Favier Amelia, Varinot Justine, Uzan Catherine, Duval Alex, Brocheriou Isabelle, Canlorbe Geoffroy
Department of Gynecological and Breast Surgery and Oncology, Pitié-Salpêtrière, Assistance Publique des Hôpitaux de Paris (AP-HP), University Hospital, 75013 Paris, France.
Centre de Recherche Saint-Antoine, Equipe Instabilité des Microsatellites et Cancer, Equipe Labellisée par la Ligue Nationale Contre le Cancer, Unité Mixte de Recherche Scientifique 938 and SIRIC CURAMUS, INSERM, Sorbonne Université, 75012 Paris, France.
Cancers (Basel). 2022 Aug 3;14(15):3783. doi: 10.3390/cancers14153783.
The objective of this systematic review was to summarize our current knowledge of the role of immunohistochemistry (IHC) markers for identifying mismatch repair-deficient (MMRd) tumors in endometrial cancer (EC). Identification of MMRd tumors, which occur in 13% to 30% of all ECs, has become critical for patients with colorectal and endometrial cancer for therapeutic management, clinical decision making, and prognosis. This review was conducted by two authors applying the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines using the following terms: "immunohistochemistry and microsatellite instability endometrial cancer" or "immunohistochemistry and mismatch repair endometrial cancer" or "immunohistochemistry and mismatch repair deficient endometrial cancer". Among 596 retrieved studies, 161 fulfilled the inclusion criteria. Articles were classified and presented according to their interest for the diagnosis, prognosis, and theragnostics for patients with MMRd EC. We identified 10, 18, and 96 articles using IHC expression of two, three, or four proteins of the MMR system (MLH1, MSH2, MHS6, and PMS2), respectively. MLH1 promoter methylation was analyzed in 57 articles. Thirty-four articles classified MMRd tumors with IHC markers according to their prognosis in terms of recurrence-free survival (RFS), overall survival (OS), stage, grade, and lymph node invasion. Theragnostics were studied in eight articles underlying the important concentration of PD-L1 in MMRd EC. Even though the role of IHC has been challenged, it represents the most common, robust, and cheapest method for diagnosing MMRd tumors in EC and is a valuable tool for exploring novel biotherapies and treatment modalities.
本系统评价的目的是总结我们目前对于免疫组化（IHC）标志物在识别子宫内膜癌（EC）中错配修复缺陷（MMRd）肿瘤方面作用的认识。MMRd肿瘤在所有EC中占13%至30%，其识别对于结直肠癌和子宫内膜癌患者的治疗管理、临床决策及预后判断至关重要。本评价由两位作者按照系统评价和Meta分析的首选报告项目（PRISMA）指南进行，使用以下检索词：“免疫组化与微卫星不稳定性子宫内膜癌”或“免疫组化与错配修复子宫内膜癌”或“免疫组化与错配修复缺陷子宫内膜癌”。在检索到的596项研究中，161项符合纳入标准。文章根据其对MMRd EC患者诊断、预后及治疗诊断的相关性进行分类和呈现。我们分别使用MMR系统（MLH1、MSH2、MHS6和PMS2）两种、三种或四种蛋白的IHC表达鉴定出10篇、18篇和96篇文章。57篇文章分析了MLH1启动子甲基化情况。34篇文章根据无复发生存期（RFS）、总生存期（OS）、分期、分级及淋巴结浸润情况，用IHC标志物对MMRd肿瘤进行预后分类。8篇文章研究了治疗诊断，强调了MMRd EC中PD-L1的重要富集情况。尽管IHC的作用受到了挑战，但它仍是诊断EC中MMRd肿瘤最常用、可靠且廉价的方法，也是探索新型生物疗法和治疗模式的宝贵工具。
