子宫内膜癌中错配修复(MMR)蛋白表达缺失筛查Lynch综合征及其临床病理特点

目的:通过分析比较子宫内膜癌患者的错配修复(MMR)蛋白表达缺失的情况,研究其与临床标准诊断之间的关系,以及MMR蛋白表达缺失者的临床病理特征。方法:收集北京大学第一医院2011年12月至2015年7月收治的313例子宫内膜癌患者的临床资料,免疫组化法分析子宫内膜癌组织中MMR蛋白(MLH1/MSH2/MSH6/PMS2)表达情况。结果:临床诊断或可疑的Lynch综合征22例(7.0%),存在MMR表达缺失者49例(15.7%)。临床诊断或可疑Lynch的患者中,存在MMR表达缺失者的比例明显升高(P=0.011),其中主要是MSH6表达缺失存在差异(P=0.004)。MSH2表达缺失和MSH6表达缺失的患者中合并高血压的比例更低(P=0.002,P=0.045)、淋巴结转移的比例更高(P=0.025,P=0.020)、肿瘤分化差(P=0.030,P=0.010);MSH6表达缺失的患者,相对年龄更小(P=0.021)。结论:免疫组化检测MMR蛋白表达缺失在诊断或可疑Lynch综合征患者中的比例更高,可用于辅助进行Lynch综合征的筛查及诊断。MMR蛋白表达缺失与患者低龄、存在淋巴结转移、肿瘤分化不良等临床病理特征相关。

The MMR(Mismatch repair) protein deficiency in endometrial carcinoma:the significance in the detection of Lynch syndrome and the correlation with clinical and pathological characteristics

Objective:To analyze the significance of mismatch repair(MMR) protein deficiency in the detection of Lynch syndrome,and the correlation with clinical and pathological characteristics.Methods:313 endometrial carcinoma patients treated in Peking University First Hospital between Dec.2011 and July.2015 were reviewed.The expression of MMR protein (MLH1/MSH2/MSH6/PMS2) was assessed by immunohistochemistry (IHC).Results:Lynch syndrome was diagnosed in 22 patients (7.0%) according to the clinical criteria,meanwhile loss of MMR expression was found in 49 patients (15.7%).Patients with possible diagnosis of Lynch syndrome tended to have higher possibility of MMR protein deficiency (P=0.011);in which MSH6 protein deficiency(P=0.004) did the main contribution.The deficiency of MSH2 and MSH6 were associated with less proportion of hypertension (P=0.002,P=0.045),higher possibility of lymph node metastasis (P=0.025,P=0.020) and poor tumor differentiation (P=0.030,P=0.010),besides the deficiency of MSH6 was correlated with younger age (P=0.021).Conclusion:The deficiency of MMR detected by IHC was more prevalent in possible Lynch syndrome patients,which could possible help detecting Lynch syndrome.The MMR protein deficiency was correlated with younger age,lymph node metastasis and poor tumor differentiation.