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

关键词:  结直肠肿瘤  p53基因  hMLH1蛋白

Key words:  colorectal tumor  p53 gene  hMLH1 protein

摘要:

［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。

Abstract:

［Objective］ To investigate the influence of mismatch repair gene hMLH1 on the mutating of p53 gene in the carcinogenesis of colorectal carcinoma. ［Method］ Immunohistochemical method was used to detect P53 and hMLH1 protein in 37 cases normal colorectal tissues,32 cases colorectal 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% respectively, difference was significantly between normal colorectal 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 significantly 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.