子宫内膜癌相关林奇综合征筛查方法的研究  

Study of Screening Methods for Lynch Syndrome in Patients with Endometrial Carcinoma

作　　者：马珂[1] 杨曦[1] 杨子慧 刘帅[1] 孟轶婷[2] 张蕾[1] 廖秦平[1] MA Ke;YANG Xi;YANG Zihui(Department of Gynecology and Obstetrics,Beijing Tsinghua Changgung Hospital,School of Clinical Medicine,Tsinghua University,Beijing 102218,China)

机构地区：[1]清华大学附属北京清华长庚医院妇产科,清华大学临床医学院,北京102218 [2]清华大学附属北京清华长庚医院病理科,清华大学临床医学院,北京102218

出　　处：《实用妇产科杂志》2023年第1期51-55,共5页Journal of Practical Obstetrics and Gynecology

基　　金：北京市属医院科研培育计划项目(编号:PX2018039);北京市医院管理中心青年人才培养“青苗”计划(编号:QML20210902)。

摘　　要：目的:在子宫内膜癌(EC)患者中应用不同方法筛查林奇综合征(LS),经二代基因测序(NGS)验证比较不同方法的敏感度和特异度,探讨EC相关LS(EC-LS)的合理筛查策略。方法:选择2015年7月至2022年3月在清华大学附属北京清华长庚医院经病理确诊的82例EC患者,应用AmsterdamⅡ标准和修订Bethesda标准进行EC-LS临床筛查,对肿瘤组织分别行免疫组织化学法(IHC)错配修复(MMR)蛋白检测、微卫星不稳定检测(MSI)和MMR基因NGS,以NGS为金标准,比较不同筛查方法和联合筛查的准确性。结果:82例EC患者中,经NGS检测确诊EC-LS 5例,发生率6.1%。AmsterdamⅡ标准及修订Bethesda标准筛查的敏感度均为40.0%,特异度分别为100.0%和96.1%;IHC法筛查发现21例患者MMR蛋白表达缺失,其中4例确诊为EC-LS,1例漏诊,敏感度80.0%,特异度77.9%;MSI法筛查发现11例患者存在高度微卫星不稳定(MSI-H),其中2例确诊为LS,3例漏诊,敏感度40.0%,特异度88.3%;IHC和MSI联合筛查可将全部5例LS检出,敏感度100.0%,特异度77.9%。4种筛查方法的敏感度、特异度差异无统计学意义(P>0.05)。结论:IHC、MSI和两者联合筛查EC-LS的敏感度、特异度相似,因联合检测费用较高,因此推荐IHC作为临床首选筛查方法。Objective:To apply different methods to screen Lynch syndrome(LS)in patients with endometrial carcinoma(EC)and compare the sensitivity and specificity of different screening methods through next generation sequencing verification,,and to explore a reasonable screening strategy for EC-related LS(EC-LS).Methods:From July 2015 to March 2022,a total of 82 EC patients diagnosed pathologically at Beijing Tsinghua Changgung Hospital were selected for EC-LS screening by using AmsterdamⅡand revised Bethesda criteria.Immunohistochemical(IHC)mismatch repair(MMR)protein detection,microsatellite instability detection(MSI)and next-generation sequencing(NGS)for MMR gene were performed on tumor tissues,respectively.Using NGS as the gold standard,the accuracy of different screening methods and joint screening was compared.Results:Of the 82 EC patients,5 patients were confirmed as EC-LS by NGS,with an incidence of 6.1%.The sensitivity of AmsterdamⅡstandard and revised Bethesda standard screening was 40.0%,and the specificity was 100.0%and 96.1%respectively.IHC screening showed that 21 patients had MMR protein lost,among which 4 patients were diagnosed as EC-LS and 1 patient was missed.The screening sensitivity was 80.0%and specificity was 77.9%.Eleven patients were found to have high microsatellite instability(MSI-H)by MSI screening,of which 2 patients were confirmed as LS and 3 patients were missed,with screening sensitivity of 40.0%and specificity of 88.3%.The combined screening of IHC and MSI could detect LS in all 5 patients with a sensitivity of 100.0%and specificity of 77.9%.The sensitivity and specificity of the four screening methods had no significant difference(P>0.05).Conclusions:There was no significant difference in the sensitivity and specificity of IHC,MSI and combined screening for EC-LS.Because of the high cost of combined detection,IHC screening is recommended as the first clinical screening method.

关 键 词：林奇综合征 子宫内膜癌 微卫星不稳定 基因检测 

分 类 号：R737.33[医药卫生—肿瘤]