大肠癌发生中突变型P53与hMLH1表达的关系

Relationship between mutant P53 and hMLH1 in the carcinogenesis of colorectal carcinoma

[目的]探讨在大肠癌发生过程中错配修复基因hMLH1对p53基因突变的影响。[方法]采用免疫组化SP法检测37例正常大肠黏膜、32例大肠腺瘤与165例大肠癌中P53及hMLH1蛋白的表达。[结果]①正常大肠黏膜组、大肠腺瘤组与大肠癌组P53蛋白的阳性表达率分别为0%、21.9%与48.5%,三组间差异有显著性意义(P<0.05);hMLH1蛋白的阳性表达率分别为100%、87.5%与87.3%,其中正常大肠黏膜组与大肠癌组的差异有显著性意义(P<0.05)。②高中分化、低分化与黏液腺癌组中P53蛋白的阳性表达率分别为53.5%、17.6%与16.7%,其中前者与后两者的差异有显著性意义(P<0.05);hMLH1蛋白的阳性表达率分别为90.8%、70.6%与50.0%,前者明显高于后两者(P<0.05)。③在大肠腺瘤轻中度不典型增生和重度不典型增生组中P53蛋白的阳性表达率分别为18.5%与40.0%(P>0.05);hMLH1蛋白的阳性表达率分别为92.6%与60.0%(P<0.05)。④大肠腺瘤中随hMLH1蛋白的表达减少P53蛋白表达增多,但无明显相关性(P>0.05);大肠癌中两者的表达呈明显负相关(P<0.05)。[结论]大肠癌发生过程中hMLH1基因的功能异常可能是p53基因突变的原因之一。

[ Objective ] To investigate the influence of mismatch repair gene hMLH1 on the mutating of p53 gene in the carcinogenesis of coloreetal carcinoma. [ Method] hnmunohistochemical method was used to deteet P53 and hMLH1 protein in 37 cases normal coloreetal tissues,32 eases coloreetal adenomas and 165 cases colorectal carcinomas. [ Results] ①In normal colorectal tissue group, colorectal adenoma group and colorectal carcinoma group the expression rates of P53 protein were 0% ,21.9% and 48.5% respectively, difference was significantly between them（ P 〈 0.05 ） ; the expression rates of hMLH1 protein were 100% ,87.5% and 87.3% respeetively, difference was significantly between normal coloreetal tissue group and colorectal carcinoma group（P 〈0.05）. ②In high - or medium -differentiated adenocarcinoma group,low differentiated adenocarcinoma group and mucous adenocarcinoma group P53 protein positive expression rates were 53.5% , 17.6% and 16.7% respectively, difference was signifieantly between the former and the latter two groups （P 〈 0.05） ; hMLH1 positive expression rates in three groups were 90.8% ,70.6% and 50.0% respectively, the latter two groups were obviously lower than the former group（P 〈 0.05 ）. ③In moderate and severe atypical hyperplasia tissue groups, expression rates of P53 protein were 18.5% and 40.0% （ P 〉 0.05 ） ; expression rates of hMLH1 were 92.6% and 60.0% （ P 〈 0.05）. ④In colorectal adenomas, expression rates of P53 protein was increased with the decreasing of hMLH1, no significant correlation was between them（ P 〉 0. 05 ） ; negative correlation was significantly between P53 and hMLH1 in colorectal carcinoma（ P 〈 0.05 ）. [ Conclusion] Afunctional of hMLH1 gene may be one of the reasons for the mutation of p53 gene in the carcinogenesis of colorectal carcinoma.