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American Journal of Pathology, Vol 142, 1155-1162, Copyright © 1993 by American Society for Investigative Pathology

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In vitro and in vivo expressions of transforming growth factor-alpha and tyrosine kinase receptors in human non-small-cell lung carcinomas

C Liu and MS Tsao
Department of Pathology, Montreal General Hospital, Quebec, Canada.

The mRNA expression of transforming growth factor-alpha (TGF-alpha), epidermal growth factor receptor (EGFR), c-erbB-2 and c-met proto- oncogenes in eight newly established cell lines and 29 primary tumors of human non-small-cell lung carcinoma (NSCLC) have been investigated. In vitro, the expressions of TGF-alpha, c-erbB-2, and c-met were consistently high in adenocarcinomas, while EGFR was expressed highest in a squamous cell carcinoma cell line. There was linear correlation between the levels of expression of TGF-alpha and EGFR or c-erbB-2, and between EGFR and c-erbB-2. The c-met expression was also correlated with those of TGF-alpha, EGFR, and c-erbB-2. In vivo, The mean mRNA levels of TGF-alpha, EGFR, and c-met, but not c-erbB-2, were higher in carcinomas than in normal lung tissues (2.8, 1.7, and 3.0 times, respectively); however, only adenocarcinomas expressed a significantly higher level of c-erbB-2 than their corresponding normal tissues (2.2 times). In 20 patients whose paired normal and tumor tissue were examined, the percentage of cases with greater than twofold increase in expression in carcinomas than normal were 55% for both TGF-alpha and EGFR, 30% for c-erbB-2, and 47% for c-met. Among the histological subtypes of NSCLC, a higher percentage of adenocarcinomas than squamous cell carcinomas over-expressed these genes, especially c-erbB-2 and c- met. Over-expression is rarely the result of gene amplification. The results suggest a differential expression of growth factor and receptor genes among the various histological subtypes of NSCLCs.

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