3428例结直肠癌错配修复蛋白状态的回顾性分析  

Mismatch repair protein expression of colorectal cancer:a retrospective analysis of 3428 cases

作　　者：刘莹 郭玉虹 罗烨 孙琳 赵帅 邵兵 臧凤琳 邱志强 孙保存 孙燕 Liu Ying;Guo Yuhong;Luo Ye;Sun Lin;Zhao Shuai;Shao Bing;Zang Fenglin;Qiu Zhiqiang;Sun Baocun;Sun Yan(Department of Pathology,Tianjin Medical University Cancer Institute and Hospital,National Clinical Research Center for Cancer,Key Laboratory of Cancer Prevention and Therapy,Tianjin,Tianjin′s Clinical Research Center for Cancer,Tianjin 300060,China)

机构地区：[1]天津医科大学肿瘤医院病理科国家肿瘤临床医学研究中心天津市“肿瘤防治”重点实验室天津市恶性肿瘤临床医学研究中心,300060

出　　处：《中华病理学杂志》2021年第4期369-375,共7页Chinese Journal of Pathology

基　　金：国家自然科学基金项目(81871990)。

摘　　要：目的探讨免疫组织化学检测在结直肠癌中分析错配修复(mismatch repair,MMR)蛋白表达的意义及注意事项。方法收集2014年7月至2018年10月天津医科大学肿瘤医院具有MMR检测结果的、术前未经新辅助治疗的手术切除结直肠癌3428例,复读MMR免疫组织化学切片,对判读有问题的病例重新染色、评估,并检测微卫星不稳定性(MSI),分析MMR表达与MSI状态及临床病理参数的关系。结果(1)3428例结直肠癌中,28例(0.8%)因当初免疫组织化学染色不佳进行重新染色,119例(3.5%)的复诊MMR结果与原判断不一致,主要集中在PMS2和MLH1。最终,261例(7.6%)为错配修复缺陷(dMMR),以MLH1、PMS2联合缺失(43.3%,113/261)为主。(2)在当初诊断时进行MSI检测的14例中,MSI与MMR结果一致的有13例;在29例进行二代测序的dMMR病例中,高度微卫星不稳定(MSI-H)与dMMR的一致率为93.1%(27/29)。其中,MSI与MMR结果不一致的病例为MSH6或PMS2单独缺失。(3)21例结直肠癌呈MLH1或MSH2单独阴性,而PMS2或MSH6呈少部分或部分(弱)阳性。其中能进行MSI检测的19例中,16例为MSI-H,2例为低度微卫星不稳定,1例为微卫星稳定。(4)与错配修复完整(pMMR)的病例相比,dMMR组女性、<50岁、具有肿瘤家族史、早期患者更多见,肿瘤更好发于右半结肠,病理类型以低分化腺癌、黏液腺癌和印戒细胞癌多见(均P<0.05)。结论免疫组织化学检测MMR蛋白表达是一种比较有效、方便的方法,但是操作流程及结果评估需要标准化,对于特殊病例需要进行MSI检测,进而指导临床治疗和评估预后。Objective To analyze the expression of mismatch repair(MMR)proteins in colorectal cancers(CRC)and to evaluate the feasibility and potential pitfalls of immunohistochemistry(IHC)analysis for MMR.Methods The IHC sections for MMR proteins were reviewed in 3428 cases of resected CRC without neoadjuvant therapy at Tianjin Medical University Cancer Institute and Hospital from July 2014 to October 2018.For the cases with unclear MMR IHC results during the initial review,IHC staining was repeated and microsatellite instability(MSI)analysis was performed.Relationships between the expression of MMR proteins and MSI status as well as the clinicopathological parameters were analyzed.Results IHC staining for MMR was repeated in 28(0.8%)cases due to poor quality of original IHC sections.Inconsistent results between the original diagnosis and re-diagnosis were found in 119(3.5%)cases,mainly resulting from PMS2 and MLH1.Finally,261(7.6%)cases of CRC showed mismatch repair deficiency(dMMR),mainly from the deficiency of both MLH1 and PMS2(43.3%,113/261).In the 14 cases with MSI results,the concordant of MSI and MMR was 13 cases.In the 29 dMMR cases with next generation sequencing(NGS)results,the concordant of MSI-high and dMMR was 93.1%(27/29).The cases with inconsistent results between MSI and MMR showed negative expression of MSH6 or PMS2.Twenty-one CRC showed negative expression of MLH1 and partially positive(or weak positive)expression of PMS2,or negative expression of MSH2 and partially positive(or weak positive)expression of MSH6.Among the 19 cases with MSI results,16 cases were MSI-high,two cases were MSI-low,and one case was microsatellite stable.Compared with mismatch repair proficiency(pMMR),dMMR was more frequently detected in female patients younger than 50 years old,with family history,at early stage(Ⅰ-Ⅱ)CRC,and in the tumors from right colon,with poor differentiation,or mucinous adenocarcinoma/signet ring cell carcinoma(all P<0.05).Conclusions At present,IHC staining is a clinically effective and convenient metho

关 键 词：结直肠肿瘤 DNA错配修复 微卫星不稳定性 免疫组织化学 

分 类 号：R735.34[医药卫生—肿瘤]