大肠腺瘤及癌变组织hMLH1和hMSH2表达与细胞凋亡的研究

目的：探讨hMLH1和hMSH2基因在大肠腺瘤及其癌变中的作用，及其表达对细胞凋亡的影响。方法：采用免疫组织化学染色检测63例大肠腺瘤、20例腺瘤癌变和20例大肠癌组织hMLH1和hMSH2表达；同时采用TUNEL法检测其细胞凋亡指数（AI）。结果：大肠腺瘤、腺瘤癌变和大肠癌组织错配修复基因hMLH1、hMSH2的表达率逐渐降低，与正常大肠相比相差显著，随腺瘤不典型增生程度增加其阳性率逐渐降低；大肠腺瘤、腺瘤癌变和大肠癌中hMLH1表达缺失者细胞凋亡指数较显著高于其阳性者，且大肠腺瘤不典型增生Ⅰ、Ⅱ、Ⅲ级hMLH1-与hMLH1＋组存在差异显著；而hMSH2-与hMSH2-间AI仅大肠腺瘤组有显著性差异，不典型增生Ⅰ、Ⅱ级组hMSH2-与hMSH2＋间AI差异显著，而不典型增生Ⅲ级组hMSH2蛋白的表达阴性与阳性间AI无统计学差异。结论：DNA错配修复基因突变或功能缺失与大肠癌的发生有关，可能系大肠癌发生过程中的早期事件，且可能与大肠肿瘤细胞凋亡活性增加相关。

A study on expression of mismatch repair gene hMLH1 and hMSH2, and apoptosis in colorectal adenomas

Objective：To explore the role of hMLH1 and hMSH2 in carcinogenesis and progression of colorectal carcinoma, and the influence on apoptosis in colorectal adenoma. Methods：To investigate the expression of mismatch repair gene hMLH1 and hMSH2 by immunohistochemistry in 63 cases of colorectal adenomas,20 cases with malignant change type in adenomas and 20 cases colorectal carcinomas （CRC）, and examine their apoptosis label index（AI） by terminal deoxynucleotiyltransferase mediated dUTP nick end labing（TUNEL）. Results：The positive rate of hMLH1 and hMSH2 in colorectal adenomas, malignant change type in adenomas and CRCs were decreased gradually,and significantly lower than that in normal mucosa. With increasing dysplasia in adenomas, the expression rate of hMLH1 and hMSH2 protein decreased gradually;The AI of tumors with overexpression hMLH1 was significantly lower than that of tumors with negative hMLH1 in colorectal malignant change type in adenomas and CRCs. AI of tumors with overexpression hMLH1 were significant lower than that of tumors with negative hMLH1 in adenomas with grade Ⅰ , Ⅱ,Ⅲ dysplasia. The AI of CRCs with defective hMSH2 was signifilycant higher than that of tumors with overexpression;the AI of tumors with overexpression hMSH2 was significantly lower than that of tumors with negative hMSH2 in adenomas with grade Ⅰ , Ⅱ dysplasia. Conclusion：The mismatch repair gene mutation and abnormal function of DNA mismatch repair maybe participate in carcinogenesis of CRCs. It may be early event in carcinogenesis of CRCs, the increase of apoptosis activities in colorectal neoplasms may be related to mutation and defect of mismatch repair gene.