Enhanced TGFα-EGFR expression and P53 gene alterations contributes to gastric tumors aggressiveness

• Published in: Cancer letters Vol. 212; no. 1; pp. 33 - 41
• Main Authors: Espinoza, Luis A, Tone, Luiz Gonzaga, Neto, José Barbieri, Costa, Roberto Silva, Wang, Qiming J, Ballejo, Gustavo
• Format: Journal Article
• Language: English
• Published: Elsevier Ireland Ltd 01.08.2004
• Subjects: EGFR; Gastric adenocarcinomas; p16 INK4; p21 WAF1/CIP1; p53; TGFα; TGFα; Gastric adenocarcinomas; p16 INK4; EGFR; p53; p21 WAF1/CIP1
• ISSN: 0304-3835; 1872-7980
• DOI: 10.1016/j.canlet.2004.03.037

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.