MMR蛋白表达结合林奇综合征肿瘤家族史在林奇综合征相关子宫内膜癌筛查中的临床应用

Clinical application of MMR protein expression combined with Lynch syndrome tumor family history in Lynch syndrome associated endometrial cancer screening

目的分析错配修复(Mismatch repair,MMR)蛋白表达结合林奇综合征(Lynch syndrome,LS)相关肿瘤个人史或家族史在临床筛查林奇综合征相关子宫内膜癌(Lynch syndrome associated endometrial cancer,LS-EC)中的应用价值。方法纳入2019年1月~2020年12月在我院经病理诊断为子宫内膜癌(Endometrial cancer,EC)患者147例,患者组织标本均采用免疫组化(Immunohistochemistry,IHC)法检测MMR蛋白表达,对MMR蛋白表达缺失或有LS相关肿瘤个人史或家族史的患者采用二代测序技术(Next-generation sequencing,NGS)检测LS相关基因。根据基因检测结果,采用易侕统计软件比较免疫组化检测MMR蛋白表达、LS相关个人史或家族史在LS-EC初筛中的预测价值。结果147例EC患者中,经免疫组化检测发现46例患者存在MMR蛋白表达缺失(d MMR),发生率为31.3%(46/147);14例患者有LS相关肿瘤个人史或家族史。共43例患者行NGS检测,10例患者确诊LS,LS发生率为6.8%,突变率最高的基因为PMS2。肿瘤个人史或家族史联合PMS2及MLH1预测LS的敏感度为100%,特异性为76.6%,AUC为0.95。结论MMR蛋白免疫组化检测可作为LS的初筛手段,在dMMR人群中以LS相关肿瘤个人史或家族史作为分流手段,可提高筛查特异性。综合筛查手段的敏感度、特异性、可及性和成本效益,推荐MMR蛋白免疫组化检测联合LS相关肿瘤个人史或家族史作为LS的筛查策略。

Objective To analyze the value of mismatch repair(MMR)protein expression combined with Lynch syndrome(LS)related tumors personal or family history in screening for Lynch syndrome associated endometrial cancer(LS-EC).Methods Selected 147 patients diagnosed with endometrial cancer in our hospital from Jan 2019 to Dec 2020.The expression of MMR protein was detected by immunohistochemistry(IHC),patients with loss of MMR protein expression or personal/family history of LS underwent next-generation sequencing(NGS)to detect Lynch-related genes.According to the genetic test results,the predicitive value of IHC and personal/family history of LS in LS-EC preliminary screening was compared by Yier statistics software.Results Among 147 patients,46 patients had loss of MMR protein expression(deficiency-MMR,dMMR),14 patients had personal/family history of LS related tumors.43patients underwent NGS test,10 patients were confirmed as LS,and the incidence of LS was 6.8%.The gene with the highest mutation rate was PMS2.The sensitivity of personal/family history of LS combined with protein expression of PMS2 and MLH1 predicting LS was 100%,the specificity was 76.6%,and the AUC was 0.95.Conclusion IHC detection of MMR protein expression can be used as a preliminary screening method for LS.The personal/family history of LS as a shunt means in the dMMR population can improve the screening specificity.Combining the sensitivity,specificity,accessibility and cost-effectiveness of the screening means,IHC detection of MMR protein expression combined with LS related tumors personal/family history is recommended as screening strategy.