Co-expression of epidermal growth factor receptor and transforming growth factor-alpha is independent of ras mutations in lung adenocarcinoma

The interaction of epidermal growth factor receptor (EGFR) and its ligand t ransforming growth factor-alpha (TGF-alpha) leads to an autocrine activatio n of the ras signaling pathway and putatively its oncogenic activity. II is thus hypothesized that the co-overexpression of EGFR-TGF alpha will be red undant hence rare in tumors with oncogenic ras mutations. To test this hypo thesis, we studied by immunohistochemistry the expression of EGFR and TGF-c r. in primary non small cell lung cancers. Such putative EGFR autocrine loo p activation was found in 73% of squamous cell carcinomas that rarely devel op ras mutations. In contrast, EGFR-TGF alpha co-expression occurred with e qual frequency in adenocarcinomas irrespective of their ras genotype. The r esults indicate that EGFR autocrine loop activity in adenocarcinoma may hav e alternative signaling activities aside from the activation of ias-MAP kin ase pathway. (C) 2000 Elsevier Science Ireland Ltd. All rights reserved.