1 and 98.3% for SCC, and the negative predictive values 92.7% and 85.2%, respectively. Median lead times, calculated from the records of 18 selected patients with complete resection of the tumour, were found to be 60 days for Cyfra 21.1 and 50 days for SCC (P > 0.05).. In cervical cancer Cyfra 21.1 is very well-correlated to the tumour burden and the extent of the disease. In the case of recurrence, this marker rises more often than SCC. We therefore propose the use of Cyfra 21.1 for the monitoring of cervical cancer.

Topics: Adult; Aged; Aged, 80 and over; Antigens, Neoplasm; Biomarkers, Tumor; Carcinoma, Squamous Cell; Female; Humans; Keratin-19; Keratins; Middle Aged; Prospective Studies; Retrospective Studies; ROC Curve; Sensitivity and Specificity; Uterine Cervical Neoplasms

An immunohistochemical study of 63 cases of uterine cervical cancer was undertaken. It was confirmed that the biological character of the cancer cells derived from the reserve cells changed over the course of invasion. Squamous cell carcinoma had positive keratin antibodies such as CK 10/13 (DE-K 13), CK 14 (NCL-LL 002) and CK 7 (OV-TL 12/30). In invasive squamous cell carcinoma, CK 14 positive cells were piled up and tended to be stained positive by PCNA and laminin. There were two types of staining, one of which revealed CK 14 strongly positive, and the other weakly positive. The first type differed from the second in depth and localization. The cells on the margin of a cluster of cancer cells were stained positive with CK 14 as in normal basal cells. The results obtained suggested: 1) squamous cell carcinoma has not only the character of normal squamous cells, but also that of the cells derived from the cervical glands. 2) cancer cells may develop in accordance with the character of basal cells, and the patterns of invasion change according to the character of basal cells in cancer tissue.

Topics: Biomarkers, Tumor; Carcinoma, Squamous Cell; Cervix Uteri; Female; Humans; Immunohistochemistry; Keratins; Neoplasm Invasiveness; Proliferating Cell Nuclear Antigen; Uterine Cervical Neoplasms

Two cell lines derived from vaginal intraepithelial neoplasias (VAINs) expressing human papillomavirus (HPV) 33 (VAIN I, UT-DEC-1) and 16 (VAIN II, UT-DEC-2) E6-E7 mRNA were studied in organotypic culture for their keratins and cell cycle regulatory proteins in relation to replicative aging. Early-passage UT-DEC-1 and UT-DEC-2 cells reproduced epithelial patterns consistent with VAIN. Cells from later passages resembled full-thickness intraepithelial neoplasia (UT-DEC-1) and microinvasive cancer (UT-DEC-2). The morphological changes were compatible with these cell lines' ability for anchorage-independent growth at later passages. Simple epithelial keratins were aberrantly expressed in both cell lines. K18 (absent in normal vaginal keratinocytes) and K17 expression increased in UT-DEC-1 and UT-DEC-2 cells at late passages. No marked differences in expression of p53 (wild type in both cell lines), mdm-2 or PCNA were detected in parallel with progression. The expression of p21WAF1/cip1 localized mostly to the upper half of the epithelium at early passage and was more intense in the HPV 16-positive UT-DEC-2 cell line expressing K10. In Northern blot analyses, the transcription pattern of the HPV 33 E6-E7 of the UT-DEC-1 cell line changed during later passages, whereas that of the HPV 16 E6-E7 of the UT-DEC-2 cell line remained unaltered. The present characterization of the phenotype of these cell lines derived from natural squamous intraepithelial lesions shows an association between simple epithelial-type keratin expression and progressive changes in growth and morphology, but fails to demonstrate consistent changes in the expression of cell cycle regulatory proteins studied in parallel with progression.

Topics: Carcinoma in Situ; Carcinoma, Squamous Cell; Cell Adhesion; Cell Culture Techniques; Cell Cycle Proteins; Cellular Senescence; Disease Progression; Epithelial Cells; Female; Gene Expression Regulation, Neoplastic; Genes, Tumor Suppressor; Humans; Keratins; Neoplasm Proteins; Papillomaviridae; Papillomavirus Infections; Phenotype; Polymerase Chain Reaction; Polymorphism, Single-Stranded Conformational; RNA, Messenger; RNA, Neoplasm; Tumor Cells, Cultured; Tumor Virus Infections; Vagina

The effects of an induction chemotherapy with THP-adriamycin, cisplatin, and peplomycin (TPP) were studied in 32 patients with operable oral cancer. The histological evaluation according to the Shimozato-Oboshi classification was Grade (G) IV in ten cases (31.3%), GIII in one case, and GIIb in four cases. Induction of apoptosis and differentiation-inducing effects, hyperkeratinization or bone formation, were observed in some cases. The overall clinical response rate and histological response rate were 63% and 47%, respectively. Grade III was obtained in seven metastatic lymph nodes of three patients. The expressions of PCNA, p53, and AgNORs before and after chemotherapy were studied. The prechemotherapeutic PCNA positive cell index (PI) of the highly responsive tumors (GIII, IV) was significantly lower than that of the poorly responsive tumors (G0-IIb) (P < 0.01). Similar results were obtained in the evaluation of p53 PI (P < 0.05), suggesting that PCNA and p53 are useful biomarkers for predicting the efficacy of TPP chemotherapy.

Topics: Antibiotics, Antineoplastic; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Apoptosis; Biomarkers, Tumor; Carcinoma, Squamous Cell; Cell Differentiation; Cisplatin; Coloring Agents; Doxorubicin; Female; Forecasting; Gene Expression Regulation, Neoplastic; Humans; Keratins; Lymphatic Metastasis; Male; Middle Aged; Mouth Neoplasms; Nucleolus Organizer Region; Osteogenesis; Peplomycin; Proliferating Cell Nuclear Antigen; Remission Induction; Silver; Treatment Outcome; Tumor Suppressor Protein p53

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

CYFRA 21-1 (CYFRA) is a newly developed tumour marker which is useful in evaluating large cell lung carcinoma, especially the squamous cell type. The purpose of this study was to assess the clinical value of CYFRA for squamous cell carcinoma of the head and neck and compare the results with squamous cell carcinoma antigen (SCCA). Serum levels of CYFRA were measured in 168 patients with a newly diagnosed head and neck squamous carcinoma. In addition, 77 patients without evidence of neoplasm were included as controls. At the same time, SCCA was also determined. The cut-off values of CYFRA and SCCA, determined at the 95th percentile of the standard Gaussian variate of controls, were 2.48 ng/ml and 1.49 ng/ml respectively. The diagnostic sensitivity of CYFRA was superior to that of SCCA, especially for nasopharyngeal carcinoma. The sensitivity of CYFRA for nasopharyngeal carcinoma was much higher (58.3%) than that of SCCA (15.5%). However, the sensitivity of CYFRA is not satisfactory in all types of squamous carcinoma. For oral cancer, the sensitivity is only 25.6%. CYFRA is a useful serum marker for patients with certain types of head and neck squamous carcinoma, such as nasopharyngeal carcinoma and hypopharyngeal carcinoma. In addition, CYFRA may be also useful in monitoring recurrence of certain types of SCCHN, which are sometimes difficult to detect.

Topics: Antigens, Neoplasm; Biomarkers, Tumor; Carcinoma, Squamous Cell; Case-Control Studies; Female; Head and Neck Neoplasms; Humans; Immunoradiometric Assay; Keratin-19; Keratins; Male; Middle Aged; Sensitivity and Specificity; Serpins

Serologic identification of the fragment of cytokeratin 19 known as CYFRA 21-1 has been used for early detection of squamous cell carcinoma of the lung. The sensitivity of the CYFRA 21-1 assay in detecting oral cancers is lower than that in detecting lung cancers. To clarify the reason for this, we compared the cytokeratin expression in these cancers, with special reference to cytokeratin 19.. Oral squamous cell carcinomas and lung squamous cell carcinomas were immunostained with cytokeratin 19, cytokeratin 10, and cytokeratin 13 antibodies. Staining intensity was scored on a graduated scale from 0 to 4.. With respect to cytokeratin 19, the stainings of all lung cancers were scored as 4, which indicates a greater expression of cytokeratin 19 than is seen in oral cancers (p < 0.01). With an average cytokeratin 19 staining score of 1.67, oral cancers ranked lowest among the antibodies. Squamous cell carcinomas of the maxillary sinus arising from pseudostratified ciliated epithelium were highly expressive of cytokeratin 19. A marker for keratinizing cells (cytokeratin 10) and a marker for squamous cells (cytokeratin 13) were expressed more frequently and intensely in oral cancers (p < 0.01) than in lung cancers (p = 0.019).. From the viewpoint of immunohistochemistry, cytokeratin 19 was found to be a tumor marker with low specificity and sensitivity in oral cancers. The staining results suggested that poor expression of cytokeratin 19 by oral squamous cell carcinoma may result in a low serum value of CYFRA 21-1 in patients with this condition.

Topics: Antibodies; Antigens, Neoplasm; Biomarkers, Tumor; Carcinoma, Squamous Cell; Coloring Agents; Epithelial Cells; Epithelium; Gene Expression Regulation, Neoplastic; Humans; Immunohistochemistry; Keratin-19; Keratins; Lung Neoplasms; Maxillary Sinus Neoplasms; Mouth Neoplasms; Sensitivity and Specificity

A rare case of primary squamous cell carcinoma surrounding Stensen's duct in a 75-year-old man is presented. The tumor was a relatively well-defined, hard, subcutaneous mass, measuring 18 x 14 x 9 mm and situated in the right cheek. Microscopic examination of an excisional biopsy specimen revealed tumor cells showing squamous differentiation, a papillary growth pattern, and ductal structures with comedo necrosis. Immunohistochemical studies showed positive reactivity for KL-1 (cytokeratin, monoclonal), epithelial membrane antigen, and carcinoembryonic antigen in some tumor cells. The origin of the tumor was thought to be the accessory parotid gland duct epithelium.

Topics: Aged; Carcinoembryonic Antigen; Carcinoma, Squamous Cell; Cell Differentiation; Cell Nucleolus; Cell Nucleus; Cell Transformation, Neoplastic; Cytoplasm; Epithelium; Humans; Keratins; Male; Mucin-1; Necrosis; Parotid Gland; Parotid Neoplasms; Salivary Ducts

This study assessed the clinical value of CYFRA 21-1 in comparison with squamous cell carcinoma antigen (SCC-Ag), carcinoembryonic antigen (CEA), and carbohydrate antigen 19-9 (CA19-9) in patients with esophageal squamous cell carcinoma. In 112 primary cancer patients, the diagnostic sensitivity of CYFRA 21-1 (33.9%) was superior to SCC-Ag (28.6%), CEA (12.5%), and CA19-9 (6.3%). Levels of CYFRA 21-1 were closely correlated with TNM stage and wee below the cutoff value in all 21 patients with stage I disease. All 38 patients with a CYFRA 21-1 level over the cutoff value among the 80 patients who underwent esophagectomy had lymph node metastases (pN1). A correlation was found between CYFRA 21-1 levels and clinical response in serial measurements of 21 patients who received chemotherapy or chemo radiotherapy. Our findings suggest that CYFRA 21-1 is not useful for diagnosis, but that it is valuable for monitoring the efficacy of therapy.

Topics: Adult; Aged; Aged, 80 and over; Antigens, Neoplasm; Biomarkers, Tumor; CA-19-9 Antigen; Carcinoembryonic Antigen; Carcinoma, Squamous Cell; Esophageal Neoplasms; Female; Humans; Keratin-19; Keratins; Male; Middle Aged; Neoplasm Staging; Serpins

Breast cancers from pre- vs. postmenopausal women display unique characteristics that may be related to differences in epithelial differentiation between these two populations. In addition to lobular development, lactational changes, and involution, breast epithelium can undergo metaplastic alterations, often in association with carcinoma. Because protein kinase C (PKC) regulates differentiation and proliferation in many cell types, we asked whether modulation of PKC activity could define biochemical differences in breast epithelium from pre- vs. postmenopausal women. Organ cultures of normal human breast were treated with PKC agonists and antagonists. Epithelial differentiation was evaluated based on morphologic criteria and the expression of cell-type specific proteins. Staurosporine, a nonspecific but extremely potent inhibitor of PKC, induced squamous metaplasia in eight of eight cases within 2 weeks of treatment. Other inhibitors of PKC, such as calphostin C and tamoxifen, had no effect on epithelial differentiation. Long-term treatment with phorbol esters also did not induce squamous metaplasia. However, stimulation of cAMP levels by forskolin and isobutyl-methyl-xanthene (IMX) rapidly induced squamous metaplasia, as has been previously reported. Surprisingly, squamous metaplasia occurred in 10 of 12 cultures derived from postmenopausal women in the absence of exogenous agents. Untreated cultures derived from premenopausal women never developed this type of epithelium (0 of 11). Therefore, breast epithelium from pre- and postmenopausal women responded differently to in vitro culture. Forskolin/IMX or staurosporine can reproduce these conditions, acting independent of menopausal status. Because staurosporine's action was unique among PKC inhibitors, staurosporine may induce squamous metaplasia of breast epithelium by a PKC-independent mechanism.

Topics: Adult; Aged; Anticarcinogenic Agents; Breast; Breast Neoplasms; Carcinogens; Carcinoma, Squamous Cell; Cell Differentiation; Cell Division; Cyclic AMP-Dependent Protein Kinases; Enzyme Activation; Enzyme Inhibitors; Female; Gene Expression Regulation, Neoplastic; Humans; Immunophenotyping; Keratin-10; Keratinocytes; Keratins; Middle Aged; Naphthalenes; Postmenopause; Premenopause; Protein Kinase C; Staurosporine; Tamoxifen; Tetradecanoylphorbol Acetate; Thrombomodulin; Tumor Cells, Cultured; Up-Regulation

Human papillomaviruses (HPV) have been implicated in the etiology of anogenital squamous epithelial tumors. Of the 65 HPV strains, subtypes HPV-16 and HPV-18 frequently are associated with malignant conditions and are capable of transforming keratinocytes in vitro. However, additional cellular changes are necessary to confer tumorigenicity to HPV-infected cells. Secondary events implicated in the progression to malignancy include loss of tumor suppressor genes such as p53 and/or activation of cellular oncogenes such as c-rasHa.. Polymerase chain reaction (PCR) was used to identify HPV-16 or HPV-18 genetic sequence in primary penile squamous cell carcinoma and two inguinal lymph node metastases. p53 and c-rasHa loci were analyzed by sequencing of PCR-amplified genomic DNA.. HPV-18 but not HPV-16 infection was found in the primary carcinoma and in inguinal metastases occurring 5 and 7 years after the initial lesion. Sequence analysis did not identify any p53 mutations in the primary carcinoma or its metastases. However, although the primary lesion and the 5-year metastasis encoded wild-type c-rasHa, the 7-year metastasis had a missense mutation within c-rasHa codon 61.. To the authors' knowledge, this is the first report of an activating c-rasHa mutation associated with squamous cell carcinoma of the penis. The presence of activated c-rasHa in the second metastasis but not in the first metastasis or the primary lesion suggests that activation of c-rasHa may be a late event in the malignant progression of HPV-18-associated penile squamous cell carcinoma. Analysis of additional samples from primary lesions and their resultant metastases is necessary to elucidate the incidence and significance of c-rasHa activation in penile squamous cell carcinoma.

Topics: Carcinoma, Squamous Cell; DNA, Viral; Gene Expression Regulation, Neoplastic; Genes, p53; Genes, ras; Humans; Keratins; Male; Middle Aged; Mutation; Papillomaviridae; Penile Neoplasms

Topics: Antigens, Neoplasm; Antigens, Surface; Carcinoma, Squamous Cell; Coloring Agents; DNA, Neoplasm; Female; Flow Cytometry; Humans; Keratins; Neoplasms; Ovarian Neoplasms; Tumor Cells, Cultured

Reduction or loss of the intercellular junctions known as desmosomes may contribute to the invasive and metastatic behaviour of various carcinomas. Previous studies have shown that metastasis of oral squamous cell carcinomas of the head and neck correlates with a reduction in immunohistochemical staining for desmoplakin and desmoglein at the invasion front. The primary aim of the present study was to extend these observations to include a third component of desmosomes, the glycoprotein desmocollin. An additional aim was to determine whether the differentiation status of tumours is reflected in their staining for cytokeratins 1, 13, and 19, and, if so, whether these parameters correlate with desmosomal staining and/or metastasis. The study included 54 primary tumours of which 28 showed lymph node metastases. The results of this investigation show that tumours can be divided into three groups according to whether they have lost staining for no, one or more than one desmosomal component. A statistically significant correlation was found between the number of desmosomal components lost and metastasis. Tumours could also be divided into five groups according to their staining for different combinations of cytokeratins. Furthermore, differentiation status as indicated both histologically and by cytokeratin staining correlated with reduced desmosomal staining and metastasis. Tumours were also examined for intensity of staining for the adhesion molecule E-cadherin. Reduction in E-cadherin staining was correlated with mode of invasion and with reduction in desmosomal staining, but not with poor differentiation as indicated by cytokeratin staining. The results of this extensive study reinforce the view that adhesive junctions and adhesion molecules contribute to the suppression of tumour invasion and metastasis.

Topics: Adult; Aged; Aged, 80 and over; Biomarkers, Tumor; Cadherins; Carcinoma, Squamous Cell; Cell Differentiation; Cytoskeletal Proteins; Desmocollins; Desmogleins; Desmoplakins; Desmosomes; Humans; Immunoenzyme Techniques; Keratins; Lymphatic Metastasis; Middle Aged; Mouth Mucosa; Mouth Neoplasms; Neoplasm Invasiveness; Neoplasm Proteins

The applicability of the experimental skin carcinogenesis model for studies of tumor development was examined by exposing the skin of various mouse strains to different chemical carcinogens and UV radiation regimens, in order to analyze the development and progression of the neoplastic process and the role of differentiation markers such as keratins. In tumor-sensitive hairy NMRI mouse skin, the chemical carcinogen, 7,12-dimethylbenz(a)-anthracene (DMBA) induced an abnormal epidermal cell differentiation and structural irregularities associated with an altered keratin expression, as well as numerous papillomas and squamous cell carcinomas. A suboptimal dose of UVB irradiation increased the number of DMBA-induced benign squamous neoplasms. Low doses of benzo(a)pyrene resulted in mild epidermal alterations, but only in one tumor. High doses of UVB induced a large number of undifferentiated spindle cell tumors with few keratinpositive cells in NMRI mice, similar though fewer tumors in hairy, heavily pigmented C57BL/6 mice, numerous papillomas and squamous cell carcinomas in hairless hr/hr mice but only two papillomas in hairy, moderately pigmented DBA/2 mice while UVA exposure produced only two papillomas in hairless SKH-1 mice. In conclusion, the extent and type of skin tumor development depended upon the induction regimen: physical, chemical, dose and duration, as well as on the skin structure: pigmentation and adnexal development, all of which have to be taken into account when relating experimental results to human conditions.

Topics: 9,10-Dimethyl-1,2-benzanthracene; Animals; Biomarkers, Tumor; Carcinogens; Carcinoma, Squamous Cell; Cell Transformation, Neoplastic; Disease Models, Animal; Female; Keratins; Mice; Mice, Inbred C57BL; Mice, Inbred DBA; Mice, Inbred Strains; Skin Neoplasms

True malignant mixed tumors (carcinosarcomas) of salivary gland origin are exceedingly rare and demonstrate malignant epithelial and stromal components. We report a case of parotid gland carcinosarcoma that showed squamous cell carcinoma and malignant fibrous hystiocytoma without clinical or histologic evidence of a preexisting pleomorphic adenoma. This tumor consisted of 2 histologically different populations of cells without evidence of a common origin from the myoepithelial cell, which is the putative precursor cell of pleomorphic adenoma and its derived carcinosarcoma. In addition to supplementing the literature, this case report includes cytohistologic and immunohistochemical analyses that provide further insights into the variable histogenesis of this neoplasm and the distinction between de novo carcinosarcoma and carcinosarcoma originating from pleomorphic adenoma.

Topics: Aged; Aged, 80 and over; Biomarkers, Tumor; Carcinoma, Squamous Cell; Carcinosarcoma; Histiocytoma, Benign Fibrous; Humans; Immunohistochemistry; Keratins; Male; Parotid Neoplasms; Tomography, X-Ray Computed

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

This study aimed to ascertain whether cathepsin D expression could be related to the stage of differentiation of oral tumors.. Human oral biopsies of 10 squamous cell carcinomas and of the corresponding perilesional normal tissues were used. The tumors had all been clinically graded as advanced stage but nonmetastatic; five were classified histopathologically as poorly differentiated.. The gene expression of cathepsin D and keratin K13 in the biopsies was measured by reverse transcription polymerase chain reaction. Ratios of tumor-to-control readings helped compensate for sample variability.. Keratin K13, as a suprabasal cell marker, tended to confirm the histological grading of the tumors (but was not otherwise useful in distinguishing tumors from normal tissue). Substantial overexpression of cathepsin D was found in the poorly differentiated tumors.. Cathepsin D overexpression is considered a prognostic indicator of metastasis. In this sample, it was also associated with dedifferentiation. Cathepsin D might serve as a valuable gauge in clinical exploration of the connection between dedifferentiation and metastasis.

Topics: Adult; Aged; Aged, 80 and over; Biomarkers, Tumor; Carcinoma, Squamous Cell; Cathepsin D; Cell Transformation, Neoplastic; Female; Humans; Keratins; Male; Middle Aged; Mouth Neoplasms; Polymerase Chain Reaction; Prognosis; RNA-Directed DNA Polymerase; RNA, Messenger

Spindle cell squamous esophageal carcinomas are distinctive polypoid "biphasic" tumors in which the sarcoma-like phenotype usually predominates over the epithelial component. To biologically assess both phenotypes, we compared the tumoral proliferative activity and DNA ploidy between the two histological components of 13 polypoid spindle cell squamous carcinomas of the esophagus. We studied the tumoral proliferative index (TPI) using MIB 1 monoclonal antibody (Ki-67) and determined the DNA histogram by image cytometry on Feulgen-stained sections. The DNA histograms were classified into four types (I to IV) according to the degree of dispersion of the DNA. The TPI of the carcinomatous regions ranged from 0.20 to 0.63 (mean, 0.44) and from 0.55 to 0.85 for the sarcoma-like areas (mean, 0.68) P < .0001. In all cases, the sarcoma-like areas were aneuploid, and 37.5% of the carcinomatous regions were diploid. Also, in all instances the carcinomatous areas were of either histogram type I or II, and the sarcoma-like areas showed histograms of type II or III. We conclude that in esophageal spindle cell squamous carcinomas the sarcoma-like phenotype differs biologically in two ways from the carcinomatous: (1) it has a higher TPI and (2) it has higher aneuploidy with a greater dispersion of the DNA content. We postulate that these characteristics could give a "growth" advantage to the sarcoma-like component of these tumors and explain its predominance over the carcinomatous component.

Topics: Aged; Carcinoma, Squamous Cell; Cell Division; DNA, Neoplasm; Esophageal Neoplasms; Female; Humans; Immunoenzyme Techniques; Keratins; Ki-67 Antigen; Male; Middle Aged; Mitotic Index; Ploidies

The chemotherapeutic agent and vitamin A metabolite retinoic acid (RA) has been used to treat many tumor types. The effects of RA are mediated by a family of ligand-dependent transcription factors, the RA receptors and the retinoid X receptors (RXR). Alterations in retinoid receptor expression have been implicated in tumorigenesis. Previous studies have shown lack of RXR-gamma expression in squamous cell carcinoma (SCC) lines. To begin to elucidate the role of RXR-gamma in the malignant transformation of SCCs, we expressed RXR-gamma in SCC lines by stable transfection. SCC lines expressing RXR-gamma produced large numbers of flat cells with abundant cytoplasm, which died and detached from the culture dish. These cells morphologically resembled the differentiated cells of normal stratified squamous epithelium in culture. These cells did not exhibit the characteristic DNA fragmentation pattern of apoptotic cells, nor did they label in a fluorescent apoptosis assay. RNase protection and Western blot analysis revealed induction of RA-responsive involucrin and keratin 10 expression, early markers of terminal differentiation. RXR-gamma expression produced significant reduction in levels of RA-responsive genes including the cyclin-dependent kinase inhibitors p21Cip1/WAF1 and p27Kip1, resulting in increased cdc2 and cdk2 kinase activity and RB phosphorylation. We concluded that RXR-gamma induced terminal differentiation in SCC lines, suggesting a potential tumor suppressor function for this transcription factor.

Topics: Blotting, Western; Carcinoma, Squamous Cell; CDC2 Protein Kinase; CDC2-CDC28 Kinases; Cell Cycle Proteins; Cell Death; Cell Differentiation; Cell Size; Cyclin-Dependent Kinase 2; Cyclin-Dependent Kinase Inhibitor p21; Cyclin-Dependent Kinase Inhibitor p27; Cyclin-Dependent Kinases; Cyclins; Down-Regulation; Enzyme Activation; Genes, Tumor Suppressor; Humans; Keratin-10; Keratins; Microtubule-Associated Proteins; Phosphorylation; Precipitin Tests; Protein Precursors; Protein Serine-Threonine Kinases; Receptors, Retinoic Acid; Retinoblastoma Protein; Retinoid X Receptors; RNA, Messenger; Transcription Factors; Transfection; Tumor Cells, Cultured; Tumor Suppressor Proteins

The stratified squamous epithelium comprises actively proliferating basal cells that undergo a program of differentiation accompanied by morphological, biochemical, and genetic changes. The transcriptional regulatory signals and the genes that orchestrate this switch from proliferation to differentiation can be studied through the keratin gene family. Given the localization of keratin 4 (K4) to the early differentiated suprabasal compartment and having previously demonstrated that targeted disruption of this gene in murine embryonic stem cells results in impairment of the normal differentiation program in esophageal and corneal epithelial cells, we studied the transcriptional regulation of the human K4 promoter. A panel of K4 promoter deletions were found in transient transfection assays to be predominantly active in esophageal and corneal cell lines. A critical cis-regulatory element resides between -163 and -140 bp and contains an inverted CACACCT motif. A site-directed mutated version of this motif within the K4 promoter renders it inactive, whereas the wild-type version is active in a heterologous promoter system. It specifically binds esophageal-specific zinc-dependent transcriptional factors. Our studies demonstrate that regulation of the human K4 promoter is in part mediated through tissue-specific transcriptional factors.

Topics: Animals; Base Sequence; Carcinoma, Squamous Cell; Cell Differentiation; Cell Line; Esophageal Neoplasms; Esophagus; Gene Expression Regulation; HeLa Cells; Humans; Keratins; Mice; Mice, Knockout; Molecular Sequence Data; Multigene Family; Mutagenesis, Site-Directed; Nuclear Proteins; Promoter Regions, Genetic; Recombinant Proteins; TATA Box; Tongue; Transfection; Tumor Cells, Cultured

Over a 32-month period at the University Hospital, Kuala Lumpur, we were able to study the cytological appearance of metastatic nasopharyngeal carcinoma (NPC) in 17 cases. This comprised 14 males and three females of which 13 were Chinese, three were Malay, and one was Indian. Their ages ranged from 27 to 64 years. Histological correlation was available in all the patients in the form of nasopharyngeal biopsies, and they were classified as per the World Health Organization classification into types I, II, and III NPC. Smears from type II NPC showed good cellularity with mainly clustered and occasionally dissociated cells, with focal columnar appearance, vesicular nuclei, prominent nucleoli, and variable amounts of cytoplasm. Clusters of malignant cell closely associated with lymphoid cells and dissociation of malignant cells were more characteristic of type III NPC. FNA cytology is now applied extensively to the diagnosis of head and neck tumours and knowledge of the cytomorphology of NPC would greatly aid in pinpointing the primary of this tumour which is notorious for presenting with early nodal metastasis.

Topics: Adult; Biopsy, Needle; Carcinoma, Squamous Cell; Female; Humans; Immunoenzyme Techniques; Keratins; Lymphatic Metastasis; Male; Middle Aged; Nasopharyngeal Neoplasms; Neoplasm Recurrence, Local

The immunohistochemical diagnosis of mesothelioma is commonly made by using a battery of antibodies that reacts with lung adenocarcinomas but not with epithelial mesotheliomas. Only recently have markers that are often expressed in mesotheliomas but not in adenocarcinomas been recognized. Some of these markers, however, require frozen tissue sections, whereas others are not commercially available, or their value remains controversial. In a recent publication, it was suggested that immunostaining for cytokeratin 5/6 could assist in distinguishing epithelial mesothelioma from lung adenocarcinoma. To determine the practical value of cytokeratin 5/6 immunostaining in the diagnosis of mesothelioma, 40 formalin-fixed, paraffin-embedded epithelial pleural mesotheliomas, 30 pulmonary adenocarcinomas, 93 nonpulmonary adenocarcinomas, 15 squamous carcinomas of the lung, 5 large cell undifferentiated carcinomas of the lung, and 12 metastatic transitional cell carcinomas to the lung were stained with the same antibody, which was obtained from a commercial source. Cytokeratin 5/6 reactivity was observed in all 40 mesotheliomas, but there was none in any of the 30 pulmonary adenocarcinomas. Focal or weak reactivity was observed in 14 of 93 nonpulmonary adenocarcinomas (10 of 30 ovarian, 2 of 10 endometrial, 1 of 18 breast, I of 7 thyroid, 0 of 10 kidney, 0 of 10 colonic, and 0 of 8 prostatic). All 15 squamous carcinomas of the lung, 6 of 12 transitional cell carcinomas metastatic to the lung, and 3 of 5 large cell undifferentiated carcinomas of the lung expressed cytokeratin 5/6. It is concluded that cytokeratin 5/6 immunostaining is not only useful in separating epithelial pleural mesotheliomas from pulmonary adenocarcinomas but also can assist in distinguishing epithelial mesotheliomas from nonpulmonary adenocarcinomas metastatic to the pleura.

Topics: Adenocarcinoma; Biomarkers, Tumor; Carcinoma, Non-Small-Cell Lung; Carcinoma, Squamous Cell; Carcinoma, Transitional Cell; Diagnosis, Differential; Epithelial Cells; Evaluation Studies as Topic; Female; Humans; Immunoenzyme Techniques; Keratins; Lung Neoplasms; Male; Mesothelioma; Pleural Neoplasms; Retrospective Studies

A case of papillary squamotransitional carcinoma of the vagina is reported. The immunohistochemical profiles (cytokeratin-7 and -20) and the detection of human papillomavirus 16 support its close relationship to conventional squamous cell carcinoma. The lesion is compared to previously reported cases of papillary transitional cell carcinoma of the vagina and papillary squamotransitional cell carcinoma of the cervix.

Topics: Aged; Aged, 80 and over; Carcinoma, Papillary; Carcinoma, Squamous Cell; Carcinoma, Transitional Cell; Female; Humans; Immunohistochemistry; Intermediate Filament Proteins; Keratin-20; Keratin-7; Keratins; Papillomaviridae; Urethra; Vaginal Neoplasms

The immunohistochemical localization and expression of 1,25-dihydroxyvitamin D3 receptors (VDR) has been investigated in normal human cervical tissue (n = 15) and in cervical carcinomas (n = 23). VDR immunoreactivity (monoclonal antibody 9A7gamma) was compared with the staining patterns of transglutaminase K, cytokeratin 10 and Ki-67 in these tumours. Moderate to strong nuclear immunoreactivity for VDR was detected in almost all cervical carcinomas analysed. VDR staining was homogeneous, with no visual differences between individual tumour cells. Some 60% of normal cervical tissues revealed weak immunoreactivity for VDR. In normal cervical tissue, nuclear VDR staining was confined to the lower cervical layers, predominantly to the basal cell layer. Both the intensity of VDR immunostaining and the number of VDR-positive cells were up-regulated in cervical carcinomas compared with normal cervical tissue. No visual correlation was found for the coexpression of VDR with markers of proliferation and differentiation. Our findings indicate that: (1) cervical tissue may be a new target organ for therapeutically applied vitamin D analogues; (2) VDR is up-regulated at the protein level in cervical carcinomas compared with normal cervical tissue; (3) up-regulation of VDR in cervical carcinoma is induced not exclusively by alterations in epithelial differentiation or proliferation, but by different, unknown mechanisms; and (4) calcitriol and new vitamin D analogues exerting fewer calcaemic side-effects may be promising new drugs for the treatment or chemoprevention of metastasizing cervical carcinomas as well as of cervical precancerous lesions.

Topics: Adenocarcinoma; Carcinoma, Squamous Cell; Cell Nucleus; Cervix Uteri; Female; Humans; Immunohistochemistry; Keratins; Ki-67 Antigen; Receptors, Calcitriol; Transglutaminases; Uterine Cervical Neoplasms

Fourier transform infrared (FTIR) microspectroscopy is emerging as a promising new tool for histopathological investigations of tissue histochemistry. This study was designed to assess whether changes in tissue biochemistry induced by well-differentiated and poorly differentiated oral/oropharyngeal squamous cell carcinoma (SCC) can be detected by infrared spectroscopy. The biopsies analyzed were each proven SCC positive and compared with tissue taken from the contralateral normal site. Individual infrared spectra, recorded from specific tissue areas, were correlated with histopathological structures normally found in the oral mucosa. Infrared mapping of these areas allows the generation of biochemical images of molecular structures such as lipids, sugars, and proteins. The visualization of DNA and tissue structures containing keratin (well expressed in all epithelia) reveals distinct differences between normal and SCC-positive biopsies. Bivariate histogram analysis of cell components (e.g., DNA and keratin) indicated that cancer cells produce a relatively homogeneous and clearly abnormal cell biochemistry, whereas differentiated epithelial cells present a very heterogeneous distribution of cellular components. Using these features, tissue containing abnormal or cancer cells can easily be distinguished from normal epithelial structures. The abnormal keratin distribution in poorly differentiated SCC and in keratin pearls (present only in well-differentiated SCC) offers insight into the process of malignant tissue transformation in squamous epithelium. Applying infrared microspectroscopy in combination with bivariate statistics to histopathological tissue thin sections provides a potential diagnostic tool for detection of cell changes in epithelial cancers.

Topics: Aged; Aged, 80 and over; Carcinoma, Squamous Cell; DNA; Female; Humans; Keratins; Male; Middle Aged; Mouth Mucosa; Mouth Neoplasms; Pharyngeal Neoplasms; Spectroscopy, Fourier Transform Infrared

Two human cancer cell lines were established from metastatic lesions of an adenocarcinoma (RAL) and a squamous cell (CAEP) carcinoma of the lung. The clinical histories of the patients from whom the cell lines were derived are reported. The lines were maintained in continuous culture with doubling times of 65 (RAL) and 50 (CAEP) hours. The RAL and CAEP cell lines, whose morphology and ultrastructural features are presented, showed extensively rearranged karyotypes with modal number of 85 (RAL) and 98 (CAEP). In particular, chromosome 2 pentasomy and several clonal markers were evident in the RAL cells, whereas a telomeric deletion of chromosome 1, del (1)(q32), was observed in the CAEP cells. The morphologic data were confirmed by high expression of specific antigens for each histotype. A marked positivity of the neuron-specific enolase (NSE) levels was evident by immunoenzymatic assays in the cell lines cytosol with respect to those present in the respective patient's sera. No amplification or rearrangements were evident in the CMYC, LMYC, NMYC, INT-2, ERBB2, HRAS, KRAS, MOS, HST-1 genes by Southern blotting analysis in each cell line. Point mutations in exon 1 of KRAS and in exon 7 of TP53 were evident by polymerase chain reaction (PCR)-DNA sequencing in the RAL cell line, whereas no alterations were present in the HRAS and RB genes. The four genes studied did not show point mutations in the CAEP cell line. The RAL cell line was resistant to all the drugs tested, whereas the CAEP cells were sensitive to vinblastine. These cell lines may represent useful experimental models to investigate lung cancer biology and anticancer drug response.

Topics: Adenocarcinoma; Aged; Biomarkers, Tumor; Carcinoembryonic Antigen; Carcinoma, Squamous Cell; Female; Genetic Markers; Humans; Karyotyping; Keratins; Lung Neoplasms; Male; Middle Aged; Phosphopyruvate Hydratase; Tumor Cells, Cultured

Four mixed Merkel cell and squamous cell carcinomas of the skin are described. The patients ranged in age from 74 to 90 years and demonstrated or had a history of previous ultraviolet or infrared damage to the skin, manifested by basal cell carcinoma, squamous cell carcinoma, actinic keratoses, solar elastosis, and erythema ab igne. Light microscopic examination of all 4 cases revealed invasive neoplasms consisting of 2 distinct but admixed cell types. The predominant cell type was consistent with Merkel cell carcinoma and was characterized by scant cytoplasm, a small dark polygonal nucleus with granular chromatin, a high mitotic rate, and cytokeratin 20 positivity. In each case, the Merkel cell component merged with a cytokeratin 20 negative squamous component characterized by abundant eosinophilic cytoplasm, intercellular bridges, and keratinization with focal squamous pearl formation. Immunohistochemical staining patterns were consistent with the usual pattern for that cell type; transitional cells were not demonstrated. The intimate admixture of the 2 antigenically different neoplastic cell types, and common etiologic role of ultraviolet and possibly infrared damage, lend support to the theory that some Merkel cell carcinomas and squamous cell carcinomas may arise from a pluripotent epidermal stem cell.

Topics: Aged; Aged, 80 and over; Carcinoma, Basal Cell; Carcinoma, Merkel Cell; Carcinoma, Squamous Cell; Cell Nucleus; Cytoplasm; Elastic Tissue; Erythema; Female; Humans; Infrared Rays; Keratins; Keratosis; Male; Mitosis; Neoplasms, Multiple Primary; Skin Aging; Skin Neoplasms; Ultraviolet Rays

Metastatic spread to cervical lymph nodes is a major determinant of outcome in head and neck cancer. One hundred and ninety-six lymph nodes dissected from fresh surgical specimens from 24 patients with primary head and neck squamous cell carcinoma (SCC) were bisected. Messenger RNA (mRNA) extracted from one half and from a segment of the primary tumour was amplified by reverse transcriptase (RT)-polymerase chain reaction (PCR) with primers flanking the fifth intron of human type II keratin K5. DNA bands resolved by agarose gel electrophoresis were confirmed as specific transcripts by sequencing. The other half of each node was fixed in formalin for histology and, in selected nodes, for immunohistology for cytokeratins. Of 153 nodes suitable for analysis, 14 nodes contained metastatic tumour detected by light microscopy and also tested positive for K5 mRNA by RT-PCR. Fifty-six nodes were histologically negative for tumour but positive for K5 mRNA, and 83 nodes were negative for both histology and K5 mRNA. Extracts of the primary tumour always reacted positively for K5 by RT-PCR, whereas lymph nodes from patients without malignancies, and blood lymphocytes from a healthy volunteer reacted negatively. RT-PCR designed to detect the presence of processed transcripts of type II keratin K5 in stratified squamous epithelial cells may be a sensitive technique to detect the presence of viable and potentially metastatic carcinoma cells in lymph nodes draining head and neck SCC.

Topics: Biomarkers, Tumor; Carcinoma, Squamous Cell; Head and Neck Neoplasms; Humans; Immunohistochemistry; Keratins; Lymphatic Metastasis; Neck; Polymerase Chain Reaction; RNA Splicing; RNA, Messenger; RNA, Neoplasm; Sensitivity and Specificity; Sequence Analysis, RNA

In stratified squamous epithelia, altered expression of keratins (Ks) is one possible marker of malignant potential. In the epithelium of the uterine cervix, presence of human papillomaviruses (HPVs) is increasingly regarded as a marker of risk for cervical cancer. However, a similar role in oral cancer and precancer remains controversial. To address these questions, formalin-fixed, paraffin-embedded oral carcinomas from Sudanese snuff dippers (n=14) and oral carcinomas from Sudanese (n=14), Swedish (n=19) and Norwegian (n=41) non-snuff dippers were examined by immunohistochemistry for expression of K types 13, 14 and 19 using monoclonal antibodies. HPV infection was searched for in all the carcinomas by in situ hybridization (ISH) using the cocktail HPV OmniProbe and the ViraType probe. Carcinomas from Sudanese (snuff dippers/non-snuff dippers) were also examined for HPV infection by polymerase chain reaction (PCR) using the general HPV primers GP5+/GP6+. For the oral carcinomas from snuff dippers, moderate to intense expression of K13 (71%; 10/14), K14 (86%; 12/14) and K19 (93%; 13/14) was found. For the oral carcinomas from non-snuff dippers, weak to moderate expression of K13 (64%; 47/74), K14 (43%; 32/74) and K19 (45%; 33/74) was found. HPV DNA was not detected in any of the carcinomas from three countries when examined by ISH. The Sudanese (from snuff dippers/non-snuff dippers) oral carcinomas were also negative for HPV DNA with the PCR. The present study shows that (i) there is a high level of expression of K13, K14 and K19 in oral carcinomas from snuff dippers compared to those from non-snuff dippers, (ii) this high level of expression may arise from dysregulation of keratinocyte proliferation and maturation caused by damaging effects of snuff, (iii) the HPV genome is not found in Sudanese (snuff dippers/non-snuff dippers), Swedish or Norwegian oral carcinomas, and (iv) this may suggest that these viruses do not play a prominent role in the aetiology of oral carcinomas from these countries.

Topics: Carcinoma, Squamous Cell; Female; Humans; In Situ Hybridization; Keratin-14; Keratins; Male; Mouth Neoplasms; Norway; Papillomaviridae; Papillomavirus Infections; Plants, Toxic; Polymerase Chain Reaction; Sudan; Sweden; Tobacco, Smokeless; Tumor Virus Infections

Extravascular fibrin deposition is frequently observed within and around neoplastic tissue and has been implicated in various aspects of tumor growth. The distribution of fibrin deposits was investigated in squamous cell carcinomas representing different stages of tumor progression of the larynx (n = 25) and hypopharynx (n = 9) by immunofluorescent techniques. Double and treble labelings were used to detect fibrinogen and fibrin in combination with marker antigens for tumor cells (cytokeratin), endothelial cells (von Willebrand factor), macrophages (recognized by KiM7), as well as factor XIII subunit A (FXIIIA) and tenascin (an embryonic extracellular matrix protein newly expressed during tumorigenesis). All tissue samples showed specific staining for fibrinogen/fibrin. Fibrin deposition was localized almost exclusively in the connective tissue compartment of tumors with characteristic accumulation at the interface of connective tissue and the tumorous parenchyma. In certain tumor samples showing highly invasive characteristics, fibrin deposits were observed in close association with tumor blood vessels in the tumor cell nodules. The overlapping reactions with polyclonal antibody to fibrinogen/fibrin and monoclonal antibody to fibrin indicate the activation of the coagulation cascade resulting in in situ thrombin activation and fibrin formation. Fibrin was crosslinked and stabilized by FXIIIA as revealed by urea insolubility test. Accumulation of phagocytozing macrophages detected by Ki M7 monoclonal antibody could be seen in areas of fibrin deposition. The blood coagulation factor XIIIA was detected in and around the cells labeled with Ki M7 antibody. Tenascin and fibrin deposits were found in the same localization in the tumor stroma and in association with tumor blood vessels within the tumor cell nodules. Neither fibrin nor tenascin were detected in the histologically normal tissue adjacent to tumors. The close association between fibrin deposits and macrophage accumulation strongly suggests the active participation of tumor-associated macrophages in the formation of stabilized intratumoral fibrin that facilitates tumor matrix generation and tumor angiogenesis.

Topics: Adult; Aged; Carcinoma, Squamous Cell; Disease Progression; Female; Fibrin; Fibrinogen; Fluorescent Antibody Technique, Indirect; Humans; Hypopharyngeal Neoplasms; Keratins; Laryngeal Neoplasms; Macrophages; Male; Middle Aged; Neoplasm Proteins; Tenascin; Thrombophilia; Transglutaminases

The expression of cholesterol sulfate (CS) is known to increase during squamous differentiation of keratinocytes and to activate the epsilon, eta, and zeta forms of protein kinase C as a signal transduction molecule for the subsequent expression of transglutaminase-1 (TG-1) and cytokeratins. To gain further insight into the regulation of cellular differentiation and tumorigenesis by CS, we examined the concentration and the potential for synthesis of CS in seven and four surgical specimens from human ovarian and uterine cervical cancer patients, respectively, and eight cell lines established from human uterine cervical cancer patients and compared them for the rate of expression of cytokeratin. CS was present in all of the uterine cervical cancer tissue specimens but only in the mucinous type of cystadenocarcinoma among ovarian cancer tissue specimens, and cytokeratin was highly expressed in the tissues with a high concentration of CS, which were classified as well-differentiated on the basis of morphological examination. Similarly, cells derived from a keratinizing type of well-differentiated cervical carcinoma demonstrated strong potential for synthesis of CS, stained positive with anti-cytokeratin antibody, and exhibited a higher specific activity of TG-1, whereas the cells without CS did not stain positive with anti-cytokeratin antibody and exhibited a lower specific activity of TG-1. These findings indicate that CS is coexpressed with TG-1 and cytokeratin in the well-differentiated types of squamous cell cancers as a tumor marker.

Topics: Biomarkers, Tumor; Carcinoma, Squamous Cell; Cholesterol Esters; Female; Humans; Immunohistochemistry; Keratins; Lipid Metabolism; Lipids; Ovarian Neoplasms; Tumor Cells, Cultured; Uterine Cervical Neoplasms; Uterine Neoplasms

Cytokeratins are epithelial markers whose expression is not lost during malignant transformation. The level of soluble cytokeratin fragment 19 was measured with an enzyme immunoassay method developed by Boehringer Mannheim (Enzymum-test CYFRA 21-1) in the serum of 200 male and 50 female patients with NSCLC (Non Small Cell Lung Cancer) lung cancer (120 planocellulare and 80 adenocarcinoma in males; 22 planocellulare and 28 adenocarcinoma in females). The comparative group comprised 50 young healthy males and 50 females without any clinical proof for malignancy or any other lung disease. The aim of this investigation was to find out if any possible statistical difference exists in the serum level of CYFRA 21-1 between patients with lung cancer and healthy controls, and also between different types of lung cancers. The mean value of serum CYFRA 21-1 in NSCLC (6.25 ng/ml) was significantly higher than in healthy controls (1.26 ng/ml) (p < 0.001). Sensitivity for CYFRA 21-1 (using 3.3 ng/ml, a cut-off value corresponding to a 98% specificity for healthy controls) in NSCLC was 60.5%. Positive CYFRA 21-1 levels were significantly higher in patient with carcinoma planocellulare (66.2%) than in adenocarcinoma (52.1%). CYFRA 21-1 levels were significantly different between squamous cell carcinoma (6.52 ng/ml) and adenocarcinoma (5.86 ng/ml) (p < 0.05). Our results indicate that CYFRA 21-1 may be a useful tumor marker in NSCLC, especially in carcinoma planocellulare. CYFRA 21-1 may also be useful in identification of the preoperative stages of diseases and the postoperative monitoring of NSCLC.

Topics: Adenocarcinoma; Antigens, Neoplasm; Biomarkers, Tumor; Carcinoma, Non-Small-Cell Lung; Carcinoma, Squamous Cell; Female; Humans; Immunoenzyme Techniques; Keratin-19; Keratins; Lung Neoplasms; Male; Sensitivity and Specificity

To investigate the utility of primer extension preamplification (PEP) in the genetic analysis of head and neck squamous tumorigenesis, microsatellite analysis was performed on matched deoxyribonucleic acid (DNA) samples extracted from 32 flow-sorted and microdissected specimens before and after PEP. Eighteen fresh and nine archival specimens were taken from invasive carcinomas, and five specimens were obtained from microdissected archival premalignant squamous epithelial lesions. Identical microsatellite patterns were observed in 276 (87%) of the 319 paired PEP and non-PEP genotypes with sufficient DNA. Overall, 13 (4%) of the PEP and 28 (8.8%) of the non-PEP fresh tissue samples failed specific microsatellite amplification. All 14 PEP-archival specimens were successfully amplified. Sorted cells showed a higher incidence (42.8%) of loss of heterozygosity (LOH) in both PEP and non-PEP samples compared with their unsorted counterparts. The results of this study indicate that (a) PEP is a simple and reliable technique for enhancing the DNA yield from small specimens; (b) flow sorting, in certain cases, improves the interpretation of genetic results; and (c) PEP may be used to compensate for PCR failure of unamplified DNA specimens in these lesions.

Topics: Carcinoma, Squamous Cell; DNA Mutational Analysis; DNA Primers; DNA, Neoplasm; Flow Cytometry; Genome, Human; Head and Neck Neoplasms; Humans; Keratins; Loss of Heterozygosity; Microsatellite Repeats; Molecular Probe Techniques; Neck Dissection; Polymerase Chain Reaction; Respiratory Tract Neoplasms

To study the differentiation of epithelial tissues within their histological context, and to identify hypothetically, on the basis of keratin pattern, the putative tissue origin of a (metastatic) carcinoma.. Using well characterised monoclonal antibodies against individual keratins 7, 8, 18, and 19, which are predominantly found in columnar epithelia, and keratins 4, 10, 13, and 14, predominantly expressed in (non)-keratinising squamous epithelia, the keratin patterns for a series of 45 squamous cell carcinomas and 44 adenocarcinomas originating from various epithelial tissues were characterised.. The predominant keratins in all adenocarcinomas proved to be 8, 18, and 19. In addition, these keratins were also abundantly present in squamous cell carcinomas of the lung, cervix, and rectum and, to a lesser extent, of the larynx, oesophagus, and tongue, but not in those of the vulva and skin. Keratins 4, 10, 13, and 14 were present in almost all squamous cell carcinomas, but also focally in some of the adenocarcinomas studied.. There is a limited differential expression of distinctive keratin filaments between squamous cell carcinomas and adenocarcinomas. Apparently, squamous cell carcinomas that originate from columnar epithelium by squamous metaplasia gain the keratins of squamous cells but retain the keratins of columnar epithelial cells. However, the simultaneous expression of two of three squamous keratins (4, 10, and 13) identifies a squamous cell carcinoma, and thus might be useful in solving differential diagnostic problems.

Topics: Adenocarcinoma; Antibodies, Monoclonal; Biomarkers, Tumor; Carcinoma, Squamous Cell; Cell Differentiation; Diagnosis, Differential; Humans; Immunoenzyme Techniques; Keratins; Neoplasm Proteins

To set the serum cut-off value of CYFRA21-1 in lung cancer patients in china, and to evaluate the clinical usefulness of CYFRA21-1 as a new tumor marker of lung cancer.. CYFRA21-1 levels were measured with two monoclonal antibodies (Ks19.1 and BM19.21) in the serum of 72 patients with lung cancer, 50 patients with benign lung diseases and 33 post-therapy lung cancer patients. To set the cut-off value, ROC curve was use.. (1) Serum concentrations of CYFRA21-1 in patients with lung cancer were significantly higher than those with benign lung diseases (P < 0.001). CYFRA21-1 levels in patients with squamous cell carcinoma were significantly higher than those in patients with any other subtypes. The more advanced the clinical stages, the higher the levels of CYFRA21-1. (2) If the threshold of CYFRA21-1 was set at 5.5 micrograms/L, its sensitivity and specificity for lung cancer were 63% and 94%, respectively. The sensitivity for squamous cell carcinoma was 78%, which was the highest among all the pathological subtypes. (3) The sensitivity of CYFRA21-1 in non-small cell lung cancer increased with the advancement of clinical stages. (4) CYFRA21-1 could be a good index in monitoring patient's condition and predicting prognosis for lung cancer. (5) When CYFRA21-1 was used as a screening index for lung cancer, the threshold of CYFRA21-1 should be set at the upper left corner of the receiver operating characteristic curve of stage I-II. The value of CYFRA21-1 in early diagnosis for non-small cell lung cancer was found limited.. CYFRA21-1 is a sensitive and specific tumor marker of non-small cell lung cancer, especially of squamous cell carcinoma.

Topics: Adenocarcinoma; Adult; Aged; Antigens, Neoplasm; Biomarkers, Tumor; Carcinoma, Non-Small-Cell Lung; Carcinoma, Small Cell; Carcinoma, Squamous Cell; Female; Humans; Keratin-19; Keratins; Lung Neoplasms; Male; Middle Aged; Neoplasm Staging

Desmosomes are predominant among the types of plaque-bearing adhering junctions found in human skin. These structures contain a set of desmosomal cadherins and cytoplasmic plaque proteins, the synthesis of which is differentiation dependent. As plakophilin 1, a member of the armadillo gene family, is an important accessory desmosomal plaque protein, we raised several monoclonal antibodies specific for this protein and applied immunohistochemical and immunoblotting procedures to study the distribution of plakophilin 1 in desmosomes in adult and fetal skin, psoriatic epidermis, various epithelial skin tumors, and keratinocyte sheets grown in culture. In epidermis, the spinous layers were prominently immunostained by plakophilin 1 antibodies, whereas the basal cell layer was only weakly stained and the stratum corneum was entirely unstained. The staining observed in psoriatic epidermis was somewhat heterogeneous. In hair follicles, the outer root sheath (ORS) was delineated in its suprabasal cell layers, with variable staining in its upper and lower parts. All basal cells of the ORS remained unstained, as did upper inner root sheath (IRS) and matrix cells of lower bulb. In eccrine sweat glands, the reaction was confined to inner dermal ductal cells, with the acini remaining unstained. The desmosomal immunostaining observed in basal cell carcinomas (BCCs) and squamous cell carcinomas (SCCs) was very heterogeneous: In general, junctions in well-differentiated stratified tumor regions were more intensely stained than sections of poorly differentiated and invasively growing BCCs and SCCs. Plakophilin 1 was also prominent in the desmosomes of keratinocyte sheets grown in culture. The cell type-specific, i.e., differentiation-dependent, distribution of desmosomal plakophilin 1 is discussed in relation both to the stratification of the cutaneous epithelia and to tumor differentiation and growth.

Topics: Bowen's Disease; Carcinoma, Basal Cell; Carcinoma, Squamous Cell; Desmosomes; Fetus; Foot; Humans; Immunohistochemistry; Keratinocytes; Keratins; Plakophilins; Proteins; Psoriasis; Skin; Skin Neoplasms

The aim of the present study was to investigate whether trivariate FCM analysis, for the simultaneous detection of two different CK subtypes in combination with DNA content, can be applied to paraffin embedded samples of different types of non-small cell lung cancer in order to evaluate the cell cycle of individual sublines. Single cell suspensions were prepared from 50 microm thick paraffin sections of 22 lung carcinomas by pepsin digestion and immunostained with CK-antibodies which were chosen to distinguish glandular differentiation (adenocarcinomas) and squamous differentiation. There was a good correlation between the immunocytochemical results of the different CK antibodies in tissue sections and in the corresponding single cell suspensions. Gating for CK-positivity revealed a higher S-phase fraction as compared to the ungated cell population. The tumor cells in adenocarcinoma cases were specifically recognized by CK7 antibodies, while well-differentiated squamous cell carcinomas were specifically stained for CK14 and/or CK17. In poorly differentiated squamous cell carcinomas simultaneous expression of CK7 and CK17 was detected in a subpopulation of the tumor cells, next to cells positive for CK7 or CK17 alone. The trivariate FCM analysis allowed the separate estimation of ploidy status and cell cycle parameters in the three different cell populations of these, apparently (phenotypically) heterogeneous, malignancies.

Topics: Adenocarcinoma; Antibodies; Carcinoma, Squamous Cell; Cell Cycle; DNA, Neoplasm; Flow Cytometry; Frozen Sections; Humans; Immunoenzyme Techniques; Keratins; Lung Neoplasms; Paraffin Embedding

In a previous study, the authors used a variety of anticytokeratin monoclonal antibodies to show that a large proportion of lung tumors cytologically diagnosed as squamous cell carcinoma contain cells expressing simple epithelial cytokeratins, suggesting that these tumors have their origin in adenocarcinoma. These findings raised the possibility that cytokeratin (CK) typing might have a diagnostic capacity not attainable by standard histopathology. The aim of the current study was to assess the value of CK typing for this purpose by determining the correlation between the diagnosis of lung tumors based on CK typing and the survival rate of the patients.. Paraffin embedded tissue sections of 66 nonsmall cell lung carcinoma (NSCLC) specimens were examined. These included 18 adenocarcinomas, 32 squamous cell carcinomas, and 16 undifferentiated carcinomas, all diagnosed surgically and histopathologically, and further classified as either Stage I or II. CK typing was performed using the streptavidin-biotin-peroxidase method, employing the following anti-CK monoclonal antibodies: Ks.B.17 (which reacts with CK 18), A3-3 (which reacts with CK 13), and E5-9 (which reacts with CK 10).. Comparison between the 5-year survival rates (5 ysr) of patients with different NSCLC indicated that all types of Stage II tumors had a much poorer prognosis than Stage I tumors. Differences found in the 5 ysr among patients with different types of Stage I tumors were not statistically significant (adenocarcinomas, 33% 5 ysr; squamous cell carcinomas, 59% 5 ysr; undifferentiated carcinomas, 36% 5 ysr; all diagnosed by conventional histopathology). Similarly, no significant differences were noted in 5 ysr between patients with tumors stained positively or negatively with monoclonal antibodies A3-3 or E5-9 (anti-CK 13 and anti-CK 10, respectively). In contrast, highly significant differences (P = 0.002) were found in the 5 ysr between patients with Stage I tumors positively or negatively stained with monoclonal antibody Ks.B.17 (23% vs. 75% 5 ysr, respectively) regardless of the histologic types of tumors. Especially informative was a combination of immunohistochemical and histologic diagnoses, with best survival rates (87% 5 ysr) in Ks.B.17 negative tumors histologically diagnosed as Stage I squamous cell carcinomas and worst survival rates (14% 5 ysr) in Ks.B.17 positive tumors diagnosed as adenocarcinomas.. The current study showed that CK 18 typing of lung tumors can provide a more accurate diagnosis and therefore facilitate the planning of more suitable therapeutic approaches.

Topics: Adenocarcinoma; Aged; Carcinoma; Carcinoma, Non-Small-Cell Lung; Carcinoma, Squamous Cell; Female; Gene Expression Regulation, Neoplastic; Humans; Immunoenzyme Techniques; Keratins; Lung Neoplasms; Male; Middle Aged; Neoplasm Staging; Predictive Value of Tests; Prognosis; Retrospective Studies; Survival Analysis

We report a case of lymphoepithelioma-like carcinoma of the skin on the right cheek of a 67-year-old man. Histologically, the entire dermis was occupied by multiple lobules of atypical epithelial tumor cell nests surrounded by inflammatory cells. Immunohistochemical examination showed that the epithelial tumor cells were positive for cytokeratin and epithelial membrane antigen. The inflammatory cells were positive for leukocyte common antigen and T-cell marker. Among the tumor nests, small ductal structures were positive for carcinoembryonic antigen. Ultrastructurally, these epithelial tumor cells had well-developed desmosomes and were joined to each other; no tonofilaments were observed in the cytoplasm. These findings strongly suggest that these tumor cells tended to differentiate to the adnexa of the skin.

Topics: Aged; Antigens, Differentiation, T-Lymphocyte; Carcinoembryonic Antigen; Carcinoma, Squamous Cell; Cheek; Cytoplasm; Desmosomes; Epithelium; Facial Neoplasms; Humans; Immunohistochemistry; Intermediate Filaments; Keratins; Leukocyte Common Antigens; Male; Mucin-1; Skin Neoplasms

Retinoids are vitamin A analogs that regulate growth and differentiation of squamous epithelial cells in vitro and in vivo. We examined the effects of retinoic acid (RA) and N-(4-hydroxy-phenyl) retinamide (HPR) on the growth properties of esophageal squamous carcinoma cell lines, and found that both RA and HPR induce morphological changes and inhibit growth. Immunofluorescence studies suggest alterations in keratins as a result of treatment with RA or HPR. In order to determine underlying molecular mechanisms, we found that RA or HPR did not induce arrest of cells in the G1 phase nor did treated cells undergo apoptosis. However, RA and HPR treatment did result in the downregulation of epidermal growth factor receptor (EGFR) which is known to bind key proproliferative ligands, such as epidermal growth factor and transforming growth factor alpha.

Topics: Antineoplastic Agents; Apoptosis; Blotting, Western; Carcinoma, Squamous Cell; Cell Division; Cell Size; ErbB Receptors; Esophageal Neoplasms; Fenretinide; Flow Cytometry; Humans; Keratins; Time Factors; Tretinoin; Tumor Cells, Cultured

The aim of this study was to evaluate the diagnostic value of three tumour markers, squamous cell carcinoma (SCC) antigen, carcinoembryonic antigen (CEA) and CYFRA 21.1, in lung cancer using a Bayesian analysis to obtain the predictive values for different pretest probabilities or prevalences. A cross-sectional study included 94 patients with lung cancer, 40 with benign lung disease, and 40 healthy controls. SCC antigen and CEA were measured in blood samples by microparticle enzyme immunoassay (MEIA), and CYFRA by enzyme-linked immunosorbent assay (ELISA). The results of tumour marker determinations were expressed as percentiles, and showed significantly higher levels in the cancer group than in the two control groups. Taking the 95th percentile of benign lung diseases as the cut-off point (specificity 95%), the following sensitivities were found: SCC 41%, CEA 31% and CYFRA 79%. After a Bayesian analysis, the best results for the three tumour markers were found in prevalences of 30-40%. The highest incremental gain was obtained by CYFRA (at prevalence of 36%, positive and negative predictive value approximately 90%). The three tumour markers were included in a stepwise regression analysis to predict lung cancer, and CYFRA was the only selected variable. We conclude that CYFRA 21.1 may be a useful marker in lung cancer when there is an intermediate pretest probability of disease.

Topics: Adenocarcinoma; Aged; Antigens, Neoplasm; Bayes Theorem; Biomarkers, Tumor; Carcinoembryonic Antigen; Carcinoma, Small Cell; Carcinoma, Squamous Cell; Cross-Sectional Studies; Enzyme-Linked Immunosorbent Assay; Female; Humans; Immunoenzyme Techniques; Keratin-19; Keratins; Logistic Models; Lung Diseases; Lung Neoplasms; Male; Middle Aged; Predictive Value of Tests; ROC Curve; Sensitivity and Specificity; Serpins

Topics: Animals; Brain Neoplasms; Carcinoma, Squamous Cell; Cattle; Cattle Diseases; Diagnosis, Differential; Euthanasia; Eyelid Neoplasms; Female; Horner Syndrome; Keratins; Pituitary Gland; Pituitary Neoplasms; Vimentin

Malignant melanoma occurring in burn scars is rare and cases of malignant melanoma and squamous cell carcinoma arising in a burn scar are extremely rare. We report a case of malignant melanoma and squamous cell carcinoma arising in one tumour on a stable thermal burn scar on the right leg of a 55-year-old man after a long latent period of about 50 years. The case was unique in that the malignant melanoma and squamous cell carcinoma occurred synchronously next to each other and produced one tumour. Immunohistochemical stainings with keratin, S-100 protein and HMB 45 clearly distinguished the two kinds of atypical tumour cells. Following the total resection of the original tumour, metastasis of malignant melanoma in the inguinal lymph node was found. This case underlines the possibility that another tumour may co-exist even if pathological observation reveals one kind of tumour.

Topics: Antigens, Neoplasm; Antigens, Surface; Burns; Carcinoma, Squamous Cell; Cicatrix; Humans; Immunohistochemistry; Keratins; Leg; Lymphatic Metastasis; Male; Melanoma; Melanoma-Specific Antigens; Middle Aged; Neoplasm Proteins; Neoplasms, Multiple Primary; S100 Proteins; Skin Neoplasms

CYFRA 21-1 measures soluble cytokeratin-19 fragments in serum and is a useful marker for lung carcinoma, especially squamous cell carcinoma (SCC). The authors conducted this study to determine the significance of CYFRA 21-1 in patients with esophageal SCC.. Expression and production of cytokeratin-19 in the authors' six established esophageal SCC cell lines were determined by immunocytochemical staining and enzyme-linked immunoadsorbent assay, respectively. The correlation between serum CYFRA 21-1 levels and expression of cytokeratin-19 in human tumors was investigated by immunohistochemical staining. The correlation between serum CYFRA 21-1 levels and clinicopathologic factors was examined in 48 patients with esophageal SCC, as were SCC antigen and carcinoembryonic antigen (CEA).. Of the 6 cell lines, 5 lines expressed cytokeratin-19 in their cytoplasm and produced soluble cytokeratin-19 fragments. Twenty-three of 48 patients had elevated CYFRA 21-1 levels (>3.5 ng/mL), whereas none of the reference group (consisting of healthy volunteers or patients with benign disease) showed positive levels. The specificity, sensitivity, and accuracy of CYFRA 21-1 were 100%, 47.9%, and 66.7%, respectively. CYFRA 21-1 showed significantly higher sensitivity and accuracy than SCC antigen or CEA (P < 0.05). Univariate analysis revealed that CYFRA 21-1 levels correlated with disease progression (including tumor size, tumor depth, and pTNM stage), resectability, and curability. There was a significant association between the level of CYFRA 21-1 and its intensity of immunohistochemical staining in vitro as well as in vivo.. CYFRA 21-1 appears to be a useful marker for human squamous cell carcinoma of the esophagus.

Topics: Adult; Aged; Aged, 80 and over; Antigens, Neoplasm; Biomarkers, Tumor; Carcinoembryonic Antigen; Carcinoma, Squamous Cell; Esophageal Neoplasms; Female; Humans; Immunohistochemistry; Keratins; Male; Middle Aged; Serpins; Tumor Cells, Cultured

To elevate the diagnostic value of the serum cytokeratin 19 fragment (CYFRA 21-1) and compare it with carcinoembryonic antigen (CEA) and tissue polypeptide antigen (TPA) in bronchogenic carcinoma, the sera of 161 patients (58 with benign pulmonary disease and 103 with bronchogenic carcinoma) was investigated using immunoradiometric assay. Sensitivities for CYFRA 21-1, CEA and TPA (using 3.5 ng ml-1, 5.0 ng ml-1, 110 U l-1, respectively, cut-off values corresponding to a 95% specificity for benign pulmonary disease) in bronchogenic carcinoma were 64, 47 and 61%, respectively. Positive CYFRA 21-1 levels were identified in 75% of patients with squamous cell carcinoma (n = 36), in 67% with adenocarcinoma (n = 45), in 17% with large cell carcinoma (n = 6), and in 50% with small cell lung cancer (SCLC) (n = 16). However, CYFRA 21-1 levels were not significantly different between squamous cell carcinoma and the other histological types. The sensitivity of the combined measurement of CYFRA 21-1 with any other tumour marker was significantly higher than that of CYFRA 21-1 measurement alone. Elevated CYFRA 21-1 levels were observed in 44% of Stages I and II (n = 18) and 72% of Stage III and IV (n = 69) patients with non-small cell lung cancer (P < 0.05). A significant inter-marker correlation was observed between CYFRA 21-1 and TPA (n = 103, r = 0.448, P < 0.0001). Twenty-one patients were monitored by CYFRA 21-1, and significantly different changes in progressive patients (P = 0.0058) and regressive patients (P = 0.016) were obtained. These results indicate that CYFRA 21-1 may be not only a sensitive tumour marker in the diagnosis of bronchogenic carcinoma, but also a useful marker for the monitoring of bronchogenic carcinoma.

Topics: Adenocarcinoma; Adolescent; Adult; Aged; Aged, 80 and over; Antigens, Neoplasm; Biomarkers, Tumor; Carcinoembryonic Antigen; Carcinoma, Bronchogenic; Carcinoma, Large Cell; Carcinoma, Small Cell; Carcinoma, Squamous Cell; Female; Humans; Immunoradiometric Assay; Keratin-19; Keratins; Lung Diseases; Lung Neoplasms; Male; Middle Aged; Sensitivity and Specificity; Tissue Polypeptide Antigen

The basosquamous cell carcinoma (BSCC) is a poorly defined and often misunderstood cutaneous malignancy.. The purpose of this study was to compare, using immunohistochemical techniques, the BSCC, basal cell carcinoma (BCC), and squamous cell carcinoma (SCC).. BSCC occurring at Pennsylvania State University over the past 10 years were identified. Choosing seven BCC, and nine SCC as controls, all specimens were stained for keratin, lack of apoptosis, glycoproteins, and altered gene products using the avidin/biotin and strep-avidin immunoperoxidase techniques. Each malignancy was then graded for the percentage of cells stained with each marker.. Of the markers studied, all stained to varying degrees the malignant aspects of the specimens. There were similar patterns between tumors, with the BSCC showing a transition zone between typical BCC and SCC. This was most striking for Ber-EP4, where over two-thirds of the BCC stained, none of the SCC, and half of the BSCC showed reactivity.. BSCC has staining patterns similar to both the BCC and SCC. The presence of a transition zone does not support the concept that all BSCC are collision tumors, but rather a differentiation of one tumor into another. We confirm earlier reports that Ber-EP4 could be used to distinguish between classic BCC and SCC. AE1/AE3, bcl-2, TGF-alpha, and p53 were not helpful in separating the tumors.

Topics: Carcinoma, Basal Cell; Carcinoma, Basosquamous; Carcinoma, Squamous Cell; Diagnosis, Differential; ErbB Receptors; Humans; Immunohistochemistry; Keratins; Membrane Glycoproteins; Proto-Oncogene Proteins c-bcl-2; Skin Neoplasms; Tumor Suppressor Protein p53

In Western countries, esophageal squamous cell carcinoma is usually advanced at presentation and is rarely diagnosed in situ. The authors studied an in situ squamous cell carcinoma that occupied the entire mucosa of a 9 cm length of esophagus, causing dysphagia for solid food in a woman aged 68 years.. The esophagectomy specimen contained a circumferential region of depressed tan mucosa in the middle and lower thirds, bordered above and below by normal squamous mucosa, without ulcer, stricture, or mass. The entire lesion was submitted for histology and evaluated with immunostains for cytokeratins and markers of Paget's cells, p53 mutation, and proliferation.. The lesion involved 45 cm2 of mucosa. Large, atypical cells with frequent mitoses occupied the basal layers of the squamous epithelium and were often separated from more superficial maturing cells by acantholysis. Pagetoid spread of tumor cells into nonneoplastic surface and gland duct epithelium was prominent. The tumor cells expressed cytokeratins of low molecular weight, p53 gene product, and proliferating cell nuclear antigen (PCNA), but lacked markers usually seen in Paget's cells in the breast or vulva. No invasion was evident.. This extensive in situ squamous cell carcinoma of the esophagus resulted from pagetoid spread of tumor cells. These cells had a phenotype suggestive of origin from primitive epidermal stem cells and also had overexpressed p53 and PCNA, but they lacked the capacity to penetrate the basement membrane. Flat, erythematous areas of esophageal mucosa seen during endoscopy could represent early squamous cell carcinoma and should be biopsied.

Topics: Aged; Basement Membrane; Carcinoma in Situ; Carcinoma, Squamous Cell; Cell Division; Deglutition Disorders; Epithelium; Esophageal Neoplasms; Esophagectomy; Female; Gene Expression Regulation, Neoplastic; Genes, p53; Humans; Keratins; Mitosis; Mucous Membrane; Mutation; Paget Disease, Extramammary; Phenotype; Proliferating Cell Nuclear Antigen; Tumor Suppressor Protein p53

Basaloid squamous cell carcinoma (BSCC) is a recently recognized, poorly differentiated variant of squamous cell carcinoma (SCC), which is located predominantly in the upper aerodigestive tract.. In this study, clinical and pathologic parameters of 17 BSCCs and 133 typical SCCs of the esophagus that underwent potentially curative resection (no distant metastases, no residual tumor) were compared. In addition, light microscopic, electron microscopic, and immunohistochemical features of BSCC were investigated, to determine whether this type of carcinoma could be differentiated from other poorly differentiated carcinomas of the esophagus.. Light microscopic study showed that BSCC was composed of relatively small tumor cells, arranged in solid lobules with abundant comedo-type necrosis. BSCC was almost invariably accompanied by areas of concomitant typical SCC, foci of squamous cell differentiation, and/or severe squamous cell dysplasia or carcinoma in situ of the adjacent mucosa. Ultrastructurally, BSCC inconsistently showed features of squamous cell differentiation. Immunohistochemically, BSCC displayed poor reactivity for antibodies against wide-range cytokeratins and cytokeratin subtypes that are typical of squamous cell epithelia (cytokeratin 13 and cytokeratin 14). Infrequently, expression of Leu7, smooth muscle actin, and S-100 protein was found. In comparison with typical SCC, the characteristic features of BSCC were older patient age, higher proliferative activity (MIB-1 labelling index), and higher apoptotic indices. No differences were found with regard to pT classification, pN classification, tumor size, blood vessel invasion, lymphatic vessel invasion, neural invasion, or patient gender. Moreover, no differences in overall survival rates were found.. BSCC is a distinct histopathologic variant of SCC, characterized by a poor degree of differentiation and high proliferative activity. However, after potentially curative resection, the prognosis of patients with BSCC of the esophagus does not differ from that of patients with typical SCC.

Topics: Actins; Adult; Age Factors; Aged; Aged, 80 and over; Antigens, Differentiation; Apoptosis; Carcinoma in Situ; Carcinoma, Basosquamous; Carcinoma, Squamous Cell; Cell Differentiation; Cell Division; Diagnosis, Differential; Epithelium; Esophageal Neoplasms; Female; Humans; Immunohistochemistry; Keratins; Male; Microscopy, Electron; Middle Aged; Mucous Membrane; Necrosis; Neoplasm Invasiveness; Neoplasm Staging; Prognosis; S100 Proteins; Sex Factors; Survival Rate

Topics: Carcinoma, Squamous Cell; Humans; Immunoenzyme Techniques; Keratins; Laminin; Neoplasm Staging; Skin Neoplasms

Cytokeratins form part of the cytoskeleton of both normal and malignant epithelium. A novel tumor marker measuring cytokeratin 19 (CK-19) fragment has been introduced and proven to be suitable for monitoring therapy and following cases of non-small cell lung cancer, squamous cell lung cancer in particular. However, whether the serum level of CK-19 fragment reflects the number of proliferating tumor mass remains unknown. We studied the CK-19 fragment produced by two human squamous cell lung cancer cell lines. In Western blotting analysis, culture supernatants of both cell lines displayed bands of 37 and 40 kDa, which represented the CK-19 fragment and the intact CK-19, respectively. Gel filtration demonstrated that a part of soluble CK-19 was released as a large complex form in culture supernatants. The level of CK-19 fragment in culture supernatants increased during the exponential growth phase. CK-19 level decreased by an addition of a cytotoxic agent to non-significant level though the transient release of CK-19 fragment occurred during the first 2 days. After all, soluble CK-19 fragments were detected in culture supernatants of human lung cancer cell lines and its level reflected proliferating cancer cells though it was not determined whether CK-19 fragments were released directly from live cells.

Topics: Carcinoma, Squamous Cell; Cell Division; Cell Survival; Humans; Keratins; Lung Neoplasms; Molecular Weight; Peptide Fragments; Tumor Cells, Cultured

We report an 85-year-old man with squamous cell carcinoma on the right pinna. Two years after the excision of the lesion, metastatic foci were found extending from the right retromandibular to the mastoid region and into the parapharyngeal space. Histopathologically, the primary tumor showed interconnecting nests of atypical cells invading into the dermis from multiple epidermal and infundibular foci. The tumor had both squamous and glandular differentiation. A peculiar finding was the presence of decapitation secretion in the glandular foci. To our knowledge, definite apocrine differentiation in squamous cell carcinoma has not previously been reported.

Topics: Adenocarcinoma; Aged; Aged, 80 and over; Apocrine Glands; Carcinoembryonic Antigen; Carcinoma, Squamous Cell; Cell Differentiation; Ear Neoplasms; Ear, External; Head and Neck Neoplasms; Humans; Keratins; Male; Mastoid; Neoplasm Invasiveness; Pharyngeal Neoplasms; Skin Neoplasms; Skull Neoplasms

Topics: Aged; Antigens, Neoplasm; Anus Neoplasms; Biomarkers, Tumor; Biopsy; Carcinoembryonic Antigen; Carcinoma, Squamous Cell; Colonoscopy; Female; Humans; Immunoradiometric Assay; Keratins; Magnetic Resonance Imaging; Male; Middle Aged; Retrospective Studies; Sensitivity and Specificity; Tissue Polypeptide Antigen; Tomography, X-Ray Computed

The keratin expression of 40 frozen tissue specimens of anal carcinoma was investigated using a panel of 17 monoclonal antibodies to 14 individual keratins. The tumours were divided into three histological subgroups showing pure squamous, squamous and basaloid, or squamous and glandular differentiation. A further assessment of the tumour grade was made. The overall profile was of expression of keratins 4, 13, 17, 18 and 19 across the majority of the tumours, with the minority expressing keratins 1 and 10, and keratin 7. Dedifferentiation was associated with loss of expression of keratinocyte keratins, particularly the cornification markers keratin 1 and 10, and K6 and 16 associated with keratinocyte hyperproliferation and differentiation. This correlated with acquisition of the simple epithelial keratins 7 and 8. Compared with the tumours as a whole, well differentiated squamous tumours (the most easily identifiable histological group) showed consistent positivity for keratins 6 and 16, expressed suprabasally, while simple keratins 18 and 19 were also found. Independent of grade, mixed tumours showed more widespread positivity for simple epithelial keratins 7, 8 and 18 and loss of expression of cornification keratins 1 and 10 and K6 and 16 compared with pure squamous tumours. The relatively limited keratin profile of pure squamous tumours, predominantly consisting of keratinocyte keratins, suggests that these malignancies are less likely to originate from the region of the anal canal where the keratin profile is heterogeneous, i.e. the anal transitional zone.

Topics: Anus Neoplasms; Biopsy; Carcinoma, Squamous Cell; Cell Differentiation; Humans; Immunohistochemistry; Keratins

Squamous carcinoma of the larynx arises from pre-existing lesions, the so-called "preneoplastic lesions". Hyperplastic lesions represent a part of their spectrum, from both clinical and biological points of view. On morphologic grounds, the most characteristic feature with prognostic value in the evaluation of preneoplastic lesions is dysplasia. It is not only nuclear alterations that are seen in the process of malignant transformation, the cytoplasmic pattern of cytokeratins changes through neoplastic progression, with a progressive reduction of the molecular weight of the produced species. Dysplasia also associates with gross alterations of the DNA content. This is in agreement with our finding of alterations of genes participating in the control of the cell cycle, p53 and p21(WAF1/cip1). p53 overexpression is detected in non-invasive squamous lesions (even in the absence of obvious dysplasia) and p21(WAF1/cip1) shows a dramatic change in the pattern of expression in dysplastic epithelium compared with the normal. However, not all genes participating in the control of the cell cycle are altered in early lesions. Overexpression of cyclin D1, a common phenomenon in advanced carcinomas, is not likely to participate in the early phases of neoplastic development.

Topics: Biomarkers, Tumor; Carcinoma, Squamous Cell; Cell Transformation, Neoplastic; Cyclin D1; Cyclin-Dependent Kinases; Cyclins; DNA, Neoplasm; Epithelium; Genes, p53; Humans; Hyperplasia; Keratins; Laryngeal Diseases; Laryngeal Mucosa; Laryngeal Neoplasms; Oncogene Proteins; Precancerous Conditions

Topics: Adenocarcinoma; Antigens, Neoplasm; Biomarkers, Tumor; Carcinoma, Small Cell; Carcinoma, Squamous Cell; Humans; Keratin-19; Keratins; Lung Neoplasms; Neoplasm Staging; Phosphopyruvate Hydratase

Soluble intercellular adhesion molecule-1 (s-ICAM-1) was measured in the sera of 131 patients with primary and 50 patients with recurrent squamous cell cancer of the head and neck (HNSCC). 30 patients with benign ear, nose and throat diseases served as controls. s-ICAM-1 levels in serum are high in patients with HNSCC, particularly in the advanced tumor stages (UICC IV). Highest levels can be measured at the time of tumor recurrence and locoregional lymph node metastases. The sensitivity (95% specificity) of s-ICAM-1 (cutoff-level: 473 ng/ml) is 4% at primary diagnosis and 12% for recurrent disease. A coefficient of correlation for s-ICAM-1 in combination with SCC, carcinoembryonic antigen and CYFRA 21-1 indicates that no correlation can be found of s-ICAM-1 compared with traditional tumor markers. Due to overlapping values in control and patient groups s-ICAM-1 is not suitable for a specific clinical use in HNSCC.

Topics: Antigens, Neoplasm; Biomarkers, Tumor; Carcinoembryonic Antigen; Carcinoma, Squamous Cell; Head and Neck Neoplasms; Humans; Intercellular Adhesion Molecule-1; Keratins; Lymphatic Metastasis; Prognosis; Serpins

The expression of cytokeratins (CKs) in normal cervical epithelium, low grade squamous intraepithelial lesions (SIL), high grade SILs and squamous cell carcinoma (SCC) were analyzed using four different monoclonal antikeratin antibodies. In normal cervical epithelium, CK 18 showed strong immunoreactivity in basal and parabasal layers. CK 19 and 14 were expressed only in the basal layer while CK 13 was found selectively n the spinal cells. As the lesions progressed from low grade SIL to high grade SIL, immunoreactivity of CK 18, 19 and 14 in the basal cell compartment increased while the expression of CK 13 decreased. In SCC, as well-differentiated tumors showed decreased immunoreactivity for CK 18, 19 and 14 with CK 13 showing a strong and focal (localized) immunoreactivity. Undifferentiated carcinomas totally lacked CK 13 reactivity. Our findings therefore suggest that expression of CK 18, 19 and 14 may be directly related to tumor grade and CK 13 may be a marker of differentiation in cervical lesions.

Topics: Adenocarcinoma; Biomarkers, Tumor; Carcinoma, Squamous Cell; Female; Humans; Immunohistochemistry; Keratins; Uterine Cervical Dysplasia; Uterine Cervical Neoplasms

The expression of the adhesion molecule CD44 variant 6 (CD44v6) was studied immunohistochemically on 38 oral squamous cell carcinomas (SCCs) and 10 biopsies of healthy oral mucosa. The relationship between the expression of CD44v6 and regional lymph node metastasis was also investigated. The expression of CD44v6 was apparently down-regulated in oral SCC, but not in normal oral mucosa. Carcinomas expressing lower levels of CD44v6 exhibited more frequent regional lymph node metastasis. The expression of CD44v6 showed no statistically significant relationship to the degree of differentiation, but tended to be down-regulated in poorly differentiated carcinoma. No significant relation was found between the expression of CD44v6 in primary and metastatic lesions.

Topics: Antibodies, Monoclonal; Carcinoma, Squamous Cell; Cell Differentiation; Cell Membrane; Coloring Agents; Down-Regulation; Epithelium; Exons; Fibroblasts; Gene Expression Regulation, Neoplastic; Humans; Hyaluronan Receptors; Immunoenzyme Techniques; Keratins; Lymphatic Metastasis; Mouth Floor; Mouth Mucosa; Mouth Neoplasms; Neoplasm Invasiveness; Tongue Neoplasms

The differential expression of cytokeratins in epithelial or squamous cells has been demonstrated to be altered during the process of carcinogenesis. This altered expression of cytokeratins (CKs) may be closely related with epithelial differentiation and may remain stable in malignant tumors. In the present study an analysis using two monoclonal antibodies, CK 8.12 antibody specific for CK type 13 and 16 and CK 8.60 antibody specific for CK type 1, 10 and 11 was done in different grades of lesions in the uterine cervix. Changes from the normal expression pattern were seen in high grade Squamous intraepithelial lesions (SIL) (CIN-2/3) and invasive squamous cell carcinoma (SCC). No conspicuous difference in the staining expression between normal/benign cervical tissue and low grade SIL (CIN-I) was evident. Statistical analysis also revealed a significant correlation between the expression of these CK types to the differentiation status of the cervical lesions analyzed. Alterations in the expression of these CKs can be correlated to the differentiation pathway which may be deregulated during cervical carcinogenesis. The findings of the present study suggest that the expression of CK types 13 and 16 and 1, 10 and 11 using CK 8.12 and CK 8.60 antibodies respectively may serve as markers of differentiation in cervical squamous neoplasms.

Topics: Adult; Analysis of Variance; Carcinoma, Squamous Cell; Cell Differentiation; Cell Transformation, Neoplastic; Cervix Uteri; Female; Humans; Immunochemistry; Keratins; Middle Aged; Uterine Cervical Dysplasia; Uterine Cervical Neoplasms

It has been demonstrated that CYFRA 21-1 (ELISA kit), which recognizes the soluble cytokeratin 19 fragment, is useful for assessing circulating tumor antigens in sera of patients with lung cancer. In this study, we compared the clinical significance of this new marker with the established squamous cell carcinoma antigen (SCC Ag), using sera from patients with head and neck malignant disease, healthy controls, and supernatants of established cell lines derived from squamous cell carcinomas and adenocarcinomas. The subjects were: Group A, 39 patients with malignant disease of the head and neck. Group B, 11 patients considered to be tumor-free after treatment. Group C, 67 patients with benign disease or healthy volunteers. Culture supernatants: 11 cell lines established from squamous cell carcinomas and adenocarcinomas. Serum levels of CYFRA 21-1 and SCC Ag of group A were significantly higher than those of group C. This finding suggests that CYFRA 21-1 is useful as a tumor marker as well as SCC Ag. CYFRA 21-1 and SCC Ag levels of patients in group A at the early and progressive stages of disease were comparable to the levels in group C. Both tumor markers are therefore useful for diagnosis of in the early stage of cancer. We attempted to set a cut-off level of CYFRA 21-1. The sensitivity of CYFRA 21-1 is higher than that of SCC Ag, especially in patients in the early stage of the disease. This finding indicates that the CYFRA 21-1 is preferable to SCC Ag as a tumor marker for the diagnosis of patients even in the early stages of malignant disease. The levels of CYFRA 21-1 in culture supernatants derived from tumor cell lines are higher than those of SCC Ag in all cell lines. The levels of CYFRA 21-1 are measurable, with levels varying with the cell line. There appears to be no correlation between the level of CYFRA 21-1 and the character of the cell lines, but this issue remains to be further investigated.

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

An organotypic, tridimensional cell culture, also called a raft system, was used to study the influence of fibroblasts on epithelial carcinogenesis in a cell line derived from laryngeal squamous cell carcinoma and harboring a mutated p53. Differences between the effects of normal fibroblasts and those of tumor-derived fibroblasts were compared by means of fibroblasts taken from the normal skin and from the tumor of a cancer patient and cultivated with epithelial carcinoma cells in an organotypic culture. To study cell contact-mediated changes, the fibroblasts were either simply embedded in collagen matrix or additionally brought into direct contact with epithelial cells. Control epithelial cells were cultivated without any fibroblasts in an organotypic model. A protein panel [p53, p21, PCNA, bcl-2, Ki67, total cytokeratin (CK), CK 8, CK 10, CK 17, CK 18, CK 19, vimentin] involved in cell cycling and epithelial differentiation was assessed immunocytochemically in all organotypic cultures with fibroblasts, in tumor cells cultivated as a monolayer, and in the original tumor sample. The most dysplastic phenotype was obtained when tumor-derived fibroblasts were used in direct contact with epithelial cells, whereas the most benign phenotype was seen when skin fibroblasts had no contact with them. The intensive staining seen for p53 can be explained by p53 mutations also reflecting the weak expression of p21 and abundant expression of PCNA. The intensive Ki67 staining seen in all sections paralleled that of PCNA and marked active cellular proliferation. The CK staining pattern seen in cultured epithelia toward embryonic CKs, CK 8 and CK 18, suggested a simple epithelial phenotype. CK 19 was found only in the epithelium where no direct contacts had occurred. Vimentin expression increased when the raft epithelium was shifting toward a more benign phenotype. The results stress the importance of the origin of fibroblasts as well as the role of direct cellular contacts in modifying the epithelial phenotype even when the epithelial cells are malignant.

Topics: Adult; Biomarkers; Carcinoma, Squamous Cell; Cell Culture Techniques; Cell Cycle; Cell Differentiation; Cells, Cultured; Coculture Techniques; Epithelial Cells; Epithelium; Fibroblasts; Humans; Keratins; Ki-67 Antigen; Laryngeal Neoplasms; Male; Proliferating Cell Nuclear Antigen; Skin; Tumor Cells, Cultured; Vimentin; Vocal Cords

The type and distribution of keratins (K) in malignant tumors of eyelids were examined immunohistochemically to understand the pathomechanism of intercellular interactions. All of the tumor cells in the basal cell carcinoma were positive for K14, which is specific for basal cells, whereas all of them were negative for K10, which is specific for suprabasal layers in stratified squamous epithelia. These findings suggest that basal cell carcinoma may consist of uniform, basal cell-like tumor cells. On the other hand, the squamous cell carcinoma and sebaceous carcinoma, which were positive for either K14 or K10 to varying extent, may consist of various tumor cells with different types and degrees of differentiation. In these tumors, K14 was frequently detected throughout the border cells of the tumor mass. Apoptotic bodies were detected at the region where this continuous distribution of K14 was interrupted. These findings may help to clarify the pathomechanism of the interactions between the tumor cells and stromal cells.

Topics: Adenocarcinoma, Sebaceous; Aged; Aged, 80 and over; Carcinoma, Basal Cell; Carcinoma, Squamous Cell; Eyelid Neoplasms; Female; Humans; Immunohistochemistry; Keratins; Male; Middle Aged

This study evaluated use of a combination assay of tumor markers in the diagnosis of oral squamous cell carcinoma.. Serum levels of four tumor markers (carcinoembryonic antigen [CEA], squamous cell carcinoma antigen [SCCA], immunosuppressive acidic protein [IAP], and cytokeratin 19 fragment [Cyfra]) were simultaneously measured in 42 patients with oral squamous cell carcinoma (O-SCC) and in 12 patients with oral benign diseases.. The positive rates were 31.0% for CEA, 38.1% for SCCA, 52.4% for IAP, and 38.1% for Cyfra in patients with O-SCC. These rates were significantly different (P < .01) from those of control patients with oral benign diseases. The sensitivity (81.0%) and accuracy (77.8%) of the combination assay uses higher than that obtained with individual markers.. A combination assay with CEA, SCCA, IAP, and Cyfra may be useful for the screening of patients with suspected oral squamous cell carcinoma.

Topics: Adult; Aged; Aged, 80 and over; Antigens, Neoplasm; Biomarkers, Tumor; Carcinoembryonic Antigen; Carcinoma, Squamous Cell; Chi-Square Distribution; Female; Humans; Keratins; Male; Middle Aged; Mouth Diseases; Mouth Neoplasms; Neoplasm Proteins; Sensitivity and Specificity; Serpins

Retinoids are natural and synthetic analogues of vitamin A and have proven activity in various types of cancer. As for head and neck squamous cell cancer (HNSCC), retinoids are especially active in leukoplakia and in preventing second primary cancers. The aim of this study was to assess the growth inhibiting activity of all-trans retinoic acid (all-trans RA) in a panel of six head and neck squamous cell cancer cell lines and to correlate this response to the mRNA expression of factors related to differentiation and receptor mediated signal transduction. Three lines showed minimal, two moderate and one strong growth inhibition after 72 h exposure to all-trans RA. Three lines with a dissimilar response were selected for further studies, the measurement of mRNA expression by northern blotting. It was found that neither the expression nor the induction of retinoic acid receptor (RAR)-alpha and -gamma and retinoic X receptor-alpha mRNA war related to sensitivity. The mRNA expression of RAR-beta was too low to be measured in the three cell lines. The most sensitive cell line was, however, the only one that expressed mRNA of squamous differentiation markers. These data suggest a relationship between the retinoid sensitivity profile and the degree of cellular differentiation.

Topics: Carcinoma, Squamous Cell; Cell Division; Cornified Envelope Proline-Rich Proteins; Gene Expression Regulation, Neoplastic; Head and Neck Neoplasms; Humans; Keratins; Membrane Proteins; Neoplasm Proteins; Proteins; Receptors, Retinoic Acid; RNA, Messenger; RNA, Neoplasm; Tretinoin; Tumor Cells, Cultured

A human squamous cell carcinoma (SCC) cell line has been established from the surgical specimen of an untreated, upper aero-digestive tract tumour, diagnosed as a squamous carcinoma, grade III, of the pyriform fossa. The tumour tissue was grown as a xenograft in an athymic nude mouse and was designated as NT-8. Histological examination of the surgical specimen and the nude mouse tumour showed that the two were identical. NT-8 was subsequently passed by subcutaneous injections into nude mice. After the 6th passage in nude mouse, the tumour was cultured in vitro where it grew as an epithelial cell line, with a typical cobblestone appearance. This cell line was designated as NT-8e. Both the primary tumour as well as xenograft and the cells in culture have retained several common morphological and biochemical characteristics. Immunological markers for epithelial cells including epithelial membrane antigen and cytokeratins were seen in all three, confirming the epithelial lineage. Characterization of the NT-8e cell line including growth parameters, anchorage-independent growth and tumorigenicity in nude mice, chromosome counts and DNA content by flow cytometry have been carried out.

Topics: Animals; Carcinoma, Squamous Cell; Cell Adhesion; Cell Culture Techniques; Cell Division; Chromosome Mapping; DNA, Neoplasm; Humans; Keratins; Kinetics; Mice; Mice, Nude; Mucin-1; Pharyngeal Neoplasms; Proliferating Cell Nuclear Antigen; Transplantation, Heterologous; Tumor Cells, Cultured

A case of a 66-year-old Japanese woman with two synchronous urinary bladder tumors, namely verrucous carcinoma and poorly differentiated squamous cell carcinoma, is described. Both tumors were accompanied by widespread squamous metaplasia in the background and unassociated with bilharzial infection. The poorly differentiated squamous cell carcinoma, having a satellite tumor in its proximity, was large and in an advanced stage. The verrucous carcinoma was small with minimal invasion to the muscularis propria. The boundary between both tumors was well defined, suggesting colliding growth appearance. Immunoexpression of cytokeratins of verrucous carcinoma was similar to that of squamous metaplasia, and significant differences between verrucous carcinoma and poorly differentiated squamous cell carcinoma were demonstrated in their immunoexpression of cytokeratins.

Topics: Aged; Biomarkers, Tumor; Carcinoma, Squamous Cell; Female; Humans; Immunohistochemistry; In Situ Hybridization; Keratins; Neoplasms, Multiple Primary; Schistosomiasis; Urinary Bladder Neoplasms

The keratin cytoskeleton is formed in different epidermal compartments by distinct polypeptides. Basal, proliferative keratinocytes express keratin (K) 5 and K14, whereas, suprabasal, post-mitotic keratinocytes express K1 and K10. Changes in this keratin pattern have been found to occur in hyperproliferative skin disorders and, in particular, throughout mouse epidermal carcinogenesis. Whereas some keratins not found in normal epidermis (K6, K16, K13, and K8) are induced at different stages of tumor development, K1 and K10 expression is lost. To determine whether K1 and K10 loss is just a consequence of the altered differentiation program or an event required for tumor progression, we generated transgenic mice carrying the human keratin 10 gene (hK10) under the control of a bovine keratin 6 gene regulatory region, which is silent in normal skin but is induced and drives transgene expression in hyperproliferative skin keratinocytes and, therefore, in skin tumors. Transgenic animals subjected to a complete carcinogenesis protocol developed tumors that contained various amounts of transgenic hK10. Although no significant difference was found in tumor number or malignancy, tumor onset was significantly delayed in transgenic mice, indicating that the presence of K10 actually impairs tumor development.

Topics: 9,10-Dimethyl-1,2-benzanthracene; Animals; Carcinogens; Carcinoma, Squamous Cell; Cattle; Cell Division; Cocarcinogenesis; Gene Expression; Humans; Keratin-10; Keratins; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Mice, Transgenic; Skin; Skin Neoplasms; Skin Physiological Phenomena; Transgenes

The immunohistochemical expression patterns of cytokeratin polypeptides and vimentin were investigated in normal epithelia and squamous cell carcinomas of the larynx with special emphasis on tumor grading. During malignant transformation of epithelial cells, the cytokeratin expression patterns changed, depending on the differentiation grade of the carcinomas. In low-grade carcinomas, the expression patterns were close to those of the normal epithelium. With increasing tumor grade, there was decreased expression of stratification cytokeratins and increased expression of basal cell, simple cell and hyperproliferation-related cytokeratins. Increasing tumor grade was also associated with the expression of vimentin, a cytoskeletal protein of mesenchymal cells. No relationship was found between vimentin expression and the presence of lymph-node metastases.

Topics: Biomarkers, Tumor; Carcinoma, Squamous Cell; Cell Division; Cell Transformation, Neoplastic; Epithelium; Humans; Keratins; Laryngeal Neoplasms; Larynx; Lymphatic Metastasis; Neoplasm Staging; Prognosis; Reference Values; Vimentin

Cytokeratins (CK) are one of the main families of intermediate filaments which make up the cytoskeleton. CK19 is strongly expressed by normal simple bronchial and respiratory epithelium as well as by their malignant counterpart. Although CK19 is a part of the cytoskeleton, a soluble fragment of this polypeptide can be released and assayed in the blood as CYFRA 21-1, new sensitive and valuable marker of non small cell lung cancer. In some cases, however, discrepancies between the serum level of CYFRA 21-1 and presence of tumor and its histological type have been observed. We studied immunohistochemically tissue localization of CK19 in tumors and non invaded lung parenchyma in a series of 34 patients surgically treated due to lung cancer. CK 19 was detected in cancer cells as well as in non neoplastic epithelium covering bronchial tree and alveolar surfaces. We found a different expression of CK19 in different histological type of tumors. The most intensive expression revealed squamous cell carcinomas and adenocarcinomas. Small cell cancer revealed poor expression of CK19. In non invaded parts of the resected lungs we found the strong expression of CK19 in the cytoplasm of regenerative II type pneumocytes occurring in large quantity in the cases of interstitial lung fibrosis concomitant with some tumors. We suggest it may be a cause of unexpectedly elevated serum levels of CYFRA 19-21 in some not oncological patients or patients with small cell lung cancer.

Topics: Adenocarcinoma; Adult; Aged; Antibodies, Monoclonal; Biomarkers, Tumor; Bronchi; Carcinoma, Large Cell; Carcinoma, Non-Small-Cell Lung; Carcinoma, Small Cell; Carcinoma, Squamous Cell; Cytoplasm; Epithelium; Female; Humans; Infant; Keratins; Lung Neoplasms; Male; Middle Aged; Neoplasm Proteins; Pulmonary Alveoli; Pulmonary Fibrosis

The increased glucose uptake seen in cancer cells correlates with the expression of human erythrocyte glucose transporter (Glut1) protein in certain human malignancies.. Our purpose was to determine Glut1 expression in cutaneous neoplasms.. A polyclonal anti-Glut1 antibody (MYM) and a standard ABC immunoperoxidase technique were used to determine Glut1 expression in invasive squamous cell carcinomas (SCCs), SCC in situ, basal cell carcinomas (BCCs), melanomas, actinic keratoses (AKs), seborrheic keratoses, common acquired nevi, and scars with regenerative epidermal hyperplasia.. All of the cases of SCC in situ, 14 of 15 (93%) of the SCC, and 13 of 15 AKs (87%) showed intense membranous staining for Glut1. Glut1 staining was present in the epidermis of 8 of 15 scars (53%) but was not detected in any BCC, even in areas of focal keratinization and squamous metaplasia. Glut1 reactivity was absent in the melanomas and seborrheic keratoses.. Glut1 expression in a cutaneous lesion strongly suggests a proliferative lesion of the squamous cell type.

Topics: Antibodies; Carcinoma in Situ; Carcinoma, Basal Cell; Carcinoma, Squamous Cell; Cell Division; Cicatrix; Dermatitis, Seborrheic; Epidermis; Epithelial Cells; Gene Expression Regulation, Neoplastic; Glucose; Glucose Transporter Type 1; Humans; Hyperplasia; Immunoenzyme Techniques; Keratins; Keratosis; Melanoma; Monosaccharide Transport Proteins; Neoplasm Invasiveness; Nevus; Regeneration; Skin Neoplasms

A study was made of the prognostic value of pretreatment measurements of tumour radiosensitivity (surviving fraction at 2 Gy, SF2) in 128 patients with stage I-III carcinomas of the uterine cervix undergoing radiotherapy. The median follow-up time was 47 months. In a univariate analysis stratifying patients according to the median value, radiosensitivity was a significant prognostic factor for overall survival, local control and metastasis-free survival. The 5-year survival rate for tumours with SF2 values below the median was 81% and was significantly greater than the rate of 51% for those with SF2 values above the median. In bivariate analyses, SF2 was shown to be independent of disease stage, tumour grade, patient age, colony-forming efficiency and tumour diameter. In a multivariate analysis, radiosensitivity was the most important variable and, after allowing for this, only stage was a significant independent predictor of treatment outcome. These data indicate that, in carcinoma of the cervix treated with radiotherapy, pretreatment tumour intrinsic radiosensitivity is an important prognostic parameter and contributes to prognosis independently of other established and putative parameters.

Topics: Adenocarcinoma; Adult; Age Factors; Aged; Carcinoma, Squamous Cell; Disease-Free Survival; Female; Humans; Immunohistochemistry; Keratins; Middle Aged; Multivariate Analysis; Neoplasm Recurrence, Local; Prognosis; Radiation Tolerance; Survival Rate; Time Factors; Treatment Outcome; Uterine Cervical Neoplasms

A case of squamous cell carcinoma of the tongue is reported with emphasis on an atypical finding of cervical lymph node metastasis visible on computed tomography. Multiple cervical lymph nodes revealed a high computed tomographic value of about 330 HU, lower than that of calcification. The lymph nodes revealed well-defined elliptical hyperechoic masses with an echogenic line and posterior shadow on ultrasonography. The appearance of a high density mass on computed tomography with a computed tomographic value lower than that of calcification may be a reliable finding of metastasis because it demonstrates the presence of marked keratinization produced by squamous cell carcinoma.

Topics: Calcinosis; Carcinoma, Squamous Cell; Humans; Keratins; Lymph Nodes; Lymphatic Metastasis; Male; Middle Aged; Neck; Radiography, Panoramic; Reproducibility of Results; Tomography, X-Ray Computed; Tongue Neoplasms; Ultrasonography

Since it was first described in 1986, basaloid-squamous cell carcinoma (BSC) has been considered a distinct variant of squamous cell carcinoma that occurs in a variety of anatomic sites, including the head and neck region. We report the characterization of the first cell line established from a basaloid-squamous cell carcinoma of the floor of the mouth. The cell line exhibited a highly invasive capacity, indicating that BSC has very aggressive behavior. This cell line may be a useful model for elucidation of the biological characteristics of BSC.

Topics: Actins; Biology; Carcinoma, Squamous Cell; Carcinoma, Transitional Cell; Cell Division; Cell Movement; Cell Separation; Culture Media; Endothelium; Epithelial Cells; Fibroblasts; Humans; Keratins; Male; Middle Aged; Mouth Floor; Mouth Neoplasms; Mucin-1; Neoplasm Invasiveness; S100 Proteins; Tongue Neoplasms; Tumor Cells, Cultured

The single cell gel electrophoresis (SCGE) assay, also known as the comet assay, is a cytogenetic technique for measuring and analyzing DNA single stranded breaks (SSB) and/or alkali labile sites within individual cells. Peripheral blood leukocytes of 22 oral squamous cell carcinoma (OSCC) patients were subjected to SCGE and the DNA damage levels (SSB) were quantified with respect to clinical staging and histopathologic grading. Highly statistically significant differences in DNA damage levels were found between normal subjects and patients with OSCC of the same age group. DNA damage levels were altered in all clinical stages and histopathological grades of oral squamous cell carcinoma. The differences were generally significant between all the clinical stages of OSCC, while in histopathologic grading the results were significant only between grades I and III. The results support the concept of a systemic host response in malignancy.

Topics: Adult; Age Factors; Alkalies; Blood; Carcinoma, Squamous Cell; Case-Control Studies; Cell Nucleus; Cytogenetics; DNA Damage; DNA, Neoplasm; DNA, Single-Stranded; Electrophoresis, Agar Gel; Female; Humans; Keratins; Leukocytes; Male; Middle Aged; Mitosis; Mouth Neoplasms; Neoplasm Invasiveness; Neoplasm Staging; Plasma Cells

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

During the development of squamous cell carcinomas of the head and neck (SCCHN), cytokeratin (CK) 18 and 19, which are typical for simple epithelia, show an elevated expression in tumor tissues. CK 8 was found to be overexpressed in cell lines of SCCHN. Epithelial tumors like normal epithelia express characteristic "pairs" of CK. The smallest of these pairs comprises CK 8 and 18. Therefore, the aim of this study was to serologically detect fragments of CK 8 and 18 (cyfra 8/18) in SCCHN patients.. Sera of 151 patients with SCCHN were tested for cyfra 8/18 (cyfra 8/18 ELISA medac, Hamburg) before treatment. Thirty sera of healthy volunteers and 43 sera of patients with benign diseases of the head and neck region served as control and reference group, respectively. Thirteen patients were followed-up clinically and serologically after surgery. The serum cyfra 8/18 concentrations of those 13 patients were compared to their clinical run.. The cut-off value for cyfra 8/18 was determined with a 95% specificity of the reference group and was fixed at 1.1 ng/ml. The sensitivity was 7%. No correlation was found between cyfra 8/18 and clinical parameters like tumor stage, grading, and tumor location. Cyfra 8/18 concentrations could be correlated to the clinical run of 5 of 13 followed-up patients.. Because of its low sensitivity, the serological detection of cyfra 8/18 must not be seen as a sufficient tumor marker for SCCHN. Its clinical applicability for regular post-surgical controls seems to be restricted and appears inferior to the clinical usefulness of cyfra 21-1.

Topics: Biomarkers, Tumor; Carcinoma, Squamous Cell; Enzyme-Linked Immunosorbent Assay; Follow-Up Studies; Humans; Keratins; Neoplasm Staging; Otorhinolaryngologic Neoplasms; Peptide Fragments; Reference Values

A 55-year-old woman, who was found to have malignant squamous cells on a routine cervical smear, underwent a conization biopsy, followed by hysterectomy with bilateral salpingo-oophorectomy. No gross tumor was present in the uterus, but both ovaries, which were of normal size, contained multiple cysts filled with light brown, soft material. Microscopic examination showed squamous cell carcinoma in situ of the cervix with contiguous spread to the endometrium, fallopian tubes, and ovaries; squamous cell carcinoma extensively replaced the endometrial and tubal epithelium, focally invaded the wall of the fallopian tubes, and involved the parenchyma of both ovaries. Although an invasive cervical carcinoma occasionally spreads to the ovary, this case illustrates that exceptionally an in situ tumor spreads along the epithelium of the upper genital tract and the ovarian surface and invades the ovary and tubes. The detection of human papillomavirus DNA in the cervical, endometrial, tubal, and ovarian tumors by the polymerase chain reaction suggests a role for human papilloma virus infection in this case.

Topics: Carcinoma in Situ; Carcinoma, Squamous Cell; Endometrial Neoplasms; Fallopian Tube Neoplasms; Female; Humans; Immunohistochemistry; In Situ Hybridization; Keratins; Middle Aged; Ovarian Neoplasms; Papillomaviridae; Uterine Cervical Neoplasms

The carcinogen 7,12-dimethylbenz(a)anthracene (DMBA) has been used to induce oral carcinogenesis of the hamster buccal mucosa in an experimental model that exhibits many of the genetic, biochemical and pathological features of human oral squamous cell carcinoma. To complement this in vivo process we have established an in vitro transformation procedure that involved the treatment of normal hamster oral mucosal keratinocytes (NHKs) with DMBA. Uptake of DMBA in NHKs was verified by observing autofluorescence of DMBA in the oral mucosal cells. Treatment doses ranged from 5, 50 and 200 ng and the NHKs were generally treated with DMBA for 1-14 days. The 200 ng dose proved to be toxic to these cells. The 5 and 50 ng treatments were found to maintain the viability of the NHKs and demonstrate anchorage-independent agarose growth, producing 18 and 40 colonies, respectively, after 14 days of treatment. Characterisation assays included determinations for cellular growth through plating efficiency, counting of cell colony number, and 3H-thymidine incorporation. Differentiation was ascertained by counting cornified cells, specification of either high or low molecular weight keratins, the percentage of cells expressing gamma glutamyl-transpeptidase (GGT), the level of p53 expression, and a determination of cell cycle. After 24 h the plating efficiency of the NHKs was found to be slightly increased following treatment with a 5 or 50 ng dose of DMBA compared to the untreated NHKs. After 14 days of incubation these doses also enhanced the number of colonies formed by the NHKs (e.g. plating efficiency). In contrast, the number of cornified cells was reduced in these colonies, while immunohistochemistry disclosed an increase in the number of NHKs expressing low molecular weight keratins, significantly lower levels of high molecular weight keratins and high levels for GGT. Flow cytometric analysis verified an increase in p53 expression (e.g. p53 wild type, 19% and p53 mutant, 66%). Cell cycle analysis of NHKs treated with DMBA (5 ng) demonstrated a shift in the number of cells in S phase (17.2%) and G2 + mitosis (11.0%). Cells from this DMBA treatment group were injected into syngeneic hamster recipient buccal pouches (10 x 10(6) cells/0.25 ml). Squamous carcinomas grew in four of six hamster buccal pouches as determined by histopathological analysis. The in vitro assay system will enhance our ability to define the genetic and molecular changes related to chemical carcinogen

Topics: 9,10-Dimethyl-1,2-benzanthracene; Animals; Carcinogens; Carcinoma, Squamous Cell; Cell Culture Techniques; Cell Cycle; Cell Transformation, Neoplastic; Cheek; Cricetinae; Dose-Response Relationship, Drug; Keratinocytes; Keratins; Mesocricetus; Mouth Mucosa; Mouth Neoplasms; Neoplasm Transplantation

The presence of squamous differentiation in transitional cell carcinomas has been variably related to prognosis and response to radiotherapy. This study sought to establish whether cytokeratin (CK) 14, normally expressed in the basal cells of squamous epithelium, could be used as a reliable marker of the emergence of a squamous phenotype in transitional cell carcinomas. In a series of 42 tumours, CK14 was expressed in areas of squamous morphology, whereas CK20 identified continuing urothelial differentiation. Furthermore, focal positivity for CK14 was present in a proportion of tumours with no morphological evidence of squamous differentiation, suggesting that it is a more sensitive marker of phenotypic switch. Investigation of CK subtypes may be more powerful than morphology alone in clinical studies of transitional cell carcinomas as CK expression profiles have been related to treatment response in other tumour types.

Topics: Biomarkers, Tumor; Carcinoma, Squamous Cell; Carcinoma, Transitional Cell; Cell Differentiation; Humans; Immunohistochemistry; Keratins; Kidney Neoplasms; Prognosis; Ureteral Neoplasms; Urinary Bladder Neoplasms; Urologic Neoplasms

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

Schistosomiasis remains one of the major public health problems of the tropics. Conservative estimates place the number of infected individuals at about 200 millions. In Egypt, carcinoma of the urinary bladder associated with schistosomiasis is the foremost oncologic problem, because of its high frequency and the late presentation of cases. A newly developed monoclonal antibody CK1K10 to keratinized grade 1 squamous cell carcinoma was used in a dot enzyme-linked immunosorbent assay (Dot ELISA) to test urine samples of 118 patients with bladder carcinoma, 291 patients with genitourinary pathology other than bladder carcinoma, in addition to 550 healthy controls. The overall sensitivity of the dot ELISA was 90% among 118 patients with bladder carcinoma. Twenty-seven of 33 transitional cell carcinoma cases (82%), 68 of the 71 squamous cell carcinoma cases (96%), 7 of 10 undifferentiated tumors cases (70%), and 4 of 4 adenocarcinoma were positive with this assay. The specificity was 90% in our sample population. A comparative study of diagnosis by cytology and dot ELISA was carried out in 57 patients with bladder carcinoma. Dot ELISA was found to be superior as a screening tool for high risk groups (P < .001 using chi-square test). Cytology detected 21% of transitional cell carcinoma, 68% of squamous cell carcinoma, 50% of adenocarcinoma, and 86% of undifferentiated tumors. The dot ELISA assay should be useful for screening high-risk groups because it does not require sophisticated equipment, is noninvasive, does not require highly trained staff, and can be performed in less than 30 minutes.

Topics: Adenocarcinoma; Antibodies, Monoclonal; Carcinoma, Squamous Cell; Carcinoma, Transitional Cell; Cytodiagnosis; Enzyme-Linked Immunosorbent Assay; Female; Humans; Keratins; Male; Pregnancy; Risk Factors; Sensitivity and Specificity; Urinary Bladder Neoplasms; Urine

The prognostic weight of histological and biological factors was compared with that of known clinical prognostic factors in a population of 108 consecutive previously untreated patients with head and neck squamous cell carcinoma. Parameters studied were: tumour vascularisation, mitotic index, histological differentiation, nuclear grade, keratinisation, desmoplasia, growth pattern, inflammation, tumour emboli in peripheral vessels, keratins 6, 13, 19 immunohistochemical expression, cytofluorometric ploidy and S-phase. In multivariate analysis (Cox), only age and nodal status had a significant impact on the overall survival, whereas T stage was the only significant factor associated with locoregional failure. The cumulative incidence of metastases was correlated not only with age, T and N stage, but also with histological differentiation. All the other histological and biological factors studied failed to provide further prognostic information. These findings may help to select patients with high metastatic risk.

Topics: Age Factors; Aged; Analysis of Variance; Biopsy; Carcinoma, Squamous Cell; Confidence Intervals; Disease-Free Survival; Female; Flow Cytometry; Follow-Up Studies; Head and Neck Neoplasms; Humans; Inflammation; Keratins; Male; Middle Aged; Mitotic Index; Multivariate Analysis; Ploidies; Predictive Value of Tests; Prognosis; Prospective Studies; Retrospective Studies; S Phase; Survival Rate; Time Factors; Treatment Outcome

High-risk human papillomaviruses (HPVs), including type 16, have been identified as factors in cervical carcinogenesis. However, the presence and expression of the virus per se appear to be insufficient for carcinogenesis. Rather, cofactors most likely are necessary in addition to viral gene expression to initiate neoplasia. One candidate cofactor is prolonged exposure to sex hormones. To examine the possible effects of estrogen on HPV-associated neoplasia, we treated transgenic mice expressing the oncogenes of HPV16 under control of the human keratin-14 promoter (K14-HPV16 transgenic mice) and nontransgenic control mice with slow release pellets of 17beta-estradiol. Squamous carcinomas developed in a multistage pathway exclusively in the vagina and cervix of K14-HPV16 transgenic mice. Estrogen-induced carcinogenesis was accompanied by an incremental increase in the incidence and distribution of proliferating cells solely within the cervical and vaginal squamous epithelium of K14-HPV16 mice. Expression of the HPV transgenes in untreated transgenic mice was detectable only during estrus; estrogen treatment resulted in transgene expression that was persistent but not further upregulated, remaining at low levels at all stages of carcinogenesis. The data demonstrate a novel mechanism of synergistic cooperation between chronic estrogen exposure and the oncogenes of HPV16 that coordinates squamous carcinogenesis in the female reproductive tract of K14-HPV16 transgenic mice.

Topics: Animals; Carcinoma, Squamous Cell; Cell Transformation, Neoplastic; Chloramphenicol O-Acetyltransferase; Delayed-Action Preparations; Estradiol; Female; Genes, Viral; Humans; Immunohistochemistry; In Situ Hybridization; Keratins; Mice; Mice, Transgenic; Oncogenes; Papillomaviridae; Proliferating Cell Nuclear Antigen; Promoter Regions, Genetic; RNA, Messenger; Uterine Cervical Neoplasms; Vaginal Neoplasms

Retinoic acid (RA) modulates the growth and differentiation of various normal and malignant cells. These effects are most likely mediated by changes in gene expression. Genes whose expression is modulated by RA may be useful as markers of growth responsiveness to retinoids. Using differential cDNA cloning we identified 10 genes regulated by RA in the head and neck squamous cell carcinoma cell line MDA886Ln. Keratin (K) 13 gene expression was the gene expression most related to the degree of sensitivity of growth to RA, as K13 was not expressed in a series of RA-resistant cell lines. Our data suggest that low K13 expression may be mechanistically related to resistance to RA-induced growth inhibition.

Topics: Carcinoma, Squamous Cell; Cell Division; DNA, Complementary; Epithelium; Gene Expression; Head and Neck Neoplasms; Humans; Keratins; RNA, Messenger; Tretinoin; Tumor Cells, Cultured

Total esophagectomy specimens from 4 patients given preoperative high dose rate intraluminal brachytherapy (HDRILBT) of 20 Gray (GY) in 2 fractions of 10 Gy each week were reviewed for radiation changes.. In all patients, preoperative biopsy specimens showed moderate to poorly differentiated squamous cell carcinoma with minimal to negligible keratin production. The esophagectomy specimens were sampled at the resection margins, the edge of irradiated length, 1 cm from the proximal and distal edge of visible tumor, the center of the tumor, and the lymph nodes.. Radiation change in the form of fibrosis was limited to the submucosa at the resection margins, the circular muscle layer at the edge of irradiated length, and full thickness at 1 cm from the edge of the visible tumor and the center of the tumor. Surface epithelium did not show any changes at the resection margins but did show basal cell hyperplasia at the edge of the irradiated length and ulceration at 1 cm from the edge of the visible tumor and the center of the tumor. Endarteritis obliterans was seen only 1 cm from the edge of the visible tumor and the center of the tumor. Necrosis, intense keratin formation, and giant cell reaction were observed at the center of the tumor. When compared with the preradiotherapy biopsies, the amount of keratin in the postradiotherapy specimens was extensive. HDRILBT may cause induction of the keratin gene in the irradiated cells to stimulate differentiation toward better differentiated cells.. HDRILBT may cause the keratin gene in the irradiated cells to induce differentiation toward better differentiated cells. Preoperative high dose rate intraluminal brachytherapy may have a role in improving the prognosis of patients with early esophageal cancer treated with a combination of radiotherapy and surgery.

Topics: Adult; Brachytherapy; Carcinoma, Squamous Cell; Cell Differentiation; Combined Modality Therapy; Endarteritis; Esophageal Neoplasms; Esophagectomy; Esophagus; Female; Giant Cells; Humans; Keratins; Lymphatic Metastasis; Male; Middle Aged; Necrosis; Neoplasm Proteins; Preoperative Care; Radiation Injuries; Radiotherapy, Adjuvant

The MIB-1 monoclonal antibody is a marker of cycling cells and the PC10 monoclonal antibody is a marker of proliferating cell nuclear antigen in paraffin sections. This study was conducted to elucidate the difference in response to radiotherapy (RT) between cervical adenocarcinomas and squamous cell carcinomas, focusing on cell proliferation.. A total of 196 biopsy specimens taken from the cervical carcinomas of 14 consecutive patients with adenocarcinoma and 62 patients with squamous cell carcinoma before and after RT at doses of 9 and 27 Grays (Gy) were investigated for MIB-1 and PC10 immunoreactivities.. In adenocarcinomas, the mean MIB-1 labeling indices before and after RT at 9 and 27 Gy were 28%, 21%, and 26%, respectively, whereas the mean PC10 labeling indices were 15%, 13%, and 14%, respectively. In squamous cell carcinomas, the mean MIB-1 labeling indices before and after RT at 9 and 27 Gy were 38%, 53%, and 26%, respectively, and the mean PC10 labeling indices were 23%, 23%, and 11%, respectively.. Cervical adenocarcinomas have a lower cycling cell population and their indices show no change during RT. Squamous cell carcinomas have a higher cycling cell population and show a transient increase of the MIB-1 cycling cell population at 9 Gy of RT. These findings suggest a difference in response to RT between adenocarcinomas and squamous cell carcinomas.

Topics: Adenocarcinoma; Aged; Aged, 80 and over; Antibodies, Monoclonal; Antigens, Neoplasm; Biomarkers, Tumor; Carcinoma, Adenosquamous; Carcinoma, Endometrioid; Carcinoma, Squamous Cell; Cell Cycle; Cell Nucleus; Female; Humans; Keratins; Ki-67 Antigen; Neoplasm Proteins; Neoplasm Staging; Nuclear Proteins; Proliferating Cell Nuclear Antigen; Treatment Outcome; Uterine Cervical Neoplasms

The CYFRA 21-1, a newly developed sandwich enzyme-linked immunosorbent assay (ELISA), was used to measure soluble cytokeratin 19 fragment in serum that is expressed in simple epithelium and its malignant counterpart. The present study was designed to investigate whether CYFRA 21-1 is a sensitive and specific tumor marker for non-small cell lung cancer.. CYFRA 21-1 assay, using two specific monoclonal antibodies (KS 19.1 and BM 19.21) for cytokeratin 19, was measured in 312 serum samples, including 164 lung cancer, 118 benign pulmonary disease, and 30 healthy individuals. The sensitivity of CYFRA 21-1 was also compared with two other markers, carcinoembryonic antigen (CEA) and squamous cell carcinoma antigen (SCC), in 164 patients with lung cancer.. The median value of healthy individuals was 1.3 ng/mL (95th percentile 1.8). In patients with benign pulmonary diseases, the median was 1.5 ng/mL (95th percentile 2.9). There is no significant difference between sexes, smoking habit, and the subgroups of benign pulmonary disease, such as tuberculosis, pneumonia, or COPD. Using the cutoff value of 3.3 ng/mL, defined at 95% specificity for benign lung disease, the sensitivities of CYFRA 21-1 for squamous cell carcinoma (n=74), adenocarcinoma (n=54), undifferentiated large cell carcinoma (n=11), and small cell lung cancer (n=25) were 62%, 39%, 36%, and 20%, respectively. Despite the cell types, the sensitivities of CYFRA 21-1 in non-small cell lung cancer (NSCLC, n=169) were 51% (CEA 42%, SCC 20%). The sensitivity of CEA was significantly higher in patients with adenocarcinoma (58%) than other markers; while in patients with squamous cell carcinoma, CYFRA 21-1 assay has the highest sensitivity. The median level of CYFRA 21-1 in squamous cell carcinoma is significantly higher than that of other cell types (Mann-Whitney test, p<0.001). The serum level and sensitivity of CYFRA 21-1 were well correlated with staging and tumor size in squamous cell carcinoma. The CYFRA 21-1 values were measured for monitoring progression of disease in 20 patients with squamous cell carcinoma. There is significant difference in paired observation of CYFRA 21-1 level in patients with progressive disease (Wilcoxon signed-rank test, p<0.05), but no difference was observed in patients with stabilized disease (p>0.1).. For patients with NSCLC, especially in squamous cell carcinoma, CYFRA 21-1 is not only a sensitive and specific tumor marker, but also may be a useful adjunctive marker for disease monitoring.

Topics: Adenocarcinoma; Antibodies, Monoclonal; Antigens, Neoplasm; Biomarkers, Tumor; Carcinoembryonic Antigen; Carcinoma, Non-Small-Cell Lung; Carcinoma, Small Cell; Carcinoma, Squamous Cell; Disease Progression; Enzyme-Linked Immunosorbent Assay; Epithelium; Female; Humans; Keratins; Lung Diseases; Lung Diseases, Obstructive; Lung Neoplasms; Male; Neoplasm Staging; Pneumonia; Sensitivity and Specificity; Serine Proteinase Inhibitors; Serpins; Sex Factors; Smoking; Tuberculosis, Pulmonary

To test and optimize photodynamic therapy of early cancers in the upper aero-digestive tract and oesophagus, we sought an appropriate animal model, which was found in the 7,12-dimethylbenz[a]anthracene-induced early squamous cell carcinoma in the Golden Syrian hamster. This chemically induced neoplasm is shown, by histology and immunohistochemistry, to pass through similar stages of early cancer development as its human counterpart. Its time sequence is highly reproducible, leading to a well differentiated carcinoma in situ and microinvasive carcinoma in the hamster cheek pouch over a period of 10 weeks.

Topics: 9,10-Dimethyl-1,2-benzanthracene; Animals; Carcinogens; Carcinoma in Situ; Carcinoma, Squamous Cell; Cheek; Cricetinae; Disease Models, Animal; Esophageal Neoplasms; Keratins; Male; Mesocricetus; Mouth Neoplasms; Neoplasm Invasiveness; Photochemotherapy; Precancerous Conditions

The expression of cytokeratins and vimentin was studied immunohistochemically in normal epithelium and 12 benign lesions of the vocal cord with the use of a broad panel of monoclonal antibodies against cytokeratins and vimentin. Histology showed that the various lesions contained hyperkeratotic, hyperplastic and atrophic epithelium, irrespective of their clinical appearance. Especially the Ck profile of the (hyper)keratotic lesions was changed in comparison with the native epithelium. Increased expression of the keratinization marker Ck 10 was associated with decreased expression of the stratification markers Cks 4 and 13. Expression of the basal cell marker Ck 14 and hyperproliferation-associated Cks 16 and 17 was increased in all the benign lesions, except in atrophic epithelium. These expression patterns differ from those observed in malignant epithelial lesions. The latter show a marked expression of simple cell Cks and vimentin and more pronounced expression of hyperproliferation-associated markers than the benign lesions.

Topics: Antibodies, Monoclonal; Carcinoma, Squamous Cell; Epithelium; Humans; Immunohistochemistry; Intermediate Filament Proteins; Keratins; Laryngeal Neoplasms; Vimentin; Vocal Cords

Cytokeratin (CK) expression was studied in squamous cell carcinomas of different subsites in the head and neck by using cryostat sections from 27 head and neck squamous cell carcinomas (HNSCCs) and 6 cell lines established from HNSCC. All tissues were analyzed immunohistochemically with a panel of monospecific anti-keratin monoclonal antibodies. Most carcinomas recapitulated the expression pattern of keratins present in the basal layer of normal epithelium from the site of tumor origin. Regional differences in the expression of simple-epithelial type of keratins in stratified (pseudostratified) epithelia were to a large extent repeated in corresponding carcinomas. In the present study, localization of various keratins were surveyed and CK 18 specific monoclonal antibodies were specifically used to distinguish SCCs of the larynx or hypopharynx from SCCs of the oral cavity. CK 18 staining of almost all tumor cells was detected in 11 of 12 SCCs of the larynx and hypopharynx, but was only detected sporadically in 3 of 9 SCCs of the oral cavity. The present results show that CK 18 typing might be useful for distinguishing sites of origin of various HNSCCs. Findings also indicate that CK 18 expression in SCC might be modulated by microenvironmental factors.

Topics: Antibodies, Monoclonal; Carcinoma, Squamous Cell; Cell Line; Diagnosis, Differential; Gene Expression Regulation, Neoplastic; Head and Neck Neoplasms; Humans; Hypopharyngeal Neoplasms; Hypopharynx; Immunoenzyme Techniques; Keratins; Laryngeal Neoplasms; Larynx; Mouth Mucosa; Mouth Neoplasms

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

The desmosomal plaque protein desmoplakin (DP), located at the juncture between the intermediate filament (IF) network and the cytoplasmic tails of the transmembrane desmosomal cadherins, has been proposed to link IF to the desmosomal plaque. Consistent with this hypothesis, previous studies of individual DP domains indicated that the DP COOH terminus associates with IF networks whereas NH2-terminal sequences govern the association of DP with the desmosomal plaque. Nevertheless, it had not yet been demonstrated that DP is required for attaching IF to the desmosome. To test this proposal directly, we generated A431 cell lines stably expressing DP NH2-terminal polypeptides, which were expected to compete with endogenous DP during desmosome assembly. As these polypeptides lacked the COOH-terminal IF-binding domain, this competition should result in the loss of IF anchorage if DP is required for linking IF to the desmosomal plaque. In such cells, a 70-kD DP NH2-terminal polypeptide (DP-NTP) colocalized at cell-cell interfaces with desmosomal proteins. As predicted, the distribution of endogenous DP was severely perturbed. At cell-cell borders where endogenous DP was undetectable by immunofluorescence, there was a striking absence of attached tonofibrils (IF bundles). Furthermore, DP-NTP assembled into ultrastructurally identifiable junctional structures lacking associated IF bundles. Surprisingly, immunofluorescence and immunogold electron microscopy indicated that adherens junction components were coassembled into these structures along with desmosomal components and DP-NTP. These results indicate that DP is required for anchoring IF networks to desmosomes and furthermore suggest that the DP-IF complex is important for governing the normal spatial segregation of adhesive junction components during their assembly into distinct structures.

Topics: alpha Catenin; beta Catenin; Cadherins; Carcinoma, Squamous Cell; Cell Adhesion; Cytoskeletal Proteins; Desmoplakins; Desmosomes; Epithelial Cells; Epithelium; Humans; Intercellular Junctions; Intermediate Filaments; Keratins; Molecular Sequence Data; Molecular Weight; Peptides; Recombinant Fusion Proteins; Trans-Activators; Tumor Cells, Cultured

Lymphoepithelioma-like carcinoma of the skin is a rare tumor with a microscopic resemblance to lymphoepitheliomatous tumors of the nasopharynx. A 62-year-old woman exhibited such a tumor on the nose together with regional lymph node metastases. Histologically, irregular islands of atypical epithelial cells unconnected to the overlying epidermis were surrounded by or mixed with numerous lymphocytes in the primary tumor. No squamous or glandular differentiation was present. Metastases to the submandibular lymph nodes appeared as glassy squamous cells that resembled trichilemmal keratinization. Staining of the tumor tissues with S-100 protein antibody revealed the presence of numerous short dendritic cells in clusters of epithelial cells. Total resection and adjunctive radiotherapy have led to a 6-year period free of recurrence. This is the second case report of this condition in Japan.

Topics: Carcinoma, Squamous Cell; Cell Differentiation; Dendritic Cells; Epidermis; Epithelium; Female; Humans; Keratins; Lymphatic Metastasis; Lymphocytes; Middle Aged; Nose Neoplasms; Radiotherapy, Adjuvant; S100 Proteins; Skin Neoplasms

Patients with head and neck squamous cell carcinoma (HNSCC) who are thought to be cured are at high risk of development of a secondary primary tumour in the mucosa of the upper aerodigestive tract and the lungs. This phenomenon is in agreement with the concept of 'field cancerization', which implies that the whole mucosa is potentially condemned to the development of neoplasia. The hypothesis advanced in this study was that early markers of carcinogenesis should therefore be present in all cells of the mucosa of patients with HNSCC. The expression of cytokeratin 16, cytokeratin 19, and histo-blood group antigen H (ABH), type 2 chain was analysed by means of immunocytochemistry on exfoliated cells taken from six sites of the upper aerodigestive tract of the 'healthy' mucosa of previously untreated HNSCC patients (n = 25) and controls (n = 10). Statistically significant differences were found in the mucosal expression of these markers between patients and controls. Since no overlap in ABH type 2 chain expression existed between patients and controls and the expression between sites in a given individual was highly correlated, this marker was considered the most promising of those tested. These data suggest that cytokeratin 16, cytokeratin 19, and ABH type 2 chain are markers of field cancerization in easily available exfoliated cells, which may be applied to monitor and/or predict the occurrence of second primary tumours.

Topics: ABO Blood-Group System; Adult; Aged; Biomarkers, Tumor; Carcinoma, Squamous Cell; Female; Head and Neck Neoplasms; Humans; Immunohistochemistry; Keratins; Male; Middle Aged; Mucous Membrane; Neoplasms, Second Primary

Approximately half of the patients diagnosed with localized esophageal cancer die of metastatic disease within the first 2 years following tumor resection. The development of monoclonal antibodies (MAbs) directed against epithelial cell-associated and tumor antigens has enabled the detection of single disseminated tumor cells in secondary organs.. We used MAbs directed against epithelial cell antigens (i.e., cytokeratins) to determine the proportion of patients with esophageal cancer who display isolated tumor cells in their bone marrow. In addition, we evaluated the prognostic significance of a finding of bone marrow tumor cells in patients with esophageal cancer whose tumors were completely resected.. Prior to the initiation of treatment, bone marrow was aspirated from both sides of the upper iliac crests of 90 patients with squamous cell carcinoma of the esophagus. Bone marrow was also obtained from a population of 30 individuals who had not been diagnosed with cancer. Tumor cells in cytologic bone marrow preparations were detected by use of an assay that employed the MAbs CK2 (directed against cytokeratin 18), KL1 (directed against a 56,000-kd pan-cytokeratin component), and A45-B/B3 (directed against an epitope common to cytokeratins 8, 18, and 19) plus the alkaline phosphatase anti-alkaline phosphatasestaining method. Bone marrow biopsies, for conventional histologic examination with Giemsa staining, were performed on 62 patients. The Kaplan-Meier method and the logrank test were used to assess disease-free and overall survival according to the presence or absence of tumor cells in the bone marrow of 42 patients with completely resected tumors. Reported P values are two-sided.. Cytokeratin-positive tumor cells were detected in the bone marrow of 37 (41.1%) of the 90 total patients. The number of tumor cells detected per 10(5) mononuclear bone marrow cells ranged from one to 82. No significant differences in the numbers of disseminated tumor cells were noted for patients diagnosed with tumors at different stages. Only two (3.2%) of 62 bone marrow specimens examined after Giemsa staining showed morphologically identifiable tumor cells. Tumor cells were not detected in the bone marrow of patients who had not been diagnosed with cancer. After a median follow-up of 15.5 months (range, 6-33 months), 15 (79.0%) of 19 patients with completely resected tumors and tumor cells in their bone marrow had relapses compared with three (13.0%) of 23 patients with completely resected tumors and no tumor cells in their bone marrow (P = .019, logrank test). Patients with completely resected tumors and tumor cells in their bone marrow had significantly shorter overall survival than corresponding patients without tumor cells in their bone marrow (P = .036, logrank test).. Dissemination of esophageal cancer cells to the bone marrow is more frequent than expected from the rare occurrence of overt skeletal metastases. In general, the presence of tumor cells in the bone marrow may be an indicator of the disseminatory potential of individual tumors.

Topics: Antibodies, Monoclonal; Azure Stains; Bone Marrow Neoplasms; Carcinoma, Squamous Cell; Esophageal Neoplasms; Female; Humans; Immunohistochemistry; Keratins; Male; Middle Aged; Survival Analysis

Immunohistochemical detection of certain low to intermediate molecular weight keratins often is impaired in routinely processed specimens due to masking of these antigens by formalin fixation. Despite standard enzymatic digestion, AE1:AE3 and CAM 5.2, two of the most currently utilized antikeratin antibody preparations, either stain weakly or fail to stain basal keratinocytes and tumors composed of basaloid keratinocytes in paraffin sections of formalin-fixed tissue. We present here our experience with the monoclonal antibody MNF116 which detects keratins 5, 6, 8, 17, and 19 (DAKO, Carpinteria, CA). We have studied 232 routinely-processed skin lesions with MNF116 and compared the staining with that of AE1:AE3 mixture or CAM 5.2. In normal skin, the staining achieved with MNF116 was particularly strong on the basal cells of the epidermis and adnexae. MNF116 was positive in all 154 epithelial tumors and negative in all but one (a leiomyosarcoma) of 78 mesenchymal and melanocytic tumors. AE1:AE3 mixture was positive in all but four poorly-differentiated squamous cell carcinomas and it was only weakly positive in most basal cell carcinomas. CAM 5.2 was positive in tumors of the sweat apparatus, Merkel cell carcinomas, metastatic carcinomas, and 5/15 basal cell carcinomas. We consider that, in routinely processed specimens, MNF116 is very useful and convenient for detection of cytokeratin expression in cutaneous lesions, and therefore helpful in the evaluation of tumors with small cells and other poorly differentiated neoplasms of the skin.

Topics: Antibodies, Monoclonal; Carcinoma, Basal Cell; Carcinoma, Squamous Cell; Humans; Immunohistochemistry; Keratins; Melanoma; Molecular Weight; Paraffin Embedding; Prospective Studies; Retrospective Studies; Skin Diseases; Skin Neoplasms

We examined full thickness specimens of oesophageal squamous dysplasia from both cancer-free and cancer patients using immunohistochemical labelling for cytokeratin subtypes 10/13 and 14 and for involucrin, binding studies for various lectins, and PAS/D staining before and after diastase treatment. We studied specimens from patients with oesophageal carcinoma (52 normal epithelia, and 49 with mild, 38 with moderate, and 32 with severe dysplasia), and 32 specimens from cancer-free patients (five normal epithelia and 16 with mild and 11 with moderate dysplasia). Abnormal cytokeratin expression patterns in atypical cells, i.e. both cytokeratin 10/13 and cytokeratin 14 immunoreactivity in the same cells was detected in 41 of 99 specimens with dysplasias in cancer patients. Helix aspersa, Erythrina cristagalli and Robinia pseudoacacia binding was consistently negative in atypical cells in squamous dysplasia. The non-atypical layer of squamous dysplasia, which was morphologically indistinguishable from the corresponding layer of normal oesophageal squamous epithelium, showed abnormal involucrin expression in 39/ 101 specimens, Helix aspersa binding in 74/106, diastase sensitive PAS staining in 52/110, Erythrina cristaglli binding in 28/107, and Robinia pseudoacacia binding in 16/100. There were no significant differences in the expression of these markers in dysplasia between cancer patients and cancer-free individuals with the exception of increased Robinia pseudoacacia binding in the non-atypical layer in cancer-free patients. The results indicate that abnormal patterns of cytokeratin expression and lectin binding occur not only in atypical cells but also in non-atypical cells in oesophageal squamous dysplasia.

Topics: Adult; Aged; Aged, 80 and over; Carcinoma, Squamous Cell; Esophageal Neoplasms; Female; Humans; Immunohistochemistry; Keratins; Lectins; Male; Middle Aged; Precancerous Conditions; Protein Binding; Protein Precursors

The CYFRA 21-1 assay is a test that has been developed recently for detection of a cytokeratin 19 fragment in serum. A diagnostic role for CYFRA 21-1 has already been proposed. The question of whether this marker is prognostically significant is important in clarifying the role of CYFRA 21-1 in clinical practice. The aim of this study was to evaluate the prognostic significance of elevated preoperative CYFRA 21-1 levels in patients with resected primary squamous-cell lung cancer (SqCC). Serum levels of CYFRA 21-1 were measured using an immunoradiometric assay (CIS bio) in 91 patients with operable SqCC. Survival and disease-free survival curves related to initial levels of this marker were estimated using the Kaplan-Meier method. In the univariate analysis the log-rank test and the log-rank test for trend were used. In the multivariate analysis the stratified log-rank test and the proportional hazard model were used. Elevated preoperative CYFRA 21-1 levels were identified in 55% of patients with SqCC. The number of patients with elevated levels of this marker increased with TNM stage (P = 0.0001). In univariate analysis elevated levels of CYFRA 21-1 were significantly associated with poor overall survival (P < 0.00005) and with disease-free survival (P < 0.00005). In multivariate analysis elevated levels of this marker were also found to be associated with poor overall and disease-free survival (P = 0.01 and P = 0.003 respectively). In conclusion, CYFRA 21-1 may be an independent prognostic parameter of survival and tumour relapse in SqCC and may be useful in identifying resected SqCC patients at high risk of treatment failure.

Topics: Adult; Aged; Biomarkers, Tumor; Carcinoma, Squamous Cell; Disease-Free Survival; Female; Humans; Keratins; Lung Neoplasms; Male; Middle Aged

The aim of the study was to test the diagnostic value of serum tumor marker CYFRA 21-1 for squamous cell lung cancer (SQCLC) in comparison with carcinoembryonic antigen (CEA). Ninety-one patients were included in this study: 56 with SQCLC-Group I, 25 with other types of lung cancer-Group II, 10 with benign respiratory tract diseases-Group III. Median CYFRA 21-1 serum concentration (ng/ml) was: in Group I: 4.52 (0.94 - > 16), in Group II: 3.58 (1.72 - > 16), in Group III: 2.05 (0.99-3.41). Median CEA serum concentration (ng/ml) was: in Group I: 4.49 (0.76 - > 20), in Group II: 3.32 (1.17 - > 20), in Group III: 3.09 (1.84-6.37). There was a highly significant difference between the levels of CYFRA 21-1 in Group I and III (p < 0.001), but there was no statistically significant difference between the levels of CEA in Group I and III. Sensitivity of CYFRA 21-1 by the cut-off 3.33 ng/ml in the diagnostics of SQCLC was 0.68, specificity 0.90, positive predictive value 0.91, negative predictive value 0.65. Sensitivity of CEA by cut-off 4.61 ng/ml was 0.5 by the same specificity 0.90. CYFRA 21-1 has high sensitivity, specificity and positive predictive value in the diagnostics of SQCLC. Sensitivity of CYFRA 21-1 is significantly higher than sensitivity of CEA in this setting.

Topics: Adult; Aged; Aged, 80 and over; Biomarkers, Tumor; Carcinoembryonic Antigen; Carcinoma, Squamous Cell; Female; Humans; Keratins; Lung Neoplasms; Male; Middle Aged; Predictive Value of Tests; Sensitivity and Specificity; Statistics, Nonparametric

The diagnostic value of a new tumor marker, CYFRA 21-1, was studied in the blood samples collected from 22 controls, and 87 pre-treatment patients with squamous cell carcinoma of the cervix. Sensitivity and specificity of CYFRA 21-1 was compared with those of squamous cell carcinoma antigen (SCC) measured in the sera of the same patients. Serum CYFRA 21-1 levels were higher in patients with squamous cell carcinoma than in controls (p < 0.05), and correlated with FIGO stage (Stage IIb-IV vs. Stage Ib-IIa, p = 0.0477). Using 2.5 ng/ml as cut-off value, elevated CYFRA 21-1 levels were found in 13.6% of controls, 34.8% of patients with Stage Ib-IIa squamous cell carcinoma of the cervix, and 63.5% of patients with Stage IIb-IV squamous cell carcinoma of the cervix. However, there was less sensitivity and specificity of CYFRA 21-1 than those of SCC in detecting squamous cell carcinoma of the cervix. CYFRA 21-1 may not be a better tumor marker than SCC for squamous cell carcinoma of the cervix.

Topics: Aged; Antigens, Neoplasm; Biomarkers, Tumor; Carcinoma, Squamous Cell; Female; Humans; Keratins; Middle Aged; Peptide Fragments; Reference Values; Serpins; Uterine Cervical Neoplasms

Cytokeratins are expressed in varying combination in the course of differentiation of epithelial cells and tumor cells. This is the first report of systematic immunohistochemical (ABC-method) investigations concerning the expression of different cytokeratin types (KL 1, CK 4, 10 and 17) within the transformation of the bronchial mucosal epithelium with epithelial hyperplasia to potential preneoplasia and early squamous cell carcinoma of the lung. In bioptical obtained specimens from 35 patients, 63 areas with diagnosis of regular bronchial mucosa (n = 10), basal cell hyperplasia (n = 9), goblet cell hyperplasia (n = 10), squamous cell metaplasia (n = 11), dysplasia I-III (n = 13), carcinoma in situ in the border zone of squamous cell carcinoma (n = 10) and in 5 surgically obtained specimens with findings of an early squamous cell carcinoma of the bronchus (n = 5), the expression of different cytokeratin types was investigated. The specimens were fixed in formalin and embedded in paraffin for lightmicroscopical and immunohistochemical investigations (ABC-method). KL 1 was detected in all regular and pathological mucosal epithelia, CK 4 in basal cells, squamous cell metaplasia, potentially preneoplastic changes and early squamous cell carcinoma of the bronchus. CK 10 was expressed only in early squamous cell carcinoma of the bronchus, and CK 17 in varying quantity in hyperplastic, preneoplastic and cancerous lesions of the bronchial mucosa. Our results reveal an increasing expression of squamous epithelial type-cytokeratins (CK 4, CK 17) in hyperplastic and metaplastic lesions of the bronchial mucosa. In dysplastic lesions and carcinomata in situ, a quantitative, as well as qualitative decrease of the CK 4- and CK 17-expression with a heterogeneous expression pattern for CK 17 was found. The heterogeneous neo-expression of CK 10 in early squamous cell carcinoma of the bronchus has to be emphasized.

Topics: Bronchial Neoplasms; Carcinoma, Squamous Cell; Humans; Immunohistochemistry; Keratins; Precancerous Conditions

Expression of human leukocyte elastase inhibitor, elafin, otherwise known as skin-derived antileukoproteinase inhibitor (SKALP), was investigated in normal and abnormal oral tissues using a specific anti-SKALP rabbit antiserum. Weak staining was observed in keratinizing epithelia of normal oral mucosa but not in non-keratinizing mucosa. Increased expression was also observed in the suprabasal layers of dysplastic oral epithelia and in well-differentiated squamous cell carcinoma, but not in basal cell carcinoma. A uniform strong expression was observed in all supra-basal layers of odontogenic keratocyst epithelia, except in regions where inflammatory infiltrate was adjacent to keratocyst epithelia. In contrast, elafin expression in a small number of dentigerous cysts and ameloblastomas was more patchy. The increased levels of elafin in keratocyst epithelia and dysplastic tissue may be a cellular homoeostatic response to generate a protective barrier preventing proteolytic degradation of underlying elastic tissue.

Topics: Ameloblastoma; Animals; Carcinoma, Basal Cell; Carcinoma, Squamous Cell; Dental Sac; Dentigerous Cyst; Elastic Tissue; Epithelium; Gene Expression Regulation; Gene Expression Regulation, Neoplastic; Gingiva; Homeostasis; Humans; Keratins; Mouth Mucosa; Mouth Neoplasms; Odontogenic Cysts; Peptide Hydrolases; Proteinase Inhibitory Proteins, Secretory; Proteins; Rabbits; Serine Proteinase Inhibitors

We investigated the incidence of micrometastases from squamous cell carcinomas of the head and neck in neck dissection specimens originally staged as pNO. A total of 76 dissection specimens from 60 patients were evaluated using serial microscopic sectioning in 10-microns intervals, H & E staining, and immunostaining with an antibody to pan-cytokeratin. Examination of 1,020 lymph nodes from 76 neck dissection specimens revealed 8 micrometastases (7.9%) in 6 specimens from 6 patients with oral and pharyngeal primaries, resulting in upstaging. Six micrometastases were located in lymph nodes 3 to 6 mm in diameter. The surgeon should be aware of the relatively high incidence of micrometastases from oral and pharyngeal carcinomas, which are undetectable preoperatively or by routine histopathologic examination. Primary tumor site (oral cavity and pharynx) and certain features of the primary can delineate a group of patients with a higher risk of harboring occult metastases who may benefit from elective treatment of the neck.

Topics: Carcinoma, Squamous Cell; Head and Neck Neoplasms; Histological Techniques; Humans; Immunohistochemistry; Keratins; Laryngeal Neoplasms; Lymph Node Excision; Lymphatic Metastasis; Mouth Neoplasms; Neoplasm Staging; Pharyngeal Neoplasms; Prognosis; Retrospective Studies

The expression of the cytokeratins (CK) 1, 5, 6, 7, 10, 13 and 14 was studied immunohistochemically in gastric biopsies from both the antrum and the body of 70 patients. Normal gastric foveolar epithelium (9 cases) Helicobacter pylori gastritis (23) and intestinal metaplasia (38) were examined. Positive staining results for CK 1, 5, 10 and 14 were not observed using the 34 beta E12 antibody. With antibodies to CK 5/6, 7 and 13 some, but not all cases, were immunoreactive. Predominantly positive staining included less than 10% of the cells and was always restricted to the tips and the juxtaluminal areas of the foveolae. No difference was seen between the antrum and the body. Comparing normal gastric mucosa with gastritis and intestinal metaplasia, cases positive for CK 5/6 were observed less frequently in intestinal metaplasia types II and II compared to the other groups. CK 7 was expressed exclusively in intestinal metaplasia. CK 13 was seen in all groups of specimens. Thus, cytokeratins typical for ductal structures (CK 7) and squamous epithelia (CK 5/6, CK 13) can be regarded as an inconstant, but not unusual observation in the gastric mucosa. Their expression may be controlled by both differentiation-related as well as environmental factors.

Topics: Adult; Carcinoma, Squamous Cell; Epithelium; Female; Gastric Mucosa; Gastritis; Helicobacter Infections; Helicobacter pylori; Humans; Intestinal Neoplasms; Keratins; Male; Middle Aged; Pyloric Antrum; Stomach Neoplasms

The authors performed a retrospective study in ultrasound to investigate new aspects in the sonomorphology of lymph node metastases of the neck. In this study, it could be demonstrated the first time that the histologic characteristics of the metastases determine the sonographic appearance. In addition to criteria such as the longitudinal/ transversal quotient, sonomorphology could support a more precise differential diagnosis of neck lymph nodes.. In 105 of 145 patients with histologically proved head and neck carcinomas, 187 lymph node metastases were detected by ultrasound. Sonomorphology was compared with the corresponding histology.. Five sonomorphologic groups could be differentiated. (1) Thirty-one percent of the metastases were homogenous. (2) Concerning the more complex morphology of lymph node metastases in ultrasound, echolucent forms could be differentiated from echogenic textures: low- or nondifferentiated and nonkeratinizing metastases appeared echolucent and cyst-like, with dorsal signal amplification. (3) Nonkeratinizing lymphomas with necrosis showed single or multiple echolucent intranodal lesions. (4) In correlation with an increasing keratinization, the echogenecity of the lymph nodes increased and intranodal echogenic inclusions appeared. (5) An extended keratinization correlated with a central echogenecity.. The morphologic assessment of lymph nodes in ultrasound allows for primary histologic and prognostic evaluation of lymph node metastases.

Topics: Aged; Aged, 80 and over; Carcinoma, Squamous Cell; Female; Head and Neck Neoplasms; Humans; Keratins; Lymph Nodes; Lymphatic Metastasis; Male; Middle Aged; Neck; Necrosis; Ultrasonography

To evaluate the usefulness of CYFRA 21-1 and SCC Ag in the diagnosis of squamous cell carcinoma (SQC) of the lung, we tested sera from 124 patients with lung cancers (squamous cell ca 72, adenoca 22, large cell ca 4, small cell ca 18 and undetermined 8) and 78 patients with inflammatory lung diseases (bronchitis 24, bronchiectasis 29, tuberculosis 19 and others 6) using immunoradiometric assay kit for cytokeratin fragment 19 (CYFRA 21-1) and radioimmunoassay kit for SCC Ag. The serum CYFRA 21-1 and SCC Ag were significantly higher in lung cancer patients compared with control subjects. However, the significant difference was restricted only to SQC. In patients with SQC, CYFRA 21-1 and SCC Ag showed significantly higher levels according to the advanced anatomic stages (stage I-IIIa vs. stage IIIb, IV, p < 0.05). There was a good correlation between CYFRA 21-1 and SCC Ag (r = 0.41, p < 0.001). Receiver operating characteristic (ROC) curves were generated from results of both tumor markers and areas under the curves (AUC) were calculated. AUC of CYFRA 21-1 (0.93) were significantly larger than that of SCC Ag (0.77) for the diagnosis of SQC (p < 0.05). Therefore, we conclude that CYFRA 21-1 is superior to SCC Ag in the diagnosis of squamous cell carcinoma of the lung.

Topics: Aged; Antigens, Neoplasm; Biomarkers, Tumor; Carcinoma, Squamous Cell; Diagnosis, Differential; Female; Humans; Keratins; Lung Diseases; Lung Neoplasms; Male; Middle Aged; Sensitivity and Specificity

Specific mRNA and protein for two major keratins, K14 and K19, were investigated in normal, dysplastic and malignant oral epithelia by combined in situ hybridization and immunohistochemistry. In normal epithelia, K14 mRNA and protein were present almost exclusively in the basal layer of non-cornified, and in rete-processes of cornified, sites. Dysplastic epithelium showed irregular extension of the K14 transcript and protein into superficial cells. In squamous cell carcinoma (SCC), K14 transcript was abundant in most samples whilst in one poorly differentiated carcinoma mRNA but no protein was detected. K19 mRNA and its protein were present predominantly in basal cells of noncornified epithelium, whereas in cornified epithelium only mRNA was detected. In dysplasias, K19 transcript was detected in all specimens but its protein was absent in most cases. Even more variations of K19 expression were observed in SSC. These findings indicate differences in the control of expression of K14 and K19 in normal epithelia and show that regulation is further disturbed during dysplastic change and malignancy.

Topics: Autoradiography; Carcinoma, Squamous Cell; Epithelium; Gene Expression Regulation, Neoplastic; Humans; Immunohistochemistry; In Situ Hybridization; Keratins; Leukoplakia, Oral; Mouth Mucosa; Mouth Neoplasms; Neoplasm Proteins; RNA Probes; RNA, Messenger

The aim of the present study was to investigate the sequential expression of placental glutathione S-transferase (GST-P) during 7,12-dimethylbenz[a]anthracene (DMBA)-induced hamster buccal pouch squamous cell carcinogenesis. Both immunohistochemical and immunoblot analyses were employed to detect the epithelial GST-P in hamster buccal pouch mucosa over a 15-week treatment regimen. No GST-P positivity was demonstrated in the pouches of the control group. GST-P positive cells were first noted as early as 1 week after DMBA applications. A gradual increase in both the mean number and size of GST-P-positive foci was noted in the first 12 experimental weeks, but a plateau level was approached thereafter. The early GST-P-positive-area were located in the basal layer, or occasionally in the middle layer, of DMBA-treated hamster buccal pouch mucosa. Later, the stained sites became enlarged and were scattered randomly in different layers or in the whole thickness of the dysplastic and non-dysplastic epithelium. The keratin layer was only occasionally involved during the first 12 weeks of DMBA treatment but positive staining was more noticeable in the final stage of the experiment. Both exophytic (8-12 weeks) and invasive (13-15 weeks) squamous cell carcinomas showed GST-P positivity, in both cytoplasmic and nuclear components. Immunoblot analysis revealed no band in the crude tissue extracts of the control pouches whereas GST-P polypeptide of molecular weight approximately 26 kD was demonstrated in DMBA-treated pouches over the whole 15-week treatment regimen. Results of the present work indicate that GST-P is a stable and persistent label for almost all of the carcinogen-altered cells during DMBA-induced hamster buccal pouch carcinogenesis. Immunohistochemically detectable GST-P may be a potential marker throughout oral chemical carcinogenesis.

Topics: 9,10-Dimethyl-1,2-benzanthracene; Animals; Biomarkers, Tumor; Carcinogens; Carcinoma, Squamous Cell; Cell Nucleus; Coloring Agents; Cricetinae; Cytoplasm; Epithelium; Gene Expression Regulation, Neoplastic; Glutathione Transferase; Immunoblotting; Immunohistochemistry; Keratins; Male; Mesocricetus; Molecular Weight; Mouth Mucosa; Mouth Neoplasms; Neoplasm Invasiveness; Placenta; Time Factors

It is generally agreed that there is a need for a routine, non-invasive screening procedure for oral cancer particularly of high risk groups. Refinements in oral exfoliative cytology now make this technique worthy of consideration for such screening. This study assesses the utility of monitoring cytokeratin expression in smears of oral cancer in comparison with assessing the keratin expression in corresponding biopsies. Smears and biopsies were taken from 34 patients with oral cancer. A panel of antibodies, CAM5.2, LH1, AE8, LP2K and LH8 recognising keratins 8, 10, 13, 19 and a basal cell marker respectively were employed. Keratins were identified using a standard immunocytochemical technique (Vectastain) and assessed on a 3 point scale, for both smears and biopsies. The vast majority of tumours were well differentiated. No particular keratin profile scen within the smear was associated with any particular state of differentiation. Although the sensitivity of K19 was greatest, its specificity was poor. The keratin antibodies with the best positive predictive value were CAM5.2 (K8) and the marker of the basal cell phenotype, LH8. The combination of down regulation of the secondary differentiation markers (K13, K10) coupled with 'simple' keratin expression (K8, K19) would seem to be the most consistent profile. We conclude that for exfoliative cytological screening to be of value as a diagnostic test it remains necessary to employ assays using more than one antikeratin antibody.

Topics: Biomarkers, Tumor; Biopsy; Carcinoma, Squamous Cell; Cytodiagnosis; Histocytochemistry; Humans; Keratins; Mouth Neoplasms; Predictive Value of Tests; Sensitivity and Specificity

To clarify the pattern of cytokeratin and vimentin expression in mixed adenocarcinoma and squamous cell carcinoma of the uterine cervix, twenty-three cases of formalin-fixed paraffin-embedded specimen were examined immunohistochemically using a panel of four different monoclonal anti-cytokeratin antibodies and anti-vimentin antibody. Fifty-seven cases of benign or malignant tissue were selected for controls. The results were summarized as follows. 1) In four cases of co-existing adenocarcinoma and squamous cell carcinoma, their immunostaining patterns were compatible with original histological cell type. 2) In four cases of adenoacanthoma, high molecular weight-cytokeratin (HCK) was positive in each acanthomatous component and only a small part of one adenocarcinomatous component. 3) In twelve cases of cervical adenosquamous carcinoma, HCK were positive in four adenocarcinomatous components. Out of eight cases with non-stained adenocarcinomatous components, six cases showed negativity for HCK even in the squamous cell carcinomatous component. 4) Though vimentin was negative in all cases of mixed type of cervical carcinoma, some cases of mixed type endometrial carcinoma were stained positively for vimentin. It was indicated from our study that adenosquamous carcinoma of the cervix could originate either in reserve cells or columunar epithelium and that vimentin positive cases could originate in the endometorial gland.

Topics: Adenocarcinoma; Antibodies, Monoclonal; Carcinoma, Squamous Cell; Female; Humans; Immunohistochemistry; Intermediate Filament Proteins; Keratins; Paraffin Embedding; Uterine Cervical Neoplasms; Vimentin

Serum soluble cytokeratin 19 fragment (CYFRA) levels were measured in 251 patients with lung cancer and 139 patients with benign lung diseases to determine the clinical usefulness of CYFRA level determination in the diagnosis and monitoring of lung cancer. Serum levels of CYFRA were measured by a 2-step sandwich ELISA method. When the cut-off value was defined as 3.5 ng/ml, which was associated with a specificity of 95% for benign lung diseases, CYFRA had a high sensitivity (53%) in all patients with lung cancer. Both the serum level of CYFRA and its sensitivity increased significantly with the increase in clinical stage. A comparison of areas under receiver operating characteristic curves showed that CYFRA had the most power of discrimination in the diagnosis of lung cancer among markers including carcinoembryonic antigen, squamous cell carcinoma antigen, carbohydrate antigen 19-9, and neuron-specific enolase. A good correlation was found between serial changes in serum CYFRA levels during therapy and clinical responses for 18 patients who underwent chemotherapy and/or radiotherapy. Our findings suggest that CYFRA may be a marker of choice for screening and monitoring of lung cancer, particularly squamous cell carcinoma.

Topics: Adenocarcinoma; Aged; Biomarkers, Tumor; Carcinoma; Carcinoma, Large Cell; Carcinoma, Non-Small-Cell Lung; Carcinoma, Squamous Cell; Enzyme-Linked Immunosorbent Assay; Female; Humans; Keratins; Lung Neoplasms; Male; Neoplasm Staging; Prognosis; Retrospective Studies; Sensitivity and Specificity; Survival Rate

Cytokeratins (CK), the intermediate filament markers for epithelial cells were analysed in 23 squamous cell carcinomas (SCC) of the tongue and 11 SCC of the alveolar mucosa (AM) by SDS-PAGE, immunoblotting and two dimensional gel electrophoresis. Normal human adult ventral tongue expresses CK nos 4, 5, 6, 13, 14, 16 (17) while the dorsal tongue expresses CK nos 1, 5, 6, 10, 14, 16 (17). CK 5 and CK 14 were not detected in a majority of samples and CK 18, a marker of simple epithelia, was aberrantly expressed in 18 samples. Normal human adult AM expresses CK nos 4, 5, 6, 13, 14, 16 (17). Among 11 SCC of AM, CK 4 and CK 5 were detected in only two samples each. CK 1 and CK 10 were aberrantly expressed in nine and one samples, respectively. The basic CKs such as CK 4, 5 and 14 were not expressed in SCC at both these sites while others like CK 1 and 18 were aberrantly expressed. Thus, non-expression of basic keratin, CK 5, of the oral lining epithelia and aberrant expression of simple epithelial keratins seem to be the major events in malignant transformation in the oral epithelia.

Topics: Adult; Alveolar Process; Carcinoma, Squamous Cell; Electrophoresis, Gel, Two-Dimensional; Electrophoresis, Polyacrylamide Gel; Humans; Immunoblotting; Keratins; Mouth Mucosa; Mouth Neoplasms; Neoplasm Proteins; Tongue Neoplasms

By using the subtractive hybridization method, two complementary DNA clones differently expressed in rat normal esophageal epithelium and squamous cell carcinoma induced by administration of precursors of N-nitrososarcosine ethyl ester were isolated. A rat homologue of the human 50-kDa type I cytokeratin 14 was cloned for the first time and shown to be expressed preferentially in squamous cell papillomas and carcinomas, whereas it was weakly expressed or absent in normal squamous epithelial cells and in hyperplastic lesions. A rat homologue of the mouse 57-kDa type II cytokeratin showed strong expression in both normal and tumor tissues. These results are well consistent with the reported alteration of keratin subspecies in human esophageal cancers, therefore, encouraging us to use this experimental system as a model for human esophageal carcinogenesis.

Topics: Animals; Carcinogens; Carcinoma, Squamous Cell; Cell Transformation, Neoplastic; DNA, Complementary; Esophageal Diseases; Esophageal Neoplasms; Esophagus; Humans; Hyperplasia; In Situ Hybridization; Keratins; Mice; Neoplasm Proteins; Nitrosamines; Papilloma; Precancerous Conditions; Rats; Rats, Wistar; Recombinant Proteins; Subtraction Technique

Reproducible multi-stage progression to invasive squamous carcinoma of the epidermis has been achieved in transgenic mice expressing the HPV16 early-region genes, including the E6/E7 oncogenes, under the control of the human keratin-14 promoter/enhancer. Although 100% of K14-HPV16 transgenic animals develop hyperplastic and/or dysplastic lesions in several inbred backgrounds, including C57BL/6, BALB/c, and SSIN/SENCAR, only mice backcrossed into the FVB/n background progress to malignant squamous cell carcinomas of two pathological grades, well differentiated and moderate/poorly differentiated (WDSC or MPDSC, respectively), each displaying characteristic patterns of malignant behavior. WDSCs typically arise within the epidermis of the ear and invade deeply into the underlying dermis but fail to metastasize, whereas MPDSCs develop on the chest and truncal skin and invariably metastasize to regional lymph nodes. The transition to the malignant state, in 21% of FVB/n transgenic mice, is characterized by alteration of the repertoire of keratin intermediate filament proteins expressed within neoplastic epidermis, such that WDSCs maintain expression of keratins common to terminally differentiating stratified keratinocytes (K10), whereas MPDSCs are distinguished from WDSCs by activation of embryonic and mucosal keratins (K13, K8, and K19). Precursor hyperplastic and dysplastic lesions are characterized by a progressively increased proliferative index, striking morphological alterations in keratinocyte cell-cell and cell-matrix interactions, and extensive remodeling of the underlying dermal stroma. Remarkably, this extensive stromal remodeling, which may facilitate both angiogenesis and eventual tumor cell invasion, develops early at the dysplastic stage in all animals well before malignant conversion.

Topics: Animals; Carcinoma, Squamous Cell; Cell Differentiation; Cell Division; Cell Transformation, Neoplastic; Disease Susceptibility; DNA-Binding Proteins; Keratins; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Mice, Inbred SENCAR; Mice, Transgenic; Neoplasm Invasiveness; Oncogene Proteins, Viral; Oncogenes; Papillomaviridae; Papillomavirus E7 Proteins; Transcription Factors

Serum levels of a cytokeratin 19 fragment, Cyfra 21-1, were measured using an immunoradiometric assay in 33 women before initial treatment and in 8 women with recurrent tumor. The serum level of Cyfra 21-1 was significantly increased in women with tumors of advanced stage (FIGO) and those with recurrence. The incidence of positivity for Cyfra 21-1 tended to increase with tumor spread. Compared with squamous cell carcinoma (SCC) antigen, the sensitivity of Cyfra 21-1 was comparable to that of SCC antigen. The serum level of Cyfra 21-1 and that of SCC antigen showed a positive correlation. While the use of the serum Cyfra 21-1 level may be limited in cervical cancer by its relatively low sensitivity, a combination assay of Cyfra 21-1 and SCC antigen may be useful in the diagnosis and follow-up of patients with cervical squamous cell carcinoma.

Topics: Adult; Aged; Aged, 80 and over; Antigens, Neoplasm; Carcinoma, Squamous Cell; Female; Humans; Immunoradiometric Assay; Keratins; Middle Aged; Neoplasm Recurrence, Local; Neoplasm Staging; Peptide Fragments; Serpins; Uterine Cervical Neoplasms

Primary neuroendocrine carcinoma of the skin (PNECS) is a rare cutaneous tumor occurring predominantly on sun-exposed skin of elderly people. This histomorphological appearance of this aggressive tumor can be highly variable depending on the predominating growth pattern. We present an unusual case of PNECS: the tumor masked by a dense lymphoid infiltrate with a well-formed follicular growth pattern. In these cases of PNECS, the differential diagnosis must be extended to lymphoid neoplasms as well as lymphoepithelial neoplasms.

Topics: Aged; B-Lymphocytes; Carcinoma, Neuroendocrine; Carcinoma, Squamous Cell; Cell Nucleus; Chromogranin A; Chromogranins; Cytoplasm; Diagnosis, Differential; Facial Neoplasms; Female; Humans; Immunohistochemistry; Keratins; Lymphocytes; Lymphoid Tissue; Neurofilament Proteins; Phosphopyruvate Hydratase; Skin; Skin Neoplasms

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

Mutations in the p53 gene are detected in greater than 50% of squamous cell carcinomas of the lung and to a lesser extent in adenocarcinomas. The p53 protein is also overexpressed in a relatively high percentage of preinvasive lesions of the bronchial epithelium. However, unlike tumor tissue, immunoreactivity does not necessarily imply that cells in preinvasive lesions carry a mutant p53 allele. In some cases, overexpression may result from a cellular checkpoint reaction to a toxic or mutagenic substance such as exposure to tobacco smoke. In any case, p53 overexpression in preinvasive lesions may serve as a biomarker for high risk assessment of lung cancer and other tumors in the aerodigestive tract. A study was designed to retrospectively analyze p53 overexpression in cells from sputum samples collected prior to histological tumor diagnosis. The rationale was based on the observation that both preinvasive and tumor cells from the bronchial epithelium are exfoliated into the airways and can be detected based on morphology in sputa. Two sets of cases were chosen: 1) patients whose first primary tumor was a squamous cell carcinoma containing a mutant p53 allele with overexpression observed in most of the tumor cells; and 2) patients whose squamous cell tumor did not contain a mutant p53 allele. Cells which stained positive for p53 expression were observed in sputum samples collected from all six patients whose tumors were positive for a mutant p53 allele. Also p53 positive cells were detected on sputum slides for two of the five cases where the tumor DNA did not contain a mutation and/or tumor cells which overexpress p53 were not detected in tissue sections. Although cells which stained positive for p53 were present in sputum from patients whose tumors contained a missense mutation, the presence of p53 overexpression was not specific for tumors which contain an altered p53 allele since overexpression was detected in sputum cells from patients whose tumor DNA did not contain a p53 mutation and/or tumor cells which stained positive for p53 were not observed in tissue sections. However, the p53 positive cells in sputa collected from the latter group of patients could have been exfoliated from other lesions which contained a mutant p53 allele. The accumulation of p53 in some sputum cells was concomitant with expression of simple epithelial type cytokeratins (CK) 8 and 18 or at least one of the other cytokeratins detected by a broad spectrum (PAN) CK antibody mi

Topics: Alleles; Carcinoma, Squamous Cell; Humans; Keratins; Lung Neoplasms; Mutagenesis; Retrospective Studies; Sputum; Tumor Suppressor Protein p53

To determine the feasibility of using cytokeratin antibodies to distinguish normal and malignant cells in human tumors using flow cytometry. The goal was ultimately to increase the accuracy of cell kinetic measurements on human tumor biopsies.. A panel of four antibodies was screened on a series of 48 tumors from two centres; 22 head and neck tumors (Amsterdam) and 26 esophagus carcinomas (Leuven). First, screening was carried out by immunohistochemistry on frozen sections to test intensity of staining and the fraction of cytokeratin-positive tumor cells. The antibody showing the most positive staining was then used for flow cytometry on the same tumor.. The two broadest spectrum antibodies (AE1/AE3, E3/C4) showed overall the best results with immunohistochemical staining, being positive in over 95% of tumors. Good cell suspensions for DNA flow cytometry could be made from frozen material by a mechanical method, whereas enzymatic methods with trypsin or collagenase were judged failures in almost all cases. From fresh material, both collagenase and trypsin produced good suspensions for flow cytometry, although the fraction of tumor cells, judged by proportion aneuploid cells, was markedly higher for trypsin. Using the best cytokeratin antibody for each tumor, two parameter flow cytometry was done (cytokeratin versus DNA content). Enrichment of tumor cells was then tested by measuring the fraction of aneuploid cells (the presumed malignant population) of cytokeratin-positive cells versus all cells. An enrichment factor ranging between 0 (no enrichment) and 1 (perfect enrichment, tumor cells only) was then calculated. The average enrichment was 0.60 for head and neck tumors and 0.59 for esophagus tumors.. We conclude that this method can substantially enrich the proportion of tumor cells in biopsies from carcinomas. Application of this method could significantly enhance accuracy of tumor cell kinetic measurements.

Topics: Aneuploidy; Antibodies, Monoclonal; Biopsy; Carcinoma, Squamous Cell; Cell Cycle; DNA, Neoplasm; Esophageal Neoplasms; Feasibility Studies; Flow Cytometry; Head and Neck Neoplasms; Humans; Immunohistochemistry; Keratins

The present study employed immunohistochemical methods to study the cytokeratin (ck) and vimentin expression in 40 cases of laryngeal squamous cell carcinoma. Specific monoclonal isoform antibodies and mixes of antibodies vs. a specific molecule were used in order to determine what cytokeratins were present as accurately as possible. In this sampling two ck patterns were identified based on whether the ck pair 8/18 was present or not. The ck 8/18 positive cases were further broken down into three sub-groups based on the expression of one of the following: the ck 4/13 pair, ck 1/10 pair or vimentin. A statistically significant relationship was found between these sub-groups, the site at which the neoplasm arose and the tendency toward regional metastases. Moreover, it was found that the presence of ck 13 in a squamous cell carcinoma is correlated with the less aggressive forms, as indicated in the literature.

Topics: Adult; Aged; Carcinoma, Squamous Cell; Female; Humans; Immunohistochemistry; Keratins; Laryngeal Neoplasms; Larynx; Male; Middle Aged; Neoplasm Metastasis; Neoplasm Staging; Retrospective Studies; Vimentin

We have developed scanning near-field optical/atomic force microscopy (SNOM/AFM). The SNOM/AFM uses a bent optical fiber simultaneously as a dynamic force AFM cantilever and a SNOM probe. Resonant frequency of the optical fiber cantilever is 15-40 kHz. Optical resolution of the SNOM/AFM images shows less than 50 nm. The SNOM/AFM system contains photon counting system and polychrometer/intensified coupled charge devise (ICCD) system to observe fluorescence image and spectrograph of micro areas, respectively. Cultured cells were stained with fluorescein isothiocyanate (FITC)-labeled anti-keratin antibody or FITC-labeled phalloidin after treatment with Triton X-100. Fluorescence and topographic images were obtained in air and water. The fluorescence images showed clear images of keratin and actin filaments. The SNOM/AFM is perfect to observe biomaterials in liquid with a liquid chamber while the topographic Images showed subcellular structures which correspond to keratin and actin filaments.

Topics: Actins; Air; Carcinoma, Squamous Cell; Chromium; Cytoskeleton; Esophageal Neoplasms; Fluorescein; Humans; Keratins; Microscopy, Atomic Force; Microscopy, Electron, Scanning; Spectrometry, Fluorescence; Tumor Cells, Cultured; Water

This study was designed to investigate the presence of nitric oxide in human squamous cell carcinoma of the head and neck. We localized the activity of nitric oxide synthase in these tumors through immunohistochemical analysis using antibodies to L-citrulline (a byproduct of nitric oxide synthase), to inducible nitric oxide synthase, and to constitutive nitric oxide synthase. We found presence of inducible enzyme in squamous cells throughout these tumors, with the highest intensity staining occurring directly around keratin pearls. Our findings suggest that inducible nitric oxide synthase activity is present in squamous cell carcinomas of the head and neck, leading us to conclude that inducible nitric oxide synthase may play a significant role in tumor growth.

Topics: Awards and Prizes; Carcinoma, Squamous Cell; Head and Neck Neoplasms; Humans; Immunoenzyme Techniques; Keratins; Mouth Mucosa; Nitric Oxide; Nitric Oxide Synthase

Epidermoid carcinomas were induced in hamster buccal pouches with use of 7.12 dimethylbenz[a]anthracene (DMBA). In five animals that served as tumor controls (Group 1), right buccal pouches were painted with DMBA (0.5% solution in mineral oil) thrice weekly for 14 weeks. In five animals (Group 2), right buccal pouches were painted with DMBA and reduced glutathione (GSH) was administered systemically by mouth. Five animals (Group 3) received vitamin E instead of glutathione. An additional 20 animals (Groups 4, 5, 6, and 7) were untreated, vehicle, glutathione, and vitamin E controls, respectively. Glutathione and vitamin E were given in doses of 10 mg/kg in 0.5 ml of mineral oil thrice weekly on days alternate to DMBA painting. Treatment by GSH and vitamin E reduced the number and size of tumors that were formed. Histopathologically, there were also fewer sites of dysplasia, carcinoma in situ, and early invasive epidermoid carcinoma than in the tumor control animals. The formalin-fixed and paraffin-embedded buccal pouch sections were stained immunohistochemically with use of monoclonal antibodies for cytokeratins. These included high-molecular-weight keratins (50,000-68,000 mol wt) 10, 13, and 8 (k10, k13, and k8, respectively). Oral carcinomas and dysplastic sites exhibited basal and suprabasal (spinous layer) high levels of k10, k13, and k8 staining. Treatment with GSH or vitamin E increased the suprabasal staining for high-molecular-weight keratins and reduced the protein expression for k10, k13, or k8. This pattern of staining was observed in dysplastic as well as in carcinoma sites. These results indicate that cytokeratin protein expression could contribute to a common biomarker analysis for chemoprevention.

Topics: 9,10-Dimethyl-1,2-benzanthracene; Animals; Antidotes; Antioxidants; Carcinogens; Carcinoma in Situ; Carcinoma, Squamous Cell; Cheek; Cricetinae; Dose-Response Relationship, Drug; Gene Expression Regulation, Neoplastic; Glutathione; Immunohistochemistry; Keratins; Male; Mesocricetus; Mouth Mucosa; Mouth Neoplasms; Vitamin E

The characteristics of the deep invasive front area of squamous cell carcinomas may reflect tumour prognosis better than other parts of the tumour. Consequently, the authors have recently developed a simple malignancy grading system based solely on the characteristics of the deep invasive front area of oral squamous cell carcinomas, which has great prognostic value. Our previous materials were somewhat heterogeneous, and the prognostic value of our system needed to be confirmed in homogeneous patient material. In the present study of 95 T1-2/N0 glottic carcinomas all treated by radiation, the high prognostic value for invasive front grading of biopsy specimens is confirmed. The grading significantly predicted local recurrence, i.e. treatment failure (P = 0.001). Histological characteristics of the deep invasive front proved to be a better indicator of prognosis than the T-category (size of tumour), and our findings may be of value in the selection of treatment. Of the individual variables in the grading system (pattern of invasion, degree of keratinization, nuclear polymorphism and host response), pattern of invasion and degree of keratinization were the strongest prognosticators in the multivariate analyses. Invasive front characteristics may also prove to be of prognostic value in other cancers.

Topics: Adult; Aged; Aged, 80 and over; Carcinoma, Squamous Cell; Female; Glottis; Humans; Keratins; Laryngeal Neoplasms; Male; Middle Aged; Multivariate Analysis; Neoplasm Invasiveness; Prognosis; Survival Analysis

To assess cell death and cellular proliferation activity, the apoptosis index, the Ki67 proliferative index and overexpression of p53 protein were evaluated in 69 oesophageal squamous cell carcinomas (ESCC), all surgically resected from Japanese patients. Apoptosis was examined by Gavrieli's method in histological sections, and proved to be significantly related to keratinization and ESCC progression. Overall labelling indices were 15.68 +/- 4.04 (positive/1,000 nuclei) and 6.79 +/- 0.64 respectively, in keratinizing and nonkeratinizing types. The apoptosis labelling index increased, especially in keratinizing lesions, from 4.50 +/- 0.59 with cancer invasion to mucosa through 11.46 +/- 2.70 with involvement of the submucosa up to 21.18 +/- 3.72 in cases of penetration to the muscularis propria or adventitia. The relationship between apoptosis, Ki67 scores and p53 expression was determined in identical cancer nests on serial sections. An inverse correlation was shown between the apoptosis score and the Ki67 score in both keratinizing and nonkeratinizing types. There was no significant correlation between apoptosis score and p53 expression, either overall or separately in keratinizing or nonkeratinizing types of ESCC. Our results suggest that a mechanism of induction of apoptosis similar to that operating in normal epidermis acts in keratinizing ESCC, and that as tumour volume increases, single cell death becomes more frequent.

Topics: Apoptosis; Carcinoma, Squamous Cell; Cell Division; Esophageal Neoplasms; Humans; Keratins; Ki-67 Antigen; Neoplasm Proteins; Nuclear Proteins; Tumor Suppressor Protein p53

Evaluation of Cyfra 21-1 (cytokeratin fraction 21-1) in squamous cell carcinoma of the head and neck.. Prospective study.. Serum Cyfra 21-1 concentration was measured in 250 samples from patients with squamous cell carcinoma of head and neck, patients with benign tumors of head and neck, healthy control subjects, and patients in remission from squamous cell carcinoma of head and neck.. Cyfra 21-1 concentration was elevated in 60% of the new patients with squamous cell carcinoma but only in 8% of patients with benign tumors and 3.5% of the healthy controls. At a cutoff of 1.3 ng/mL, the sensitivity of the test was 60%, the specificity was 94%, positive predictive value was 75%, and negative predictive value was 89%. The marker levels tended to follow the clinical course of the disease and were useful for therapy monitoring. Cyfra 21-1 levels were in good correlation with the tumor stage expressed by the local (T) and the lymphatic spread (N) and were inversely correlated with histologic grade, eg, higher in poorly differentiated carcinoma than in well-differentiated squamous cell carcinoma.. Cyfra 21-1 evaluation in head and neck squamous cell carcinoma is worthwhile for performance of an ample study that will prove and establish its routine use.

Topics: Adult; Aged; Biomarkers, Tumor; Carcinoma, Squamous Cell; Female; Head and Neck Neoplasms; Humans; Keratins; Male; Middle Aged; Predictive Value of Tests; Prospective Studies; Sensitivity and Specificity

The purpose of this study was to evaluate the serum tumor markers CYFRA 21-1 and squamous-cell carcinoma antigen (SCC) in the follow-up of squamous-cell cervical cancer patients. One hundred-ninety-three serum samples, which were collected pretherapeutically and during follow-up of 30 patients suffering from squamous-cell cervical cancer FIGO stage III, were analyzed for SCC and CYFRA 21-1. Cutoff values for SCC and CYFRA 21-1 were 3 and 3.3 micrograms/liter, respectively. Fifteen cases were keratinizing and 15 nonkeratinizing squamous-cell carcinomas. Serum tumor marker results were correlated to the results of the clinical and radiologic examinations. We calculated sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of serum SCC and serum CYFRA 21-1 for the whole study group and separately for the keratinizing and nonkeratinizing squamous-cell carcinoma group. Sensitivity, specificity, PPV, and NPV of serum SCC were 66, 91, 93, and 60%, respectively. Serum CYFRA 21-1 showed a sensitivity of 63%, specificity of 96%, PPV of 96%, and NPV of 59%. The combination of SCC and CYFRA 21-1 increased the sensitivity to 78%, with a specificity, PPV, and NPV of 87, 91, and 69%, respectively. In keratinizing squamous-cell carcinoma serum SCC, CYFRA 21-1 and the combination of both had a sensitivity of 76, 64, and 85%, respectively. In nonkeratinizing squamous-cell carcinoma sensitivity was 58, 61, and 72%, respectively. The detection of cervical cancer recurrences with SCC is improved by the combination with CYFRA 21-1. Especially in nonkeratinizing squamous-cell carcinoma CYFRA 21-1 showed promising results.

Topics: Antigens, Neoplasm; Biomarkers, Tumor; Carcinoma, Squamous Cell; Female; Follow-Up Studies; Humans; Keratins; Neoplasm Recurrence, Local; Predictive Value of Tests; Retrospective Studies; Sensitivity and Specificity; Serpins; Uterine Cervical Neoplasms

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

Using digoxigenin-labelled cRNA probes, relationships between morphological characteristics and in situ hybridization for cytokeratin (CK)-mRNAs were analysed in cases of squamous-cell carcinoma of variable differentiation and in balloon-cell formation within the oesophageal mucosa. The present results were correlated to our previous findings on normal oesophageal epithelium. Our results from in situ hybridization study on oesophageal squamous-cell carcinoma provide strong evidence that changes in CK expression occur with differences in malignant potential. Cells of poorly differentiated carcinoma lose an ability to produce CK-mRNAs characteristic of their normal progenitor cells. Moderately differentiated and, still more pronounced, well differentiated carcinoma cells retain an ability to produce CKs characteristic of their tissue of origin (CK 6, CK 14, CK 15 and CK 19). Furthermore, well differentiated carcinoma cells may also gain an ability to synthesize new types of CKs that are not characteristic of the normal oesophageal epithelium (CK 8 and CK 18 characteristic of most simple epithelia, and CK 10 characteristic of keratinizing epithelia). Moreover, some oesophageal CK-genes are expressed in an obviously higher amount (CK 6, CK 14, and CK 19), but the expression of genes coding for the oesophageal differentiation-related CKs (CK 4 and CK 13) is obviously decreased or apparently lost. At the interface zone, observed in sections of well differentiated carcinomas, CK 8 and CK 18 mRNA were expressed in intermediate cell layers, and the centrally located cell layers were found positive for CK 10 mRNA. These findings largely extend the existing results from immunoblotting and immunohistochemical studies. The reduced or non-detectable expression of oesophageal differentiation-related CK-mRNAs (CK 4 and CK 13) on the appearance of balloon cells, suggests molecular changes that may be a marker for pathological progression. In addition, the abundant expression of CK 6 and CK 14 mRNA within areas of balloon-cell formation showing basal hyperplasia, and the higher expression of CK 19 in comparison with normal epithelium, points rather to de-differentiation than to normal vertical differentiation of the oesophageal epithelium. Whether CK-mRNAs can be used as biomarkers for evaluation of oesophageal pathologies remains to be further elucidated.

Topics: Carcinoma, Squamous Cell; Epithelium; Esophageal Neoplasms; Esophagus; Gene Expression; Humans; In Situ Hybridization; Keratins; Mucous Membrane; RNA Probes; RNA, Complementary; RNA, Messenger

Lymphoepithelioma-like carcinoma of the skin (LLCS) is a rare cutaneous neoplasm that histologically resembles nasopharyngeal lymphoepithelioma. Conventional surgical excision carries a considerable rate of recurrence (three of 11 reported cases with such treatment, with one patient dying of metastatic disease). We report the first case of lymphoepithelioma-like carcinoma of the skin treated with Mohs micrographic surgery. Because of its tendency to occur on the face and its potential for recurrence after incomplete removal, this tumor is a good candidate for treatment with Mohs micrographic surgery. Immunohistochemical staining of frozen sections for cytokeratins may help to detect neoplastic cells that may be obscured by the dense lymphoplasmacytic infiltrate associated with this tumor.

Topics: Aged; Carcinoma, Squamous Cell; Humans; Immunohistochemistry; Keratins; Male; Mohs Surgery; Nose Neoplasms; Skin Neoplasms

Five out of 4,172 operated maxillary cysts (3 developed within the maxillary and 2 in the mandible) presented a malignant change of epithelium. In all these 5 cases histology demonstrated a transition from normal to cancerous epithelium. The overall percentage of malignant change was of 0.12%, with 0.077% for non-keratinized epithelium lining odontogenic cysts (3 cases) and 0.65%, that is 8 times higher, for keratinized ones (2 cases). Keratinization of cystic epithelium and chronic inflammatory lesions were the main risk factors.

Topics: Adult; Aged; Carcinoma, Squamous Cell; Cell Transformation, Neoplastic; Epidermal Cyst; Epithelium; Female; Humans; Keratins; Male; Mandibular Diseases; Mandibular Neoplasms; Maxillary Diseases; Maxillary Neoplasms; Middle Aged; Odontogenic Cysts; Radicular Cyst

We report on six patients with tumours of visceral organs (three patients with endometrial adenocarcinoma with squamous cell differentiation, one patient with atypical hyperplasia of endometrium, and two patients with adenocarcinoma of the colon with squamous cell differentiation), where unquestionable differentiation into shadow cells was observed. In all six cases the shadow cells were found mostly in the morules of immature squamous cells. The shadow cells were morphologically identical, on the light microscopical and ultrastructural level, to similar cells found in pilomatricomas. They were often accompanied by granulomatous giant cell reaction and calcification.

Topics: Adenocarcinoma; Adult; Carcinoma, Squamous Cell; Cell Differentiation; Colonic Neoplasms; Endometrial Neoplasms; Endometrium; Female; Humans; Hyperplasia; Keratins; Male; Microscopy, Electron; Middle Aged; Uterine Neoplasms; Uterus

We wanted to investigate the diagnostic and prognostic significance of serum CYFRA 21-1, especially in predicting the risk of recurrence in patients with operable squamous cell lung cancer. Serum levels of CYFRA 21-1 were measured using an immunoradiometric assay (CIS bio) in 76 patients with squamous cell lung cancer (64 operable and 12 with unresectable tumours), 22 with other non-small-cell type (12 with adenocarcinoma and 10 with large-cell type) and 45 with nonmalignant lung diseases. Elevated preoperative CYFRA 21-1 levels were identified in 63% of patients with squamous cell type (SqCC), 33% with adenocarcinoma, and 30% with large-cell carcinoma type. The diagnostic specificity of the assay was 96%. Positive CYFRA 21-1 levels were observed in 33% of stage I, 52% of stage II, 76% of stage IIIa and 83% of stage IIIb patients with SqCC type. Statistically significant differences were obtained between stages I and II and between II and IIIa, but not between stages IIIa and IIIb. Recurrence-free survival probability for patients with elevated serum CYFRA 21-1 levels before surgery was 63% (24/38) versus 92% (24/26) for patients with normal serum CYFRA 21-1 levels. However, the difference was not statistically significant when adjusted for the TNM stage (primary tumour, regional lymph node involvement, occurrence of distant metastasis). In 9 of the 10 patients with increased trend for CYFRA 21-1 during follow-up, elevated serum CYFRA 21-1 levels preceded (7) or coincided (2) with the clinical detection of tumour recurrence, providing a predictive value of an increased trend of 90%.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adenocarcinoma; Biomarkers, Tumor; Carcinoma, Non-Small-Cell Lung; Carcinoma, Squamous Cell; Humans; Immunoradiometric Assay; Keratins; Lung Neoplasms; Multivariate Analysis; Neoplasm Recurrence, Local; Prognosis; Proportional Hazards Models; Risk Factors; Sensitivity and Specificity; Survival Analysis

The detection of cytokeratins in neoplastic tissues by immunohistochemical methods has numerous diagnostic and investigative applications, because cytokeratins are usually conserved in tumour cells during malignant transformation. Recently, however, it has been reported that progression to malignancy is associated with commencement of expression of low-molecular-weight cytokeratins. In the present study, 42 specimens from 35 cases of squamous cell carcinoma (SCC) of the skin were analysed by immunohistochemical techniques, using polyclonal anti-involucrin antibody and a panel of monoclonal antikeratin antibodies, in order to investigate the nature and differentiation of SCCs. The expression of cytokeratins and involucrin in well-differentiated SCCs was similar to that in normal epidermis. In contrast with well-differentiated SCCs, the expression of differentiation-specific cytokeratins and involucrin was diminished in the immature tumour cells in proportion to the malignancy of the SCCs. Some antibodies, however, stained all tumour cells, irrespective of the degree of malignancy. Furthermore, expression of simple epithelial and non-cornifying stratified squamous epithelial cytokeratins was observed in atypical tumour cells of poorly differentiated SCCs. It is of interest that similar expression was noted in many tumour cells in the lymph node metastases and in some tumour cells in the primary cutaneous lesions. Cytokeratin expression similar to that in normal epidermal keratinocytes was conserved in well-differentiated SCCs, but the expression of cytokeratins changed during progression to malignant transformation. The expression of simple epithelial or non-cornifying stratified squamous epithelial cytokeratins in cutaneous SCCs may be a marker for their capability of invasion and metastatic potential.

Topics: Antibody Specificity; Carcinoma, Squamous Cell; Cell Transformation, Neoplastic; Humans; Immunohistochemistry; Keratins; Lymph Nodes; Lymphatic Metastasis; Protein Precursors; Skin Neoplasms

The expression of cytokeratins (CK) 19, 8, 18, 13, 10 and 7 was examined in 35 cases of squamous cell carcinomas of the oesophagus (10 well-differentiated, 13 moderately-differentiated, and 12 poorly-differentiated) and the adjacent mucosa by means of a panel of monoclonal antibodies on frozen sections. The study was undertaken to assess the pattern of expression of these keratins in oesophageal tumours and its relation to the degree of differentiation. The normal oesophageal epithelia expressed CK19 in 86%, CK18 in 17% and CK13 in 14% of cases. CK8, CK10 and CK7 immunoreactivity was not observed. The tumours expressed CK19 in 86%, CK8 in 46%, CK18 in 97%, CK13 in 83%, CK10 in 34% and CK7 in 29% of cases. Thus, the so-called simple epithelial markers CK18 and CK19 occurred in the majority of oesophageal squamous cell carcinomas. CK13 (the so-called non-keratinizing squamous epithelial marker) was only infrequently demonstrated in the non-neoplastic oesophageal mucosa, and its expression was more frequent in carcinomas. CK10 was not demonstrated in non-neoplastic mucosa, but was mostly associated with well-differentiated carcinomas. We therefore conclude that the pattern of expression of cytokeratins in oesophageal carcinomas is different from that in normal oesophageal epithelia and varies with differentiation.

Topics: Adult; Aged; Aged, 80 and over; Biomarkers; Carcinoma, Squamous Cell; Epithelium; Female; Gastrointestinal Neoplasms; Humans; Immunohistochemistry; Keratins; Male; Middle Aged

Retinoids are promising agents for therapy of squamous cancers. In vitro, retinoids decrease expression of differentiation markers in head and neck squamous carcinoma cells. Little information is available on effects of retinoids on head and neck squamous carcinoma cell xenograft growth in vivo. To address this issue, head and neck squamous carcinoma cells (line 1483) were established as xenografts in nude mice. Control tumors grew rapidly with doubling times of 4-6 days to mean volumes of 1696 mm3 after 24 days. Histological analyses indicated the formation of well-differentiated squamous carcinoma cells exhibiting pronounced stratification (basal and suprabasal cells) and keratinization (keratin pearls) with abundant stroma. Cytokeratin 19 expression was restricted to the basal cell layers, and cytokeratin 4 expression was abundant in suprabasal cells. Mice were treated daily with 30 mg/kg 9-cis retinoic acid, 20 mg/kg all-trans-retinoic acid, or 60 mg/kg 13-cis retinoic acid by p.o. gavage on a schedule of 5 days/week over 4 weeks. Low micromolar (1.48-3.67 microM) and nanomolar (200-490 nM) concentrations of 9-cis retinoic acid and all-trans-retinoic acid were measured in plasmas and xenografts, respectively, 30 min after dosing. Retinoid treatment produced a marked suppression of the squamous cell differentiation of tumor cells manifest by decreased keratinization, loss of stratification, and accumulation of basal cells. This was accompanied by large decreases in the number of CK4-positive cells and concomitant increases of CK19-positive cells. REtinoic acid receptor-beta expression was also increased by 2.9-9.7-fold after chronic retinoid treatment. 9-cis retinoic acid and all-trans-retinoic acid decreased tumor volumes by 23 +/- 5 (SE) and 19 +/- 3%, respectively (P < or = 0.05); 13-cis retinoic acid was inactive. These retinoids did not decrease the rate of exponential tumor growth but increased the latent period until exponential growth began. These studies demonstrate that retinoids do not universally decrease tumor growth but profoundly suppress squamous cell differentiation in vivo in this xenograft model.

Topics: Animals; Antineoplastic Agents; Biomarkers, Tumor; Carcinoma, Squamous Cell; Cell Differentiation; Cell Division; Dose-Response Relationship, Drug; Female; Humans; Keratins; Mice; Mice, Nude; Mouth Neoplasms; Neoplasm Transplantation; Receptors, Retinoic Acid; Retinoids; RNA, Messenger; Transplantation, Heterologous; Tumor Cells, Cultured

Cytokeratins are epithelial markers whose expression is not lost during malignant transformation. Cyfra 21-1 is a cytokeratin-19 fragment that is soluble in serum and may be a useful circulating tumor marker.. The aims of this study were (1) to confirm sensitivity and specificity of Cyfra 21-1 in detecting non-small cell lung cancer (NSCLC) and especially the squamous cell subtype, (2) to assess the potential relationship between Cyfra 21-1 and disease stage of the disease in NSCLC, and (3) to evaluate prognostic effect of Cyfra 21-1 in NSCLC.. An immunoradiometric assay of serum Cyfra 21-1 was performed in 161 patients with lung cancers and 71 others with benign lung diseases. The ability of Cyfra 21-1 to detect different histologic subtypes of lung cancer vs benign lung diseases was assessed through receiver operating characteristic (ROC) curves and comparisons with other tumor markers such as carcinoembryonic antigen, neuron-specific enolase, and squamous cell carcinoma antigen. Comparisons of Cyfra 21-1 levels according to histologic subtype and disease stage were done using Kruskal-Wallis test. Independent prognostic value of Cyfra 21-1 was studied with a multivariate analysis of survival (Cox's model).. Using a threshold of 3.3 ng/mL for Cyfra 21-1, sensitivity and specificity were, respectively, 0.59 and 0.94 in NSCLC, 0.68 and 0.94 in the subgroup of the squamous cell carcinoma, and 0.19 and 0.94 in small cell lung cancer. Cyfra 21-1 levels were significantly higher in advanced NSCLC than in early-stage disease. All 29 patients with serum concentrations > 32 ng/mL had stage IIIB-IV and only one of 14 patients with stage I-II disease had Cyfra 21-1 level > 18 ng/mL. In the multivariate analysis of survival, Cyfra 21-1 was an independent prognostic factor along with performance status and disease stage in NSCLC.. Cyfra 21-1 is a sensitive and specific tumor marker of NSCLC, especially of squamous cell subtype. It also reflects the extent of the disease and has an independent prognostic role along with performance status and disease stage in NSCLC.. A high level of Cyfra 21-1 in apparently early-stage NSCLC should be an indication for more extensive workup before thoracotomy. The independent prognostic role of Cyfra 21-1 level may be useful in stratifying populations with advanced NSCLC or early-stage resected NSCLC as elevated Cyfra 21-1 levels might identify those patients at high risk for treatment failure.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Biomarkers, Tumor; Carcinoma, Non-Small-Cell Lung; Carcinoma, Squamous Cell; Female; Humans; Immunoradiometric Assay; Keratins; Lung Diseases; Lung Neoplasms; Male; Middle Aged; Predictive Value of Tests; Prospective Studies; ROC Curve; Sensitivity and Specificity

As part of a study on the relationship of tumour phenotype and behaviour, we have characterized two head and neck squamous cell carcinoma cell lines, derived from human laryngeal carcinomas and designated HLaC'79 and HLaC'82. Cytogenetic analysis revealed that HLaC'79 and HLaC'82 shared 10 major chromosome rearrangements indicating that the cell lines had a common origin. In the extremely complex chromosomal patterns, abnormalities were found in chromosomes 1, 3 (surplus 3q) and 5 (i(5p) x 2). Both cell lines displayed constitutive expression of vimentin and were capable of anchorage-independent growth in agarose gels. However, in spite of their common origin specific differences were found. Cells of HLaC'79 were spindle shaped and formed tumours in athymic mice. In contrast, cells of HLaC'82 had a compact morphology, contained less vimentin, were more contact inhibited and were not tumorigenic. These results indicate that malignant transformation in HLaC'82 was partially reversed.

Topics: Carcinoma, Squamous Cell; Cell Line; Cell Transformation, Neoplastic; Humans; Intermediate Filament Proteins; Intermediate Filaments; Karyotyping; Keratins; Laryngeal Neoplasms; Tumor Cells, Cultured; Vimentin

A case of mixed tumor of the vagina or spindle cell epithelioma is presented and the literature on this rare type of tumor is reviewed. Immunohistochemical findings suggest an epithelial origin. Follow-up studies indicate benign behavior. However, recurrent tumors were reported suggesting careful follow-up observation after excision of extended primary tumors.

Topics: Adult; Biomarkers, Tumor; Carcinoma, Squamous Cell; Diagnosis, Differential; Female; Humans; Keratins; Mixed Tumor, Mullerian; Vagina; Vaginal Neoplasms

The synthetic retinobenzoic acid RE-80 was evaluated for its potential as an inductor of tumor cell differentiation and as a chemopreventive agent. A minimally toxic dose of RE-80 in vitro produced morphologic changes typical differentiation in epidermal tumor cell colonies. Indirect immunofluorescence indicated induction of a differentiation-associated keratin of internal stratified epithelia, K13, and inhibition of the differentiation-associated epidermal keratin K1. Cultured cells were skin-grafted to athymic nu/nu mice to evaluate RE-80 effects on early stage malignant progression in vivo. When tumors had grown to 3 to 4 mm in diameter, mice were treated by intraperitoneal injection with RE-80 (67 micrograms, 170 mmol, i.p., two times per week) or vehicle (100 microliters 20% ethanol). Papillomas (benign) and moderately differentiated squamous cell carcinomas were reduced in volume about 4-fold by RE-80 treatment. Larger, poorly differentiated squamous cell carcinomas were unaffected. RE-80 resulted in a lower proportion of proliferative cells (detectable by bromodeoxyuridine incorporation) and a higher proportion of moderately to well differentiated tumors after 40 days of treatment compared with control tumors, which were mainly poorly differentiated squamous cell carcinomas. K13 induction in vitro was correlated with response to retinoid in vivo. Induction of differentiation may be mechanism of the response to RE-80 in vivo since carcinoma cells expressing K13 did not incorporate bromodeoxyuridine and were on a terminal pathway.

Topics: Animals; Antineoplastic Agents; Benzoates; Carcinoma, Squamous Cell; Cell Differentiation; Disease Models, Animal; Keratins; Mice; Mice, Nude; Papilloma; Skin Neoplasms; Tetrahydronaphthalenes; Tumor Cells, Cultured

Immunohistochemical detection of bone marrow micrometastases has been reported as a prognostic marker in colorectal cancer. The aims of this study were to evaluate the potential advantage of flow cytometry as an objective method of identifying and quantifying micrometastatic deposits within bone marrow and to determine the prevalence and quantity of micrometastases in patients undergoing surgery for gastrointestinal cancers.. Flow cytometry was first validated by a controlled "spike" experiment in which varying numbers of neoplastic epithelial cells were added to bone marrow, and cytometry was performed in a blinded fashion. Three neoplastic cell lines (colonic and esophageal) with varying degrees of expression of cytokeratin-18 were used. Epithelial cells were detected by dual staining with fluorescence-labeled, monoclonal anti-cytokeratin, and propidium iodide.. Cytometry reproducibly detected the presence of > or = 10 neoplastic cells per 10(5) marrow cells. Micrometastases were found in 20%-30% of patients undergoing potentially curative resection of colorectal and gastroesophageal adenocarcinomas. There was a trend toward increasing positivity for marrow deposits with advanced Dukes' staging of colorectal cancer.. Flow cytometric assessment of bone marrow is a reliable, objective, and quantitative method of detecting micrometastatic deposits found in a substantial subset of patients undergoing surgery for gastrointestinal adenocarcinomas.

Topics: Adenocarcinoma; Antibodies, Monoclonal; Bone Marrow Neoplasms; Carcinoma, Squamous Cell; Colorectal Neoplasms; Esophageal Neoplasms; Flow Cytometry; Gastrointestinal Neoplasms; Humans; Keratins; Prognosis; Prospective Studies; Stomach Neoplasms

Spindle cell carcinomas of the salivary gland are extremely rare, with only a few cases having been previously reported. We present a 55-year-old man with a rapidly enlarging mass in the left parotid gland. Despite radical surgery, the tumour recurred, and led to death 11 months later. Histopathologically, the tumour was composed of two components, a squamous cell carcinoma component and a spindle cell sarcomatoid component. A diagnosis of primary spindle cell carcinoma of the parotid gland was made. Immunohistochemical studies revealed keratin positivity and vimentin negativity in the squamous cell carcinoma component: the spindle cell sarcomatoid component was positive for vimentin and negative for keratin, but showed focal positivity for epithelial membrane antigen. The origin of the sarcomatoid component and the differential diagnosis from malignant mixed tumours are discussed.

Topics: Carcinoma, Squamous Cell; Humans; Immunohistochemistry; Keratins; Male; Middle Aged; Parotid Neoplasms

Liarozole showed antitumoral activity in the Dunning AT-6sq, an androgen-independent rat prostate carcinoma. To investigate its potential mechanism of action, the effects of the drug doses (ranging from 3.75 to 80 mg/kg b.i.d.) on endogenous plasma and tissue all-trans-retinoic acid levels and on the differentiation status of the tumor cells were evaluated. To follow modulation of differentiation, cytokeratins were localized in the (un)treated tumors by immunocytochemistry and quantitatively determined by immunoblotting. Results showed that liarozole statistically significantly reduced tumor weight from 30 mg/kg upwards and induced accumulation of all-trans-retinoic acid both in plasma and tumors. In the tumors, a statistically significant accumulation was already noted from 7.5 mg liarozole/kg upwards. Concomitantly, the differentiation status shifted from a keratinizing towards a non-keratinizing squamous carcinoma, which was further confirmed by the cytokeratin profile of the carcinoma (presence of CK 8, 10, 13, 14, 18, 19). Immunoblotting revealed an overall decrease in cytokeratin content, except for CK 8. These findings suggest that the antitumoral properties of liarozole might be related to an increase in the degree of tumor differentiation through accumulation of all-trans-retinoic acid.

Topics: Animals; Antibodies, Monoclonal; Antineoplastic Agents; Carcinoma, Squamous Cell; Dose-Response Relationship, Drug; Gene Expression Regulation, Neoplastic; Imidazoles; Immunoblotting; Immunohistochemistry; Keratins; Male; Neoplasm Transplantation; Organ Size; Prostate; Prostatic Neoplasms; Random Allocation; Rats; Rats, Inbred F344; Tretinoin; Tumor Cells, Cultured; Vimentin

The urinary CYFRA 21-1 value corrected for urinary creatinine (ng/ml/creatinine), was studied in the urine of patients with urothelial tumors. To examine its clinical significance we studied urinary CYFRA 21-1 excretion (ng/ml/creatinine), in a total of 22 urine samples from patients with bladder cancer, 7 from patients with renal pelvic and ureteral tumor, 6 from patients with urinary infection 6 from patients with urinary diversion called ileal conduit, and 8 from healthy adult men. The excretion of CYFRA 21-1 in urine was determined by two specific monoclonal antibodies (Ks 19.1 and BW 19.21). The mean value of urinary CYFRA 21-1 in healthy adult men was 1.96 +/- 1.33 (mean +/- SD) ng/ml/creatinine. Urinary CYFRA 21-1 showed a higher value in the urine of urinary infection and urinary diversion. As to bladder cancer, urinary CYFRA 21-1 showed a higher value in a larger volume of tumor than in a smaller volume of tumor in transitional cell carcinoma regardless of the grade and stage. These findings suggest that urinary CYFRA 21-1 may be a non-specific marker in urothelial tumors.

Topics: Adult; Aged; Biomarkers, Tumor; Carcinoma, Squamous Cell; Carcinoma, Transitional Cell; Cystitis; Female; Humans; Keratins; Male; Middle Aged; Peptide Fragments; Urologic Neoplasms

The aim of this study was to evaluate serial determinations of CYFRA 21-1 in the follow-up of patients treated surgically for non-small cell lung cancer in order to predict the risk of tumour recurrence. Serum levels of CYFRA 21-1 were measured using an immunoradiometric assay (CIS bio) in 57 patients with operable non-small cell lung cancer (NSCLC): 25 with squamous cell carcinoma (SqCC), 20 with adenocarcinoma (AC), 12 with large cell carcinoma (LCC) and 30 with non-malignant lung diseases. Elevated preoperative CYFRA 21-1 levels were identified in 44% of all patients with NSCLC. The diagnostic specificity of the assay was 97%. Positive CYFRA 21-1 levels was observed in 30% of stage I, 33% of stage II, and 55% of stage IIIa. Statistically significant differences were obtained between stages I and IIIa, II and IIIa, but not between stages I and II. During follow-up recurrence was observed in 19 of 57 (33%) NSCLC patients. Recurrence-free survival probability for patients with elevated serum CYFRA 21-1 levels before surgery was 52% (13/25), versus 81% (26/32) for patients with normal serum CYFRA 21-1 levels (p < 0.01). In 15 patients with increased trend for CYFRA 21-1, elevated serum CYFRA 21-1 levels preceded (13 patients) or coincided (2 patients) with the clinical detection of tumour recurrence, providing a predictive value of an increased trend of 87%. In the multivariate analysis the association of the increase of CYFRA 21-1 level with a higher risk of recurrence is statistically significant (p < 0.001).

Topics: Antibodies, Monoclonal; Biomarkers, Tumor; Carcinoma, Non-Small-Cell Lung; Carcinoma, Squamous Cell; Humans; Immunoradiometric Assay; Keratins; Lung Neoplasms; Multivariate Analysis; Neoplasm Recurrence, Local; Predictive Value of Tests; Prognosis; Sensitivity and Specificity; Survival Rate

There are few specific pathologic findings that can be relied on to distinguish primary thymic carcinomas from lung carcinomas with mediastinal extension or showing metastasis to the anterior mediastinum. The immunohistochemical reactivity on frozen sections of thymic carcinomas and lung carcinomas, which are histologically similar to each other, was examined with the use of monoclonal antibodies to cytokeratins 7 and 13. Among keratinizing squamous cell carcinomas, all thymic carcinomas reacted with antibody specific for cytokeratin 7 (9/9, 0%), whereas no staining reaction was seen in lung carcinomas (0/5, 0%) (p < 0.01). This finding can be used as a diagnostic aid in primary thymic keratinizing squamous cell carcinomas to expedite treatment and prognosis. Cytokeratin 7 and cytokeratin 13 monoclonal antibodies reacted with almost all cases of thymic carcinoma. Applications of monoclonal antibodies specific for certain cytokeratins, especially 7 and 13, may be helpful in the diagnosis of other subtypes of thymic carcinomas.

Topics: Antibodies, Monoclonal; Carcinoma, Squamous Cell; Diagnosis, Differential; Humans; Immunohistochemistry; Keratins; Lung; Lung Neoplasms; Thymoma; Thymus Gland; Thymus Neoplasms

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

A case of metastatic bronchogenic carcinoma to the gingiva in a 47-year-old male is reported. The gingival lesion developed as a quickly growing mass and appeared 2 months after surgical excision and radiotherapy of the lung carcinoma were completed. The gingival tumor was histopathologically diagnosed as a poorly differentiated squamous carcinoma. Comparative cytologic studies showed similarities between the gingival metastasis and the previous lung cancer.

Topics: Antigens, Neoplasm; Carcinoma, Bronchogenic; Carcinoma, Squamous Cell; Gingival Neoplasms; Humans; Keratins; Lung Neoplasms; Male; Middle Aged; Mitosis; Mucin-1; Neoplasm Proteins

Malignant lymphoepithelial lesions (MLEL) are rare tumors of the salivary glands that show high incidence in Inuit Canadians, Alaskans, and Greenland Eskimos. The tumors are usually anaplastic or poorly differentiated squamous cell carcinomas. Focal spindle cell elements have been rarely reported. The tumors have been epidemiologically linked to Epstein-Barr virus infection. We present a case of malignant lymphoepithelial lesion showing exclusive spindle cell morphology. The patient is a 44-year-old male Inuit Canadian who presented with a long-standing history of a left parotid mass. The mass did not show evidence of rapid growth or facial nerve involvement. Parotidectomy was performed. The tumor was histologically composed of spindle cells nodules in a background of lymphocytes. The spindle cells showed no evidence of cytologic atypia but were mitotically active. Immunohistochemical staining for low-molecular-weight cytokeratin was only focally positive. The differential diagnosis included a mesenchymal neoplasm and malignant lymphoepithelial lesion. Electron microscopic examination confirmed the squamous nature of the neoplasm. Intracytoplasmic viral particles were also identified ultrastructurally. In situ hybridization for Epstein-Barr virus mRNA using a 30-base oligonucleotide probe specific for the EBER-1 gene showed very high level of expression in the tumor cells. No expression was noted in the adjacent parotid gland tissue. Our findings confirm the squamous nature of malignant lymphoepithelial lesions despite the spindle cell morphology occasionally seen in these neoplasms. They also confirm the strong role of Epstein-Barr virus infection in the pathogenesis of these tumors. This may have further diagnostic and therapeutic implications.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Base Sequence; Carcinoma, Squamous Cell; Genes, Viral; Herpesvirus 4, Human; Humans; In Situ Hybridization; Inclusion Bodies; Keratins; Male; Molecular Sequence Data; Parotid Neoplasms; RNA, Messenger; RNA, Viral

In this study, I investigated the molecular weights of keratin-subunits in the tissue of esophageal cancer by enzyme-labeled antibody technique with four kinds of antikeratin monoclonal antibodies with different spectrums of reacting keratin-subunits. Further more, the correlation between the molecular weights of keratin-subunits and clinicopathological factors was evaluated, and that between the molecular weights and the prognosis was studied also. The positive rates of four kinds of primary antibodies did not correlate to clinical feature or prognosis, and each primary antibody showed different attitude regarding correlation to histopathological factors. I analyzed the molecular weights of keratin-subunits increased in the carcinoma tissue by the difference of staining intensities of four monoclonal antibodies. The histological findings of the cases with carcinoma tissues in which 48, 56 kd keratins increased were in high malignancy compared with other groups, and their prognosis was significantly poor. Examination of prognostic factors with multivariate analysis revealed that the increase of 48, 56 kd keratins in the carcinoma tissues was the most important determining factor of prognosis next to lymphatic invasion.

Topics: Adult; Aged; Aged, 80 and over; Antibodies, Monoclonal; Biomarkers, Tumor; Carcinoma, Squamous Cell; Esophageal Neoplasms; Female; Humans; Immunoenzyme Techniques; Keratins; Male; Middle Aged; Molecular Weight; Multivariate Analysis; Neoplasm Invasiveness; Neoplasm Metastasis; Neoplasm Staging; Prognosis

In head and neck squamous cell carcinoma a reliable serum marker of carcinogenesis should be of predictive value for the development of recurrent disease or a second primary tumour. At the moment, such a tumour marker is not available. Recently, elevated levels of cytokeratin 19-fragments (Cyfra 21-1) have been detected in the serum of patients with lung cancer, in particular with squamous cell carcinoma. Cytokeratin 19 is an intermediate cell filament protein expressed in simple epithelia and their malignant counterparts. Therefore, in this prospective study, a standardized sandwich enzyme-linked immunosorbent assay for soluble cytokeratin 19 fragments was tested in the serum of 20 patients with a previously untreated head and neck squamous cell carcinoma. The results were compared with that of 20 control individuals. Our results showed significantly higher Cyfra 21-1 concentrations in the serum of patients with cancer (10.21 +/- 3.03 ng/ml) than the controls (7.2 +/- 2.63 ng/ml). After radical treatment the marker levels dropped significantly to 1.65 +/- 1.07 ng/ml. Cyfra 21-1 appears to be of value as a circulating tumour marker for head and neck squamous cell carcinoma especially in monitoring disease control.

Topics: Adult; Aged; Biomarkers, Tumor; Carcinoma, Squamous Cell; Enzyme-Linked Immunosorbent Assay; Epithelium; Female; Follow-Up Studies; Forecasting; Gene Expression Regulation, Neoplastic; Head and Neck Neoplasms; Humans; Keratins; Linear Models; Male; Middle Aged; Neoplasm Recurrence, Local; Neoplasm Staging; Neoplasms, Second Primary; Peptide Fragments; Prospective Studies

Of 291 immunosuppressed renal transplant recipients (RTRs) with surviving allografts attending the Royal London Hospital, 171 patients (59%) were found to have warty keratoses. On histological analysis, the lesions in 50 patients (17%) showed partial-thickness dysplasia, and 34 (12%) had one or more invasive squamous cell carcinoma (SCC) and/or one or more in situ SCC or full-thickness dysplasia. We examined the claim that squamoproliferative lesions in RTRs possess distinctive histopathological features that differ from those of similar lesions occurring sporadically in the nonimmunosuppressed population. We compared 40 squamoproliferative lesions from RTRs with 40 matched squamoproliferative lesions from nonimmunosuppressed patients; lesions were coded and their source was unknown to the assessors. Two dermatopathologists independently assessed the cases and gave scores for 11 histological features that have been reported to be characteristic of such lesions in the immunosuppressed population. These included a warty architecture, koilocytes, and multinucleate giant cells. Using these criteria, it was not possible to distinguish lesions of immunosuppressed patients from those of immunocompetent people.

Topics: Carcinoma in Situ; Carcinoma, Squamous Cell; Cytoplasmic Granules; Diagnosis, Differential; Epithelium; Female; Giant Cells; Graft Survival; Humans; Hyalin; Immunocompetence; Immunosuppression Therapy; Keratins; Keratosis; Kidney Transplantation; Male; Neoplasm Invasiveness; Papilloma; Skin Neoplasms; Transplantation, Homologous; Warts

Topics: Antigens, Neoplasm; Carcinoma, Squamous Cell; Cell Nucleus; Cytoplasm; Epidermis; Gene Expression Regulation; Gene Expression Regulation, Neoplastic; Humans; Keratinocytes; Keratins; Keratoacanthoma; Ki-67 Antigen; Neoplasm Proteins; Nuclear Proteins; Precancerous Conditions; Skin Neoplasms; Tumor Suppressor Protein p53

Keratoacanthomas are benign skin tumors that grow rapidly but eventually regress. They occur most commonly in sun-exposed skin and are histologically remarkably similar to squamous cancers. Since mutations of the p53 tumor suppressor gene are found frequently in cutaneous squamous cell carcinomas, we hypothesized that p53 mutations might contribute to the development of keratoacanthomas. To address this question, we did p53 immunohistochemistry with a polyclonal rabbit antiserum, CM-1, that binds both mutant and wild-type p53 proteins. Although wild-type p53 protein degrades rapidly and is generally undetected by immunohistochemistry, mutant p53 protein has a longer half-life and accumulates to detectable levels. We tested 26 formalin-fixed keratoacanthomas and 4 normal skin biopsies. Positive nuclear staining was detected in 20 of 26 (77%) of the keratoacanthomas and in none of the normal skin samples. Nuclear staining occurred in the outermost layer of the neoplasms and not in the keratin-filled central cores. Since nuclear p53 protein within a cutaneous squamous cell carcinoma usually correlates with missense mutation, these data suggest that p53 mutations contribute to the development of this benign neoplasm. The histologic similarity to squamous cell carcinoma and the accumulation of p53 protein suggest progression toward malignancy, but the invariable regression of these tumors suggests an arrest at some point in multistage carcinogenesis. If this model is correct, then genetic analysis of keratoacanthomas may provide clues to the later stages of squamous carcinogenesis including local invasion and metastasis.

Topics: Animals; Carcinoma, Squamous Cell; Cell Nucleus; Coloring Agents; Disease Progression; Fixatives; Formaldehyde; Genes, p53; Half-Life; Humans; Image Processing, Computer-Assisted; Immunohistochemistry; Keratins; Keratoacanthoma; Mutation; Neoplasm Regression, Spontaneous; Rabbits; Remission, Spontaneous; Skin; Skin Neoplasms; Sunlight; Tumor Suppressor Protein p53

Histologic grade seems to be of limited prognostic significance in patients with vulvar carcinoma. However, the study of cytokeratin expression is of potential interest because it allows a more precise evaluation of the degree of squamous differentiation. This study was conducted to investigate whether differences in cytokeratin expression exist between normal vulvar epithelium and vulvar carcinoma and whether these differences are prognostically significant.. The expression of several differentiation markers, i.e., cytokeratin (CK) 10, CK 13, and involucrin, was studied in samples of 41 vulvar carcinomas. The expression of CK 8, 10, 13, and 14 was compared with CK expression in normal vulvar epithelium and was correlated with tumor grade and tumor growth pattern. Tumor growth pattern was considered type A if infiltrating tumor cell nests showed a layer of small, basaloid cells bordering the surrounding mesenchymal tissue and was considered type B if this was not the case. Prognosis was based on whether disease recurred or not.. Sixteen patients had disease recurrence. No prognostic significance of tumor grade was found. Tumor growth pattern was prognostically significant: in patients with a type A tumor, recurrence was observed less often than in patients with a type B tumor (P = 0.03). Cytokeratin 14, typical for basal cells of normal vulvar epithelium, was expressed in all tumors, whereas CK 8 was not expressed in any tumor. A relationship between tumor growth pattern and the concordant expression of differentiation markers was observed: in 55% of type A tumors and in none of type B tumors, concordant expression of CK 10, CK 13, and involucrin was found.. The expression of differentiation markers in vulvar carcinoma is related strongly to the tumor growth pattern, and this pattern is prognostically significant.

Topics: Biomarkers, Tumor; Carcinoma, Squamous Cell; Cell Differentiation; Female; Humans; Immunoenzyme Techniques; Keratins; Multivariate Analysis; Prognosis; Protein Precursors; Recurrence; Vulvar Neoplasms

The grading of squamous cell carcinoma (SCC) of the esophagus as proposed by the World Health Organization (WHO) has not yet proved to be prognostically significant. Therefore, the prognostic impact of various histologic parameters was investigated and compared with that of the WHO grading.. Hematoxylin and eosin-stained tumor samples from 138 patients with SCC of the esophagus who underwent potentially curative resection (no residual tumor or distant metastases) were evaluated for the following histologic parameters: degree of keratinization, nuclear polymorphism, pattern of invasion, mitotic activity, and inflammatory response. The prognostic impact of these parameters was analyzed by univariate and multivariate survival analyses.. In the univariate analysis, the inflammatory response (P = 0.0006), pattern of invasion (P = 0.0011), and nuclear polymorphism (P = 0.0161) were the only parameters that correlated with survival. However, in a multivariate survival analysis including these parameters, only pattern of invasion (P = 0.0010) and inflammatory response (P = 0.0076) were prognostically significant. Based on these results, a new prognostic score system was defined that correlated significantly with survival in the univariate survival analysis (P = 0.0002). In contrast, the WHO histologic grade was not prognostically significant. In the multivariate Cox regression analysis, the new prognostic score system proved to be an independent prognostic parameter (P = 0.0062), ranking next to pT classification (P = 0.0001) and pN classification (P = 0.0014).. For SCC of the esophagus, histologic grading based on pattern of invasion and inflammatory response had an independent prognostic impact, whereas the grading system proposed by the WHO had no significant prognostic value.

Topics: Adult; Aged; Carcinoma, Squamous Cell; Cell Nucleus; Esophageal Neoplasms; Female; Humans; Keratins; Male; Middle Aged; Mitosis; Multivariate Analysis; Prognosis; Survival Analysis

The well-documented specificity of anticytokeratin monoclonal antibodies for detection of epithelial micrometastatic cancer cells in bone marrow as a prognostic indicator inspired us to apply this approach to patients with squamous cell carcinomas (SSC) of the head and neck region. The sensitivity of the broad-spectrum anticytokeratin monoclonal antibody (mAb) A45-B/B3 used for tumor cell detection was demonstrated by immunostaining of cryostat sections from the respective primary tumors. Analysis of 31 patients with SSC revealed A45-B/B3-positive cells in 10 cases (32.3%) at frequencies of 1-207 per 1 x 10(6) mononuclear cells. Most specimens displayed isolated tumor cells, while cell clusters were found in only two cases (6.5%). The present data suggest that hematogenous dissemination of cancer cells is more frequent than expected from clinicopathologic staging of patients with SSC of the head and neck region.

Topics: Adult; Aged; Aged, 80 and over; Antibodies, Monoclonal; Biomarkers, Tumor; Bone Marrow; Carcinoma, Squamous Cell; Coloring Agents; Epithelium; Female; Humans; Immunoglobulin G; Immunohistochemistry; Keratins; Lymph Node Excision; Male; Middle Aged; Mouth Neoplasms; Neoplasm Staging; Neoplastic Cells, Circulating; Prognosis; Sensitivity and Specificity

Malignant transformation is often associated with alterations in the expression of normal differentiation markers, which may serve as intermediate end points in carcinogenesis and cancer prevention. To identify early changes in differentiation markers during head and neck cancer development, we examined the expression of cytokeratins (CK1, CK8, CK13, and CK19) and involucrin by immuohistochemical methods in surgical specimens from 29 head and neck squamous cell carcinoma patients that included, in addition to carcinoma, adjacent dysplastic lesions (17 cases), hyperplastic lesions (21 cases), and adjacent histologically normal tissues (15 cases) and in specimens from 31 subjects with premalignant oral lesions (e.g, oral leukoplakia) without cancer, CK13 and involucrin were detected in all specimens from the cancer patients, and no differences in their expression were found among the different histopathological group. CK8 was detected in only 2.7% (1 of 36) of adjacent normal and hyperplastic tissues but in 58.8% (10 of 17) and 75.9% (22 of 29) of dysplastic and carcinoma tissues. The corresponding figures for CK19 expression in adjacent normal, hyperplastic, dysplastic, and carcinoma tissues were 13.3, 70, 71.4, and 82.1%, respectively. The expression of CK1 was not related to the progression from normal to malignant. In the leukoplakia lesions, CK8 CK13, CK19 and involucrin were detected in 13.8, 100, 74.2 and 100% of the specimens, respectively. These results demonstrate that CK19 expression increases in hyperplastic lesions and continues to be expressed in dyplastic and malignant lesions, whereas CK8 expression in low in adjacent normal and hyperplastic tissues and increases only in dysplastic and malignant lesions. Thus, CK19 and CK8 could be markers of sequential premalignant changes in head and neck carcinogenesis.

Topics: Biomarkers, Tumor; Carcinoma, Squamous Cell; Culture Techniques; Disease Progression; Head and Neck Neoplasms; Humans; Immunohistochemistry; Keratins; Sensitivity and Specificity

Since in vitro derived tumor cell lines usually correspond to their tumors of origin, a potential biological difference between a primary tumor and its derivative metastases and recurrent tumors should be reflected in established tumor cell lines. The aim of this study was to determine useful cellular markers in permanent tumor cell lines of head and neck squamous cell carcinomas (SCC) and to evaluate a possible relationship between these markers and the origin of selected cell lines. The cell lines, established in the laboratory of T. Carey at the University of Michigan (UM) (Ann Arbor, Mich., USA), were derived from primary tumor and its metastases (UM-SCC 10A, 10B), primary tumor and its recurrent tumors (UM-SCC 14A, 14B, 14C) and single tumors (UM-SCC 11B, 17A, 22B). An additional tumor cell line (HLac 79) was isolated by H.-P. Zenner (Tubingen, Germany) and a clone (8029 NA) with its cisplatin-resistant subline (8029 DDP4) was established in our laboratory. As markers we chose three groups known to be related to growth behavior and/or tumor differentiation: cytoskeletal proteins, oncogene products and membrane-associated antigens. These markers were detected by immunohistochemical methods using commercially available monoclonal antibodies. The "metastatic" and "recurrent" cell lines showed changes in comparison to the corresponding "parental" lines, which could be associated with a higher degree of de-differentiation, such as the occurrence of vimentin and neuroectodermal proteins, loss of HLA-ABC or HLA-DR and increased expression of epidermal growth factor receptor. The expression of cytokeratins was more stable and dissociation of the classical cytokeratin pairs was observed only in a few cases. Oncogene products were practically identical in cell lines from parental and recurrent or metastatic tumors. These data serve not only as a basis for further experiments with these cell lines but also provide information about the biological significance of various markers in newly established cell lines from primary tumors.

Topics: Antibodies, Monoclonal; Biomarkers, Tumor; Carcinoma, Squamous Cell; Cisplatin; Clone Cells; Cytoskeletal Proteins; Drug Resistance, Neoplasm; ErbB Receptors; Head and Neck Neoplasms; HLA Antigens; HLA-A Antigens; HLA-DR Antigens; Humans; Immunohistochemistry; Keratins; Neoplasm Recurrence, Local; Oncogene Proteins; Pilot Projects; Tumor Cells, Cultured; Vimentin

In the current study a comparative analysis of keratin typing and DNA content was carried out in human lung tumors from transthoracic fine needle aspiration biopsies (TFNAB) (18 patients) or from surgically resected tumor tissues (14 patients). According to the cytologic and histologic features, 2 of the 32 tumors were diagnosed as benign tumors, 11 as squamous cell carcinomas, 12 as adenocarcinomas, and 7 as undifferentiated large cell carcinomas. Two cases in the adenocarcinoma and one in the undifferentiated large cell carcinoma groups were pulmonary metastasis or second primary tumors. Malignant cells of tumors which reacted positively with KK8.60 anticytokeratin polypeptides No. 10 and 11 (and hence contain keratinizing cells) displayed diploid DNA content in a flow cytometric assay regardless of their cytologic or histologic appearance. In contrast, all tumors which lacked such positive cells (most of which were defined as adenocarcinomas and undifferentiated tumors) were hyperdiploid. The close correlation between high DNA content and both malignancy and the absence of advanced squamous differentiation (keratinization) suggests that such combined analysis may provide new tools for the cytologic diagnosis and prognosis of lung cancers.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Biomarkers, Tumor; Biopsy, Needle; Carcinoma, Non-Small-Cell Lung; Carcinoma, Squamous Cell; Cell Cycle; Diploidy; DNA, Neoplasm; Female; Flow Cytometry; G1 Phase; Humans; Keratins; Lung Neoplasms; Male; Middle Aged; Neoplasm Staging; Resting Phase, Cell Cycle

Seven biopsy specimens from squamous-cell carcinomas of the uterine cervix were examined by RT-PCR for human-papilloma-virus(HPV)-specific transcripts. With our HPV18-transcription-specific primer pair (5' nts 127-149; 3' nts 587-607), all 7 were shown to contain one strong viral mRNA signal from the early 6/early 7 open reading frames (E6/E7 ORFs). Sequence analysis of the cloned PCR product proved that the transcript was generated by splicing out an intron in E6 from nucleotides 233 to 416, thereby corresponding to the HPV18 E6* spliced mRNA. Nine out of 9 metastatic and 5 of 7 histologically negative lymph nodes from the same patients were also found to be positive for the same mRNA transcript. However, 4 HPV18 unrelated primary tumors and the connected regional pelvic lymph nodes (3 metastatic, 7 histologically negative) were negative for the HPV18 E6* mRNA. Cytokeratin signals indicating tumor cells of epithelial origin were detected in 7 out of the 9 transcript-positive lymph nodes with histological signs of metastasis and in 2 out of the 5 transcript-positive histologically negative lymph nodes. This suggests that the dispersion of the epithelial monoclonal tumor cells was lymphogenic in origin.

Topics: Adult; Base Sequence; Carcinoma, Squamous Cell; DNA Primers; DNA, Neoplasm; DNA, Viral; Female; Gene Amplification; Genes, Viral; Globins; Humans; Hysterectomy; Keratins; Lymph Nodes; Middle Aged; Molecular Sequence Data; Neoplasm Staging; Papillomaviridae; Pelvis; Polymerase Chain Reaction; RNA, Messenger; RNA, Viral; Transcription, Genetic; Uterine Cervical Neoplasms

This study examined the expression of TGF-beta cell-surface receptors, the response to exogenous TGF-beta 1 and the autocrine production of TGF-beta in normal and squamous cell carcinoma-derived human oral keratinocytes with variable degrees of cellular differentiation. TGF-beta receptor expression, the response to exogenous ligand and the autocrine production of TGF-beta appeared unrelated to cellular differentiation. Cells expressed variable proportions of type-I, -II and -III TGF-beta receptors. The expression of type-III receptors correlated inversely with the expression of type-I receptors, but there was no relationship between type-II and either type-I or type-III TGF-beta receptors. Normal cells and the majority (7 of 8) of tumour-derived keratinocytes were inhibited by exogenous TGF-beta 1 and the degree of inhibition correlated with the expression of type-I, but not type-II or type-III, TGF-beta receptors. One tumour-derived cell line was refractory to exogenous TGF-beta 1 although it expressed all 3 receptor types. Endogenous TGF-beta was produced by both normal and tumour-derived keratinocytes and correlated inversely to the expression of type-I, but not type-II, TGF-beta receptors. Further, cells that produced more autocrine TGF-beta had a diminished response to exogenous TGF-beta 1. The data indicate a complex interaction between the expression of TGF-beta cell-surface receptors, endogenous ligand production and the cellular response to exogenous TGF-beta 1.

Topics: 3T3 Cells; Animals; Carcinoma, Squamous Cell; Cell Differentiation; Cell Line; Culture Media, Conditioned; Humans; Keratinocytes; Keratins; Mice; Mouth Mucosa; Mouth Neoplasms; Receptors, Transforming Growth Factor beta; Transforming Growth Factor beta; Tumor Cells, Cultured; Vimentin

The Cyfra 21.1 assay is a newly developed test which measures in serum a fragment of cytokeratin 19. We evaluated this marker in 212 patients with non-small-cell lung cancer (NSCLC), predominantly stage 3a-b and 4, and compared it with three other markers: carcinoembryonic antigen (CEA), squamous cell carcinoma antigen (SCC) and tissue polypeptide antigen (TPA). Sensitivities for Cyfra 21.1, TPA, CEA and SCC (using cut-off levels corresponding to a 95% specificity for benign lung diseases) were 40%, 40%, 42% and 19% respectively. The sensitivity of CEA was significantly higher in patients with adenocarcinomas compared with the other three markers, while the sensitivity of Cyfra 21.1 and TPA was significantly higher in patients with squamous cell carcinomas. The value of Cyfra 21.1 for monitoring disease during chemotherapy could be evaluated in 23 patients with squamous cell carcinomas. When the cases of lead time were included a concordance between clinical evaluations according to WHO response criteria and evaluations according to changes in the marker levels of 74% was found. The criteria defined for marker response were a 65% decrease in the marker level for a partial response and a 40% increase for progressive disease. In particular, increasing levels of this marker indicated usually disease progression. In conclusion, Cyfra 21.1 is a useful serum marker for patients with NSCLC, especially for disease monitoring of patients with squamous cell carcinoma during and after chemotherapy.

Topics: Adult; Aged; Aged, 80 and over; Antibodies, Monoclonal; Biomarkers, Tumor; Carcinoembryonic Antigen; Carcinoma, Non-Small-Cell Lung; Carcinoma, Squamous Cell; Female; Humans; Keratins; Lung Neoplasms; Male; Middle Aged; Neoplasm Staging; Radioimmunoassay

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

Lymphoepithelioma describes an undifferentiated carcinoma of the nasopharyngeal region characterized by a pronounced reactive lymphocytic infiltrate, often obscuring the neoplastic epithelial component. In recent years, histologically similar lesions have been reported in a number of other sites. We report such a lesion in the breast of a 65-yr-old woman; this site of involvement has not previously been described. The unusual histologic appearance raised other diagnostic possibilities and was a dilemma on frozen section. Immunostains for epithelial markers were particularly useful in delineating the scant epithelial neoplastic elements among the abundant lymphocytic component. In situ hybridization for Epstein Barr viral DNA was negative.

Topics: Aged; Breast Neoplasms; Carcinoma, Lobular; Carcinoma, Squamous Cell; Female; Humans; Immunoenzyme Techniques; Keratins; Leukocyte Common Antigens

The authors compared 69 cases of surgically proven invasive squamous cell carcinoma (ISCC) of uterine cervix with 48 cone biopsy specimens that showed cervical intraepithelial neoplasia (CIN) grade III. Histologic features that were preferentially associated with ISCC included the following: giant bizarre cells (66.7% in ISCC, 6.26% in CIN III, P < .01); large keratinized cells (87% in ISCC, 0% in CIN III, P < .01); keratin pearls (40.6% in ISCC, 0% in CIN III, P < .01); necrosis (79.7% in ISCC, 8.3% in CIN III, P < .01); and neovascularization (56.5% in ISCC, 0% in CIN III). In 51 (74%) cases of ISCC, a CIN III component was present, of which 18 (35.3%) showed large keratinized cells or keratin pearls in the in situ components. None of the CIN III cases showed more than one of the above features. In the ISCC group, the above features occurred with similar frequency in microinvasive and frankly invasive tumors. The authors' results agree with previous Papanicolaou-smear cytologic studies, which found that ISCC can be distinguished accurately from CIN III by the morphology of the neoplasm. The authors concluded that cervical biopsy specimens that show two or more of the above features are highly suggestive of ISCC, even when stromal tissue is absent or insufficient for the assessment of invasion. Furthermore, in cervical biopsy specimens showing CIN III, the presence of large keratinized cells or keratin pearls may signify the presence of invasive lesions elsewhere in the cervical mucosa.

Topics: Adult; Aged; Aged, 80 and over; Carcinoma, Squamous Cell; Female; Giant Cells; Humans; Keratins; Middle Aged; Necrosis; Neoplasm Invasiveness; Neoplasm Staging; Neovascularization, Pathologic; Uterine Cervical Dysplasia; Uterine Cervical Neoplasms

Individual disseminated epithelial tumour cells were detected in bone marrow aspirates in 41 of 108 patients (37%) with squamous cell cancer of the head and neck region by an immunocytochemical technique based on monoclonal antibodies raised against the cytokeratin No. 19. In the clinical stage I (T1N0M0) tumour cells were detected only in 26.3% of the patients, whereas in stage IV (T4N0M0, T(all)N2-3M0, T(all)N(all)M1) almost twice as many patients (47.7%) presented with tumour cells in the bone marrow. Apparently, grade of differentiation of the tumour (grading) had no influence on the spread of single tumour cells. An influence of the different localisations of the primary tumour on tumour cell spread or the rate of tumour recurrence cannot as yet be discovered. Cytokeratin No. 19 expressing cells were not detectable in the bone marrow of 18 patients with non-malignant disease. Seventy-three patients were included in a follow-up study with a mean observation time of 25 months (range: 4-52 months). The presence of epithelial cells at the time of primary treatment appears to indicate a significantly higher risk of development of local or distant tumour recurrences (p = 0.01). Of 46 patients initially exhibiting no tumour cells in the bone marrow, only 14 had a clinical recurrence. Whereas 17 of 27 patients who presented with tumour cells in the bone marrow developed either a local tumour recurrence or distant metastases in different organs. Patients presenting with bone marrow tumour cells showed a significantly shorter disease-free survival than those without (p = 0.002).(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Biomarkers, Tumor; Biopsy, Needle; Bone Marrow; Bone Neoplasms; Carcinoma, Squamous Cell; Head and Neck Neoplasms; Humans; Immunoenzyme Techniques; Keratins; Leukocyte Common Antigens; Neoplasm Recurrence, Local; Prognosis

Enzyme immunoassay CYFRA 21-1, a novel lung tumor marker presented in serum (upper limit of normal values: 3.5 ng/ml) was measured in 84 patients with lung cancer and 141 patients with benign respiratory diseases. The positive rate for CYFRA 21-1 in primary lung cancer was 70.3% and the false positive rate in respiratory diseases was 24.1%. In respect to the histological types of lung cancer, CYFRA 21-1 was elevated in 85.0% of squamous cell carcinoma and in 64.8% of other cell types of primary lung cancer. Elevated CYFRA 21-1 levels were found in 40% of Stage I-II, in 80.0% of Stage IIIA-B, and in 73.5% of Stage IV. The overall diagnostic efficiency was 53.4% for CYFRA 21-1 and 44.5% for CEA, respectively. Receiver operating characteristic (ROC) curve analysis suggested that CYFRA 21-1 test has an advantage over CEA. From the results of this study, CYFRA 21-1 was more efficient than CEA as primary diagnostic marker in lung cancer.

Topics: Biomarkers, Tumor; Carcinoembryonic Antigen; Carcinoma, Non-Small-Cell Lung; Carcinoma, Squamous Cell; Female; Humans; Immunoenzyme Techniques; Keratins; Lung Neoplasms; Male; Prognosis

The distribution of keratins in N-methyl-N'-nitro-N-nitrosoguanidine-induced oesophageal carcinomas in shrews was tested immunohistochemically, using a panel of seven different monoclonal antibodies. The studies were done on methacarn-fixed paraffin-embedded tissue, using the labelled streptavidin biotin method, and the relationship between morphological characteristics and keratin reaction patterns in carcinomas was analysed and compared with that in adjacent "normal" oesophageal epithelium. In the normal oesophageal epithelia, KL1, AE1, AE3, CK8.12, and CK4.62 stained suprabasal cells, 312C8-1 reacted to basal cells, and KS-1A3 labelled all epithelial cells. In squamous cell carcinomas, almost all the cancer cells were labelled strongly by 312C8-1 and weakly by KS-1A3, while a few cells in the centres of the keratinized foci were stained by KL1, AE1, AE3, CK8.12, and CK4.62. Like human oesophageal carcinomas, shrew oesophageal carcinomas maintain expression of human keratin 14, as determined by 312C8-1. The expression of human keratin 13, as determined by KS-1A3, was down-regulated.

Topics: Animals; Antibodies, Monoclonal; Carcinoma, Squamous Cell; Esophageal Neoplasms; Female; Immunohistochemistry; Keratins; Methylnitronitrosoguanidine; Shrews

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

Two monoclonal antibodies (MAbs) were established in 20 clones of MAbs generated against cytokeratin fraction extracted from canine squamous cell carcinoma to investigate the expression of intermediate filament proteins during tumorigenesis. These MAbs were confirmed to react with purified cytokeratin by ELISA. One monoclonal antibody, MAb32 reacted all layers of epidermis except the cornified layer and mammary myoepithelial cells but not any epithelial cells. Another antibody named MAb24 exclusively reacted the basal monolayer of epidermis, the stratum germinativum. Any positive reactions with MAb24 were not detected in normal mammary gland. From the analysis by two-dimensional gel electrophoresis followed by immunoblotting, it was revealed that MAb24-recognizing cytokeratin subunit gave a molecular weight of 57 kilodalton and a isoelectric-pH value of pI5.1, indicating type I (acidic) cytokeratin. In intraductal papillomas developed in canine mammary glands, most tumor cells were positively stained with MAb32 in addition of myoepithelial cells while no positive reaction with MAb24 was seen. In ductal carcinomas, MAb24-positive cytokeratin was begun to express by tumor cells with positive reaction of MAb32 where these cells showed infiltrative growth into the stroma. We therefore proposed that 57 kilodalton-type I cytokeratin was a molecular marker for malignant transformation in canine mammary tumor and these antibodies could be useful tools to investigate the change of cytokeratin expression during tumorigenesis.

Topics: Adenofibroma; Animals; Antibodies, Monoclonal; Biomarkers, Tumor; Carcinoma, Ductal, Breast; Carcinoma, Squamous Cell; Cell Transformation, Neoplastic; Dog Diseases; Dogs; Electrophoresis, Polyacrylamide Gel; Enzyme-Linked Immunosorbent Assay; Epithelium; Female; Immunoblotting; Keratins; Mammary Glands, Animal; Mammary Neoplasms, Animal; Papilloma, Intraductal

To model human papillomavirus-induced neoplastic progression, expression of the early region of human papillomavirus type 16 (HPV16) was targeted to the basal cells of the squamous epithelium in transgenic mice, using a human keratin 14 (K14) enhancer/promoter. Twenty-one transgenic founder mice were produced, and eight lines carrying either wild-type or mutant HPV16 early regions that did not express the E1 or E2 genes were established. As is characteristic of human cancers, the E6 and E7 genes remained intact in these mutants. The absence of E1 or E2 function did not influence the severity of the phenotype that eventually developed in the transgenic mice. Hyperplasia, papillomatosis, and dysplasia appeared at multiple epidermal and squamous mucosal sites, including ear and truncal skin, face, snout and eyelids, and anus. The ears were the most consistently affected site, with pathology being present in all lines with 100% penetrance. This phenotype also progressed through discernible stages. An initial mild hyperplasia was followed by hyperplasia, which further progressed to dysplasia and papillomatosis. During histopathological progression, there was an incremental increase in cellular DNA synthesis, determined by 5-bromo-2'-deoxyuridine incorporation, and a profound perturbation in keratinocyte terminal differentiation, as revealed by immunohistochemistry to K5, K14, and K10 and filaggrin. These K14-HPV16 transgenic mice present an opportunity to study the role of the HPV16 oncogenes in the neoplastic progression of squamous epithelium and provide a model with which to identify genetic and epigenetic factors necessary for carcinogenesis.

Topics: Animals; Carcinoma, Squamous Cell; Cell Differentiation; Cell Division; Ear; Filaggrin Proteins; Keratins; Mice; Mice, Transgenic; Oncogene Proteins, Viral; Papillomaviridae; Papillomavirus E7 Proteins; Phenotype; Precancerous Conditions; Promoter Regions, Genetic; RNA, Viral; Skin; Skin Neoplasms

The levels of the new tumour marker CYFRA 21-1 were assessed in 115 patients with non-small cell lung cancer (NSCLC) and in 45 patients with non-malignant lung disease. Increased levels of CYFRA 21-1 were observed in 47.8%, mostly in patients with squamous cell carcinoma (SCC; 69.1%). Serum CYFRA 21-1 levels were correlated with the stage of SCC type. Positive CYFRA 21-1 levels in patients with SCC were present in 40% of stage I, 61.1% of stage II, and 85.2% of stage III. In addition, SCC patients who presented mediastinal lymph nodes (N2) demonstrated higher serum CYFRA 21-1 levels, compared with patients without mediastinal lymph nodes metastases (N0 or N1). With regard to tumour size, significant difference was observed between T1, T2 and T3. The study also showed that the percentage of patients who survived 18 months with normal preoperative level of CYFRA 21-1 was higher compared with those patients with elevated preoperative levels of this marker, but the differences were not statistically significant.

Topics: Adenocarcinoma; Antigens, Neoplasm; Biomarkers, Tumor; Carcinoembryonic Antigen; Carcinoma, Large Cell; Carcinoma, Non-Small-Cell Lung; Carcinoma, Squamous Cell; Evaluation Studies as Topic; Female; Humans; Keratins; Lung Diseases; Lung Neoplasms; Lymphatic Metastasis; Male; Neoplasm Staging; Peptide Fragments; Serpins

The purpose of the present study was to establish culture conditions for human uterine cervical epithelial cells on permeable support and to determine how it affects cervical cell differentiation. Human ectocervical epithelial cells (hECE), HPV-16 immortalized hECE cells (ECE16-1) and Caski cells were grown on collagen-coated filters. Culture conditions, density of cells in culture and expression of epithelial and cervical-cell phenotypic markers were determined and compared in cells grown on filter and on solid support. Compared with the latter, cultures on filter had a higher cell density, hECE cells stratified to 5-12 cell layers compared to 1-3 on solid support, and cells of all three types expressed intercellular tight junctions. The cytokeratin profiles revealed differences between the three cell types as well as differences within the same cell species when grown on filter, compared to solid support. Of particular importance was the finding of a higher expression of K-13 in hECE grown on filter compared to solid support; K-13 is a marker of ectocervical cell differentiation. The cytokeratin profiles of the cultured hECE, ECE16-1 and Caski cells resembled those of ectocervical, squamous metaplastic and endocervical epithelia, respectively. hECE and ECE16-1 expressed involucrin protein, the level of which in both was higher in cells grown on filter compared to solid support. Polarization of the cultures was determined by morphology (stratification of hECE cells, expression of pseudomicrovilli in the apical cell membrane), selective apical vs. basolateral secretion of [35S]methionine- and [35S]cysteine-, [3H]fucose- and [14C]glucosamine-labeled molecules, and positive short-circuit current (Isc) under voltage-clamp conditions. Confluency of the cultures was determined by measuring transepithelial unidirectional fluxes of inert molecules with different molecular weights (MWs) through the paracellular pathway, and by measuring transepithelial conductance. The results indicated transepithelial permeability of 7-22.10(-6) cm.sec-1, which was 5-100 fold smaller compared to blank inserts, with a cut-off MW of 40-70 kDa for hECE and Caski cells. Transepithelial conductance ranged 18.5 to 51.5 mS.cm-2, indicating a leaky but confluent epithelia. Collectively the results indicate the epithelial nature of the cells and their improved differentiation when grown on filter support; hECE is a model for ectocervical epithelium while ECE16-1 and Caski express phenoty

Topics: Carcinoma, Squamous Cell; Cell Differentiation; Cell Line, Transformed; Cell Polarity; Cells, Cultured; Ceramics; Cervix Uteri; Collagen; Culture Techniques; Epithelial Cells; Epithelium; Female; Humans; Hydrocortisone; Keratins; Permeability; Polytetrafluoroethylene; Protein Precursors; Tretinoin; Tumor Cells, Cultured; Uterine Cervical Neoplasms; Vimentin

During the treatment of five cases of thymic carcinoma, we conducted a clinicopathological and immunohistochemical study. The patients included four males and one female, whose ages ranged from 50 to 69 years. The histologic breakdown was squamous cell carcinoma in four and small cell carcinoma in one. Immunohistochemically, the squamous cell carcinomas were positive for cytokeratin (intermediate molecular weight) and keratin. However, staining was negative for Leu-7 and chromogranin. A complete resection was achieved in only one case. In all four of the remaining cases, the resection was incomplete due to invasion into adjacent organs and disseminated lesions. Thymic carcinoma is a tumor for which a higher response rate can be expected from multidisciplinary therapy than that for lung cancer. Therefore, it is desirable, from the clinical view, to determine clinical staging and to establish standard operative procedures comprising mediastinal lymph node dissection as well as effective chemotherapy. With respect to pathology, it is hoped that an improved histologic classification will be developed.

Topics: Carcinoma, Small Cell; Carcinoma, Squamous Cell; Female; Humans; Immunohistochemistry; Keratins; Male; Middle Aged; Phosphopyruvate Hydratase; Thymoma; Thymus Gland; Thymus Neoplasms

The diagnostic value of the water-soluble cytokeratin 19 fragment CYFRA 21-1 in lung cancer was assessed in comparison with carcinoembryonic antigen, squamous cell carcinoma antigen, and neuron-specific enolase. The cut-off value, defined as 95% specificity versus a group of 526 patients suffering from benign chest diseases, was set at 3.3 micrograms/l for cytokeratin 19 fragment CYFRA 21-1 (carcinoembryonic antigen: 7.8 micrograms/l, squamous cell carcinoma antigen: 1.9 micrograms/l, neuron-specific enolase: 13.7 micrograms/l). Elevated pretreatment cytokeratin 19 fragment CYFRA 21-1 concentrations were recorded: in 112 of 244 (46%) patients with all histological types of lung cancer (carcinoembryonic antigen: 32%, squamous cell carcinoma antigen: 25%, neuron-specific enolase: 28%), in 89 of 177 (50%) patients with non-small cell lung cancer (carcinoembryonic antigen: 33%, squamous cell carcinoma antigen: 24%, neuron-specific enolase: 12%), in 47 of 81 (58%) patients with squamous cell carcinoma (carcinoembryonic antigen: 23%, squamous cell carcinoma antigen: 32%, neuron-specific enolase: 14%), in 27 of 63 (42%) patients with adenocarcinoma (carcinoembryonic antigen: 44%, squamous cell carcinoma antigen: 14%, neuron-specific enolase: 9%), in 15 of 33 (45%) patients with other non-small cell lung cancer (carcinoembryonic antigen: 36%, squamous cell carcinoma antigen: 24%, neuron-specific enolase: 14%), and in 20 of 55 (36%) patients with small cell lung cancer (carcinoembryonic antigen: 32%, neuron-specific enolase: 77%). Three of 12 patients with undefined histological type showed cytokeratin 19 fragment CYFRA 21-1 elevations. The best performance in terms of sensitivity and diagnostic accuracy was attained with the cytokeratin 19 fragment CYFRA 21-1 test in squamous cell carcinoma. In small cell lung cancer neuron-specific enolase was confirmed to be superior to the other markers. Cytokeratin 19 fragment CYFRA 21-1 concentrations increased with the extent of the malignant disease in non-small cell lung cancer. The positivity rate of cytokeratin 19 fragment CYFRA 21-1 in tumour stage TNM I was only 23% (carcinoembryonic antigen: 23%, squamous cell carcinoma antigen: 14%), i.e. the markers under study cannot be used for the diagnosis of early stage disease. Cytokeratin 19 fragment CYFRA 21-1 differentiated significantly between squamous cell carcinoma and the other histological types (p < 0.01). In addition, cytokeratin 19 fragment CYFRA 21-1 distinguishe

Topics: Adenocarcinoma; Antigens, Neoplasm; Biomarkers, Tumor; Carcinoembryonic Antigen; Carcinoma, Non-Small-Cell Lung; Carcinoma, Squamous Cell; Female; Humans; International Cooperation; Keratins; Lung Neoplasms; Male; Peptide Fragments; Phosphopyruvate Hydratase; Sensitivity and Specificity; Serpins

In a comparison of flow cytometric DNA measurements on fresh and paraffin-embedded material from primary squamous cell carcinomas of the head and neck region, we discovered that previously undetected aneuploid clones could be detected by dual parameter analysis of cytokeratin and DNA applied to disintegrated cells from paraffin sections. Using this new approach the correlation coefficient between DNA-indices from fresh and paraffin-embedded material increased from 0.423 to 0.904.

Topics: Aneuploidy; Carcinoma, Squamous Cell; DNA, Neoplasm; Epithelium; Fixatives; Flow Cytometry; Formaldehyde; G1 Phase; Head and Neck Neoplasms; Humans; Keratins; Paraffin Embedding; Resting Phase, Cell Cycle

Recurrence of squamous cell carcinoma (SCC) following Mohs micrographic surgery is uncommon. However, such cases do exist, presumably because of incomplete excision. Identification of single cells or small clumps of SCC tumor may be extremely difficult and can be compromised by inflammatory reaction.. The purpose of this study was to evaluate the benefits of incorporating rapid cytokeratin (CK) stains into Mohs technique.. Simple modification of standard immunoenzyme techniques allows keratin-specific staining to be achieved in less than 90 minutes on Mohs cryostat sections. We used the rapid labeled streptavidin biotin anticytokeratin method at the stage when no tumor was apparent by hematoxylin and eosin staining in 20 patients with large, aggressive, or recurrent invasive SCCs.. In eight cases, single cells or small clumps of SCC tumor were identified utilizing AE-1 monoclonal antibody. These patients subsequently underwent further surgery, including wider tumor resection, superficial parotidectomy, or postoperative radiation therapy.. The rapid CK antibody staining technique enhances the sensitivity of tumor identification in Mohs micrographic surgery, and should reduce tumor recurrence rates.

Topics: Carcinoma, Squamous Cell; Humans; Immunoenzyme Techniques; Keratins; Mohs Surgery; Skin Neoplasms; Staining and Labeling

The expression of cytokeratin (CK) subclasses was immunohistologically investigated in normal laryngeal epithelia by the ABC technique using monospecific monoclonal antibodies. There are two types of epithelium in the larynx; squamous epithelium of the glottis and ciliated epithelium mainly of the supraglottis. A difference in expression pattern was observed between these two epithelia only in 3 CKs, specifically CK-8, CK-13 and CK-19. In the glottis, CK-8 was negative in all layers, CK-13 was positive in the suprabasal and superficial layers, and CK-19 was strongly positive in the basal layer, but apparently reduced in suprabasal layers and completely negative in the superficial layers. In the supraglottis, on the contrary, CK-8 was positive except in the basal layer, CK-13 was negative in all layers, and CK-19 was positive in all layers. When ciliated epithelia were reduced to squamous metaplasia, the epithelial cells were morphologically similar to the squamous cells, and the CK expression also showed the same pattern. In proximity to this squamous metaplasia, however, there were lesions whose cell type morphologically still resembled that of the ciliated epithelium, but whose pattern of CK expression had already been reduced to that of the squamous cell.

Topics: Carcinoma, Squamous Cell; Epithelium; Humans; Immunohistochemistry; Keratins; Laryngeal Mucosa; Laryngeal Neoplasms; Larynx; Metaplasia

The present study was designed to determine whether CYFRA 21-1, measuring cytokeratin 19, could be a specific and sensitive tumour marker for non-small cell lung cancer (NSCLC). Serum measurements were made at diagnosis in 2250 patient samples by an immunoradiometric "sandwich type" assay, using two cytokeratin 19 specific monoclonal antibodies. Among healthy individuals (n = 711) and patients with benign lung disease (n = 546), 95 percentiles were 1.2 and 2.95 ng/ml, respectively. Cumulative distribution analysis curves were established. From these data, 3.3 ng/ml gave 96% specificity. Using this cutoff, the sensitivity for small cell lung cancer was 16% (n = 74) compared to 41% for NSCLC (n = 547). In histological sub-groups, sensitivity was 57% for squamous cell lung cancer, 34% for undifferentiated large cell carcinoma and 27% for adenocarcinoma, the level of CYFRA 21-1 was correlated with tumour size and UICC stage. In squamous cell lung cancer, the sensitivity of the squamous cell carcinoma marker was 30%, 25% for carcinoembryonic antigen and 46% for tissue polypeptide antigen, using the same series of samples and cutoffs defined at 96% specificity. In conclusion, CYFRA 21-1 is a sensitive tumour marker for NSCLC, especially squamous cell lung cancer.

Topics: Adolescent; Adult; Aged; Biomarkers, Tumor; Carcinoma, Non-Small-Cell Lung; Carcinoma, Small Cell; Carcinoma, Squamous Cell; Female; Humans; Keratins; Lung Diseases; Lung Neoplasms; Male; Middle Aged; Neoplasm Staging; Neoplasms; Peptide Fragments; Retrospective Studies; Sensitivity and Specificity

The identification of pretreatment markers with predictive significance for the presence of lymph node metastases and treatment outcome in low stage cancer of the uterine cervix is clinically important. Because the presence of differentiation-related markers varies in this type of cancer, the authors investigated whether loss of these markers is related to a poor clinical course.. An indirect immunoperoxidase technique was applied to formalin fixed, paraffin embedded tissue sections of 80 patients with International Federation of Gynecology and Obstetrics Stage IB and IIA primary squamous cell cervical carcinomas for detection of expression of cytokeratin 10 and 13, and involucrin. Comparisons were made of the expression of each of these markers among 40 patients with regional node metastases and 40 age-matched patients with no lymph node metastases. Differences in the frequency of expression of these markers also were analyzed in relation to histopathologic characteristics, recurrence, and survival.. Expression of cytokeratin 10, 13, and involucrin was found in 24, 64, and 53%, respectively, of all patients studied. The authors found no differences between patients with positive regional lymph nodes and those with negative lymph nodes. Expression of cytokeratin 13 and involucrin was associated with tumor grade (P = 0.01). No relationship was found between expression of the markers used and recurrence or survival in the entire group. Within the lymph node-positive group, however, the survival rate of patients with tumors with cytokeratin 13 expression was significantly higher than that of patients with tumors lacking cytokeratin 13 expression (P = 0.02).. Expression of cytokeratin 10, 13, or involucrin in the primary tumor is of no predictive value with respect to the presence of regional lymph node metastases in low stage squamous cell cervical cancer. However, cytokeratin 13 expression appears to be of prognostic significance in patients with positive regional lymph nodes.

Topics: Adult; Aged; Antibodies, Monoclonal; Biomarkers; Carcinoma, Squamous Cell; Female; Humans; Immunoenzyme Techniques; Keratins; Lymphatic Metastasis; Middle Aged; Neoplasm Staging; Prognosis; Protein Precursors; Retrospective Studies; Uterine Cervical Neoplasms

The ability of all-trans-retinoic acid (RA) to modulate the growth and squamous differentiation of four head and neck squamous cell carcinoma cell lines (183, 886, 1483, and SqCC/Y1) was examined, and the relationship of their state of squamous differentiation and RA responsiveness to the expression of cytosolic RA-binding proteins (CRABPs), nuclear RA receptors (RARs), and retinoid X receptors (RXRs) was investigated. RA inhibited proliferation of all but the 183 cell line and suppressed squamous differentiation markers K1 keratin, type 1 transglutaminase, and involucrin mRNAs and proteins to varying degrees in 183, 1483, and SqCC/Y1 cells. Traces of CRABP-I mRNA were detected only in the 886 cells, whereas CRABP-II mRNA was detected in the other three cell lines. RA suppressed CRABP-II expression in SqCC/Y1 cells but had no effect on its expression in the other cell lines. All cell lines expressed mRNAs for RAR-alpha, RAR-beta, RAR-gamma, and RXR-alpha. The RAR-beta mRNA level was lowest in the SqCC/Y1 cells, and RXR-beta and RXR-gamma were not detected in any of the cell lines. RA treatment increased the levels of the three RAR mRNAs in most of the cell lines but had no effect on the RXR mRNAs. The CRABP-II mRNA level in SqCC/Y1 cells was lowest in cells grown in serum-free medium and increased when the cells were grown in medium with 5 or 10% serum. In contrast, the RXR-alpha mRNA level was inversely related to serum concentration. The results show that, in head and neck squamous cell carcinoma cells, there are no simple relationships among the expression of CRABPs, RARs, and RXRs and either squamous differentiation or response to RA-induced growth inhibition or suppression of squamous differentiation.

Topics: Carcinoma, Squamous Cell; Cell Differentiation; Head and Neck Neoplasms; Humans; Keratins; Protein Precursors; Receptors, Retinoic Acid; RNA, Messenger; Transglutaminases; Tretinoin; Tumor Cells, Cultured

Expression of cytoskeletal proteins has been shown to be dependent on the differentiation status of the tissue. In the present study, expression of two cytoskeletal proteins normally present in terminally differentiated keratinocytes, namely cytokeratin types 10/11 and involucrin, were studied in different stages of tumour progression in the oral mucosa. Results showed that cytokeratins 10/11 and involucrin strongly correlated with the differentiation status of cells. High expression was observed in non-dysplastic hyperplastic epithelium as compared to normal, dysplastic and neoplastic epithelium. In addition, various grades of dysplasia showed an inverse correlation with expression of these proteins. Statistical analysis of the results also showed a negative correlation between the differentiation of upper spinal cells and the stage of tumour progression. It therefore appears that the proteins studied may be useful as markers for epithelial carcinogenesis.

Topics: Biomarkers, Tumor; Carcinoma, Squamous Cell; Cell Differentiation; Cell Transformation, Neoplastic; Humans; Immunoenzyme Techniques; Keratinocytes; Keratins; Leukoplakia, Oral; Mouth Mucosa; Mouth Neoplasms; Protein Precursors

We investigated the expression of keratin subtypes 7, 8, 10, 13, 14, 17, 18 and 19 in the normal cervix, in cervical intraepithelial neoplasia (CIN) lesions and in cervical carcinomas, using a selected panel of monoclonal keratin antibodies, reactive with routinely processed, formalin fixed paraffin embedded tissue fragments. The reaction patterns derived for each keratin antibody were compared with known expression patterns of the various epithelia, previously examined in frozen tissues. Although the reactivity of the antibodies was generally acceptable, considerable modifications to the manufacturers' staining instructions were often necessary. For some antibodies, which were previously thought to be reactive with fresh frozen tissue only, we developed staining protocols rendering them reactive with routinely processed material. As with previous findings in frozen sections we observed increasing expression of keratins 7, 8, 17, 18 and 19 with increasing grade of CIN. In cervical carcinomas the differences in keratin detectability between the main categories were more pronounced than in frozen sections, probably due to fixation and processing. For routine pathology, keratin phenotyping of cervical lesions may be of value in classification. The fact that keratin 7 was detected for the first time in reserve cells, and that this keratin was also found to be expressed in a considerable number of CIN lesions and cervical carcinomas supports the suggestion that reserve cells are a common progenitor cell for these lesions.

Topics: Adenocarcinoma; Antibodies, Monoclonal; Carcinoma, Adenosquamous; Carcinoma, Neuroendocrine; Carcinoma, Squamous Cell; Epithelial Cells; Epithelium; Female; Histological Techniques; Humans; Immunoenzyme Techniques; Keratins; Uterine Cervical Dysplasia; Uterine Cervical Neoplasms

Formalin-fixed and paraffin-embedded tissue specimens of six cases of extraocular sebaceous carcinoma were studied immunohistochemically with eight anti-keratin monoclonal antibodies, 34 beta B4, 35 beta H11, Ks13.1, Ks19.1, PKK1, LP34, KL1 and AE1. The staining patterns of sebaceous carcinoma were compared with those of normal sebaceous glands and other skin cancers which should be distinguished from sebaceous carcinoma histopathologically. The other skin cancers compared were eccrine porocarcinoma, malignant clear cell hidradenoma, extramammary Paget's disease with underlying adenocarcinoma, malignant trichilemmoma, and squamous cell carcinoma. Most cases of sebaceous carcinoma were stained with 35 beta H11, Ks19.1, LP34, KL1 and AE1, while normal sebaceous glands were positive only with 35 beta H11, LP34, KL1 and AE1. By immunostaining, sebaceous carcinoma was distinguishable from extramammary Paget's disease with underlying adenocarcinoma, squamous cell carcinoma, malignant trichilemmoma, and eccrine porocarcinoma, but was not clearly distinguishable from malignant clear cell hidradenoma. These findings demonstrate that sebaceous carcinoma shows positive reactions with antibodies to simple epithelial keratin, probably as a result of neoplastic transformation, and that immunohistochemical examination using anti-keratin monoclonal antibodies is useful in distinguishing sebaceous carcinoma from several other skin cancers.

Topics: Acrospiroma; Adenocarcinoma, Sebaceous; Antibodies, Monoclonal; Carcinoma, Squamous Cell; Humans; Immunohistochemistry; Keratins; Neoplasms, Basal Cell; Paget Disease, Extramammary; Sebaceous Gland Neoplasms; Skin Neoplasms; Sweat Gland Neoplasms

Serum samples from 137 lung cancer patients were examined by RIA to evaluate the clinical efficacy of the new tumor marker, CYFRA 21-1, which could identify the soluble fragment of cytokeratin 19. The cut-off value was determined to be 2.2 ng/ml according to the receiver operating characteristic curve. The sensitivity, specificity and accuracy of the RIA for CYFRA 21-1 were 57.7, 91.9 and 64.9%, respectively. The serum concentration of CYFRA 21-1 and the sensitivity of the assay increased as the disease progressed. Histologically, the sensitivity was highest for squamous cell carcinomas (SQ) (76.5%) in comparison with adenocarcinomas (47.8%) and small cell lung cancers (42.1%) (P < 0.01, P < 0.05, respectively). The sensitivities for SQ were 60.0, 83.3, 80.0 and 100% at stages I, II, III and IV, respectively. When compared with CEA (45.3%) and squamous cell carcinoma related antigen (SCC) (22.6%) in all lung carcinomas, CYFRA 21-1 showed the highest sensitivity (57.7%), (P < 0.05, P < 0.01, respectively). In SQ, the sensitivity of the CYFRA 21-1 RIA was significantly higher than that of the assay for SCC (47.1%) (P < 0.05). In patients with adenocarcinomas, the sensitivity of the CYFRA 21-1 assay was almost the same as that for CEA (49.3%). In a combination of CYFRA 21-1 and CEA for non-small cell lung cancers (NSCLC), the sensitivity and accuracy increased to 75.4 and 78.1%, respectively, although the specificity decreased to 86.5%. It is concluded that CYFRA 21-1 could replace SCC, a less satisfactory tumor marker, for SQ of the lung. The potentiality of the combination of CYFRA 21-1 and CEA for NSCLC should be estimated using larger samples in the near future.

Topics: Adenocarcinoma; Biomarkers, Tumor; Carcinoma, Small Cell; Carcinoma, Squamous Cell; Female; Humans; Keratins; Lung Neoplasms; Male; Middle Aged; Radioimmunoassay; Sensitivity and Specificity

To obtain a better understanding of the cellular and hormonal mechanisms responsible for the malignant bone resorption associated with metastatic carcinoma, we sought to identify whether tumor cells or tumor infiltrating macrophages were capable of lacunar bone resorption.. Tumor cells and tumor-infiltrating macrophages (TIMS), (nonspecific esterase and F4/80 positive: cytokeratin and tartrate-resistant acid phosphatase and calcitonin response negative), were isolated from carcinomas that developed after subcutaneous implantation of human breast, colon, and cervical carcinoma cell lines into MFI athymic nude mice. These cells were cultured alone or with stromal cells on bone slices and evidence of lacunar resorption sought by scanning electron microscopy.. After 7 to 14 days in co-culture with UMR106 osteoblast-like cells in the presence of 1,25-dihydroxy vitamin D3, only cells of the TIM population differentiated into osteoclast-like cells (nonspecific esterase-negative: tartrate-resistant acid phosphatase-positive) capable of extensive lacunar bone resorption.. Cells within the TIM population but not tumor cells are capable of differentiation into osteoclast-like cells which can resorb bone extensively. Both 1,25 dihydroxyvitamin D3 and bone stromal cells are necessary for this to occur. TIM differentiation into cells capable of lacunar resorption could account for a component of the extensive osteolysis associated with carcinomatous skeletal metastases.

Topics: Adenocarcinoma; Animals; Bone Resorption; Breast Neoplasms; Calcitonin; Calcitriol; Carcinoma, Squamous Cell; Cell Differentiation; Cells, Cultured; Colonic Neoplasms; Female; Humans; Immunohistochemistry; Keratins; Macrophages; Mice; Mice, Nude; Microscopy, Electron, Scanning; Neoplasm Transplantation; Osteoblasts; Osteoclasts; Time Factors; Tumor Cells, Cultured; Uterine Cervical Neoplasms

Simple epithelial keratins K7, K8, and K18 are present in no more than trace amounts in normal stratified squamous epithelial but have been reported in squamous cell carcinomas. With the aim of determining the level at which keratin synthesis is regulated in vivo, we have compared the expression of mRNA by in situ hybridization and protein by immunohistochemistry for K7, K8, and K18 in a series of normal, dysplastic, and malignant oral epithelia. In normal epithelia mRNAs for K7, K8, and K18 were present in basal and lower spinous cells but adjacent sections were generally negative for the respective proteins. In severe dysplasia there was irregular suprabasal extension of K8 and K18 mRNAs in all cases and their proteins were expressed in more than half of the cases. The carcinomas expressed K8 and K18 mRNAs homogeneously and were strongly reactive for these keratin proteins but K7 expression appeared reduced in malignancy. These results are consistent with the post-transcriptional regulation of K7, K8, and K18 expression in normal epithelia and the presence of their proteins in dysplastic and malignant epithelia suggests the release of these epithelial cells from a post-transcriptional block on K8 and K18 translation. Alternatively, rapid degradation of K8 and K18 protein might be occurring in normal epithelia but be suppressed in dysplasia and malignancy.

Topics: Base Sequence; Carcinoma, Squamous Cell; Humans; In Situ Hybridization; Keratins; Molecular Sequence Data; Mouth Mucosa; Mouth Neoplasms; Oligonucleotide Probes; Reference Values; RNA, Messenger

We describe 13 cases of tricholemmal carcinoma, a rarely recognized cutaneous adnexal neoplasm. The patients were nine men and four women. In general, the tumors presented as slow-growing epidermal papules, indurated plaques, or nodules showing predilection for sun-exposed, hair-bearing skin. The lesions were most frequently misdiagnosed clinically as basal cell carcinoma. Histologically, they showed a variegation of growth patterns including solid, lobular, and trabecular; they were characterized by a proliferation of epithelial cells with features of outer root sheath differentiation, including abundant glycogen-rich, clear cytoplasm, foci of pilar-type keratinization, and peripheral palisading of cells with subnuclear vacuolization. Because of their variable growth pattern, overt cytologic atypia, abundant clear cytoplasm, occasional pagetoid intraepidermal spread, and brisk mitotic activity, these tumors may pose difficulties for diagnosis and be confused with other malignant skin tumors with clear cell changes. Despite the seemingly malignant cytological appearance of these lesions, clinical follow-up in 10 cases showed no recurrence or metastasis over a period of 2-8 years. Thus, conservative surgical excision with clear margins appears to be the treatment of choice for these neoplasms.

Topics: Adult; Aged; Aged, 80 and over; Carcinoma, Basal Cell; Carcinoma, Squamous Cell; Cytoplasm; Diagnosis, Differential; Epidermal Cyst; Epithelium; Female; Follow-Up Studies; Glycogen; Hair Diseases; Humans; Keratins; Male; Middle Aged; Mitosis; Neoplasms, Basal Cell; Skin Diseases; Skin Neoplasms; Vacuoles

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

Topics: Adult; Aged; Carcinoma, Basal Cell; Carcinoma, Squamous Cell; Humans; Immunoenzyme Techniques; Keratins; Middle Aged; Neoplasm Metastasis; Skin Neoplasms

Pretreatment sera of 78 patients with squamous cell cervical cancer were tested for the presence of cytokeratin 19 (CK 19) fragments to determine the relationship among this parameter, tumor stage, various histopathologic characteristics, and prognosis. For the quantitative determination of CK 19 fragments in serum, the enzyme assay Cyfra 21-1 was used. This assay, based on the simultaneous sandwich principle, utilizes two different monoclonal antibodies. The test was considered positive when levels of Cyfra 21-1 were > or = 1.2 micrograms/liter. Cyfra 21-1 was positive in the majority of patients and in all patients with advanced disease (FIGO III or IVa). A highly significant relationship was found between pretreatment Cyfra 21-1 level and FIGO stage (P < 0.0001). Mean Cyfra 21-1 concentration was elevated in the case of macroinvasive disease (FIGO Ib, IIa, IIb, III, IVa). A distinct relationship was found between tumor size (P < 0.001; r = 0.73) and Cyfra 21-1 level. In the univariate Cox analysis Cyfra 21-1 level was significantly related to both disease-free interval (P < 0.0001) and survival (P < 0.0001) of patients. Patients with an increased Cyfra 21-1 level had a significantly worse prognosis. However, in the stepwise Cox regression analysis, these variables had no additional value over known prognostic factors such as FIGO stage and tumor size. It is concluded that Cyfra 21-1 may be of significance as an additional marker in the management of patients with cervical cancer, but further investigation is needed.

Topics: Adult; Aged; Aged, 80 and over; Analysis of Variance; Biomarkers, Tumor; Carcinoma, Squamous Cell; Disease-Free Survival; Female; Humans; Immunoenzyme Techniques; Keratins; Life Tables; Middle Aged; Neoplasm Staging; Peptide Fragments; Prognosis; Proportional Hazards Models; Reagent Kits, Diagnostic; Survival Rate; Uterine Cervical Neoplasms

Recent research observations suggest that the keratoacanthoma (KA) is a form of resolving squamous cell carcinoma (SCC). The mechanism by which this resolution takes place has not been fully explored, although it may have an immunological basis. To investigate this, we compared 15 clinically and histologically diagnosed KAs and 15 SCCs with regard to cellular infiltrate and keratin expression. We found that KAs have significantly higher numbers of CD3+ and CD4+ cells invading their epidermal component than SCCs. The T lymphocytes infiltrating KAs were more immunologically active, as greater numbers expressed the interleukin-2 receptor (IL-2R) than those in SCCs. It is of interest that CD36 was expressed by a significantly greater proportion of tumour cells within KAs than SCCs. This was also the case for the intercellular adhesion molecule ICAM-1, and the differentiation marker keratin 10. Overall, these findings suggest that KA regression is immunologically mediated, with activated (IL-2R+) CD4+ T lymphocytes and adhesion molecules playing a pivotal role in the immune response.

Topics: Aged; Aged, 80 and over; Antigens, CD; Carcinoma, Squamous Cell; CD3 Complex; CD36 Antigens; CD4 Antigens; Epidermis; Humans; Immunohistochemistry; Intercellular Adhesion Molecule-1; Keratins; Keratoacanthoma; Lymphocyte Activation; Middle Aged; Platelet Membrane Glycoproteins; Receptors, Interleukin-2; Remission, Spontaneous; Skin Diseases; Skin Neoplasms; T-Lymphocytes

Expression of cytokeratins 7, 8, 10, 14, 18 and 19 was studied in 48 cases of advanced (stage II and III) squamous cell carcinomas of the uterine cervix. Despite of the degree of differentiation, the expression of simple epithelia cytokeratins 8 (72.9%) and 19 (97.9%) was high. A subset of eight (16.6%) predominantly poorly differentiated tumours had the expression restricted to simple epithelia pattern (cytokeratin 7 and/or 8 and 18 and/or 19). In twenty cases (41.7%) the cytokeratin 14 was added to this pattern, representing an intermediate differentiation level, while the other twenty tumours, usually exhibiting more pronounced squamous differentiation had the most complete cytokeratin pattern including class 10. This grouping was of no prognostic significance but might represent a valuable tool in the classification of cervical squamous cell carcinoma.

Topics: Carcinoma, Squamous Cell; Female; Histocytochemistry; Humans; Keratins; Uterine Cervical Neoplasms

Differences in gene transcription between RNA samples extracted from oral normal and squamous cell carcinoma (SCC) tissue were examined using the technique of cDNA library differential plaque screening. A differentially expressed transcript was selected on the basis of it being under-expressed in the cancer tissue and was identified, using DNA sequencing, as cytokeratin 14. The level of cytokeratin 14 transcription in RNA samples extracted from a range of oral SCC and normal tissue, as well as "white patch" lesions, was then investigated. Cytokeratin 14 appeared to be significantly under-expressed in oral cancer specimens studied compared to normal and white-patch tissue (P < 0.01). The trend for higher levels of cytokeratin 14 transcription in the dysplastic "white patch" samples compared to that observed for the malignant tissue (P < 0.05) suggests that the decrease in cytokeratin 14 transcription is a late event in the carcinogenic pathway.

Topics: Adolescent; Adult; Aged; Base Sequence; Carcinoma, Squamous Cell; DNA Probes; Female; Gene Expression; Gene Library; Humans; In Situ Hybridization; Keratins; Male; Middle Aged; Molecular Sequence Data; Mouth Mucosa; Mouth Neoplasms; Precancerous Conditions; RNA, Messenger; Transcription, Genetic

We established a human tongue cancer (well-differentiated squamous cell carcinoma) xenograft line, LK-1, in nude mice. LK-1 showed logarithmic growth from 5 to 7 weeks after transplantation, and the take rate for 25 generations was 95.0%. We confirmed the expression of cytokeratins 1, 5, 7, 10, 14, 16, 17, 18 and 19, and type I, III, IV and V collagens by electrophoretical and immunohistochemical analyses. Although the amount of type I, IV and V collagens increased gradually from 5 weeks after transplantation, the distribution of type IV collagen was often discontinuous in the cancer basement membrane. From these data we concluded that LK-1 is an excellent model for the investigation of the cell biology of well-differentiated oral squamous cell carcinoma, and for examining the effects of clinical therapies for this disease.

Topics: Adult; Animals; Biomarkers, Tumor; Carcinoma, Squamous Cell; Cell Differentiation; Collagen; Female; Humans; Intermediate Filament Proteins; Keratins; Male; Mice; Mice, Inbred BALB C; Mice, Nude; Neoplasm Invasiveness; Neoplasm Proteins; Neoplasm Transplantation; Tongue Neoplasms; Tumor Cells, Cultured

The profile of keratin expression in benign warts from various cutaneous and mucosal sites along with dysplastic warts and squamous cell carcinomas has been examined using a panel of monospecific antibodies to epithelial keratins. Viral warts and verrucous keratoses from immunosuppressed renal transplant recipients show a spectrum of squamous atypia from benign lesions, from minimal changes to full thickness dysplasia. Changes associated with malignancy include loss of differentiation-specific keratins 1 and 10 together with expansion of basal cell epitopes and inappropriate expression of simple epithelial keratins 8, 18, and 19 in advanced squamous cell carcinoma. This late expression of keratins 8 and 18 contrasts with early expression of keratin 17 in all dysplastic lesions examined. Keratin 17 is found suprabasally in hyperproliferative lesions, including benign warts, but marked basal plus suprabasal expression is seen increasingly in malignantly transformed epidermis. These findings were not specific to immunosuppression, as shown by identical findings in control squamous cell carcinoma from nonimmunosuppressed individuals. Keratin 17 expression may prove prognostically helpful when assessing dysplasia in epidermal tumors.

Topics: Biomarkers; Carcinoma, Squamous Cell; Cell Transformation, Neoplastic; Cell Transformation, Viral; Condylomata Acuminata; Epithelium; Female; Humans; Immunohistochemistry; Keratins; Skin; Skin Diseases; Skin Neoplasms; Warts

One hundred forty-one head and neck squamous cell carcinomas were analyzed for keratin (K) 6, 13 and 19. Staining was evaluated by light microscopy (with or without grading) and image analyzer and expressed as a percentage of positive versus all tumor surface (PSA). Both techniques rendered strongly correlated results. Strong expression was noted in 108 carcinomas (76.1%) for K6, in 18 (12.7%) for K19 and in 21 (14.8%) for K13 (P = .001). One hundred thirty-six (96%) tumors were positive for K6, and their PSA ranged from 0.6% to 48.8%; K19, 48 cases (0.2-44%); K13, 59 (0.2-38.1%). Expression of K6 was related to differentiation. K19 was expressed mainly in moderately and poorly differentiated tumors, and K13 was manifest more in well-differentiated carcinomas or in keratinized areas of less-differentiated ones. Nineteen (13.38%) tumors were positive for both K13 and K19. K19 thus was related to tumor progression and K13 to differentiation. There was no correlation with tumor site or TNM category.

Topics: Adult; Aged; Carcinoma, Squamous Cell; Discriminant Analysis; Female; Gene Expression; Head and Neck Neoplasms; Humans; Image Processing, Computer-Assisted; Immunohistochemistry; Keratins; Male; Middle Aged; Neoplasm Metastasis; Prognosis

Stratified squamous epithelia have been shown to preferentially express a site-specific pattern of keratin intermediate filaments. Retinoic acid (RA) is known to modulate expression of the basal cell keratins K19 and K5. Expression of these genes is dependent on extracellular RA concentration. We have found that K19 mRNA levels increase over time in cultured keratinocytes exposed to elevated concentrations of RA. K5 mRNA levels decrease in response to RA in a similar fashion. The observed changes in K5 message are primarily the result of RA-induced alterations in gene transcription. However, the RA-mediated induction of K19 mRNA is not the result of increased transcription but is primarily due to enhanced mRNA stability. These results suggest that an RA-dependent post-transcriptional mechanism modulates K19 intermediate filament expression in stratified squamous epithelia.

Topics: Carcinoma, Squamous Cell; Cell Nucleus; Cells, Cultured; Cytoplasm; Half-Life; Humans; Keratinocytes; Keratins; Receptors, Retinoic Acid; RNA Processing, Post-Transcriptional; RNA, Messenger; Transcription, Genetic; Tretinoin; Tumor Cells, Cultured

We report a well-documented case of fatal thyroid cancer with histopathological characteristics of primary squamous carcinoma. A possible primary tumour elsewhere was excluded. The possible histogenesis of this unusual tumour and the therapy of choice are briefly discussed.

Topics: Aged; Biopsy, Needle; Carcinoma, Squamous Cell; Female; Humans; Keratins; Lymphatic Metastasis; Thyroid Neoplasms

FF-6 is a transplantable squamous cell carcinoma which originally arose in the facial skin of a DA rat. It was established after maintaining the tumor in the subcutaneous tissue or peritoneal cavity of DA rats conventionally for over 30 generations. When the soybean-sized original FF-6 tumor was transplanted subcutaneously, it became an oval, hard, whitish, solitary and thumb-head-sized nodule within one month. After intraperitoneal transplantation of FF-6, it formed many nodules ranging from miliary to thumb-head size, which adhered and/or metastasized to many abdominal organs. When FF-6, cut into small pieces, was injected into the lower lip, the tumor grew bigger in situ, and metastasized to regional lymph nodes. Histologically, FF-6 was characterized as a well-differentiated squamous cell carcinoma, showing positive staining with anti-keratin, anti-laminin, anti-collagen type IV, anti-fibronectin and UB-14 antibodies. This transplantable tumor may be useful for analyzing the mechanisms of proliferation and metastasis of squamous cell carcinoma in vivo, and the host defence mechanism in rats, as well as being a suitable model of human squamous cell carcinoma.

Topics: Animals; Carcinoma, Squamous Cell; Cell Division; Cell Line; Collagen; Fibronectins; Humans; Immunohistochemistry; Keratins; Laminin; Lymphatic Metastasis; Neoplasm Metastasis; Neoplasm Transplantation; Rats; Rats, Inbred Strains; Skin Neoplasms; Thymus Neoplasms

Recent studies of an endemic occurrence of chronic arsenism in a limited area on the southwest coast of Taiwan are focusing on its cytokeratin analysis in hopes of tracing the disease's biochemical expression. Specimens were obtained from uninvolved skin and arsenical cancers including Bowen's disease, basal cell carcinoma, and squamous cell carcinoma. In this study, we used two-dimensional polyacrylamide gel electrophoresis to analyse cytokeratin expression. Progressive alterations in cytokeratin expression were found in various skin lesions. These include an expression of K16 in the uninvolved skin; K16 and K6 in Bowen's disease; and K16, K6 and K17 in squamous cell carcinoma and basal cell carcinoma. In addition, we found that the K1 isoelectric variants shifted to more acidic forms with the complete absence of K1 in basal cell carcinoma. K16 expression in uninvolved skin indicates that it is nevertheless in a hyperproliferative status. K17 was expressed in squamous cell carcinoma and basal cell carcinoma, but not in Bowen's disease. The progressive impairment of phosphorylation of K1 and K2 in the process of chronic arsenism provides us with a suitable model for studying the biological significance of phosphorylation in intermediate filaments during chemical carcinogenesis.

Topics: Arsenic Poisoning; Bowen's Disease; Carcinoma, Basal Cell; Carcinoma, Squamous Cell; Chronic Disease; Electrophoresis, Polyacrylamide Gel; Humans; Keratins; Poisoning; Skin; Skin Neoplasms; Taiwan

A human monoclonal antibody, BM2, was produced by a hybridoma line generated by fusion of lymph node cells from a patient with squamous cell carcinoma (SCC) of the tongue with human B-lymphoblastoid cell line HO-323. BM2, an IgM class antibody, was reactive with all of the SCC cell lines tested. Frozen sections of normal and malignant tumor specimens were investigated to examine the reactivity of BM2 towards them. All 35 oral SCC specimens reacted with BM2. Normal stratified squamous epithelium showed positive staining in basal cells, but no staining was seen in other layers of the stratified epithelium, simple epithelium, and tissues of nonepithelial origin. Ductal basal cells of normal salivary gland also showed positive staining. Western blotting and immunoprecipitation analysis revealed that BM2 recognized 52 kDa membrane-associated protein. BM2 may therefore be a useful tool for biological and clinical studies of SCC.

Topics: Adenocarcinoma; Antibodies, Monoclonal; Antigens, Neoplasm; Carcinoma, Squamous Cell; Epithelial Cells; Epithelium; Fluorescent Antibody Technique; Formaldehyde; Humans; Hybridomas; Immunoglobulin Isotypes; Immunoglobulin M; Immunohistochemistry; Keratins; Membrane Proteins; Mitosis; Mouth Mucosa; Neuraminidase; Periodic Acid; Pronase; Submandibular Gland; Tumor Cells, Cultured

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

Primary squamous cell carcinomas of the endometrium are rare tumours. We have studied 7 primary and 2 secondary squamous cell carcinomas immunohistochemically with anti-all-cytokeratin (KL 1), anti-CEA and anti-vimentin. The non-keratinizing carcinomas and the non-keratinizing component of the keratinizing carcinomas showed a strong expression of vimentin. Contrary to this, the keratinizing parts were strongly positive with anti-CEA. Additionally, some cases showed a direct transformation of the (dysplastic) glandular endometrial epithelium into neoplastic squamous cells. These findings suggest that the primary squamous cell carcinoma of the endometrium is the result of a bidirectional differentiation of pluripotent endometrial precursor cells. Like in other non-endometrioid adenocarcinomas, such metaplasias develop from pluripotent Müllerian epithelium. They show various differentiations, perhaps endocervical determination with keratinization and positive reaction against CEA or primitive endometrioid with squamous cell appearance, positive anti-vimentin reaction and non-keratinization.

Topics: Adult; Aged; Aged, 80 and over; Carcinoembryonic Antigen; Carcinoma, Squamous Cell; Endometrial Neoplasms; Female; Humans; Immunohistochemistry; Keratins; Middle Aged; Vimentin

In a retrospective pilot study we compared morphologically the first biopsies of 20 patients suffering from oral squamous cell carcinoma (OSCC) where preoperatively performed radiation therapy [gamma rays (cobalt-60)] was successful with 20 patients who underwent the same therapy without the expected success. All specimens were formalin fixed and paraffin embedded. We performed haematoxylin and eosin staining and immunohistochemistry (ABC-method) applying broad spectrum cytokeratin, cytokeratin (CK) 1 + 2, 3 + 6, 13 and anti-proliferating cell nuclear antigen (PCNA, PC10). The specimens of the patients with success of the radiotherapy showed statistically higher levels of PCNA positive tumour cells, measured by a computerised morphometric analysis system (VIDAS). These specimens showed significantly less CK 3-6 positive tumour cells than the specimens of the patients with failure of this therapy. The difference in the content of proliferating cell nuclear antigen might explain the different results of the performed radiation therapy. The difference in cytokeratin 3 + 6 expression might be linked with the different amount of benign hyperproliferation. Prospective studies are planned to prove the results.

Topics: Adult; Aged; Aged, 80 and over; Carcinoma, Squamous Cell; Cell Division; Female; Humans; Immunoenzyme Techniques; Keratins; Logistic Models; Male; Middle Aged; Mouth Neoplasms; Nuclear Proteins; Pilot Projects; Prognosis; Proliferating Cell Nuclear Antigen; Retrospective Studies; Treatment Outcome

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

Recently K1 keratin peptide (K1, 68 kDa) was found to be present in two kinds of cultured human squamous cell carcinomas (HSCs) using a low-salt aqueous solution, rather than the high-salt solution containing Triton X-100 employed by many researchers up until now. To confirm whether this phenomenon is universal in cultured HSCs we analyzed K1 peptide in four other kinds of HSCs using the same procedures. Moreover, the K1 peptide detected was a little unusual with respect to solubility versus urea concentration. Epidermal K1 peptide is usually solubilized by 6-8 M urea and reductant; however, the K1 peptide in cultured HSCs was about 80-90% extracted by 1-2 M urea in a stepwise extraction procedure. This finding may have important implications regarding evaluation of keratin extracted from normal epidermal and cultured keratinocytes.

Topics: Blotting, Northern; Blotting, Western; Carcinoma, Squamous Cell; Electrophoresis, Gel, Two-Dimensional; Humans; Keratins; Neoplasm Proteins; RNA, Neoplasm; Tumor Cells, Cultured

Cytokeratin expression in rat lung tumors was studied using polypeptide-specific monoclonal antibodies (MAbs) to human cytokeratins 4, 5, 7, 8, 10, 13, 14, 18 and 19. Experiments were performed on tumor fragments derived from 5 experimental rat squamous-cell lung tumors and one adenocarcinoma, as well as on cell lines obtained from the same tumors. The aims of this study were to investigate the differentiation profile of the rat tumor tissue and established tumor cell lines based on light and electron microscopical features and on cytokeratin phenotype, to characterize the tumor type and degree of differentiation of the lung tumors maintained during passaging in experimental animals, and to compare the cytokeratin expression pattern in transplanted tumors with that of the cultures derived from these tumors. Our results indicate that, in general, the antibodies used cross-react with rat cytokeratins and that these MAbs can be used to phenotype rat lung carcinomas. Both the tumor fragments and the cultured cells revealed a similar pattern of cytokeratin expression. In addition, the degree of differentiation was maintained upon prolonged culturing in vitro. MAbs to cytokeratin sub-types can therefore be used to distinguish the main sub-types of rat lung tumors and can give an indication about the degree of differentiation.

Topics: Adenocarcinoma; Animals; Blotting, Western; Bronchial Neoplasms; Carcinoma, Squamous Cell; Cell Differentiation; Fluorescent Antibody Technique; Immunoenzyme Techniques; Keratins; Microscopy, Electron; Rats; Tumor Cells, Cultured

Expression of keratins 1, 6, 15, 16, and 20 was examined in normal cervical epithelia, squamous metaplasia, various grades of cervical intraepithelial neoplasia, and both squamous cell carcinomas and adenocarcinomas of the cervix with monospecific antibodies. Ectocervical epithelium contains all of these keratins except keratin 20. They show a heterogeneous distribution, with a basally restricted detection of keratin 15. Endocervical columnar cells were found to contain significant amounts of keratin 16, whereas the subcolumnar reserve cells expressed considerable amounts of keratin 15 and 16, and frequently keratin 6. These reserve cell keratins were also found in immature and mature squamous metaplastic epithelium. In the cervical intraepithelial neoplastic lesions they were generally found with increasing intensity as the severity of the lesion progressed. In the keratinizing variety of squamous cell carcinoma of the cervix, these three keratins seem to constitute an important part of the intermediate filament cytoskeleton, whereas in nonkeratinizing squamous cell carcinoma, they occur to a much lesser extent. Surprisingly, these keratins were also occasionally found in adenocarcinomas. From these data we conclude that the keratin phenotype of reserve cells and endocervical columnar cells is more complex than previously suggested. In particular, the keratins occurring in reserve cells are also present in most of the premalignant and in a considerable number of the malignant lesions of the cervix. The differentiation features of the various carcinoma types are, however, reflected in their specific keratin filament composition.

Topics: Adenocarcinoma; Carcinoma; Carcinoma, Squamous Cell; Cervix Uteri; Epithelium; Female; Humans; Immunohistochemistry; Keratins; Metaplasia; Reference Values; Uterine Cervical Neoplasms

Although cytokeratin expression is said to alter with the state of tumor differentiation, few studies appear to have confirmed this in fresh tissue biopsies from oral squamous cell carcinomas. Previous studies have been limited by the number of antibodies utilized, small sample size, or lack of information regarding tumor differentiation. A panel of 8 antikeratin antibodies (of which five recognised the simple epithelial keratins, 8, 18 and 19) were applied to fresh tissue biopsies from 24 oral cancer and 15 normal oral mucosal biopsies. A standard immunocytochemical technique was followed (Vectastain ABC method), with keratin expression graded on a 3 point scale. Our analysis indicated that simple epithelial keratins (K8, K18, K19) were not confined to the more poorly differentiated tumors. This may be relevant to tumor prognosis.

Topics: Antibodies, Monoclonal; Biomarkers, Tumor; Carcinoma, Squamous Cell; Humans; Immunohistochemistry; Keratins; Mouth Neoplasms; Neoplasm Proteins; Prognosis

As a basic study, an analysis was made, using flow cytometry (FCM), of a mixture of KB cells and lymphocytes after Propidium Iodide (PI)- Fluorescein Isothiocyanate (FITC) double strain. As a result, DNA histogram of only KB cells could be drawn. As a clinical application an analysis was made, using FCM, of tumor of the head and neck after double stain. It enabled the drawing of DNA histogram of only epithelial cells (cancer cells). Changes in DNA histogram of keratin positive cells were classified into three types: Type I: the same diploid type as whole cells, Type II: the same aneuploid type as them, and Type III: the different aneuploid type as them. Among 22 cases of malignant tumor there were 3 cases of Type I, 6 cases of Type II, and 13 cases of Type III. This method could contribute greatly to the detection of cancer cells and DNA diagnosis, and thus be useful clinically.

Topics: Biomarkers, Tumor; Carcinoma, Squamous Cell; DNA, Neoplasm; Epithelium; Fibroblasts; Flow Cytometry; Head and Neck Neoplasms; Humans; Keratins; Leukocyte Count; Lymphocytes; Ploidies

The nuclear DNA contents of atypical mesothelial cells from five patients who had an eosinophilic pleural effusion (EPE) were studied by the use of DAPI (4',6-diamidino-2-phenylindole dihydrochloride) DNA staining. Analysis of the nuclear DNA content revealed a polyploid pattern, with a major peak in the tetraploid region. Using an immunocytochemical technique, the atypical mesothelial cells showed a positive reaction for cytokeratin. In contrast carcinoembryonic antigen (CEA) was always negative in these cells. It is suggested that the atypical mesothelial cells with EPE had a higher rate of proliferation than did the normal mesothelial cells.

Topics: Adult; Aged; Biomarkers; Biomarkers, Tumor; Carcinoembryonic Antigen; Carcinoma, Squamous Cell; Cell Division; Cell Nucleus; Crohn Disease; DNA; Eosinophilia; Epithelium; Female; Humans; Indoles; Keratins; Lung Neoplasms; Male; Mediastinal Cyst; Membrane Glycoproteins; Mucin-1; Pleural Effusion; Pneumonia; Pneumothorax; Polyploidy

Alterations in the pattern of keratin expression are a common feature of skin-tumor development. In this study, we investigated whether the loss of epidermal keratin 1 (K1) and its replacement by mucosal keratin 13 (K13) is unique to mouse skin tumors induced by 7,12-dimethylbenz[a]anthracene (DMBA) and 12-O-tetradecanoylphorbol-13-acetate (TPA), since it has been reported that human epidermal tumors do not exhibit aberrant expression of K13. With that purpose, we analyzed the keratin profiles of 16 DMBA-induced hamster skin tumors using monospecific antibodies against K1 and K13. Although all the tumors expressed K1, they also showed an overall tendency towards loss of this keratin; furthermore, none of the tumors expressed K13. Previous studies have suggested that the induction of K13 in mouse skin is related to the mutation of the Ha-ras gene by the initiating agent DMBA, a mutation consistently found in murine DMBA/TPA-induced tumors and rarely found in human skin tumors. Therefore, we also evaluated the tumors for the presence of codon-61 mutations by direct sequencing of DNA extracted from paraffin-embedded tissue sections. Only three tumors showed an A-->T transversion in the second nucleotide of Ha-ras codon 61. However, presence of the mutation did not correlate with K1 staining. Although hamster skin tumors were induced by the same initiator as were mouse skin tumors, hamster skin tumors did not show the same keratin profile. Moreover, their immunohistochemical expression of K1 and K13 and their codon 61 sequences resembled that of their human counterparts. These results suggest that the aberrant expression of K13 may be unique to murine skin. Furthermore, although codon 61 Ha-ras mutation appears to be related to keratin alterations in the mouse model, this mutation is not sufficient to produce the same biochemical changes in other species.

Topics: 9,10-Dimethyl-1,2-benzanthracene; Animals; Base Sequence; Carcinoma, Squamous Cell; Cheek; Cricetinae; DNA, Neoplasm; Genes, ras; Immunoenzyme Techniques; Keratins; Male; Mesocricetus; Molecular Sequence Data; Papilloma; Point Mutation; Polymerase Chain Reaction; Sequence Analysis, DNA; Skin Neoplasms; Species Specificity

The endometrial carcinoma cell lines EC-MZ-1, 2, 3, 5, 9, and 11 were established between 1986 and 1990. Four cell cultures were started from endometrial tissue, one from ascites, and one from a lymph node metastasis. Lines have to date been subcultured up to 180 times and the doubling time varies between 26 hr and 3 weeks. Immunocytochemically the coexpression of cytokeratin (predominantly simple-epithelial cytokeratin polypeptides) and vimentin intermediate filaments was detectable in all cell lines, but three lines (EC-MZ-5, 9, 11) expressed vimentin only at low level. By transmission electron microscopy the tumor cells exhibited features of epithelial differentiation. After subcutaneous transplantation into nude mice three lines (EC-MZ-1, 2, 5) produced slow-growing tumors. The histological classification of these tumors ranged from moderately differentiated adenocarcinoma to undifferentiated carcinoma and closely corresponded to the original tumor. Even after long-term in vitro culture, without any addition of estrogens to the culture medium, the moderately differentiated receptor-positive cell line (EC-MZ-2) retained its morphological differentiation. The cells were propagated without estrogens in the culture medium. The estrogen and progesterone receptor levels of cultured cells were determined. Three lines (EC-MZ-1, 2, 3) were positive for the progesterone receptor in low passage number only, the other cell lines were negative for both receptors. The transplantable lines were investigated for hormonal receptor expression in ovariectomized nude mice. In the moderately differentiated cell line (EC-MZ-2) we observed an enhanced expression of the estrogen receptor under optimal stimulation of the nude mouse with estradiol benzoate. There was no effect on the expression of the progesterone receptor.

Topics: Adenocarcinoma; Adenocarcinoma, Papillary; Adult; Aged; Aged, 80 and over; Animals; Carcinoma, Squamous Cell; Endometrial Neoplasms; Endometriosis; Female; Humans; Immunohistochemistry; Keratins; Lymphatic Metastasis; Mice; Mice, Nude; Microscopy, Electron; Microscopy, Electron, Scanning; Middle Aged; Neoplasm Invasiveness; Neoplasm Transplantation; Receptors, Estrogen; Receptors, Progesterone; Tumor Cells, Cultured; Vimentin

Squamous syringometaplasia (SS) is defined as a mature squamous metaplasia of the eccrine ducts. We prospectively evaluated its frequency and clinical and pathological features in a series of 21 patients. SS was found in association with several diseases, chiefly chronic ulcers. The patient' ages ranged between 20 and 80 years and there was no sex predominance. The involved eccrine ducts were usually located in the superficial and mid dermis and displayed inner keratinization. The stimulus required for SS is unknown. Differential diagnosis between SS and well-differentiated squamous cell carcinoma (SCC) depends on the preservation of a lobular configuration and the absence of epithelial dysplasia or invasion.

Topics: Adult; Aged; Aged, 80 and over; Carcinoma, Squamous Cell; Diagnosis, Differential; Eccrine Glands; Female; Humans; Immunohistochemistry; Keratins; Male; Metaplasia; Middle Aged; Prospective Studies; Reference Values; Skin; Sweat Gland Neoplasms

We have previously demonstrated that cytokeratin levels are coordinately regulated in normal cultured human keratinocytes. In the present study we examine the mechanism of this regulation using human squamous cell carcinoma (SCC) cells. Treatment of SCC-13 cells with 20 or 200 nM trans-retinoic acid results in nearly complete suppression of cytokeratin K5 and K6 expression. This change is accompanied by a simultaneous reduction (> 20-fold) in the level of the mRNAs encoding K5 and K6. Transcriptional analysis indicates that the transcription rate of the K5 and K6 genes drops by approximately four to fivefold in retinoid treated nuclei. Retinol (2000 nM) also promotes this change. In contrast, cytokeratin K19 does not increase in the presence of retinoic acid, thus the normal coordinate regulation of keratin gene expression by retinoids appears to be uncoupled in SCC-13 cells. However, this does not represent a general defect in positive regulation of gene expression by retinoids, since in a transient transfection assay trans-retinoic acid positively regulates a reporter plasmid containing the retinoid response element from the retinoic acid receptor-beta gene. The synthetic retinoids Ro 13-6298 (ethyl ester) and its metabolic derivative Ro 13-7410 (free acid) are both active in modulating the differentiation of normal keratinocytes. In contrast, only Ro 13-7410 is active in SCC-13 cells. As Ro 13-6298 binds poorly to the retinoic acid receptors, this suggests that SCC-13 cells, unlike normal keratinocytes, lack the ability to convert Ro 13-6298 to the active Ro 13-7410.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Base Sequence; Carcinoma, Squamous Cell; DNA, Neoplasm; Gene Expression Regulation, Neoplastic; Humans; Keratins; Molecular Sequence Data; Retinoids; Skin Neoplasms; Transcription, Genetic; Transfection; Tumor Cells, Cultured

Eighty-one epithelial lesions were studied immunohistologically for cytokeratin protein expression using three anticytokeratins CAM 5.2, NCL5D3 and RCK102. Consistent differences were noted between squamous and glandular neoplasms. Squamous and cutaneous carcinomas were found to preferentially express higher molecular weight cytokeratins than adenocarcinomas. In addition, tumours of similar morphology from different sites showed differences in expression of these markers. Differences in pattern were also found between benign and malignant lesions in the case of liver and urinary bladder. Thus the value of cytokeratin profile analysis in characterisation of epithelial neoplasms is confirmed and may be useful in distinguishing benign from malignant tumours in some instances.

Topics: Antibodies, Monoclonal; Biomarkers, Tumor; Carcinoma, Squamous Cell; Epithelium; Humans; Immunohistochemistry; Keratins; Neoplasms; Neoplasms, Glandular and Epithelial

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Antibodies, Monoclonal; Biomarkers, Tumor; Carcinoma, Squamous Cell; Female; Humans; Keratins; Lung Neoplasms; Male; Middle Aged

We have established two cisplatin-resistant human lung squamous-carcinoma cell lines, PC10-B3 and PC10-E5, from their original cell line PC10. To discover which proteins are associated with cisplatin resistance, we carried out a two-dimensional gel electrophoresis to analyze differences in protein alteration between PC10, PC10-B3 and PC10-E5. A protein spot M(r) 50 kDa, pI5.3, was reduced markedly and a spot M(r) 50 kDa, pI4.9 was increased when PC10-B3 and PC10-E5 were compared with PC10. A spot M(r) 58 kDa, pI5.8 newly appeared only in PC10-E5. Cell fractionation showed that the M(r) 50 kDa, pI5.3 (p50-5.3) and the M(r) 50 kDa, pI4.9 fell within the nuclear fraction, while the M(r) 58 kDa, pI5.8 was found among the cytosol and microsomal fractions. Microsequencing after in situ digestion of the dramatically reduced spot p50-5.3 revealed that it was identical to 50 kDa, type I keratin (K14). Moreover, a retinoic acid-mediated K14 reduction was concomitant with a 4.0-fold increase in cisplatin resistance in PC10. Our report is the first to suggest the possible association of marked K14 reduction and cisplatin resistance in PC10-B3 and PC10-E5.

Topics: Amino Acid Sequence; Carcinoma, Squamous Cell; Cell Survival; Cisplatin; Clone Cells; Drug Resistance; Humans; Keratins; Lung Neoplasms; Molecular Sequence Data; Tumor Cells, Cultured

We describe an animal model to induce the histogenesis of squamous metaplasia of the cervical columnar epithelium, a condition usually preceding cervical neoplasia. This model is based on dietary retinoid depletion in female mice. Control sibling mice fed the same diet but with all-trans-retinoic acid (at 3 micrograms/g diet) showed the normal endocervical epithelial and glandular columnar morphology, typical of a simple epithelium without subcolumnar reserve cells. The stratified squamous ectocervical epithelium of these mice fed all-trans retinoic acid showed intense immunohistochemical staining in basal and suprabasal cells with mono-specific antibodies against keratins K5, K14, K6, K13, and, suprabasally, with antibodies specific for K1 and K10. At the squamocolumnar junction, the adjacent columnar epithelium (termed "suprajunctional") did not show staining for K5, K14, K6, K13, K1, and K10 but specifically stained for keratin K8, typical of simple epithelia and absent from the adjacent ectocervical squamous stratified lining (termed "subjunctional"), in striking contrast. Sections of the squamocolumnar junction from mice kept on the vitamin A-deficient diet for 10 weeks showed suprajunctional isolated patches of reserve cells, proximal and distal to the junction. These cells were detected prior to any symptoms of vitamin A deficiency, such as loss of body weight or respiratory discomfort. The subcolumnar reserve cells induced by vitamin A deficiency displayed positive staining for K5 and K14. As deficiency became severe, the reserve cells occupied the entirety of the suprajunctional basement membrane. This epithelium eventually became stratified and squamous metaplastic, the squamocolumnar junction was no longer discernible, and the entire endocervical epithelium and the endometrial glands lost K8 positivity, while acquiring K5, K14, K6, K13, K1, and K10 keratins typical of the ectocervix under normal conditions of vitamin A nutriture. Vitamin A deficiency also altered keratin expression and localization in squamous subjunctional epithelium. In situ hybridization studies for K1 and K5 mRNA showed their major site of expression at the basal (K5) and immediately suprabasal (K1) cell layers. The localization of both K5 and K1 proteins in these same cell layers, and above, is consistent with transcriptional regulation of these keratins. Early vitamin A deficiency caused the appearance of single subcolumnar reserve cells expressing K5 mRNA. After these ce

Topics: Animals; Carcinoma, Squamous Cell; Cervix Uteri; Diet; Disease Models, Animal; Epithelium; Female; Immunohistochemistry; In Situ Hybridization; Keratins; Metaplasia; Mice; Mice, Inbred BALB C; Mice, Nude; Phenotype; Precancerous Conditions; Retinoids; RNA, Messenger; Tretinoin; Uterine Cervical Neoplasms; Vitamin A Deficiency

A case of basaloid squamous carcinoma that involves the posterior buccal mucosa is described. The major histopathologic feature is a carcinoma with a basaloid pattern in association with squamous differentiation. The basaloid cells exhibit large and vesicular nuclei and eosinophilic clear or vacuolated cytoplasm. Cells are distributed in cords, trabeculae, or lobules that occasionally show glandular arrangement. The majority of the tumor cells are positive for keratin and a large group of cells distributed in glandular arrangement are positive also for vimentin.

Topics: Adult; Carcinoma, Squamous Cell; Carcinoma, Transitional Cell; Humans; Keratins; Male; Mouth Mucosa; Mouth Neoplasms; Vimentin

Atypical fibroxanthoma is a bizarre, cytologically malignant but usually clinically benign, lesion which typically arises in sun-damaged skin of the head and neck region in the elderly. Classically, its morphology is said to represent the dermal counterpart of pleomorphic malignant fibrous histiocytoma. We have identified 10 cases of a more monomorphic spindle-celled, fascicular variant which, paradoxically, was often mistaken for a clinically malignant lesion because it lacked the pleomorphism of conventional atypical fibroxanthoma. These tumours all arose in the head and neck region as polypoid lesions in the elderly. The tumours were confined to the dermis, often had an epidermal collarette, showed an eosinophilic fascicular morphology and were highly mitotic. All 10 were vimentin positive and five showed very focal actin positivity. Desmin, keratin and S-100 protein were negative in all cases. The clinical course was benign in all cases, justifying their accurate recognition. The principal differential diagnoses are spindle cell squamous carcinoma, spindle cell melanoma and leiomyosarcoma. Immunohistochemistry plays a key role in this distinction.

Topics: Aged; Aged, 80 and over; Carcinoma, Squamous Cell; Desmin; Diagnosis, Differential; Female; Fibrosarcoma; Humans; Immunohistochemistry; Keratins; Leiomyosarcoma; Male; Melanoma; Middle Aged; Mitosis; S100 Proteins; Skin Neoplasms; Vimentin

The relationship between the histological grading of malignancy and the expression of vimentin and cytokeratin was studied in 43 cases of oral squamous cell carcinoma. Immunohistochemical analysis was carried out with the avidin-biotin method using monoclonal antibody anti-vimentin, and the peroxidase anti-peroxidase method using the polyclonal antibody anti-cytokeratin. All cases were classified according to the histological malignancy grading system proposed by Anneroth. All of the carcinomas were found to express cytokeratin, while 60.4% expressed vimentin. Vimentin was particularly noted in all tumors scored to have highly malignant cells.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Antibodies, Monoclonal; Biomarkers, Tumor; Carcinoma, Squamous Cell; Female; Humans; Immunoenzyme Techniques; Keratins; Male; Middle Aged; Mouth Neoplasms; Prognosis; Vimentin

It was hypothesised that one may be able to visualise field changes, which are proposed to exist around tumours, as alterations in keratin intermediate filament protein expression. Standard immunohistochemical analysis using a panel of monoclonal anti-keratin antibodies was applied to fresh tissue sections to look for subtle changes in epithelial differentiation not visible in H&E sections. Such changes were observed in clinically normal epithelium from oral cancer patients, involving primarily substantial expression of keratins K8/K7 (using CAM 5.2) in the basal cells of 12 out of 34 biopsies, and also a trend towards a reduction in the complexity of keratin differentiation. Monitoring such changes may prove to be a valuable adjunct to conventional H&E staining if found to have prognostic and diagnostic significance.

Topics: Adult; Aged; Aged, 80 and over; Carcinoma, Squamous Cell; Cytoskeleton; Female; Humans; Immunohistochemistry; Keratins; Male; Middle Aged; Mouth; Mouth Neoplasms; Mucous Membrane

Monoclonal antibody (G6K12) specific for differentiated keratinocytes was developed using in vitro immunization against the SCC-25 cell line. G6K12 only recognized stratified portions of cultured SCC-25 cells. Immunohistochemical examination using normal human oral mucosa showed that specific G6K12-reactivity was limited to the lower spinous-cell layers, while this antibody weakly bound to cells in basal-cell layers as well as in the upper spinous, granular and cornified-cell layers. G6K12 was also reactive to keratinocytes in most moderately- and well-differentiated SCC tissues. Immunoelectron microscopic examination further demonstrated that the G6K12-immunoreactive area was at the outer surface of the entire plasma membrane, including the microvilli of stratified SCC-25. G6K12-binding was reduced 50% by the treatment of native cells with glycoendoceramidase for 2 h. These results suggest that G6K12 recognizes a plasma membrane-anchored glycoconjugate which is specific for differentiated keratinocytes.

Topics: Animals; Antibodies, Monoclonal; Antigens, Differentiation; Antigens, Neoplasm; Biomarkers, Tumor; Carcinoma, Squamous Cell; Enzyme-Linked Immunosorbent Assay; Epithelium; Fluorescent Antibody Technique; Humans; Hybridomas; Immunoglobulin M; Keratinocytes; Keratins; Mice; Microscopy, Immunoelectron; Mouth Mucosa; Papilloma

The immunohistochemical expression patterns of cytokeratins 8 and 18 and vimentin were examined in frozen sections of 120 human mucosal squamous cell carcinomas with special emphasis on the topological distribution in the tumour. This was done in order to evaluate in squamous cell carcinoma a particular expression pattern observed recently by us in transitional cell carcinoma of the urinary tract and designated as an 'interface phenomenon'. This phenomenon implying maximum expression of cytokeratins 8 and 18 at the tumour front, and to a lesser extent also in areas of intratumorous stroma contact, was also found in about 50 per cent of the squamous cell carcinomas examined. It was even found for vimentin, which contrasted with transitional cell carcinoma. The percentages of occurrence of the phenomenon varied for the different sites of origin of the tumour. Tumour grade did not influence the results. These findings further support the idea that invasive carcinoma cells interacting with the stromal micro-environment display a characteristic intermediate filament phenotype that deviates from the pattern expected on the basis of their direction of differentiation. These changes might reflect phenotype involved in invasive, migrating, and proliferating activities.

Topics: Carcinoma, Squamous Cell; Esophageal Neoplasms; Female; Head and Neck Neoplasms; Humans; Immunoenzyme Techniques; Keratins; Lung Neoplasms; Neoplasm Invasiveness; Neoplasm Proteins; Vimentin; Vulvar Neoplasms

Mouse skin carcinomas arise from a small subpopulation of benign papillomas with an increased risk of malignant conversion. These papillomas arise with limited stimulation by tumor promoters, appear rapidly, and do not regress, suggesting that they differ in growth properties from the majority of benign tumors. The transforming growth factor beta (TGF-beta) proteins are expressed in the epidermis and are growth inhibitors for mouse keratinocytes in vitro; altered TGF-beta expression could influence the growth properties of high-risk papillomas. Normal epidermis, tumor promoter-treated epidermis, and skin papillomas at low risk for malignant conversion express TGF-beta 1 in the basal cell compartment and TGF-beta 2 in the suprabasal strata. In low-risk tumors, 90% of the proliferating cells are confined to the basal compartment. In contrast, the majority of high-risk papillomas are devoid of both TGF-beta 1 and TGF-beta 2 as soon as they arise; these tumors have up to 40% of the proliferating cells in the suprabasal layers. Squamous cell carcinomas are also devoid of TGF-beta, suggesting that they arise from the TGF-beta-deficient high-risk papillomas. In some high-risk papillomas, TGF-beta 1 loss can occur first and correlates with basal cell hyperproliferation, while TGF-beta 2 loss correlates with suprabasal hyperproliferation. Similarly, TGF-beta 1-null transgenic mice, which express wild-type levels of TGF-beta 2 in epidermis but no TGF-beta 1 in the basal layer, have a hyperproliferative basal cell layer without suprabasal proliferation. In tumors, loss of TGF-beta is controlled at the posttranscriptional level and is associated with expression of keratin 13, a documented marker of malignant progression. These results show that TGF-beta expression and function are compartmentalized in epidermis and epidermal tumors and that loss of TGF-beta is an early, biologically relevant risk factor for malignant progression.

Topics: Animals; Base Sequence; Carcinoma, Squamous Cell; Cell Division; Cell Transformation, Neoplastic; Epidermal Cells; Epidermis; Female; Keratins; Mice; Mice, Transgenic; Molecular Sequence Data; Papilloma; Risk; Skin Neoplasms; Transforming Growth Factor beta

The expression of distinct cytokeratin subtypes in squamous cell carcinomas (SQCC) of the larynx was examined by immunohistochemistry with a panel of monoclonal antibodies (MABs) and different immunophenotypes were correlated with known prognostic factors, such as tumor site, local extension, degree of morphologic differentiation and lymph node metastasis. Among 50 cases of laryngeal SQCC tested, all 22 low grade tumors (Broders I and II) reacted strongly with MABs AE1, AE3 and KB.12, which corresponds to the phenotype of non-neoplastic squamous epithelium of the larynx. MABs K8.13 and K8.60 were negative only in 1 and 4 cases respectively. In these tumors CAM5.2 was either negative (18 cases) or weakly positive (4 cases). In contrast, we found that of 28 high grade SQCC (Broders III and IV) tested, strong reactivity with MABs AE1, AE3, K8.12 and K8.13 was restricted to smaller subsets, whereas CAM5.2 immunoreactivity was seen in 16 cases (57%). By morphological criteria 31 out of 50 cases in our series of SQCC showed keratinization and 30 of these 31 showed coexpression of cytokeratins identified by MABs AE3, K8.12, K8.13 and K8.60 and 29 cases by MAB AE1. The remaining non-keratinizing SQCC showed heterogeneous immunoreactivity for AE1, AE3 and K8.12 in 13 cases, for K8.13 in 12 cases and for K8.60 in 5 cases. Thirty of the 50 SQCC tested had no known lymph node metastasis and of these, 29 reacted with MABs AE1, AE3, K8.12 and K8.13 respectively, the remaining cases being either unreactive or only weakly reactive. Statistical analysis showed no significant differences between cytokeratins expression in SQCC and either anatomical location or local extension (pT).(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Antibodies, Monoclonal; Carcinoma, Squamous Cell; Humans; Immunohistochemistry; Keratins; Laryngeal Mucosa; Laryngeal Neoplasms; Prognosis; Reference Values; Staining and Labeling

Multiple lesions of dermal squamous cell carcinoma are found at a low frequency (0.04%) in the carcasses of young meat-type chickens at slaughter. For this study, affected carcasses (n = 308) were removed from the processing line, and lesions were characterized by size, distribution, and morphology. Carcasses were also sexed and examined for evidence of metastasis. Nodular (n = 297) and ulcerative (n = 1,707) lesions were counted and examined. Most lesions were present in the pectoral, dorsopelvic, and femoral feather tracts. Few lesions (n = 11) were found in wing tracts. Mean diameter was 5.4 mm for ulcerative lesions and 3.1 mm for nodular lesions. Histologic sections of ulcerative (n = 579) and nodular (n = 113) lesions were examined. Small nodular lesions originated from hyperplastic feather follicle epithelium. Nodules contained keratin-filled cysts lined by squamous epithelium that were associated with isolated islands and infiltrating cords of dermal keratinocytes. Loss of surface epithelium resulted in noduloulcerative and ulcerative lesions. Invasion of underlying skeletal muscle and evidence of visceral metastasis were not present, but invasion through elastic laminae and into the subcutis was present in 20.5% (134/654) of the lesions examined. The nodular lesions in these carcasses were morphologically similar to early nodular lesions previously described in live chickens as avian keratoacanthomas. A retrospective study compared selected production parameters and disease condemnations to the prevalence of squamous cell carcinoma in 665 flocks of broiler chickens. There was a positive correlation (P < 0.0001) with the occurrence of airsacculitis but a negative correlation with increased age and condemnations for leukosis (P < 0.0001).(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Animals; Carcinoma, Squamous Cell; Keratinocytes; Keratins; Poultry; Poultry Diseases; Prevalence; Retrospective Studies; Skin Neoplasms

It is known that cytokeratin 19 is particularly abundant in carcinoma of the lung.. A sandwich enzyme-linked immunosorbent assay called CYFRA 21-1 was, therefore, developed to detect soluble cytokeratin 19 fragments in serum using two specific monoclonal antibodies (Ks 19.1 and BM 19.21). The authors investigated the clinical significance of this new marker compared with the established markers carcinoembryonic antigen (CEA), squamous cell carcinoma antigen (SCC), neuron-specific enolase (NSE), carbohydrate antigen (CA) 19-9, CA 125, CA 15-3, CA 72-4, alpha-fetoprotein, and prostate-specific antigen in a pilot study on 1741 serum samples from patients with various benign and malignant diseases.. Postulating a specificity of 95% versus benign diseases of the lung, the diagnostic sensitivity of CYFRA 21-1 in lung cancer (independent of histologic type) at primary diagnosis was superior (47%) to CEA (27%), SCC (15%), and NSE (16%). Especially in squamous cell carcinomas of the lung, the true-positive test results were much higher for CYFRA 21-1 (60%) than for CEA (18%) or SCC (31%).. In small cell lung carcinomas, NSE was confirmed as the marker of first choice. For all of the other solid tumors investigated, CYFRA 21-1 showed no better profile of specificity and sensitivity than the established markers.

Topics: Antibodies, Monoclonal; Antigens, Neoplasm; Biomarkers, Tumor; Carcinoma, Squamous Cell; Enzyme-Linked Immunosorbent Assay; Female; Humans; Keratins; Lung Neoplasms; Male; Neoplasms; Phosphopyruvate Hydratase; Pilot Projects; Retrospective Studies; Sensitivity and Specificity; Serpins

Both papillomas and squamous cell carcinomas (SCC) induced in mouse epidermis by initiation with 7,12-dimethylbenz[a]anthracene (DMBA) and promotion with 12-O-tetradecanoylphorbol-13-acetate (TPA) exhibit aberrant expression of a type I keratin, K13, that is normally characteristic of terminal differentiation of internal stratified epithelia. There is evidence that the aberrant expression of K13 depends on the presence of an activated ras gene in mouse epidermal keratinocytes (Sutter et al., Mol Carcinog 4:467-476, 1991). To assess the general validity of this hypothesis, we investigated both aberrant K13 expression and activation of each of the three members of the ras gene family in epidermal tumors induced in four different mouse strains (SKH-1 hr, SENCAR, BALB/c, and C3H/He) by chronic irradiation with ultraviolet (UV) B. The tumor collection comprised nine papillomas and 30 well or poorly differentiated SCC. Aberrant K13 expression occurred in only five of 39 tumors and was restricted to SCC of both types. This indicates that aberrant K13 expression in UV-induced epidermal tumors was intrinsically different from that in chemically induced tumors. Polymerase chain reaction analysis of the tumors for different point mutations in codons 12, 13, and 61 of the Ha-ras and Ki-ras genes and in codon 61 of the N-ras gene revealed that only one of the well differentiated tumors from a SKH-1 hr mouse exhibited a GGA-->GAA mutation in codon 12 of the Ha-ras gene. Although this tumor was also positive for aberrant K13 expression, such a correlation could not be made for the remaining K13-expressing tumors. This indicates that the activation of one of the members of the ras gene family is not a general prerequisite for the aberrant expression of K13 in mouse epidermal keratinocytes.

Topics: Animals; Base Sequence; Carcinoma, Squamous Cell; Gene Expression Regulation, Neoplastic; Genes, ras; Keratins; Mice; Mice, Inbred BALB C; Mice, Inbred C3H; Molecular Sequence Data; Neoplasms, Radiation-Induced; Papilloma; Point Mutation; Skin Neoplasms; Transcriptional Activation; Ultraviolet Rays

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

Topics: Antineoplastic Combined Chemotherapy Protocols; Biopsy, Needle; Carcinoma, Squamous Cell; Cobalt Radioisotopes; Cytoplasm; Diagnosis, Differential; Fluorouracil; Follow-Up Studies; Head and Neck Neoplasms; Humans; Keratins; Mitomycin; Neoplasm Recurrence, Local; Prospective Studies; Radiotherapy, High-Energy

The expression of cytokeratins (CK) 1, 4, 5/6, 8, 13, 18, 19 and 20 and involucrin in 42 cases of squamous cell carcinomas from various locations was examined. The tumours expressed CK5/6 in 55%, CK8 in 76%, CK13 in 43% and CK19 in 95% of cases. The CK5/6-positive primary tumours were from uterine cervix, head and neck, lung, skin, oesophagus and urinary bladder, and the CK13-positive primary tumours were from uterine cervix, lung and vulva. Metastatic squamous cell carcinomas from head and neck more frequently expressed CK5/6 and 13, 7/7 (100%) and 6/7 (86%) compared with 3/5 (60%) and 0/5 (0%) in the primary squamous cell carcinomas. Few cases were CK1, CK4 and CK18 immunoreactive. CK20 immunoreactivity was not observed. Involucrin was expressed in 71% of tumours, and most of the involucrin-positive cells were located at the central parts of tumour cell clusters except for one case in which the peripheral cells around tumour cell clusters were positive. Thus, expression of the so-called simple epithelial markers CK8 and CK19 occurs in the majority of squamous cell carcinomas. The absence of CK20 immunoreactivity may be helpful in differential diagnosis.

Topics: Carcinoma, Squamous Cell; Female; Humans; Immunohistochemistry; Keratins; Lung Neoplasms; Lymphatic Metastasis; Mouth Neoplasms; Protein Precursors; Skin Neoplasms; Urinary Bladder Neoplasms; Uterine Neoplasms

Fifteen laryngeal squamous cell carcinomas were investigated for the presence of transforming growth factor alpha (TGF-alpha) and epidermal growth factor (EGF) using immunohistochemical methods. In a recent study the same material was characterized for epidermal growth factor receptors (EGF receptors) which were confined predominantly to the undifferentiated cells. The expression of this growth factor system in malignant cells may play a role in carcinogenesis and/or tumour growth. All carcinomas were positive for TGF-alpha and 12 were positive for EGF. In moderately-to-well differentiated carcinomas, the immunoreactivity was mainly detected in the cytologically more differentiated cells. Nine sections included both laryngeal stratified squamous epithelium of normal appearance and carcinoma. The immunoreactivity was here again localized in the cytologically more differentiated cells above the basal cell layer. The present investigation and our previous results confirm the existence of EGF receptors, TGF-alpha and EGF in laryngeal carcinomas. In addition, we conclude that the conditions do exist for growth factors to act through an autocrine system in poorly differentiated tumours and through a paracrine system in the moderately-to-well differentiated tumours.

Topics: Carcinoma, Squamous Cell; Cell Differentiation; Cytoplasm; Endothelium; Epidermal Growth Factor; Epithelium; Exocrine Glands; Female; Humans; Immunohistochemistry; Keratins; Laryngeal Muscles; Laryngeal Neoplasms; Macrophages; Male; Mucins; Neoplasm Staging; Transforming Growth Factor alpha

Only five cases of basaloid squamous cell carcinoma (BSCC), a rare tumor of head and neck, have been reported to involve the floor of mouth.. Clinicopathologic and immunohistochemical features of eight BSCC of floor of mouth were studied to evaluate the significance of the basaloid features.. Five patients were male and three were female. Their mean age was 52 years (range, 39-59). At presentation, one patient was diagnosed with Stage II disease, four were diagnosed with Stage III disease, and three were diagnosed with Stage IV disease. Aside from typical squamous differentiation, each patient had a component of basaloid cells arranged in irregular nests, cords, or pseudoglandular spaces with a brisk mitotic rate, myxoid stroma, and marked tendency for perineural invasion. A panel of immunostains yielded the following results: keratin, +8/8; carcinoembryonic antigen, +3/8; and S-100, chromogranin, and neuron-specific enolase were negative. Mucin stains were negative in all cases. Ultrastructural characterization of three BSCC revealed squamous differentiation of the basaloid cells and a peculiar basal membrane-like material in between them. No neurosecretory granules were present. Seven patients underwent surgery; six of them were also treated with postoperative radiation therapy. In two cases, chemotherapy was added at recurrence. One nonresectable patient received radiation and chemotherapy. At the last follow-up, five patients were dead of disease within 13 months from the diagnosis. One patient died of an unknown cause. Two patients were still alive at the time of this report, 4 and 2 months after treatment. Seven patients had recurrent disease. The authors compared these data with a control group of patients with conventional squamous cell carcinoma (SCC).. The authors' results indicate that BSCC of floor of mouth is an aggressive variant of SCC and is prognostically worse than the conventional SCC, regardless of the grade of the latter.

Topics: Adult; Carcinoembryonic Antigen; Carcinoma, Squamous Cell; Carcinoma, Transitional Cell; Female; Humans; Keratins; Male; Middle Aged; Mouth Floor; Mouth Neoplasms; Neoplasm Staging; Prognosis; Survival Rate

Cytokeratins are intermediate filaments of the cytoskeleton that are expressed by bronchial epithelium and its neoplastic counterpart, lung cancer. A new immunoradiometric assay referred to as CYFRA 21-1 makes it possible to titrate in the serum a cytokeratin 19 fragment. This study deals with the sensitivity, specificity and applicability of this serum marker in squamous cell carcinoma. Sera from non malignant pulmonary diseases were taken as controls. In comparison with carcinoembryonic antigen (CEA), squamous cell carcinoma antigen (SCC T-A4) and neuron specific enolase (NSE), CYFRA 21-1 was the most accurate marker. The area under the CYFRA 21-1 ROC curve was significantly greater than those of CEA, SCC T-A4 and NSE. Using a 3.6 ng/ml threshold, as determined by the ROC curve, CYFRA 21-1 was significantly correlated with tumor mass.

Topics: Antigens, Neoplasm; Biomarkers, Tumor; Carcinoembryonic Antigen; Carcinoma, Squamous Cell; Female; Humans; Keratins; Lung Neoplasms; Male; Middle Aged; Neoplasm Staging; Phosphopyruvate Hydratase; Radioimmunoassay; Sensitivity and Specificity; Serpins

A spontaneous squamous cell carcinoma was diagnosed in the oral cavity of an adult female squirrel monkey (Saimiri sciureus). Immunohistochemical analysis of the neoplasm demonstrated cytokeratin and vimentin, but not S100 or desmin in the neoplastic epithelial cells.

Topics: Animals; Carcinoma, Squamous Cell; Desmin; Female; Immunohistochemistry; Keratins; Monkey Diseases; Mouth Neoplasms; S100 Proteins; Saimiri; Vimentin

The expression of differentiation associated high PM Keratin polypeptides of the oral mucosa lesions were studied by immunohistochemical and immunoblotting techniques applied to adjacent sections of each biopsy specimen. The material studied included specimens of leukoplakia, verrucous carcinoma, squamous cell carcinoma, adenocarcinoma and keratoacanthoma. Little or no expression of 65-67 Kd keratins was evident in squamous cell carcinoma and adenocarcinoma. Hyperkeratotic (both benign and dysplastic) lesions such as verrucous carcinoma, leukoplakia, and keratoacanthoma, showed great variations in the intensity of 65-67 bands and a very irregular immunohistochemical staining pattern. Increased amounts of horny substance was usually accompanied by absence of, or decreased expression of 65-67 Kd keratins, thus indicating a change in the polypeptide composition of the horny layer in pathological conditions of the oral epithelium.

Topics: Adenocarcinoma; Antigens, Differentiation; Carcinoma, Squamous Cell; Carcinoma, Verrucous; Cell Differentiation; Electrophoresis, Polyacrylamide Gel; Humans; Immunoblotting; Immunoenzyme Techniques; Immunohistochemistry; Keratins; Keratoacanthoma; Leukoplakia, Oral; Mouth Mucosa; Mouth Neoplasms

Bladder washing specimens containing inflammatory or squamous cells have been difficult to accurately analyze with single-parameter DNA flow cytometric (FCM) methods.. The anticytokeratin 18 antibody, CK5, was used in a multiparameter assay of 275 bladder washing and voided urine specimens to immunoselect only the bladder transitional cells for DNA analysis.. Flow cytometric detection of transitional cell carcinoma was increased by immunoselection of CK5-positive cells in specimens from patients with disease. Unfortunately, a similar increase in hyperdiploid cells in pathologically benign specimens was observed, which resulted in a false-positive rate of 45%. In some instances, multiparameter FCM assays with CK5 could detect aneuploid cell populations not clearly evident by single-parameter analysis.. However, the results from this study of the hyperdiploid cell fraction showed that the increased sensitivity resulting from the use of CK5 was not clinically useful because of the decrease in specificity.

Topics: Animals; Antibodies, Monoclonal; Antibodies, Neoplasm; Carcinoma, Squamous Cell; Carcinoma, Transitional Cell; DNA, Neoplasm; Flow Cytometry; Humans; Keratins; Male; Mice; Urinary Bladder; Urinary Bladder Neoplasms

An expression of desmosomal glycoprotein 1 (DG 1) was immunohistochemically examined in 77 biopsies and 21 metastatic cervical lymph nodes of oral squamous cell carcinomas (SCC). In the primary tumors the DG 1 expression was significantly reduced at the invasive site of poorly differentiated and highly invasive tumors. In cases of metastases in cervical lymph nodes, the DG 1 staining at the invasive site of the primary tumor was significantly less than that of nonmetastatic cases. The DG 1 expression in the metastatic lymph nodes was as weak as that in the primary tumor. Thus, we suggest that immunohistochemical investigation of DG 1 expression in oral SCC is valuable in predicting tumor behavior.

Topics: Carcinoma, Squamous Cell; Cell Adhesion Molecules; Cell Transformation, Neoplastic; Cytoskeletal Proteins; Desmoglein 1; Desmoplakins; Desmosomes; Humans; Immunoenzyme Techniques; Immunohistochemistry; Keratins; Lymphatic Metastasis; Mouth Neoplasms; Neoplasm Invasiveness; Neoplasm Staging; Staining and Labeling

The tissue labelling of a panel of monoclonal antikeratin antibodies (LL001, LL002, LL003, LP2K, BA17, LP34, CAM5.2, and LH1) recognising keratins 1, 5, 8, 10, 14, 18, and 19 were investigated in frozen and formalin-fixed normal skin. Antibodies LL001, LL003, BA17, LP34, CAM5.2, and LH1 were found to be reactive in formalin-fixed material and were used to study 23 basal cell carcinomas, 8 squamous cell carcinomas, 5 keratoacanthomas, 5 Bowen's disease, and 6 clear cell acanthomas. All these tumours demonstrated a loss of keratin 10 expression as demonstrated by loss of labelling with LH1. Keratin 14 expression, as demonstrated by LL001, was reduced but present in all the tumours except squamous cell carcinomas and keratoacanthomas where increased labelling was observed in the more differentiated areas of these tumours. Simple epithelial keratin expression was demonstrated by positive labelling with CAM5.2 and keratin 19 by BA17 in a third of basal cell carcinomas and squamous cell carcinomas. Three of the five keratoacanthomas labelled with BA17, indicating the presence of keratin 19 in these lesions. These results support the concept that keratin expression is a phenotypic marker of the state of differentiation or malignant transformation and that patterns of keratin expression are not specific to any particular premalignant or malignant disorder.

Topics: Antibodies, Monoclonal; Axilla; Bowen's Disease; Carcinoma, Basal Cell; Carcinoma, Squamous Cell; Freezing; Humans; Immunohistochemistry; Keratins; Keratoacanthoma; Reference Values; Skin; Skin Neoplasms; Tissue Fixation

In order to clarify the histogenesis and the direction of differentiation of spindle-cell and sarcomatous components of esophageal carcinosarcoma, 20 cases of the disease were reviewed histologically and immunohistochemically using the avidin-biotin-peroxidase complex method with monoclonal and polyclonal antibodies to various keratins, vimentin, desmin, muscle specific actin and S-100 protein. A gradual transition between carcinomatous and spindle cell sarcomatous components was present histologically in all 20 cases. Positive immunoreactivity for keratins was found in carcinomatous areas in all cases. Spindle cells in the transitional areas were positive for keratins in nine cases and for vimentin in five. Two cases demonstrated trace positive reactions to both keratin and vimentin in the same areas of transitional spindle cells between carcinomatous and sarcomatous components. The sarcomatous component showed an immunohistochemically positive reaction for vimentin in ten cases and for desmin in two. In one of the 20 cases, chondrosarcomatous cells were seen which showed a positive reaction to S-100 protein but were negative to keratin. The findings strongly suggested that neoplastic epithelial cells may show dedifferentiation to transforming spindle cells and also disdifferentiation to non-epithelial sarcoma like chondrosarcoma and leiomyosarcoma.

Topics: Actins; Adult; Aged; Anaplasia; Carcinoma, Squamous Cell; Carcinosarcoma; Cell Nucleus; Cytoplasm; Desmin; Esophageal Neoplasms; Female; Humans; Immunoenzyme Techniques; Immunohistochemistry; Keratins; Male; Middle Aged; Neoplasm Invasiveness; S100 Proteins; Sarcoma; Vimentin

The largest keratin peptide (K1, 68KD) has not been detectable in cultured human squamous cell carcinomas. However, quite recently, the K1 peptide was clarified to be present in two kinds of cultured HSC by using a low salt aqueous solution, rather than the high salt and Triton X-100 employed by many previous researchers (Biochem. Biophys. Res. Commun., 182, 1440-1445, 1992). To determine whether this phenomenon is common or not in cultured HSCs, I further demonstrated the K1 peptide by extracting it with two different buffers and by 2D-PAGE, immunological techniques, and Northern blot analysis, using another kind of HSC. Until now, keratin extraction has been done using high salt/Triton X-100 solution, during which K1 peptide may be removed because it has developed an affinity with the buffer. Many investigators may have therefore overlooked it.

Topics: Blotting, Northern; Carcinoma, Squamous Cell; Electrophoresis, Polyacrylamide Gel; Humans; Immunoblotting; Keratins; Molecular Weight; Peptides; Tumor Cells, Cultured

Monoclonal antibodies E3 against cytokeratin No. 17 were used for immunohistochemical examination of samples from 19 squamous-cell carcinomas of the uterine cervix and 10 cases of squamous-cell metaplasia of the endocervix. The above antibodies selectively labelled reserve cells of the cervical canal mucosa, basal layer of mature metaplastic epithelium and parabasal and basal cells of immature metaplastic squamous epithelium. In large-cell keratinizing, non-keratinizing and small-cell carcinomas, the expression of cytokeratin No. 17 revealed tendency to basal orientation and was in many respects similar to that in metaplastic squamous epithelium. It was suggested that all the squamous-cell carcinomas studied originated from reserve (metaplastic) cells.

Topics: Adult; Antibodies, Monoclonal; Carcinoma, Squamous Cell; Cervix Uteri; Female; Humans; Immunohistochemistry; Keratins; Metaplasia; Middle Aged; Molecular Weight; Uterine Cervical Neoplasms

A case is reported of malignant pilomatricoma confirmed by immunohistochemistry using anti-human hair keratin (anti-HHK) antibody prepared by the authors. The tumor occurred in the soft tissue of the inguinal region of an 88-year-old woman, with later invasion of the epidermis. No other possible primary lesion was found at autopsy. Histologically, the tumor was squamous cell carcinoma with nests of tumor cells and shadow cell-like necrotic cells showing central keratinization and focal calcification. Immunohistochemically, the hair keratin was positive in this tumor and in benign pilomatricomas exclusively. All other skin lesions and various squamous cell carcinomas examined were negative for this antigen. The staining patterns of commercial antiepidermal keratin and antiinvolucrin antibodies were significantly different from that of anti-HHK in normal skin and in these lesions. To the authors' knowledge, this is the first case of malignant pilomatricoma tested with anti-HHK staining. Malignant pilomatricoma is generally a low-grade malignant tumor, but it can metastasize and be fatal as it was in this case.

Topics: Aged; Aged, 80 and over; Biomarkers; Blotting, Western; Carcinoma, Squamous Cell; Electrophoresis, Polyacrylamide Gel; Female; Hair; Humans; Immunoenzyme Techniques; Keratins; Scalp; Skin Neoplasms

To date, the largest keratin peptide(K1, 68 KD) has been absent in cultured human squamous cell carcinomas. Using a low salt aqueous solution, not containing high salt and Triton X-100, as a washing buffer for keratin extraction, followed by two dimensional polyacrylamide gel electrophoresis, immunological techniques and Northern blot analysis, we demonstrated K1 peptide in two kinds of cultured human squamous cell carcinomas. Until now keratin extraction has been done using high salt/Triton X-100 solution during which K1 peptide may be removed together developed an affinity with the buffer. Many investigators may have therefore overlooked K1.

Topics: Amino Acid Sequence; Base Sequence; Blotting, Northern; Carcinoma, Squamous Cell; Cell Differentiation; Cell Line; Electrophoresis, Gel, Two-Dimensional; Electrophoresis, Polyacrylamide Gel; Humans; Keratins; Molecular Sequence Data; Molecular Weight; Oligodeoxyribonucleotides; RNA, Messenger; RNA, Neoplasm; Tumor Cells, Cultured

An immunohistochemical study of squamous metaplasia (n = 10), dysplasia (n = 18), squamous cell carcinoma (n = 48) and 3 cases of adenosquamous carcinoma of the uterine cervix with anti-56KD keratin and 68KD keratin antibodies was performed. In the cases of squamous metaplasia, there were two types of staining of which one type had 56KD positive and 68KD negative and another type had both positive. In the cases of dysplasia, there were two types of staining the same as in squamous metaplasia. But in the cases of carcinoma in situ (CIS) (n = 25), there were three types of staining of which the first type had both 56KD and 68KD negative (n = 7), the second type had 56KD positive and 68KD negative (n = 15), and the third type had both 56KD and 68KD positive (n = 3). In invasive carcinoma (n = 23), there were two types of staining the same as in dysplasia of which one type had 56KD positive and 68KD negative (n = 17) and another type had both positive (n = 6). The keratin negative cases in CIS showed morphologically atypical reserve cell hyperplasia composed of atypical small cells with round nuclei and had a small lesion compared with other types. This result suggested that keratin negative CIS was an early form of CIS which was keratin positive. The results indicating that all dysplasia had 56KD keratin positive and CIS had not always 56KD keratin positive suggested that dysplasia was not always a precursor lesion of CIS.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adenocarcinoma; Antibodies, Monoclonal; Carcinoma in Situ; Carcinoma, Squamous Cell; Cell Transformation, Neoplastic; Cervix Uteri; Female; Humans; Hyperplasia; Immunoenzyme Techniques; Keratins; Metaplasia; Molecular Weight; Neoplasms, Multiple Primary; Uterine Cervical Neoplasms

Six patients with adenosquamous carcinoma (ASqC) of the pancreas were studied clinicopathologically and immunohistochemically. In five of six ASqC tumors, both malignant squamous and glandular elements were reactive with CA 19-9, ST 439, and keratin antibodies. In contrast, a portion of the glandular element in the remaining one ASqC was reactive with CA 19-9 and ST 439 antibodies, but that of the squamous cell carcinoma (SqCC) was not reactive. However, SqCC of this tumor was intensely reactive with keratin antibody. These immunohistochemical results suggest that the histogenesis in one ASqC tumor was different from that of the other 5 ASqCs, and that this tumor may be a collision tumor rather than transformation to SqCC from adenocarcinoma, which is a very rare pattern of histogenesis in ASqC. The patients with ASqC of the pancreas showed shorter survivals following operations because of systemic metastasis including liver metastasis.

Topics: Adenocarcinoma; Aged; Aged, 80 and over; Antigens, Tumor-Associated, Carbohydrate; Carcinoma, Squamous Cell; Female; Humans; Immunohistochemistry; Keratins; Liver Neoplasms; Male; Middle Aged; Neoplasm Invasiveness; Neoplasm Staging; Pancreatic Neoplasms; Survival Rate

Thirty cases of poorly differentiated carcinomas of the skin were examined for the expression of vimentin. All cases expressed cytokeratins; in addition, 12 cases were positive for vimentin. These were all non-reactive with antibodies to S100 protein, HMB45 and desmin. The finding of vimentin in poorly differentiated squamous cell carcinomas underscores the need for caution in the use of immunohistochemical stains for tumor typing. Cutaneous squamous cell carcinomas are an addition to the list of epithelial tumors which are known to coexpress vimentin intermediate filaments. Other carcinomas which consistently express vimentin include those of renal, endometrial, thyroid, pulmonary, ovarian, salivary gland, adrenal and more recently, those of breast and prostatic origin.

Topics: Actin Cytoskeleton; Carcinoma, Squamous Cell; Cell Transformation, Neoplastic; Humans; Immunohistochemistry; Keratins; Skin Neoplasms; Vimentin

The various cytokeratin polypeptides in oral epithelia are expressed in dependence on site and formation of a stratum corneum. Certain cytokeratins occur permanently and others occasionally. In fibrous hyperplasia and Lichen ruber planus, patterns of cytokeratins did not deviate significantly from normal. In some but not all cases of squamous cell carcinoma and leukoplakia studied, marked aberrations of pattern were characterized by (i) appearance of cytokeratin No. 19, (ii) somewhat more frequent occurrence of cytokeratins Nos. 8 and 18, (iii) proteolytic modifications of cytokeratins, and (iv) partial loss of a few site-specific cytokeratins. The aberrations may be taken as additional diagnostic criteria for differentiation between non-aggressive and potentially aggressive leukoplakic lesion, even if they are not correlated with the conventional histological grading of dysplasia.

Topics: Adolescent; Adult; Aged; Carcinoma, Squamous Cell; Female; Gingiva; Humans; Hyperplasia; Keratins; Keratosis; Leukoplakia, Oral; Lichen Planus; Male; Middle Aged; Molecular Weight; Mouth Diseases; Mouth Mucosa; Mouth Neoplasms

Discrimination of benign from malignant is fundamental to accurate histologic diagnosis. This article describes a series of nine patients with cutaneous squamous cell carcinoma who were noted to have in the vicinity of their neoplasm seemingly benign but biologically significant dermal granulomatous inflammation to cornified cells (GRC).. Two patients were reported as having this finding alone on incisional biopsy specimens only to have subsequent biopsy specimens demonstrate bona fide malignant neoplasms. On Mohs' frozen sections, four patients were noted to have GRC without concomitant tumor and four patients had GRC admixed with tumor. Two patients who demonstrated GRC but no neoplasm on final Mohs' sections had development of recurrent neoplasm after the initial procedure.. In the setting of suspected or proved cutaneous squamous cell carcinoma, GRC signifies the presence of viable neoplasm and warrants additional tissue resection.

Topics: Adult; Aged; Aged, 80 and over; Carcinoma, Squamous Cell; Cells; Female; Granuloma, Foreign-Body; Humans; Inflammation; Keratins; Male; Middle Aged; Neoplasm Recurrence, Local; Skin Neoplasms

The expression patterns of basement membrane components and keratin intermediate filament proteins were studied in normal human bronchial epithelium and 56 lung carcinomas using monoclonal antibodies to laminin, type VII collagen and the individual keratins 14, 16, 17 and 18. In normal lung, laminin and type VII collagen were present between the epithelium and the lamina propria of bronchi and bronchioles. Keratin 14 was expressed in the basal cells, keratin 17 in the basal and some suprabasal cells and keratin 18 in the columnar cells of the bronchi and bronchioles. Keratin 16 was not present in normal bronchial epithelium. Laminin was found in all subtypes of lung carcinoma, but type VII collagen was present only in squamous cell carcinomas, where it showed a reduction in expression with decreasing differentiation. Type VII collagen was not identified in adenocarcinomas, small cell carcinomas or carcinoids. Antibodies to basal cell keratins 14 and 17 also displayed positivity only in squamous cell carcinomas, although no correlation with the degree of differentiation could be observed. Keratin 16 appeared to be a marker of the squamous phenotype, rather than of hyperproliferation. The keratin 18 marker for columnar epithelial cells showed a reaction pattern opposite to that of the basal cell keratins, being extensively present in adenocarcinomas, small cell carcinomas and carcinoids, with less expression in squamous cell carcinomas. This study shows a correlation between the presence of type VII collagen and the basal cell keratins 14 and 17, and a negative correlation between these components and keratin 18. These findings are likely to be useful in identifying lung cancer subtypes.

Topics: Adenocarcinoma; Antibodies, Monoclonal; Carcinoid Tumor; Carcinoma, Small Cell; Carcinoma, Squamous Cell; Collagen; Humans; Immunoenzyme Techniques; Keratins; Laminin; Lung Neoplasms

Antibodies to cytokeratins (CKs) have found extensive application in the differential diagnosis of epithelial tumors. The chain-specific anti-CK reagents appear to be of practical value for further subtyping of carcinomas. The authors have produced a novel anti-CK 18 monoclonal antibody (ACK-156) using a modified immunization procedure that included sequential injections of human epidermal keratin, cyclophosphamide, and enriched cytoskeletal extracts from a human lung carcinoma cell line. This protocol effectively amplified clones with reactivity toward CK epitopes not present in epidermal keratin. Monospecificity of the antibody was confirmed by immunoblot analysis using both total cell lysates and cytoskeletal extracts as antigens. Immunoperoxidase staining of adenocarcinomas from a variety of sites, including lung, was strongly positive. Squamous cell carcinomas of lung were also strongly stained whereas squamous cell carcinomas of head and neck origin were stained focally or not at all. In contrast, several commercially available anti-CK 18 monoclonal antibodies did not distinguish squamous cell carcinomas of lung from those of head and neck origin. Immunoblot analysis of tumor lysates corroborated the tissue staining results and revealed that the commercially available antibodies that were tested recognize at least one other low molecular weight peptide in addition to the CK 18 peptide recognized by ACK-156.

Topics: Adenocarcinoma; Antibodies, Monoclonal; Carcinoma, Squamous Cell; Cytoskeleton; Electrophoresis, Polyacrylamide Gel; Epitopes; Humans; Hybridomas; Immunoblotting; Immunologic Techniques; Keratins; Lung Neoplasms; Peptide Mapping; Staining and Labeling

An 84-year-old woman suffered for 1 year from intermittent vaginal bleeding. Clinical examination revealed a large ulcerative cervical tumor that was histologically classified as well-differentiated squamous cell carcinoma. Acantholytic areas, apoptotic cell death, and pronounced amyloid deposition characterized the tumor. No evidence of papilloma virus infection was found in immunohistochemical examination or in nucleic acid in situ hybridization. Amyloid formed globular structures surrounded by neoplastic cells that reacted with cytokeratin antibodies. Although the amyloid itself was not labeled, electron microscopy showed filamentous degeneration of the squamous cells analogous to that described in different types of cutaneous keratin-derived amyloidoses. It was concluded that similar pathogenetic mechanisms are involved both in the cutaneous amyloidosis and in the amyloid deposition of squamous cell carcinoma.

Topics: Aged; Aged, 80 and over; Amyloid; Carcinoma, Squamous Cell; Female; Humans; Keratins; Microscopy, Electron; Plasma Cells; Uterine Cervical Neoplasms

Initiation and promotion in mouse skin carcinogenesis produce multiple benign tumors, squamous papillomas, but only a few squamous cell carcinomas. The spontaneous conversion from the benign to the malignant phenotype occurs over many months and in stages, but induced malignant conversion can be accomplished more rapidly by exposure of papilloma-bearing mice to mutagens or by transfection of papilloma cell lines with specific oncogenes. The analysis of genetic targets responsible for carcinogen-induced neoplastic progression would be facilitated by the development of in vitro models where the process is rapid, focal, and quantitative. To this end, primary newborn mouse keratinocytes were initiated in vitro by the introduction of the v-rasHa oncogene via a defective retrovirus. Recipient cells produce squamous papillomas and have a high proliferation rate in culture medium with 0.05 mM Ca2+, but fail to grow in medium with 0.5 mM Ca2+ which is permissive for growth of malignant keratinocytes. When v-rasHa-keratinocytes were exposed to mutagens in vitro, proliferative foci emerged after culture in 0.5 mM Ca2+ for 4 weeks. These foci stained intensely red with rhodamine stain, could be easily quantitated, and readily incorporated bromodeoxyuridine. Dose-response studies with several mutagens indicated that the number of foci increased with concentration to the point where excessive cytotoxicity developed. Mutagens varied in potency for producing foci in the following order: cis-diamminedichloroplatinum greater than or equal to benzo(a)pyrene diolexpoxide I greater than N-methyl-N'-nitro-N-nitrosoguanidine greater than or equal to 4-nitroquinoline-N-oxide greater than N-acetoxy-acetyl- aminofluorene. The tumor promoter 12-O-tetradecanoylphorbol-13-acetate was inactive in the assay. A subset of cell lines derived from foci produced malignant tumors in vivo, while others were not tumorigenic. Analysis of DNA from cell lines and tumors revealed that most tumorigenic cell lines maintained the v-rasHa genome, whereas the viral sequences were deleted in nontumorigenic cell lines. Immunohistochemical analysis indicated that proliferative foci and quiescent v-rasHa keratinocytes expressed keratin 8, a marker of v-rasHa expression in cultured keratinocytes. Cells in foci, but not v-rasHa control cells, expressed keratin 13, a marker which is strongly associated with the malignant progression of skin tumors in vivo. This in vitro assay provides a quantitative model to

Topics: Animals; Animals, Newborn; Base Sequence; Carcinogens; Carcinoma, Squamous Cell; Cell Transformation, Neoplastic; Cells, Cultured; Epidermal Cells; Epidermis; Genes, ras; Keratinocytes; Keratins; Methylnitronitrosoguanidine; Mice; Mice, Inbred BALB C; Molecular Sequence Data; Oligodeoxyribonucleotides; Papilloma; Polymerase Chain Reaction; Skin Neoplasms; Tetradecanoylphorbol Acetate; Transfection

Cellular expression of keratins (intermediate filaments) can be demonstrated by immunocytochemistry using unfixed tissue. However, for practical reasons, provision of fresh tissue to the laboratory is often difficult. Recently a fresh tissue transport medium (Patent applied for) has been developed which allows keratin immunocytochemistry to be performed up to 4 days after biopsy. In this study oral mucosal biopsies from 10 patients were hemisected, half placed in the new transport medium at 4 degrees C and the other half immediately frozen in liquid nitrogen. After 4 days frozen sections of both halves of the biopsies were stained by immunocytochemistry using various antikeratin antibodies. The morphology and staining characteristics of the two halves of the biopsies were then assessed. No significant difference could be found in either morphology or preservation of keratin expression in specimens stored in transport medium, as compared to those in liquid nitrogen. This new transport medium may offer considerable advantage for the provision of a histologic and immunocytochemical diagnostic service.

Topics: Cacodylic Acid; Carcinoma, Squamous Cell; Culture Media; Freezing; Gelatin; Humans; Immunoenzyme Techniques; Intermediate Filament Proteins; Keratins; Leukoplakia, Oral; Lichen Planus; Mouth Diseases; Mouth Mucosa; Mouth Neoplasms; Nitrogen; Specimen Handling; Staining and Labeling

The keratin expression pattern in oral stratified epithelium is related to the cellular differentiation level. The normal pattern shows the keratin pair K5 and K14 in the stratum basale whereas K1 and K10, or K4 and K13, are the two pairs associated with differentiating suprabasal cells. Monoclonal and polyclonal antibodies to individual keratins (K10, K13 and K14) were used in a two-color immunofluorescence staining method to study their coexpression in single cells. Altered keratin expression in premalignant and malignant lesions indicated abnormal differentiation. Monospecific keratin antibodies were suggested to be useful for evaluation of epithelial differentiation changes in oral dysplasias and oral squamous cell carcinomas.

Topics: Biomarkers, Tumor; Carcinoma in Situ; Carcinoma, Squamous Cell; Epithelium; Fluorescent Antibody Technique; Humans; Keratins; Leukoplakia, Oral; Microscopy, Fluorescence; Mouth Mucosa; Mouth Neoplasms; Photography; Precancerous Conditions

Expression of keratins (cytokeratins, CK) in healthy feline epithelia and 2 established feline mammary carcinoma cell lines was examined immunohistochemically and by use of immunoblotting analysis. A panel of specific anti-CK monoclonal antibodies (MAb) identifying epitopes unique to individual keratins or shared by 2 (or 3) CK polypeptides was used. Besides already available anti-human CK MAb, this panel of MAb consisted of 9 newly generated anti-human CK MAb and 1 newly generated anti-feline CK MAb. Immunohistochemical analysis on normal epithelia revealed that most of the anti-human CK MAb and the anti-feline CK MAb reacted with both feline and human epithelia, with a comparable tissue distribution pattern. However, slight differences in CK tissue distribution pattern between human beings and cats were detected by one MAb. Immunoblotting analysis revealed that all anti-human CK MAb that were immunohistochemically reactive with feline tissues detected analogous CK in cats, indicating the presence of a number of common epitopes on human and feline CK. Two continuous cell lines derived from 2 distinct feline mammary adenocarcinomas, K248C and K266, were analyzed with respect to their CK phenotype. Although no difference in CK expression between the 2 cell lines was detected in vitro, a difference in CK phenotype was detected on subcutaneous transplantation of the 2 cell lines into nude mice. Although the K248C-induced adenocarcinomas maintained the same CK phenotype as observed in vitro, the CK pattern of the K266 heterotransplants, growing as adenosquamous carcinomas, changed with squamous differentiation. Our findings confirm the high degree of homology between mammalian CK, and on the basis of those findings, we suggest that CK proteins provide a set of markers valuable for the characterization of normal and neoplastic feline tissues and for studies of squamous metaplasia.

Topics: Adenocarcinoma; Animals; Antibodies, Monoclonal; Antibody Specificity; Carcinoma, Squamous Cell; Cats; Epithelium; Fluorescent Antibody Technique; Immunoblotting; Immunohistochemistry; Keratins; Mammary Neoplasms, Animal; Tissue Distribution; Tumor Cells, Cultured

The sensitivity of outbred SENCAR mice and inbred SENCAR (SSIN) mice to multistage carcinogenesis was studied. Tumors were induced using either 7,12-dimethylbenz[a]anthracene or N-methyl-N'-nitro-N-nitrosoguanidine as initiators and 12-O-tetradecanoylphorbol-13-acetate or benzoyl peroxide as promoting agents. Although the number of papillomas per mouse was higher in SSIN than in outbred SENCAR mice, the number of carcinomas observed in the SSIN strain was significantly lower regardless of the initiator or promoter used. It was also observed that the expression of markers of premalignant progression (i.e., dysplasia, expression of keratin K13, and loss of keratin K1 expression) was markedly suppressed in SSIN papillomas. After 50 wk of promotion with 12-O-tetradecanoylphorbol-13-acetate, the pattern of expression of K13 and K1 in SSIN mice was comparable to the pattern observed in outbred SENCAR mice after 10 to 20 wk of promotion with 12-O-tetradecanoylphorbol-13-acetate. It was also observed that 67% of the tumors induced in SSIN mice by initiation with 7,12-dimethylbenz[a]anthracene exhibited a mutation in codon 61 of the Ha-ras-1 gene. This latter finding suggests that the differences observed in tumor progression between the inbred strain and the outbred stock are not related to a genetic alteration in the Ha-ras-1 gene but rather to an independent event that we have postulated to involve a putative suppressor gene. The data reported here suggest that the putative gene(s) that confers susceptibility to tumor promotion was segregated from the gene(s) involved in tumor progression during selection and inbreeding of the SENCAR mouse stock.

Topics: 9,10-Dimethyl-1,2-benzanthracene; Animals; Benzoyl Peroxide; Carcinoma, Squamous Cell; Female; Genes, ras; Keratins; Methylnitronitrosoguanidine; Mice; Mutation; Papilloma; Skin Neoplasms; Species Specificity; Tetradecanoylphorbol Acetate

The importance of cervical squamous metaplasia and human papillomavirus 16 (HPV 16) infection for cervical carcinoma has been well established. Nearly 87% of the intraepithelial neoplasia of the cervix occur in the transformation zone, which is composed of squamous metaplastic cells with unclear origin. HPV DNA, mostly HPV 16, has been found in 90% of cervical carcinomas, but only limited experimental data are available to discern the role of HPV 16 in this tissue specific oncogenesis. We have initiated in vivo studies of cultured endocervical cells as an experimental model system for development of cervical neoplasia. Using a modified in vivo implantation system, cultured normal endocervical epithelial cells formed epithelium resembling squamous metaplasia, whereas those immortalized by HPV 16 developed into lesions resembling carcinoma in situ. In contrast, their ectocervical counterparts formed well differentiated stratified squamous epithelium and a lesion with mild dysplastic change, respectively. The HPV 16-immortalized cells showed in vivo cytokeratin expression patterns similar to their respective normal counterparts, confirming their different origins. Thus, this study provides direct experimental evidence for the transformation of simple epithelial cells of endocervical origin into stratified squamous metaplasia and indicates the differential susceptibility of endo- and ectocervical epithelial cells for conversion to cancer by HPV 16.

Topics: Animals; Carcinoma, Squamous Cell; Cell Line, Transformed; Cell Transformation, Neoplastic; Cells, Cultured; Cervix Uteri; Epithelium; Female; Humans; Immunohistochemistry; Keratins; Metaplasia; Mice; Mice, Nude; Microscopy, Electron; Mucins; Papillomaviridae; Transplantation, Heterologous; Uterine Cervical Neoplasms

Primary intraosseous carcinoma (P1OC) of the jaws is rare. They either arise de novo or as a consequence of malignant transformation of a benign cyst or tumor. A 56-year-old patient with a P1OC of the mandible arising from an odontogenic keratocyst is described.

Topics: Carcinoma, Squamous Cell; Cell Transformation, Neoplastic; Humans; Jaw Cysts; Keratins; Male; Mandibular Diseases; Mandibular Neoplasms; Middle Aged; Odontogenic Tumors

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

In normal epidermis, the expression of keratins 1 and 10 is associated with the loss of proliferative capacity and the onset of terminal differentiation. Keratins 1 (K1) and 10 (K10) are commonly expressed in the differentiating layer of benign tumors, but are lost during progression from the benign to the malignant state in skin carcinogenesis. Active gene constructs of mouse K1 and K10 were introduced into papilloma and carcinoma cell lines derived from keratinocytes to analyze the consequences of the expression of these keratins on the organization of the endogenous cytoskeletal network and on the mitotic activity of the recipient cells. Exogenous K1 integrated into the preexisting keratin K5/K14 network of both SLC-1 carcinoma and 308 papilloma cells. The formation of a recombinant cytoskeleton was more restricted for K10 than for K1 and appeared to be related to a requirement for cessation of cell division before K10 could integrate. The integration of exogenous K1 filaments into the endogenous keratin network was compatible with sustained proliferation of SLC-1 carcinoma cells in vitro. However, the exogenous gene was not expressed in tumor grafts in vivo. In contrast, stable K1 or K10 transfectants could not be selected in 308 cells, suggesting that benign tumor cells expressing suprabasal keratins cannot sustain proliferation.

Topics: Animals; Blotting, Northern; Blotting, Western; Carcinoma, Squamous Cell; Cell Division; Cell Line; Cytoskeleton; Keratins; Mice; Mice, Inbred BALB C; Neoplasm Transplantation; Papilloma; RNA, Neoplasm; Skin Neoplasms; Transfection

Lectins bind tightly to carbohydrate moieties on cell surfaces. Alterations in lectin binding have been reported to accompany epidermal cell differentiation, marking alterations in membrane sugars during this process. The presence of UEA I (Ulex europaeus agglutinin I) L-fucose-specific lectin-binding sites has been used as a marker for terminally differentiated (committed) keratinocytes. In this article, we report the presence of UEA-I-binding sites on squamous keratinocytes of well-differentiated squamous cell carcinomas, with patchy loss of UEA I positivity on poorly differentiated cells of squamous cell carcinomas, suggesting a possible use for this technique in the rapid assessment of less differentiated areas within the squamous cell tumor. The absence of UEA-I-binding sites on basal cell carcinomas may be related to an inability of cells comprising this tumor to convert the L-D-pyranosyl moiety on basal cells to the L-fucose moiety, resulting in an inability of basal cell carcinoma cell to undergo terminal differentiation into a committed keratinocyte.

Topics: Carcinoma, Basal Cell; Carcinoma, Squamous Cell; Cell Transformation, Neoplastic; Endothelium, Vascular; Epidermis; Epithelium; Fucose; Humans; Keratinocytes; Keratins; Lectins; Plant Lectins; Receptors, Cell Surface; Receptors, Mitogen; Skin Neoplasms

Three human lung squamous carcinoma cell lines (NX002, CX140 and CX143) demonstrate features of squamous differentiation including involucrin synthesis and competence to form cornified envelopes. 12-O-Tetradecanoylphorbol 13-acetate inhibits growth of these cell lines and this growth inhibition is associated with enhanced differentiation.

Topics: Antigens, Neoplasm; Carcinoma, Squamous Cell; Cell Differentiation; Cell Division; Humans; Keratins; Lung Neoplasms; Protein Precursors; Tetradecanoylphorbol Acetate; Tumor Cells, Cultured

Recent studies have suggested that the epithelial expression of two leukocyte-related proteins, human class II HLA-DR antigen and myelomonocytic L1 antigen, depends on a certain state of cellular maturation and differentiation. We have studied HLA-DR and L1 expression in oral squamous cell carcinomas. The epithelial distribution of these proteins was evaluated in relation to differentiation alterations by two-color immunofluorescence staining with cytokeratins (K14 and K13) as a baseline. HLA-DR was infrequently expressed in oral carcinomas, apparently being unrelated to the degree of differentiation and the subepithelial leukocyte infiltration. L1 was generally present in oral epithelium but disappeared in the most invasive cells of carcinomas. These cells were also K14 and K13 negative suggesting an abnormal state of differentiation. L1 has been suggested to have an inhibitory effect on casein kinases I and II, enzymes possibly associated with cell proliferation; it might therefore exert an inhibitory effect on tumor growth. Its absence could be an interesting aspect of the invasiveness of oral carcinoma cells.

Topics: Antigens, Surface; Carcinoma, Squamous Cell; Cell Adhesion Molecules, Neuronal; Cell Differentiation; Epithelium; Fluorescent Antibody Technique; HLA-DR Antigens; Humans; Keratins; Leukocyte L1 Antigen Complex; Mouth Mucosa; Mouth Neoplasms; Neoplasm Invasiveness

Keratins have been demonstrated to be suitable markers of changes taking place during epithelial neoplasia. Therefore, we analyzed 18 mouse skin tumors (nine papillomas and nine squamous cell carcinomas), induced either by two-stage carcinogenesis with 7,12-dimethylbenz[a]anthracene(DMBA)/12-O-tetradecanoylphorbol-13-acetat e or complete carcinogenesis with DMBA, by immunofluorescence with a monoclonal antibody to keratin (K) 8 (TROMA-1). Immunoperoxidase staining and immunoblotting were also used on selected tumor samples to further explore for the presence of K8. All of the papillomas tested were negative for the presence of K8, whereas the carcinomas were positive. The level of K8 expression in carcinomas showed a positive correlation with the degree of malignancy. Northern blot analysis using a K8 cDNA probe suggested that control of K8 expression in mouse skin tumors occurs at the transcriptional level. Double-label immunofluorescence staining using TROMA-1 and RK13 antibodies demonstrated that K8 did not generally colocalize with K13, a keratin normally found in internal stratified epithelial but aberrantly expressed in mouse epidermal tumors. Furthermore, tumors expressing high levels of K8 showed a reduced expression of K13. Histological examination of immunoperoxidase-stained tumors demonstrated that K8-positive cells were mainly found in anaplastic areas, whereas K13 foci were restricted to well-differentiated regions. Our results demonstrate that K8 expression is a marker of late stages of carcinoma progression in the mouse skin carcinogenesis model.

Topics: 9,10-Dimethyl-1,2-benzanthracene; Animals; Blotting, Northern; Carcinoma, Squamous Cell; Electrophoresis, Polyacrylamide Gel; Epithelium; Female; Fluorescent Antibody Technique; Gene Expression; Genes, ras; Immunoenzyme Techniques; Keratins; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Mutation; Papilloma; RNA; Skin Neoplasms; Tetradecanoylphorbol Acetate

Keratin expression in human cervical squamous cell carcinoma (SCC) lines differed significantly from both normal and human papillomavirus (HPV) immortalized exocervical cells. Keratin 14 (K14) expression, determined by protein synthesis and mRNA levels, was dramatically down-regulated in the cervical SCC lines while keratin 5 (K5) expression was not. K14 expression was similarly down-regulated in an HPV-16 immortalized cervical cell line after tumorigenic transformation with recombinant v-Ha-ras DNA. Cultures derived from nude mouse tumor explants also exhibited an altered keratin profile and the levels of K14 protein synthesis, as well as K14 mRNA, were not detectable. In both cases K5 protein synthesis was not significantly down-regulated. In addition, neoplastic cervical SCC lines exhibited up-regulation of keratins 7, 8, 13, and 19, combined with slight down-regulation of keratins 6 and 16. Epidermal keratinocytes responded in a different manner to exocervical cells. Transfection of human papillomavirus-immortalized epidermal keratinocytes with the BglII N fragment of herpes simplex virus 2 produced a neoplastic cell line, but K5 and K14 expression remained unchanged. Thus, neoplastic transformation of human exocervical cells, both in vivo (spontaneous cervical SCC) and in vitro (HPV-16- and v-Ha-ras-induced cervical SCC), is accompanied by characteristic changes in keratin expression. The specific down-regulation of K14 in these tumorigenic cervical cells, in the absence of significant changes in the expression of K5, implies that the normal coordinate regulation of K5 and K14 gene expression has been uncoupled.

Topics: Blotting, Northern; Carcinoma, Squamous Cell; Cell Line, Transformed; Cervix Uteri; Down-Regulation; Electrophoresis, Gel, Two-Dimensional; Female; Genes, ras; Humans; Keratins; Papillomaviridae; RNA, Messenger; Transfection; Uterine Cervical Neoplasms; Uterine Neoplasms

Keratin 19 (K-19) expression has been strongly correlated with dysplasia in oral epithelium. Expression of K-19 was evaluated by immunoperoxidase staining in formalin-fixed normal ectocervical tissue, normal endocervical tissue, cervical dysplasia, squamous metaplasia, atrophic epithelium, cervical condylomas, and invasive carcinoma to determine if a correlation of K-19 expression with dysplasia was present in the cervical epithelium. Uniform expression of K-19 was seen in endocervical epithelium and in the basal layer of normal ectocervical epithelium in all areas where these epithelia were present. Cervical dysplasia without associated condylomatous changes showed increased expression of K-19 in suprabasal epithelium, corresponding to the level of immature cells. Squamous metaplasia was characterized by scattered cells with increased staining (patch-quilt pattern). There was considerable overlap in the patterns of K-19 expression in dysplastic and metaplastic epithelium. Thus K-19 staining pattern could not be used as a distinctive marker for dysplasia in the cervical epithelium. Atrophic epithelium showed a characteristic uniform but low-level expression of K-19 in suprabasal areas. This pattern may be of diagnostic use in differentiating atrophic lesions from dysplasia. Condylomas showed focal loss of K-19 in the basal layer, suggesting induction of premature differentiation in the basal layer by human papillomavirus infection. Invasive carcinomas showed variable patterns. K-19 is a marker of immature cervical squamous epithelium, with generally distinctive but sometimes overlapping patterns of expression in various diagnostic categories.

Topics: Atrophy; Carcinoma, Squamous Cell; Cell Transformation, Neoplastic; Cervix Uteri; Condylomata Acuminata; Epithelium; Female; Humans; Immunohistochemistry; Keratins; Uterine Cervical Diseases; Uterine Cervical Neoplasms

Recognition of premalignant lesions in the oral epithelium has the potential to increase survival rates for squamous cell carcinoma of the oral cavity. It has previously been reported that cytokeratin 19 (CK19), a 40-kd epithelial cytoskeletal protein within the suprabasal squamous epithelium, is a specific marker of moderate-to-severe dysplasia and carcinoma in situ in oral cavity squamous epithelium. In contrast, normal epithelium and hyperplastic lesions reportedly express CK19 only in the basal layer if at all. The authors chose to test and extend this hypothesis by studying suprabasal CK19 expression and dysplasia of the oral cavity and upper aerodigestive tract in paraffin-embedded specimens that had been fixed in alcohol, a superior fixative for the preservation of cytokeratins. The authors examined 56 alcohol-fixed, paraffin-embedded specimens including 37 from the oral cavity, using two antibodies specific for CK19 (Ks19.1 and 4.62), an antibody to the nuclear proliferation marker, proliferating cell nuclear antigen (PCNA) (19A2), and an antibody to the putative tumor suppressor gene, p53 (pAb1801). The lesions were classified as normal, hyperplasia, mild dysplasia, moderate dysplasia, severe dysplasia/carcinoma in situ, or invasive squamous cell carcinoma, following standard histologic criteria. Immunocytochemically stained sections were scored for the presence or absence of suprabasal CK19, suprabasal PCNA, and p53 positivity, regardless of location. The immunostaining patterns of the two anti-CK19 antibodies were essentially equivalent. Except for one laryngeal specimen, normal epithelium, when positive, showed CK19 expression only in scattered cells throughout the basal layer. Proliferating cell nuclear antigen-positive nuclei were found exclusively in the basal layer. In areas of hyperplasia, CK19 immunostaining was absent or confined to the basal layer in 20 of 38 specimens and was expressed in suprabasal cells in 18 of 38 hyperplastic specimens. Proliferating cell nuclear antigen immunostaining in all cases of hyperplasia was limited to the basal layer. Severe dysplasia and carcinoma in situ showed suprabasal CK19 staining in six of nine specimens and no CK19 staining in three of nine specimens. In contrast, suprabasal PCNA immunostaining was found in all dysplasia and carcinoma in situ cases. p53 expression was detected in three of nine severe dysplasia/CIS specimens and was immunocytochemically undetectable in all normal, hyperplasia, an

Topics: Antigens, Neoplasm; Carcinoma, Squamous Cell; Genes, p53; Humans; Hyperplasia; Immunohistochemistry; Keratins; Mouth; Mouth Mucosa; Mouth Neoplasms; Mutation; Nuclear Proteins; Pharynx; Precancerous Conditions; Proliferating Cell Nuclear Antigen; Tissue Fixation

Lymphoepithelioma is a malignant epithelial neoplasm of the nasopharynx. Similar malignancies--lymphoepitheliomalike carcinomas--of salivary glands, thymus, larynx, lung, stomach, and uterus have been described. We present here a case of lymphoepitheliomalike carcinoma of the skin in an 84-year-old woman. Histologically this neoplasm presented as a fairly discrete dermal aggregate of syncytial nests of epithelioid-appearing cells that displayed no squamous or glandular differentiation, surrounded by a dense lymphocytic infiltrate. Results of immunophenotypic studies showed expression of high molecular weight cytokeratins and increased density of dermal dendrocytes within and adjacent to the tumor. No Epstein-Barr viral genomic sequences were detected by in situ hybridization, which suggests that cutaneous neoplasms may have different etiologic agents compared with similar tumors, found to be associated with this DNA-containing virus, arising in extracutaneous sites. The combined light microscopic and immunohistochemical assessment of this rate cutaneous neoplasm permits distinction of lymphoepitheliomalike carcinoma from benign/malignant lymphoproliferative disorders or neuroendocrine carcinomas.

Topics: Aged; Aged, 80 and over; Carcinoma, Squamous Cell; DNA, Viral; Female; Herpesvirus 4, Human; Humans; Immunohistochemistry; Immunophenotyping; Keratins; Nucleic Acid Hybridization; Skin Neoplasms

The incidence of micrometastases in cervical lymph nodes from squamous cell carcinomas of the head and neck was studied using routine histopathological examination. Micrometastases were found in 66 lymph nodes in 41 of the 92 tumor-positive neck dissection specimens. The detection of these micrometastases influenced postoperative treatment in 3 of the 77 patients with neck node metastases. The value of additional sectioning for detecting micrometastases was thus assessed. Sectioning at a deeper level in 600 originally histopathologically negative lymph nodes from 64 patients revealed 7 additional micrometastases in 5 patients. Antikeratin staining with a mixture of two monoclonal antibodies (AE1 and AE3) revealed 4 micrometastases in 739 originally histopathologically negative lymph nodes in 3 of 13 patients studied. Because of the unknown prognostic significance of micrometastases and the consequent arbitrary consequences for postoperative treatment, present findings show that the extra workload of immunostaining and deeper sectioning does not warrant their routine use in clinical practise.

Topics: Carcinoma, Squamous Cell; Head and Neck Neoplasms; Humans; Immunohistochemistry; Keratins; Lymph Node Excision; Lymph Nodes; Lymphatic Metastasis; Neck; Prognosis

Formalin-fixed, paraffin-embedded biopsy specimens of 17 cases of squamous cell carcinoma of Marjolin's ulcer (SCC-MU), 6 cases of common SCC (SCC), and 5 cases of basal cell carcinoma (BCC) were stained with three monoclonal antikeratin antibodies (CAM 5.2, MAK-6, and MA-903), a monoclonal antivimentin antibody (V9), and a polyclonal anticarcinoembryonic antigen antiserum (A115). Neoplastic cells of SCC-MU, SCC, and BCC showed consistently negative staining for CAM 5.2. A wide range of reactivity, from negative to diffuse strong positivity, among neoplastic cells of SCC-MU and SCC was noted with MAK-6. Alternatively, neoplastic cells of SCC-MU, SCC, and BCC consistently showed diffuse moderate to strong reactivity with MA-903. These findings imply that SCC-MU has largely high-molecular-weight keratins. They also showed a wide range of reactivity with V9. However, neoplastic cells of five of the six SCC and five cases of BCC were negative for V9. These findings suggest that neoplastic cells of SCC-MU contain vimentin in higher frequency than in the more usual SCC.

Topics: Adult; Aged; Aged, 80 and over; Antibodies, Monoclonal; Biopsy; Carcinoembryonic Antigen; Carcinoma, Basal Cell; Carcinoma, Squamous Cell; Cicatrix; Female; Humans; Immunohistochemistry; Keratins; Male; Middle Aged; Skin; Skin Neoplasms; Ulcer; 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

The distribution of the 52 kDa keratin 13 was evaluated immunohistochemically, using the AE8 monoclonal antibody. Various squamous and transitional cell epithelial lesions and representative control tissues were studied. This antibody performed adequately in formalin-fixed and paraffin-embedded tissue, but like keratin immunohistochemistry in general, required protease pretreatment. Keratin 13 was found consistently in the suprabasal layers of squamous epithelia of oral cavity, tonsils, larynx, esophagus, lower female genital tract, and transitional urothelium, but it was absent in the epidermis. Generally, various forms of squamous metaplasia were AE8-positive. In dysplasia, AE8 reactivity was considerably decreased or even absent despite the presence of apparent suprabasal maturation. In differentiated squamous cell carcinomas, AE8 immunoreactivity was usually limited to a few cells in the center of the keratinized foci. However, in 10% of squamous cell carcinomas, a significant number of tumor cells was positive. Only well-differentiated urothelial carcinomas showed AE8 immunoreactivity, while poorly differentiated tumors were negative. Interestingly, a Brenner's tumor showed a high number of AE8-positive epithelial cells. Our results show that the expression of keratin 13, as immunohistochemically determined by AE8 antibody, is significantly down-regulated in squamous cell malignancies. Its possible value as an adjunct to diagnosis of dysplasia should be investigated further.

Topics: Antibodies, Monoclonal; Carcinoma, Squamous Cell; Carcinoma, Transitional Cell; Cervix Uteri; Female; Humans; Immunohistochemistry; Keratins; Larynx; Metaplasia

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

Retinoids (vitamin A analogues) inhibit the squamous differentiation of normal and malignant epithelial cells. This study investigated the ability of the head-and-neck squamous-cell carcinoma (HNSCC) cell line 1483 to undergo squamous differentiation in the absence and presence of beta-all-trans retinoic acid (RA). The growth of these cells in culture is accompanied by an increase in keratinocyte transglutaminase, involucrin and keratin KI, 3 established markers of squamous cell differentiation. Higher levels of these differentiation markers were detected in cells cultured in delipidized serum (DLS), from which endogenous retinoids have been extracted, than in cells cultured in fetal bovine serum (FBS), which contains retinoids. Treatment with I microM RA decreased the levels of the various differentiation markers in cells cultured in either FBS or DLS as revealed by immunofluorescent labelling of permeabilized cells and by immunoblotting of cell extracts using specific monoclonal or polyclonal antibodies. The cells' ability to cross-link proteins to form envelopes under the plasma membrane was stimulated in the presence of calcium ionophore but inhibited by RA. These results indicate that the malignant 1,483 HNSCC cells recapitulate the main characteristics of normal squamous-cell differentiation in culture and that RA suppresses this differentiation as it does in normal keratinizing epithelial cells.

Topics: Calcium; Carcinoma, Squamous Cell; Cell Differentiation; Fluorescent Antibody Technique; Head and Neck Neoplasms; Humans; Immunoblotting; Ionophores; Keratinocytes; Keratins; Neoplasm Proteins; Protein Precursors; Retinoids; Transglutaminases; Tretinoin; Tumor Cells, Cultured

40 invasive carcinomas and 80 preinvasive lesions of the uterine cervix were studied immunohistochemically; 40 benign lesions served as controls. On histological and immunohistochemical examination, invasive and preinvasive carcinomas were subdivided in the squamous (large cell, ectocervical) type and the reserve cell (small, large or clear cell, endocervical) type. Immunohistochemically, 100% of the invasive and preinvasive squamous cell carcinomas were positive with anticytokeratins 13, 14, 16 and negative with anticytokeratin 8 and anti-CEA. Most of the invasive and preinvasive reserve cell carcinomas showed a coexpression of cytokeratins 13, 14, 16, 8 and CEA. The subdivision of invasive carcinomas of the ecto- and endocervix into squamous cell and reserve cell types made by means of their structural differences is substantiated and re-evaluated by their immunohistochemical reactions. Both types of carcinomas retain the complex pattern of cytokeratins shown by their cells of origin. The reserve cell carcinomas, in addition, acquire a coexpression for CEA that indicates malignant transformation. The subdivision is of clinical importance because both types of carcinomas vary in their mode and speed of invasion and spread and in their association with HPV infection.

Topics: Carcinoembryonic Antigen; Carcinoma, Squamous Cell; Female; Humans; Immunoenzyme Techniques; Keratins; Neoplasm Invasiveness; Precancerous Conditions; Uterine Cervical Neoplasms

In order to obtain a more objective method to evaluate epithelial disorders and carcinomas of the hypopharynx, the expression pattern of cytokeratins (CKs) was investigated by ABC technique using several kinds of monoclonal antibodies that react monospecifically with each subclass of CKs. In normal epithelia, CK-19 was strongly positive in the basal layer but apparently reduced in suprabasal layers and completely negative in superficial layers, while CK-13 showed a striking contrast to CK-19, being expressed within the whole thickness of epithelia except only in the basal layer. These 2 subclasses were also observed in "abnormal" epithelia, and characteristic changes of their combination were demonstrated in proportion to the histological gradings. In invasive carcinomas, CK-19 was strongly positive in all carcinoma cells of poorly differentiated carcinomas. It was sporadically positive in moderately differentiated carcinomas, the more differentiated the more sporadic. It was completely negative in well differentiated carcinomas. CK-13, on the other hand, was negative in poorly differentiated carcinomas but positive in keratinized cells of moderately or well differentiated carcinomas. Strong expression of CK-1 was observed only in well keratinized cells of hyperkeratotic epithelia and well differentiated carcinomas. These characteristic findings are consistently observed in all samples and, then, may be useful in evaluating epithelial disorders and carcinomas of the hypopharynx, when used in conjunction with standard histological techniques. It seems most likely that these results play a part in investigating normal and abnormal processes of cell differentiation.

Topics: Carcinoma, Squamous Cell; Epithelium; Humans; Hypopharyngeal Neoplasms; Hypopharynx; Immunohistochemistry; Keratins; Precancerous Conditions

A system of histological grading based on retrospective analysis of 239 patients with squamous cell carcinoma of the penis is presented. A new scoring system with 4 histological grades was used. The results of this study confirm previous reports that penile cancer is usually a highly (50%) or moderately (29%) differentiated squamous cell carcinoma. Poorly differentiated carcinomas and cancers of other types are very rare. The new grading system was found to be practical and a correlation between histological grade, clinical findings and prognosis was established. Patients with grade 1 tumours had an exceptionally favourable prognosis, with more than 80% being long-term survivors; for these patients, treatment with delayed side effects should be avoided and new forms of treatment should be explored.

Topics: Adult; Age Factors; Aged; Carcinoma, Squamous Cell; Cell Transformation, Neoplastic; Humans; Inflammation; Keratins; Male; Methods; Middle Aged; Penile Neoplasms; Prognosis; Retrospective Studies