hMLH1基因甲基化与微卫星不稳定在散发性结肠癌中的意义

摘要

Objective To investigate hMLH1 gene methylation and microsatellite instability(MSI) in sporadic colon cancer and their relationship with clinicopathological features.Methods The fresh resected tumor tissues of 60 cases with sporadic colon cancer and corresponding normal mucosa tissues were collected to extract DNA.The level of hMLH1 gene methylation and status of MSI were detected by PCR.The relationship between expression of hMLH1 gene promoter methylation and clinicopathological factors and the relationship between MSI and methylation were analyzed.Results Among 60 cases,hMLH1 gene methylation was positive in 18 cases,which was significantly correlated with the age and location of the tumors (P ＜ 0.05).MSI was positive in 14 cases,including 10 cases of hMLH1 gene methylation in tumor tissues detected at the same time.In 42 cases of non hMLH1 methylation tumor tissues,MSI was positive only in 4 cases(P ＜ 0.05).Conclusion The hMLH1 gene methylation and MSI are closely related in patients with sporadic colon cancer,which may be one of the important pathogenesis of sporadic colon cancer.%目的 探讨人类错配修复基因(hMLH1)甲基化和微卫星不稳定性(MSI)在散发性结肠癌中的表达及其与临床病理特征的关系.方法 收集60对散发性结肠癌手术切除新鲜肿瘤组织及自身正常黏膜组织,提取DNA并PCR扩增检测hMLH1基因甲基化水平和MSI状态,分析二者间的表达、hMLH1基因启动子甲基化与临床病理特征关系,以及MSI与甲基化关系.结果 60例研究对象中,肿瘤组织hMLH1基因启动子甲基化表阳性率为30.0％(18/60),正常组织中无hMLH1基因启动子甲基化表达阳性例数,差异有统计学意义(P＜0.05).hMLH1基因启动子甲基化与患者发病年龄及肿瘤部位有关(P＜0.05).MSI阳性率为23.3％ (14/60),正常组织中无MSI表达阳性例数,差异有统计学意义(P＜0.05).在18例甲基化肿瘤组织中MSI阳性率为55.6％(10/18),而在42例非甲基化肿瘤组织中MSI阳性例数为4例(9.5％),差异有统计学意义(P＜0.05).结论 hMLH1基因甲基化和MSI在散发性结肠组织癌与自身正常黏膜组织的阳性表达水平存在显著差异,hMLH1基因启动子甲基化与MSI有关.