乙肝相关性肝癌MLH1与p53的表达及其意义

Significance of MLH1 and p53 expression in HBV related- hepatocellular carcinoma

目的探讨MLH1与p53在乙型肝炎病毒(hepatitis B virus,HBV)感染相关性肝癌(hepatocellular carcinoma,HCC)中的表达及其意义。方法选取原位肝移植手术术后HBV相关性HCC伴肝硬化患者238例,应用免疫组化的方法检测肝癌组织和癌旁组织中MLH1与p53的表达情况,并以25例正常肝组织和良性肝病组作为对照。结果 MLH1在肝癌组织的阳性表达率为31.09%(74/238),在癌旁组织的表达阳性率为26.05%(62/238),良性肝病对照组阳性表达率为48.00%(12/25),各组表达的差异无统计学意义(P=0.053)。相关性分析显示,MLH1基因的表达与患者肝移植术前AFP含量(r=0.221,P=0.001)及术后的复发(r=-0.159,P=0.014)有相关性,与HCC组织病理学Edmondson分级(P=0.060)及TNM分期(P=0.065)有相关趋势。p53在肝癌组织的表达阳性率为47.06%(112/238),在癌旁组织的表达阳性率为0.84%(2/238),良性肝病对照组均为阴性,p53蛋白的表达在癌组织中明显高于其在癌旁及良性肝病中的表达(P=0.000);p53表达情况与患者肝移植术前AFP含量有相关性(r=0.172,P=0.008),与血管侵犯(P=0.053)及肿瘤数量(P=0.051)有相关趋势。结论 MLH1蛋白表达下调可能与HBV相关性肝癌的发生及术后的复发有关,且MLH1与p53蛋白在肝癌中的表达有一定的关联性。

Objective To study the expression of MLH1 and p53 in HBV related-hepatocellular carcinoma（HCC）, both of the specificity of the expression.Method Objects were 238 patients of HBV related-HCC with cirrhosis in this hospital who had been in the liver transplantation operation from 2003 to 2013.We examined the expression of MLH1 and p53 in 238 patients with HCC and adjacent tissues by immunohistochemistry.As the normal controls were normal liver tissue and benign liver disease.Results The ex-pression of theMLH1postive in the HCC tissues was 31.09%（74/238）, with 26.05%（62/238） in cancer adjacent tissues,with 48.00%（12/25）in benign liver diseases tissues.The expression in each group had no significant difference （P=0.053）.However, by clinicopathologic rank correlation analysis, the expression of MLH1 was associated with tumour recurrence after liver transplantation （r=-0.159,P=0.014）and the AFP levels （r=0.221, P=0.001）,and had certain trend with Edmondson-Steiner Grading（P=0.060）and TNM（P=0.065）.The expression of the p53 postive in the HCC tissues was 47.06%（112/238）,with 0.84%（2/238）in the cancer adjacent.However, the expression of benign liver diseases tissues were all negative.The expression of p53 protein in tumour tissues was significantly higher than that in cancer adjacent tissues and benign liver diseases tissues （P=0.000）,There was association between expression of p53 and vascular invasion （P=0.053） and tumorons numbers （P=0.051）.Conclusion Down-regulation of MLH1 expression at the mRNA and protein levels is observed in association with developing hepatocellular carcinoma and relapses. MLH1 has significant correlation with p53.