MET receptor is overexpressed but not mutated in oral squamous cell carcinomas.

Oral squamous cell carcinoma (SCC) is a neoplasm characterized by a high degree of local invasion and an elevated rate of metastasis to cervical lymph nodes. It has been shown that the Hepatocyte Growth Factor/Scatter Factor Receptor Met is constitutively activated in many human tumors of epithelial origin and that it plays a critical role to confer invasive properties to neoplastic cells. Most frequently, Met activation is due to receptor overexpression, but also point mutations in the tyrosine kinase domain can lead to deregulated activation. Here we show that in all the primary tumors examined this receptor is overexpressed. Direct sequencing of Met mRNAs failed to find any activating mutation in its intracellular domain. Moreover, in cell lines derived from squamous cell carcinomas, HGF-induced activation of Met resulted in the acquisition of invasive properties. All together these data suggest that the MET oncogene is involved in progression of squamous cell carcinoma toward an invasive-metastatic behavior.     

Cytokeratins in normal lung and lung carcinomas. I. Adenocarcinomas, squamous cell carcinomas and cultured cell lines

The various epithelial cells of the lower respiratory tract and the carcinomas derived from them differ markedly in their differentiation characteristics. Using immunofluorescence microscopy and two-dimensional gel electrophoresis of cytoskeletal proteins from microdissected tissues we have considered whether cytokeratin polypeptides can serve as markers of cell differentiation in epithelia from various parts of the human and bovine lower respiratory tract. In addition , we have compared these protein patterns with those found in the two commonest types of human lung carcinoma and in several cultured lung carcinoma cell lines. By immunofluorescence microscopy, broad spectrum antibodies to cytokeratins stain all epithelial cells of the respiratory tract, including basal, ciliated, goblet, and alveolar cells as well as all tumor cells of adenocarcinomas and squamous cell carcinomas. However, in contrast, selective cytokeratin antibodies reveal cell type-related differences. Basal cells of the bronchial epithelium react with antibodies raised against a specific epidermal keratin polypeptide but not with antibodies derived from cytokeratins characteristic of simple epithelia. When examined by two-dimensional gel electrophoresis, the alveolar cells of human lung show cytokeratin polypeptides typical of simple epithelia (nos. 7, 8, 18 and 19) whereas the bronchial epithelium expresses, in addition, basic cytokeratins (no. 5, small amounts of no. 6) as well as the acidic polypeptides nos. 15 and 17. Bovine alveolar cells also differ from cells of the tracheal epithelium by the absence of a basic cytokeratin polypeptide. All adenocarcinomas of the lung reveal a "simple-epithelium-type" cytokeratin pattern (nos. 7, 8, 18 and 19). In contrast, squamous cell carcinomas of the lung contain an unusual complexity of cytokeratins. We have consistently found polypeptides nos. 5, 6, 8, 13, 17, 18 and 19 and, in some cases, variable amounts of cytokeratins nos. 4, 14 and 15. Several established cell lines derived from human lung carcinomas (SK-LU-1, Calu -1, SK-MES-1 and A-549) show a uniform pattern of cytokeratin polypeptides (nos. 7, 8, 18 and 19), similar to that found in adenocarcinomas. In addition, vimentin filaments are produced in all the cell lines examined, except for SK-LU-1.(ABSTRACT TRUNCATED AT 400 WORDS)     

Elevated GAPDH expression is associated with the proliferation and invasion of lung and esophageal squamous cell carcinomas

Glyceraldehyde‐3‐phosphate dehydrogenase, is one of the most investigated housekeeping genes and widely used as an internal control in analysis of gene expression levels. The present study was designed to assess whether GAPDH is associated with cancer cell growth and progression and, therefore may not be a good internal control in cancer research. Our results from clinical tissue studies showed that the levels of GAPDH protein were significantly up‐regulated in lung squamous cell carcinoma tissues, compared with the adjacent normal lung tissues, and this was confirmed by western blotting and immunohistochemistry. GAPDH knockdown by siRNA resulted in significant reductions in proliferation, migration, and invasion of lung squamous carcinoma cells in vitro. In a nude mouse cancer xenograft model, GAPDH knockdown significantly inhibited the cell proliferation and migration/invasion in vivo. In summary, GAPDH may not be an appropriate internal control for gene expression studies, especially in cancer research. The role of GAPDH in cancer development and progression should be further examined in pre‐clinical and clinical studies.     

BCL10 expression is unrelated to clinico-pathological parameters or prognoses for oral squamous cell carcinomas

BCL-10 (B-cell lymphoma 10) has been linked to a pro-apoptotic gene in mucosa-associated lymphoid tissue (MALT) lymphomas. We describe the expression of BCL10 in oral squamous cell carcinoma (OSCC) and its relation to clinical, pathological and prognostic parameters. We carried out a retrospective study of 50 patients in Spain who were diagnosed with OSCC. We constructed a tissue microarray of the samples to study the expression of BCL10 using immunohistochemistry. Diffuse and homogeneous staining was observed in the nuclei and cytoplasms of most neoplastic cells of the vast majority of tumors and no significant differences were seen in different areas of the tumors. The expression was unrelated to any clinical or pathological parameters including tumor stage. The intra-class coefficient was 0.97, which indicates the minimal variability among the determinations.     

BCL10 expression is unrelated to clinico-pathological parameters or prognoses for oral squamous cell carcinomas

Abstract

BCL-10 (B-cell lymphoma 10) has been linked to a pro-apoptotic gene in mucosa-associated lymphoid tissue (MALT) lymphomas. We describe the expression of BCL10 in oral squamous cell carcinoma (OSCC) and its relation to clinical, pathological and prognostic parameters. We carried out a retrospective study of 50 patients in Spain who were diagnosed with OSCC. We constructed a tissue microarray of the samples to study the expression of BCL10 using immunohistochemistry. Diffuse and homogeneous staining was observed in the nuclei and cytoplasms of most neoplastic cells of the vast majority of tumors and no significant differences were seen in different areas of the tumors. The expression was unrelated to any clinical or pathological parameters including tumor stage. The intra-class coefficient was 0.97, which indicates the minimal variability among the determinations.     

Screening for lung cancer.

The survival from bronchogenic carcinoma is highly dependent upon stage at the time of treatment. This is particularly true for squamous cell carcinoma, adenocarcinoma, and large cell carcinoma, but holds true for small cell carcinoma as well. The problem presented to the medical profession has been to find a practical means of detecting lung cancer while it is still at an early stage. Three studies in progress have indicated that a larger proportion of the patients may be found to have early stage lung cancer when screened with a combination of chest X-rays and sputum cytology. However, the detection of these early stage cases has not yet been translated into an improvement in the overall mortality rate from lung cancer.     

Polymorphisms in the aurora-A gene is not associated with lung cancer in the Turkish population

Lung cancer, a complex neoplasm of lung tissue, is influenced by several environmental and genetic factors which could be changed in each individual. Aurora-A gene is related to mitotic events such as: chromosome instability, cell cycle regulation, spindle formation, and kinetechore-microtubule connections. This centrosomic serine/threonine kinase provides a strong connection between mitotic errors and carcinogenesis. The genomic alterations such as single nucleotide polymorphisms (SNPs) can exist in molecular pathways of lung cancer. Therefore, we evaluated the role of genetic polymorphisms of Aurora-A gene in the lung cancer in the Turkish population. Genotypes of five Aurora-A polymorphisms (F31I, V57I, 6328G/A, P50L, and S104L) were determined in 102 healty controls and 102 new diagnosed lung cancer cases. All samples were genotyped with DNA sequence technique. There were not any genotype variations in P50L, S104L, and 6328G/A polymorphisms. The frequencies of both genotypes F31I and V57I in lung cancer patients were not significantly different from those in controls (p > 0.05). A multivariable logistic regression analysis including patient characteristics, such as age and gender, did not change the results.