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Open AccessArticle

Mismatch Repair Universal Screening of Endometrial Cancers (MUSE) in a Canadian Cohort

1
Department of Human Genetics, McGill University, Montreal, QC H3A 0C7, Canada
2
Department of Pathology, McGill University Health Centre, Montreal, QC H4A 3J1, Canada
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Division of Gynecologic Oncology, Departments of Obstetrics and Gynecology, Oncology, and Pathology, McGill University and McGill University Health Centre, Montreal, QC H4A 3J1, Canada
4
Department of Pathology, Jewish General Hospital, Montreal, QC H3T 1E2, Canada
5
Division of Medical Genetics, Department of Specialized Medicine, McGill University Health Centre, Montreal, QC H4A 3J1, Canada
6
Cancer Research Program, Research Institute of the McGill University Health Centre, McGill University, Montreal, QC H4A 3J1, Canada
*
Author to whom correspondence should be addressed.
Curr. Oncol. 2021, 28(1), 509-522; https://doi.org/10.3390/curroncol28010052
Received: 19 August 2020 / Revised: 8 September 2020 / Accepted: 30 October 2020 / Published: 15 January 2021
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. View Full-Text
Keywords: lynch syndrome; endometrial; universal screening; mismatch repair; genetic; cancer predisposition; Canadian; immunohistochemistry lynch syndrome; endometrial; universal screening; mismatch repair; genetic; cancer predisposition; Canadian; immunohistochemistry
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MDPI and ACS Style

Lawrence, J.; Richer, L.; Arseneau, J.; Zeng, X.; Chong, G.; Weber, E.; Foulkes, W.; Palma, L. Mismatch Repair Universal Screening of Endometrial Cancers (MUSE) in a Canadian Cohort. Curr. Oncol. 2021, 28, 509-522. https://doi.org/10.3390/curroncol28010052

AMA Style

Lawrence J, Richer L, Arseneau J, Zeng X, Chong G, Weber E, Foulkes W, Palma L. Mismatch Repair Universal Screening of Endometrial Cancers (MUSE) in a Canadian Cohort. Current Oncology. 2021; 28(1):509-522. https://doi.org/10.3390/curroncol28010052

Chicago/Turabian Style

Lawrence, Jessica; Richer, Lara; Arseneau, Jocelyne; Zeng, Xing; Chong, George; Weber, Evan; Foulkes, William; Palma, Laura. 2021. "Mismatch Repair Universal Screening of Endometrial Cancers (MUSE) in a Canadian Cohort" Curr. Oncol. 28, no. 1: 509-522. https://doi.org/10.3390/curroncol28010052

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