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目的探讨胰腺癌中微卫星不稳定性(MSI)与hMLH1启动子甲基化及蛋白表达之间的联系,揭示胰腺癌发生的分子机制。方法从35例胰腺癌患者的正常胰腺组织、癌组织中提取DNA;SSCP法检测标本中微卫星不稳定性发生情况;免疫组织化学法检测错配修复基因 hMLH1在胰腺癌中的表达情况;MSP法检测hMLH1基因启动子甲基化状态。结果 35例胰腺癌中微卫星高度不稳定7例,低度不稳定14例,稳定11例,正常组织中没有出现微卫星不稳定,两者之间差异有统计学意义(P<0．05)。hMLH1在微卫星不稳定胰腺癌组织中常为缺失表达,在微卫星稳定胰腺癌组织中呈正常表达。35例胰腺癌中hMLH1启动子CpG岛甲基化发生率为60％ (21／35),正常组织中未发现甲基化,两者之间差异有统计学意义(P<0．05)。结论与胰腺癌有关的错配修复基因hMLH1启动子CpG岛甲基化是hMLH1基因失活的重要机制,而hMLH1的表达失活则可能导致MSI的产生,促进胰腺癌的发生。
Objective To investigate the relationship between microsatellite instability (MSI) and hMLH1 promoter methylation and protein expression in pancreatic cancer and to reveal the molecular mechanism of pancreatic cancer. Methods DNA was extracted from normal pancreatic tissues and cancerous tissues of 35 patients with pancreatic cancer. The incidence of microsatellite instability was detected by SSCP method. The expression of mismatch repair gene hMLH1 in pancreatic cancer was detected by immunohistochemistry. The expression of MSP Methylation status of hMLH1 gene promoter. Results In 35 cases of pancreatic cancer, microsatellite instability was found in 7 cases, low instability in 14 cases and stable in 11 cases. There was no microsatellite instability in normal tissues, the difference was statistically significant (P <0.05 ). hMLH1 is often deleted in microsatellite instability pancreatic cancer tissues and expressed normally in microsatellite-stabilized pancreatic cancer tissues. The methylation of CpG island of hMLH1 promoter in 35 cases of pancreatic cancer was 60% (21/35), no methylation was found in normal tissues, the difference was statistically significant (P <0.05). Conclusion CpG island methylation of the mismatch repair gene hMLH1 associated with pancreatic cancer is an important mechanism of inactivation of hMLH1 gene. However, the inactivation of hMLH1 may lead to the production of MSI and promote the development of pancreatic cancer.