错配修复基因hMLH1和hMSH2在散发性大肠癌中的表达及其意义

目的 探讨错配修复基因hMLH1和hMSH2在散发性大肠癌(SCC)组织中的表达及其临床意义.方法 采用免疫组化Max Vision二步法对63例SCC标本中的癌组织、距癌灶3 cm以外的癌旁组织、距癌灶10 cm以外的正常组织中hMLH1和hMSH2蛋白的表达进行检测.结果 hMLH1蛋白在63例正常大肠组织、癌旁组织和SCC组织中的阳性表达率分别为95.2%、85.7%和81.0%,hMLH1蛋白在SCC组织中的阳性表达率明显低于正常大肠组织(P＜0.05).hMSH2蛋白在63例正常大肠组织、癌旁组织和SCC组织中的阳性表达率分别为76.2%、66.7%和52.4%,hMSH2蛋白在SCC组织中的阳性表达率明显低于正常大肠组织(P＜0.01).hMLH1蛋白在＜60岁的SCC患者组织中的阳性表达率(100%)明显高于≥60岁的SCC患者组织(75.0%,P＜0.05),在有淋巴结转移的SCC组织中的阳性表达率(50.0%)明显低于无淋巴结转移的SCC组织(93.3%,P＜0.05).hMSH2蛋白在＜60岁的SCC患者组织中的阳性表达率(80.0%)明显高于≥60岁的SCC患者组织(43.8%,P＜0.05),在癌组织浸润至肠壁浆膜层SCC组织中的阳性表达率(61.5%)明显高于浸润至黏膜下层和肌层的SCC组织(37.5%,P＜0.05).SCC组织中hMLH1和hMSH2蛋白的表达呈正相关关系(r=0.254,P＜0.01).结论 hMLH1和hMSH2蛋白在SCC组织中的表达均有一定的缺失,并且与患者的年龄、淋巴结转移和癌组织浸润的范围有关.hMLH1和hMSH2基因可以作为临床预测和判断SCC发生和发展有用的实验室指标.

Expression and significance of mismatch repair genes hMLH1 and hMSH2 in sporadic colorectal carcinoma

Objective To investigate the expression and clinical significance of mismatch repair genes hMLH1 and hMSH2 in sporadic colorectal carcinoma tissues. Methods The expression of hMLH1and hMSH2 proteins was detected in the 63 sporadic colorectal carcinoma samples by immunohistochemical staining, including tumor tissue,adjacent tissue at 3 cm from the carcinoma, and normal tissue at 10 cnm away from the tumor. Results The positive rate of hMLH1 protein expression in the 63 normal colorectal tissues, adjacent tissues and sporadic colorectal carcinoma tissues was 95.2%, 85.7% and 81.0%,respectively. The positive rate of hMLH1 protein expression was significantly lower in the tumor than in normal colorectal tissues ( P ＜ 0.05 ). The positive rate of hMSH2 protein in the 63 normal colorectal tissues, adjacent tissues and sporadic colorectal carcinoma tissues were 76.2%, 66.7% and 52.4%,respectively. The positive rate of hMSH2 protein expression was significantly lower in the tumor than in normal colorectal tissues (P ＜ 0.01 ). The positive rate of hMLH1 protein expression was significantly higher in the tumor tissue of patients aged younger than 60 years ( 100% ) than that in patients ≥ 60 years(75.0%,P ＜0.05) . The positive rate of hMLH1 protein expression in the tumor tissue accompanied by lymphatic metastasis was 50.0%, significantly lower than that ( 93.3% ) in tumors without lymphatic metastasis ( P ＜0.05). The positive rate of hMSH2 protein expression in the tumor tissue of patients aged younger than 60years was 80. 0%, significantly higher than that (43.8%) in the cases ≥ 60 years ( P ＜ 0.05 ). The positive rate of hMSH2 protein expression in the tumor tissues with invasion reaching to the intestinal serosa (61.5%) was significantly higher than that ( 37.5% ) in the tumors invading to submucosa or muscular layer (P ＜ 0.05 ). There was a positive correlation between the expressions of hMLH1 and hMSH2 proteins in the sporadic colorectal carcinomas. Conclusion There is a certain loss of expression of hMLH1 and hMSH2 proteins in sporadic colorectal carcinoma,and is correlated with the age of patients, lymphatic metastasis and different depth of cancer invasion. HMLH1 and hMSH2 may be used as a useful laboratory marker in clinical judgement of occurance and development of sporadic colorectal carcinoma.