Mismatch Repair Universal Screening of Endometrial Cancers (MUSE) in a Canadian Cohort
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 eff...
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| Format: | Article |
| Language: | English |
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MDPI AG
2021-01-01
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| Series: | Current Oncology |
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| Online Access: | https://www.mdpi.com/1718-7729/28/1/52 |
| _version_ | 1797520713457860608 |
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| author | Jessica Lawrence Lara Richer Jocelyne Arseneau Xing Zeng George Chong Evan Weber William Foulkes Laura Palma |
| author_facet | Jessica Lawrence Lara Richer Jocelyne Arseneau Xing Zeng George Chong Evan Weber William Foulkes Laura Palma |
| author_sort | Jessica Lawrence |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-10T08:00:31Z |
| format | Article |
| id | doaj.art-e3cec1abab9842c5a57f215f02c84080 |
| institution | Directory Open Access Journal |
| issn | 1198-0052 1718-7729 |
| language | English |
| last_indexed | 2024-03-10T08:00:31Z |
| publishDate | 2021-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Current Oncology |
| spelling | doaj.art-e3cec1abab9842c5a57f215f02c840802023-11-22T11:30:21ZengMDPI AGCurrent Oncology1198-00521718-77292021-01-0128150952210.3390/curroncol28010052Mismatch Repair Universal Screening of Endometrial Cancers (MUSE) in a Canadian CohortJessica Lawrence0Lara Richer1Jocelyne Arseneau2Xing Zeng3George Chong4Evan Weber5William Foulkes6Laura Palma7Department of Human Genetics, McGill University, Montreal, QC H3A 0C7, CanadaDepartment of Pathology, McGill University Health Centre, Montreal, QC H4A 3J1, CanadaDepartment of Pathology, McGill University Health Centre, Montreal, QC H4A 3J1, CanadaDivision of Gynecologic Oncology, Departments of Obstetrics and Gynecology, Oncology, and Pathology, McGill University and McGill University Health Centre, Montreal, QC H4A 3J1, CanadaDepartment of Pathology, Jewish General Hospital, Montreal, QC H3T 1E2, CanadaDivision of Medical Genetics, Department of Specialized Medicine, McGill University Health Centre, Montreal, QC H4A 3J1, CanadaDepartment of Human Genetics, McGill University, Montreal, QC H3A 0C7, CanadaDepartment of Human Genetics, McGill University, Montreal, QC H3A 0C7, CanadaBackground: 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.https://www.mdpi.com/1718-7729/28/1/52lynch syndromeendometrialuniversal screeningmismatch repairgeneticcancer predisposition |
| spellingShingle | Jessica Lawrence Lara Richer Jocelyne Arseneau Xing Zeng George Chong Evan Weber William Foulkes Laura Palma Mismatch Repair Universal Screening of Endometrial Cancers (MUSE) in a Canadian Cohort Current Oncology lynch syndrome endometrial universal screening mismatch repair genetic cancer predisposition |
| title | Mismatch Repair Universal Screening of Endometrial Cancers (MUSE) in a Canadian Cohort |
| title_full | Mismatch Repair Universal Screening of Endometrial Cancers (MUSE) in a Canadian Cohort |
| title_fullStr | Mismatch Repair Universal Screening of Endometrial Cancers (MUSE) in a Canadian Cohort |
| title_full_unstemmed | Mismatch Repair Universal Screening of Endometrial Cancers (MUSE) in a Canadian Cohort |
| title_short | Mismatch Repair Universal Screening of Endometrial Cancers (MUSE) in a Canadian Cohort |
| title_sort | mismatch repair universal screening of endometrial cancers muse in a canadian cohort |
| topic | lynch syndrome endometrial universal screening mismatch repair genetic cancer predisposition |
| url | https://www.mdpi.com/1718-7729/28/1/52 |
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