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Universal tumor screening in a population with MSH6- and PMS2-associated Lynch syndrome
Authors:Haukur Einarsson  Johanna Run Runarsdottir  Thordur Tryggvason  Petur Snaebjornsson  Agnes Smaradottir  Vigdis Stefansdottir  Asgeir Thoroddsen  Reynir Arngrimsson  Jon Gunnlaugur Jonasson  Sigurdis Haraldsdottir
Institution:1. Department of Pathology, Landspitali University Hospital of Iceland, Reykjavik, Iceland;2. Department of Internal Medicine, Landspitali University Hospital of Iceland, Reykjavik, Iceland;3. Department of Pathology, Netherlands Cancer Institute, Amsterdam, the Netherlands;4. Department of Oncology, Landspitali University Hospital of Iceland, Reykjavik, Iceland;5. Department of Genetics and Molecular Medicine, Landspitali University Hospital of Iceland, Reykjavik, Iceland;6. Department of Obstetrics and Gynecology, Landspitali University Hospital of Iceland, Reykjavik, Iceland;7. Faculty of Medicine, University of Iceland, Reykjavik, Iceland;1. Department of Biomedical and Clinical Sciences “L. Sacco”, University of Milan, Milan, Italy;2. Pediatric Radiology and Neuroradiology Department, Vittore Buzzi Children’s Hospital, Milan, Italy;3. COALA (Center for diagnosis and treatment of leukodystrophies), Vittore Buzzi Children''s Hospital, Milan, Italy;4. Child Neuropsychiatry Unit, UONPIA ASST Rhodense, Milan, Italy;5. Pediatric Clinical Research Center Fondazione Romeo ed Enrica Invernizzi, University of Milan, Milan, Italy;6. Laboratory Genetic Metabolic Diseases, Amsterdam Gastroenterology Endocrinology Metabolism, Amsterdam UMC, Vrije Universiteit Amsterdam, University of Amsterdam, Amsterdam, The Netherlands;7. Molecular Genetics Section, Medical Genetics Laboratory, Papa Giovanni XXIII Hospital, Bergamo, Italy;8. Child Neurology Unit, Vittore Buzzi Children''s Hospital, Milan, Italy;1. School of Women’s and Children’s Health, University of New South Wales, Randwick, New South Wales, Australia;2. Centre for Clinical Genetics, Sydney Children’s Hospital, Randwick, New South Wales, Australia;3. Sydney Health Ethics, Sydney School of Public Health, Faculty of Medicine and Health, The University of Sydney, New South Wales, Australia;4. Victorian Clinical Genetics Services, Parkville, Victoria, Australia;5. Murdoch Children’s Research Institute, Parkville, Victoria, Australia;6. UWA Centre for Medical Research, University of Western Australia, Nedlands, Western Australia, Australia;7. Harry Perkins Institute of Medical Research, Nedlands, Western Australia, Australia;8. NSW Health Pathology East Genomics Laboratory, Randwick, New South Wales, Australia;1. Division of Dermatology, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel;2. Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel;3. Faculty of Health Sciences, Ben Gurion University of the Negev, Be’er Sheva, Israel;4. Genetic Institute, Soroka University Medical Center, Be’er Sheva, Israel;5. Institute of Pathology, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel;1. Department of Tumor Biology, Institute of Cancer Research, The Norwegian Radium Hospital, Oslo, Norway;2. Institute of Medical Genetics, Division of Cancer and Genetics, Cardiff University School of Medicine, Heath Park, Cardiff, United Kingdom;3. Applied Tumor Genomic Research Program, University of Helsinki, Helsinki, Finland;1. Department of Obstetrics and Gynecology, Northwestern University Feinberg School of Medicine, Chicago, IL;2. Departments of Pathology and Obstetrics, Gynecology and Reproductive Sciences, University of Pittsburgh School of Medicine, Pittsburgh, PA;3. Center for Medical Genetics and Genomics, UPMC Magee-Womens Hospital, Pittsburgh, PA;4. Department of Obstetrics & Gynecology and Women’s Health, Montefiore Medical Center, Albert Einstein College of Medicine, New York, NY;5. Department of Obstetrics and Gynecology, Prisma Health, Columbia, SC;1. amedes MVZ wagnerstibbe, Hannover, Germany;2. Medizinische Hochschule Hannover, Hanover, Germany;3. Institute of Medical Informatics and Statistics, Kiel University, University Hospital Schleswig-Holstein Campus Kiel, Kiel, Germany
Abstract:PurposeUniversal screening for Lynch syndrome (LS) on resected colorectal carcinomas (CRCs) and endometrial carcinomas (ECs) was implemented in Iceland in 2017 using immunohistochemistry (IHC) for mismatch repair (MMR) proteins. We examined the efficacy of the universal screening algorithm to detect LS and the diagnostic accuracy of MMR IHC by comparing results with a population-based genotype database.MethodsAll patients diagnosed with CRC or EC per the Icelandic Cancer Registry from 2017 to 2019 who had tumor MMR IHC performed were included. Pathology reports and patient charts were reviewed. MMR IHC stains were crossmatched with genotyping results obtained from the deCODE database.ResultsIHC staining was done on 404 patients with CRC and 74 patients with EC. A total of 61 (15.1%) patients with CRC and 15 (20.3%) patients with EC were MMR-deficient. MMR IHC had 88.9% sensitivity in identifying patients with LS and a positive predictive value of 10.7%. Only 50% of individuals were appropriately referred for genetic testing, leading to underdiagnosis of LS.ConclusionUniversal screening for LS using MMR protein IHC in CRC and EC accurately identified patients appropriate for genetic testing in a population with MSH6 and PMS2 LS predominance. Because of lack of referral to genetic counseling, only 50% of patients with LS were identified through the screening algorithm.
Keywords:Colorectal carcinoma  Endometrial carcinoma  Genetic counseling  MMR deficient  MMR proficient
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