胃癌中p16蛋白表达和p16基因启动子甲基化的研究

p16 protein expression and promoter methylation of p16 gene in gastric cancer

目的:探讨胃癌中p16基因的失活机制。方法:采用免疫组织化学SP方法检测40例胃癌组织和43例正常胃黏膜组织中p16蛋白的表达情况,采用甲基化特异性PCR(MSP)方法研究40例胃癌组织和35例正常胃黏膜组织p16基因启动子的甲基化状况。结果:23例胃癌组织的p16基因启动子发生了甲基化,甲基化发生率为58%,正常胃黏膜组织中未发现甲基化,两组间比较差异有显著性(P<0.01)。31例胃癌组织中的p16蛋白表达阴性,正常胃黏膜组织中6例表达阴性,两组间差异有显著性(P<0.01)。胃癌组织中,MSP方法和免疫组织化学方法结果间差异无显著性(P>0.05)。结论:胃癌的发生与p16基因失活关系密切,启动子甲基化可能抑制了蛋白的表达,这种途径可能是胃癌中p16基因失活的重要机制。

Objective To investigate the mechanism of p16 gene inactivation in gastric cancer. Methods The expression of p16 protein in the tissues from 40 gastric cancers and 43 normal gastric mucosas were detected by immunohistochemical method, so were the promoter region methylation of p16 gene in the specimens from 40 gastric cancers and 35 normal gastric mucosas by methylation-specific PCR （MSP）. Results The promoter region of p16 gene was methylated in 23 specimens of carcinoma, with a methylation frequency of 58%, while no methylation was detectable in the normal gastric mucosas, revealing a significant difference between cancerous tissue and normal mucosa （P〈0.01）. There were significant differences in the occurrence of loss of p16 protein expression between the cancerous tissue and the normal mucosa （31 vs 6,P 〈 0,01）. The outcomes of detecting the cancerous tissue did not differ significantly between immunohistochemistry and MSP （P 〉 0.05）. Conclusions Gastric carcinogenesis is closely associated with p16 gene inactivation. Promoter methylation may inhibit the level of protein expression which can be an important mechanism of p16 gene inactivated in gastric cancer.