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目的 探讨错配修复基因hMLH1和hMSH2表达在大肠癌发生中的作用及其与细胞增殖间的关系。方法 采用免疫组织化学染色法对 63例大肠腺瘤、2 0例腺瘤癌变和 2 0例大肠癌的hMLH1和hMSH2、PCNA和Ki 67表达进行检测。结果 大肠腺瘤、癌变和大肠癌中hMLH1、hMSH2阳性表达率逐渐降低 ,与正常大肠粘膜相比相差显著 (P <0 0 1) ,腺瘤不典型增生分级增加其阳性率亦逐渐降低。腺瘤不典型增生Ⅱ、Ⅲ级、腺瘤癌变和大肠癌中hMSH2 - 者 ,其PCNALI显著低于hMSH2 + 者 (P <0 0 5 ) ;hMSH2表达缺失的大肠癌 ,其Ki 67LI较阳性者显著降低 (P <0 0 5 )。 3组大肠病变hMLH1阳性与阴性表达组间 ,其PCNALI和Ki 67LI无差异显著性。结论 提示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 ,并对大肠肿瘤细胞增殖活性有所影响
Objective To investigate the role of mismatch repair genes hMLH1 and hMSH2 in the development of colorectal cancer and its relationship with cell proliferation. Methods The expressions of hMLH1, hMSH2, PCNA and Ki 67 in 63 cases of colorectal adenoma, 20 cases of adenoma and 20 cases of colorectal cancer were detected by immunohistochemical staining. Results The positive rates of hMLH1 and hMSH2 in colorectal adenoma, canceration and colorectal cancer decreased gradually, which were significantly different from those in normal colorectal mucosa (P <0.01). The positive rate of hMLH1 and hMSH2 in colorectal adenoma also decreased gradually with the increase of atypical hyperplasia grade. (P <0.05). The expression of hMSH2 in colorectal cancer patients with more negative expression of hMPH2 was higher than that of hMSH2 + patients with hMSH2- Significantly lower (P <0.05). There was no significant difference between PCNALI and Ki 67LI in 3 groups of hMLH1 positive and negative expression of colorectal lesions. The results suggest that the mismatch repair gene mutation or loss of function is associated with the occurrence of colorectal cancer and may be an early event in the process of colorectal cancer and may affect the proliferation activity of colorectal cancer cells