MLH1、MSH2、MSH6和PMS2蛋白在结直肠癌中的表达及在Lynch综合征筛查中的意义

摘要

目的 探讨错配修复(mismatch repair,MMR)蛋白MLH1、MSH2、MSH6和PMS2在结直肠癌中的表达及其临床意义.方法 采用免疫组化EnVision两步法检测102例结直肠癌组织中MLH1、MSH2、MSH6和PMS2蛋白表达缺失情况,分析蛋白表达缺失与结直肠癌临床病理特征的关系,并对其中20例进行微卫星不稳定(microsatellite instability,MSI)检测.结果 102例结直肠癌有15例(14.7％)发生MMR蛋白表达缺失,MLH1、MSH2、MSH6、PMS2蛋白表达缺失率分别为12.7％ (13/102)、3.9％ (4/102)、4.9％ (5/102)、10.8％ (11/102).结直肠癌标本中MLH1、MSH2、MSH6、PMS2的蛋白表达缺失与患者性别、年龄、肿瘤大小、浸润深度、淋巴结转移无关(P ＞0.05);MLH1与PMS2蛋白表达缺失与组织学分化高低相关(P＜0.05).进行MSI检测的10例MMR蛋白缺失病例中有2例(2.0％)为高频微卫星不稳定(microsatellite instability-high,MSI-H),其余8例为微卫星稳定(microsatellite stability,MSS);另10例无MMR蛋白缺失的病例微卫星状态均为低频微卫星不稳定(microsatel-lite instability-low,MSI-L)/MSS.结论 免疫组化检测MLH1、MSH2、MSH6和PMS2的缺失可以用于Lynch综合征的初筛,对结直肠癌患者行MMR免疫组化检测和MSI联合检测可提高Lynch综合征的诊断率.%Purpose To investigate the expression of mismatch repair proteins MLH1,MSH2,MSH6 and PMS2 and their clinical significance in colorectal cancer.Methods Immunohistochemical analysis was used to detect MLH1,MSH2,MSH6 and PMS2 protein expression in formalin-fixed paraffin-embedded tissues from 102 colorectal cancer patients,and microsatellite instability (MSI) was tested in 20 cases.The relationship between MMR protein expression and clinical pathological features was also analyzed.Results 15 cases (14.7％) had MMR protein loss.The loss rate of MLH1,MSH2,MSH6 and PMS2 protein was 12.7％ (13/102),3.9％ (4/102),4.9％ (5/102) and 10.8％ (11/102),respectively.MLH1,MSH2,MSH6 and PMS2 protein losses were not related with gender,age,tumor size,depth of invasion and lymph node metastasis (P ＞ 0.05).MLH1 and PMS2 protein losses were related to histological differentiation (P ＜0.05).MSI was detected in 10 Lynch syndrome candidates.2 cases (2.0％)of high-frequency microsatellite instability (MSI-H) were identified,and the remaining 8 cases were MSS.However,10 cases without MMR expression abnormality all showed MSI-L/MSS.Conclusion Immunohistochemical detection of MLH1,MSH2,MSH6 and PMS2 can be used as primary screening for Lynch syndrome and its combination with MSI test can effectively increase the diagnostic rate in Lynch syndrome.