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 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.
Espinoza
Luis A
LA
Department of Genetics, School of Medicine of Ribeirão Preto, Universidade de Sao Paulo, Ribeirão Preto, SP 1404900, Brazil. lae2@georgetown.edu
Tone
Luiz Gonzaga
LG
Neto
José Barbieri
JB
Costa
Roberto Silva
RS
Wang
Qiming J
QJ
Ballejo
Gustavo
G
D000230:Adenocarcinoma / Q000235:genetics* / Q000473:pathology*; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000096:biosynthesis / Q000494:pharmacology; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000096:biosynthesis / Q000494:pharmacology; D004252:DNA Mutational Analysis; D004791:Enzyme Inhibitors / Q000494:pharmacology; D066246:ErbB Receptors / Q000096:biosynthesis*; D016158:Genes, p53; D006801:Humans; D007150:Immunohistochemistry; D009361:Neoplasm Invasiveness; D015398:Signal Transduction; D013274:Stomach Neoplasms / Q000235:genetics* / Q000473:pathology*; D016211:Transforming Growth Factor alpha / Q000096:biosynthesis*
C493956:CDKN1A protein, human; D019941:Cyclin-Dependent Kinase Inhibitor p16; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D004791:Enzyme Inhibitors; D016211:Transforming Growth Factor alpha; D066246:ErbB Receptors