散发性结直肠癌hMLH1和hMSH2蛋白表达

目的　研究hMLH1及hMSH2两种错配修复 (mismatchrepair,MMR)蛋白在散发性结直肠癌中的表达变化并评估其可能的临床意义。方法　应用EnVision免疫组化两步法检测 1 1 1例散发性结直肠癌中hMLH1和hMSH2的蛋白表达变化 ,采用Kaplan Meier曲线、Log rank检验分析hMLH1蛋白表达变化与患者生存率之间的关系。 结果　 1 1 1例散发性结直肠癌中 ,hMLH1失表达有 1 9例 ,占 1 7 1 % (1 9/ 1 1 1 ) ,hMSH2失表达有 2例 ,占 1 8% (2 / 1 1 1 ) ,两者之和占总散发性结直肠癌病例的 1 8 9% (2 1 / 1 1 1 )。hMLH1或hMSH2蛋白失表达与患者肿瘤部位、组织学类型密切相关。近端结肠、低 -未分化腺癌及黏液腺癌中MMR异常表达比例高 (P <0 0 5 ) ,而与患者年龄、性别、肿瘤大体类型、肿块大小、浸润深度、淋巴结转移与否以及患者的Dukes分期均无显著性相关 (P >0 0 5 )。癌组织中hMLH1正常表达及失表达患者的 5年生存率分别为 6 9 5 7%及73 6 8% ,8年生存率分别为 5 3 5 8%及 73 6 8% ,8年生存率差别较明显 ,然差别无统计学显著性 (P >0 0 5 )。结论　一定比例的散发性结直肠癌中存在MMR基因的缺陷 ,其中hMLH1所起的作用远远大于hMSH2 ,hMLH1失表达与否可能成为有意义的远期生存预后指标

Altered expression of hMLH1 and hMSH2 proteins in sporadic colorectal carcinoma and its clinical significance

Purpose To evaluate the abnormal mismatch repair(MMR) gene (mainly hMLH1 and hMSH2) expression in sporadic colorectal carcinoma(SCC) and its clinical significance. Methods One hundred and eleven cases of formalin fixed paraffin embedded SCC were retrospectively analyzed using EnVision immunohistochemical method with the two monoclonal mouse antibodies against hMSH2 and hMLH1 gene products. The prognostic value of the hMLH1 abnormal expression was assessed using univariate survival analysis. Results Loss of hMLH1 and hMSH2 expression was found in 17 1% and 1 8% SCC respectively. There was a highly significant correlation between the observed lost immunoexpression and several clinical and pathological characteristics described as the phenotypic profile of the RER pathway, such as right sided location ( P <0 05), poorly differentiated and undifferentiated carcinoma and mucinous carcinoma ( P <0 05). There was no significant correlation between the loss of MMR immunoexpression and patients' age, gender, tumor gross type, tumor size, invasive depth, lymph node metastasis, distant metastasis and Dukes stage. The 5 year survival rates were 73 68% and 69 57% in hMLH negative expression cases and normal expression ones, respectively. The 8 year survival rates were 73 68% and 53 58% in hMLH negative expression cases and normal expression ones, respectively. However, these differences between the two groups of patients were not significant ( P >0 05, Log rank test). Conclusions There are a subset of SCC displaying MMR defective and hMLH1 plays more important roles in SCC than hMSH2 does. The use of immunohistochemical method to detect the abnormal MMR expression might be a useful method to predict the long term prognosis of SCC.