散发性结直肠癌hMSH_2的表达及与MIN的关系

Association between expression of hMSH2 and microsatellite instability in sporadic colorectal cancer

目的：观察ｈＭＳＨ２表达改变和微卫星不稳定性（ＭＩＮ）在散发性结直肠癌发生中的作用。方法：应用免疫组化法检测７７例散发性结直肠癌及癌旁正常粘膜组织中ｈＭＳＨ２蛋白的表达，并用ＰＣＲ变性聚丙烯酰胺凝胶电泳银染法检测肿瘤组织的ＭＩＮ状况。结果：肿瘤组织中ｈＭＳＨ２蛋白表达阳性率为５５％，远低于癌旁正常粘膜９４％的阳性率。正常粘膜中ｈＭＳＨ２蛋白均有核内定位，而肿瘤组织中定位呈多样性，浆及浆核型增多。肿瘤组织中ｈＭＳＨ２蛋白的表达状况与表示肿瘤预后的临床病理参数没有统计学关系。与肿瘤的ＭＩＮ资料比较，发现ＲＥＲ＋肿瘤ｈＭＳＨ２蛋白表达阳性率为２８％，而ＲＥＲ－肿瘤为７１％，显示ｈＭＳＨ２蛋白表达与ＭＩＮ间有较好的一致性。结论：ｈＭＳＨ２基因改变在散发性结直肠癌的发生中起着一定的作用。

Purpose To evaluate the role of hMSH2 in the pathogenesis of sporadic colorectal carcinoma. Methods The protein expression of hMSH2 was examined by immunohistochemistry in paraffinembedded normal and neoplastic tissues from 77 sporadic colorectal cancer. Results hMSH2 protein was detected in 94% normal mucosa, but only in 55% neoplastic tissues. The localization of protein was always demonstrated to be nuclear in normal tissue but more often cytoplasmic or nuclearcytoplasmic in tumor tissue. There was no significant differences in expression of protein among tumors with different clinicpathological parameters. However, the expression of hMSH2 protein was associated with tumor MIN, which was detected only in 8 of 29 RER+ tumors, but 34 of 48 RER- tumors. Conclusion These results have implications for tumorgenic mechanisms of hMSH2 gene, and suggest that examination of protein expression by immunohistochemistry may be a direct and objective method with prescreening tumors with mutations in the MMR g