增强的转化生长因子α-表皮生长因子受体（TGFα-EGFR）表达及P53基因改变促成胃肿瘤的侵袭性。

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

作者信息

Espinoza Luis A, Tone Luiz Gonzaga, Neto José Barbieri, Costa Roberto Silva, Wang Qiming J, Ballejo Gustavo

机构信息

Department of Genetics, School of Medicine of Ribeirão Preto, Universidade de Sao Paulo, Ribeirão Preto, SP 1404900, Brazil.

出版信息

Cancer Lett. 2004 Aug 20;212(1):33-41. doi: 10.1016/j.canlet.2004.03.037.

DOI:10.1016/j.canlet.2004.03.037

PMID:15246559

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 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.

摘要

我们确定了p53、p16(INK4)和p21(WAF1/CIP1)表达的改变是否会影响共表达转化生长因子α（TGFα）和表皮生长因子受体（EGFR）的一部分胃腺癌的侵袭性。在早期和晚期腺癌中均观察到TGFα - EGFR免疫阳性（26%），其中88%显示p53免疫反应性。单链构象多态性（SSCP）分析显示，在这些肿瘤中81%的p53基因在第5 - 8外显子发生突变。在深度浸润性肿瘤中，p53免疫反应强度显著更高（P < 0.013）。在共表达TGFα - EGFR的样本中，93%和76%检测到p16(INK4)和p21(WAF1/CIP1)免疫反应性，但水平与p53及其他临床病理参数无关。我们得出结论，潜在依赖TGFα - EGFR自分泌环生长的胃腺癌在存在异常p53时表现出更强的侵袭性。