p53 genetic abnormalities and P-glycoprotein expression in stump and primary gastric carcinomas.
p53 genetic abnormalities and P-glycoprotein expression in stump and primary gastric carcinomas.
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发表时间：
2007-03
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通讯作者：
I. Oliver;J. Lacueva;V. Barberá;T. Caldés;A. Teruel;D. Costa;J. Medrano;T. Pérez-Vázquez;Paz Quesada;J. Ferragut;R. Calpena
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作者：
I. Oliver;J. Lacueva;V. Barberá;T. Caldés;A. Teruel;D. Costa;J. Medrano;T. Pérez-Vázquez;Paz Quesada;J. Ferragut;R. Calpena
背景/目的p53基因的遗传异常可能在残胃癌和胃内型原发性胃癌的发生中起重要作用。此外，它们可以调节P-gp表达，产生化学抗性。本研究旨在分析两种肿瘤中p53基因异常及p53基因状态对P-gp表达的影响。方法：对42例胃癌石蜡包埋标本进行研究，其中GSC 17例，IPGC 25例。PCR产物直接测序法检测P53基因第5-9外显子的遗传异常。P53和P-糖蛋白（P-gp）通过标准的链霉亲和素-生物素免疫过氧化物酶法进行评估。使用抗p53 D 07和抗P-gp C494作为一抗。结果发现14例p53突变，其中GSC 5例（29%），IPGC 9例（36%）。十三个突变是碱基对取代，产生氨基酸序列的变化。8个突变位于外显子7（57%）。12例GSC（71%）和15例IPGC（60%）的P53核表达阳性。只有两个癌（1 IPGC和1 GSC）窝藏p53突变没有显示任何p53的表达。除1例有p53突变的胃癌外，其余胃癌均呈中等或高水平P-gp表达。而P-gp表达在p53突变组和非p53突变组之间无显著性差异。结论：在GSC和IPGC中发现的p53基因改变可能起源于相似的发病途径。p53基因状态和P-gp表达之间没有相关性，尽管大多数携带p53突变的癌显示中等或高P-gp表达。
BACKGROUND/AIMS Genetic abnormalities of the p53 gene may play a major role in the carcinogenesis of gastric stump carcinomas (GSC) and intestinal-type primary gastric carcinomas (IPGC). Also, they may modulate P-gp expression producing chemoresistance. The aim of this article is to analyze p53 genetic abnormalities and the influence of p53 gene status on P-gp expression in both types of carcinomas. METHODOLOGY Forty-two paraffin-embedded samples of gastric carcinomas corresponding to 17 GSC and 25 IPGC were studied. P53 genetic abnormalities in exon 5-9 were screened by direct sequencing of PCR products. P53 and P-glycoprotein (P-gp) were assessed by a standard streptavidin-biotin immunoperoxidase method. Anti-p53 DO7 and anti-P-gp C494 were used as primary antibodies. RESULTS Fourteen p53 mutations were found, 5 in GSC (29%) and 9 in IPGC (36%). Thirteen mutations were base-pair substitutions that produced a change in the amino acid sequence. Eight mutations were located at exon 7 (57%). P53 nuclear immunopositivity was observed in 12 GSC (71%) and 15 IPGC (60%). Only two carcinomas (1 IPGC and 1 GSC) harboring a p53 mutation did not show any p53 expression. All except one of the gastric carcinomas having a p53 mutation showed medium or high P-gp expression. However, there was no difference in P-gp expression between tumors with and without p53 mutation. CONCLUSIONS The p53 genetic alterations found in GSC and IPGC could originate from a similar pathogenetic pathway. No association was demonstrated between p53 gene status and P-gp expression, although most of the carcinomas harboring a p53 mutation showed medium or high P-gp expression.