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

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 TGFalpha and EGFR. Immunopositivity for TGFalpha-EGFR (26%) was observed in both early and advanced adenocarcinomas, and 88% of the...

Full description

Saved in:
Bibliographic Details
Published in:Cancer letters 2004-08, Vol.212 (1), p.33-41
Main Authors: Espinoza, Luis A, Tone, Luiz Gonzaga, Neto, José Barbieri, Costa, Roberto Silva, Wang, Qiming J, Ballejo, Gustavo
Format: Article
Language:English
Subjects:
Adenocarcinoma - genetics
Adenocarcinoma - pathology
Cyclin-Dependent Kinase Inhibitor p16 - biosynthesis
Cyclin-Dependent Kinase Inhibitor p16 - pharmacology
Cyclin-Dependent Kinase Inhibitor p21
Cyclins - biosynthesis
Cyclins - pharmacology
DNA Mutational Analysis
Enzyme Inhibitors - pharmacology
Genes, p53
Humans
Immunohistochemistry
Neoplasm Invasiveness
Receptor, Epidermal Growth Factor - biosynthesis
Signal Transduction
Stomach Neoplasms - genetics
Stomach Neoplasms - pathology
Transforming Growth Factor alpha - biosynthesis
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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 TGFalpha and EGFR. Immunopositivity for TGFalpha-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 TGFalpha-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 TGFalpha-EGFR autocrine loop for growing exhibit increased aggressiveness in the presence of aberrant p53.
ISSN:0304-3835