Enhanced TGF$alpha;-EGFR expression and P53 gene alterations contributes to gastric tumors aggressiveness

Abstract

We determined whether alterations in the expression of p53, p16 INK4 and p21 WAF1/CIP1 influence the invasiveness of a subset of gastric adenocarcinomas co-expressing TGFα and EGFR. Immunopositivity for TGFα-EGFR (26%) was observed in both early and advanced adenocarcinomas, and 88% of these showed immunoreactivity for p53. SSCP analysis revealed that in 81% of these tumors the p53 gene was mutated in exons 5–8. The intensity of p53 immunoreactivity was significantly higher ( P <0.013) in deeply invasive tumors. p16 INK4 and p21 WAF1/CIP1 immunoreactivity was detected in 93 and 76% of the samples co-expressing TGFα-EGFR but the levels were not correlated with those of p53 and other clinico-pathological parameters. We conclude that gastric adenocarcinomas potentially dependent upon the TGFα-EGFR autocrine loop for growing exhibit increased aggressiveness in the presence of aberrant p53.