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Mismatch Repair Universal Screening of Endometrial Cancers (MUSE) in a Canadian Cohort
Current Oncology ( IF 2.6 ) Pub Date : 2021-01-15 , DOI: 10.3390/curroncol28010052
Jessica Lawrence , Lara Richer , Jocelyne Arseneau , Xing Zeng , George Chong , Evan Weber , William Foulkes , Laura Palma

BACKGROUND Approximately 2-6% of endometrial cancers (ECs) are due to Lynch Syndrome (LS), a cancer predisposition syndrome caused by germline pathogenic variants (PVs) affecting the DNA mismatch repair (MMR) pathway. Increasingly, universal tissue-based screening of ECs has been proposed as an efficient and cost-effective way to identify families with LS, though few studies have been published on Canadian cohorts. The purpose of this study was to evaluate the feasibility and overall performance of a universal immunohistochemistry (IHC) screening program for women with EC within a single Canadian university hospital centre. METHODS AND RESULTS From 1 October 2015 to 31 December 2017, all newly diagnosed ECs (n = 261) at our centre were screened for MMR protein deficiency by IHC. MMR deficiency was noted in 69 tumours (26.4%), among which 53 had somatic MLH1 promoter hypermethylation and were considered "screen-negative". The remaining MMR-deficient cases (n = 16) were considered "screen-positive" and were referred for genetic counselling and testing. Germline PVs were identified in 12/16 (75%). One additional PV was identified in a screen-negative individual who was independently referred to the Genetics service. This corresponds to an overall LS frequency of 5.0% among unselected women with EC, and 6.4% among women diagnosed under age 70 years. Our algorithm detected MMR gene pathogenic variants in 4.6% and 6.2% of unselected individuals and individuals under age 70 years, respectively. Four germline PVs (30.8%) were identified in individuals who did not meet any traditional LS screening criteria. CONCLUSIONS Universal IHC screening for women with EC is an effective and feasible method of identifying individuals with LS in a Canadian context.

中文翻译:

加拿大队列中子宫内膜癌 (MUSE) 的错配修复普遍筛查

背景大约 2-6% 的子宫内膜癌 (EC) 是由林奇综合征 (LS) 引起的,这是一种癌症易感综合征,由影响 DNA 错配修复 (MMR) 途径的种系致病变异 (PV) 引起。越来越多的基于组织的 ECs 筛查被提议作为一种有效且具有成本效益的方式来识别患有 LS 的家庭,尽管很少有关于加拿大队列的研究发表。本研究的目的是评估在一个加拿大大学医院中心内对患有 EC 的女性进行通用免疫组织化学 (IHC) 筛查计划的可行性和整体性能。方法和结果 2015年10月1日至2017年12月31日,我中心所有新诊断ECs(n=261)均通过IHC筛查MMR蛋白缺乏症。在 69 个肿瘤(26.4%)中发现 MMR 缺陷,其中 53 个具有体细胞 MLH1 启动子高甲基化,被认为是“筛选阴性”。剩余的 MMR 缺陷病例(n = 16)被认为是“筛查阳性”,并被转介进行遗传咨询和检测。在 12/16 (75%) 中鉴定了种系 PV。在一名被独立转诊到遗传学服务的筛查阴性个体中发现了一个额外的 PV。这对应于未选择的 EC 女性的总体 LS 频率为 5.0%,诊断为 70 岁以下的女性的总体 LS 频率为 6.4%。我们的算法分别在 4.6% 和 6.2% 的未选择个体和 70 岁以下个体中检测到 MMR 基因致病变异。在不符合任何传统 LS 筛查标准的个体中鉴定出四个种系 PV (30.8%)。
更新日期:2021-01-15
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