{"corpus_id":54319474,"paper_sha":"00b976a042f69d3819a0b4a787e5273b0ac99635","doi":"10.1097/PGP.0000000000000557","arxiv_id":null,"pmid":30383610,"pmcid":null,"mag_id":2899513215,"dblp_id":null,"acl_id":null,"title":"Mismatch Repair Protein Expression in Endometrioid Intraepithelial Neoplasia/Atypical Hyperplasia: Should We Screen for Lynch Syndrome in Precancerous Lesions?","year":2019,"publication_date":"2019-11-01","venue":"International Journal of Gynecological Pathology","journal":{"name":"International Journal of Gynecological Pathology","pages":"533 - 542","volume":"38"},"journal_issn":null,"journal_title":null,"publication_types":["JournalArticle"],"pubmed_pub_types":["Journal Article"],"s2_fields_of_study":["Biology","Medicine"],"reference_count":39,"citation_count":34,"influential_citation_count":1,"is_open_access":false,"arxiv_categories":null,"arxiv_license":null,"arxiv_journal_ref":null,"mesh_headings":[{"d":"Adult","mj":false,"ui":"D000328"},{"d":"Carcinoma in Situ","mj":false,"qs":[{"q":"genetics","mj":true,"ui":"Q000235"},{"q":"pathology","mj":false,"ui":"Q000473"}],"ui":"D002278"},{"d":"Colorectal Neoplasms, Hereditary Nonpolyposis","mj":false,"qs":[{"q":"genetics","mj":true,"ui":"Q000235"},{"q":"pathology","mj":false,"ui":"Q000473"}],"ui":"D003123"},{"d":"DNA Methylation","mj":false,"ui":"D019175"},{"d":"DNA Mismatch Repair","mj":false,"qs":[{"q":"genetics","mj":true,"ui":"Q000235"}],"ui":"D053843"},{"d":"DNA-Binding Proteins","mj":false,"qs":[{"q":"genetics","mj":false,"ui":"Q000235"}],"ui":"D004268"},{"d":"Endometrial Hyperplasia","mj":false,"qs":[{"q":"genetics","mj":true,"ui":"Q000235"},{"q":"pathology","mj":false,"ui":"Q000473"}],"ui":"D004714"},{"d":"Endometrial Neoplasms","mj":false,"qs":[{"q":"genetics","mj":true,"ui":"Q000235"},{"q":"pathology","mj":false,"ui":"Q000473"}],"ui":"D016889"},{"d":"Female","mj":false,"ui":"D005260"},{"d":"Humans","mj":false,"ui":"D006801"},{"d":"Immunohistochemistry","mj":false,"ui":"D007150"},{"d":"Middle Aged","mj":false,"ui":"D008875"},{"d":"Mismatch Repair Endonuclease PMS2","mj":false,"qs":[{"q":"genetics","mj":false,"ui":"Q000235"}],"ui":"D000070976"},{"d":"MutL Protein Homolog 1","mj":false,"qs":[{"q":"genetics","mj":true,"ui":"Q000235"}],"ui":"D000070957"},{"d":"Precancerous Conditions","mj":false,"qs":[{"q":"genetics","mj":true,"ui":"Q000235"},{"q":"pathology","mj":false,"ui":"Q000473"}],"ui":"D011230"},{"d":"Promoter Regions, Genetic","mj":false,"qs":[{"q":"genetics","mj":false,"ui":"Q000235"}],"ui":"D011401"}],"chemicals":[{"n":"DNA-Binding Proteins","ui":"D004268","reg":"0"},{"n":"G-T mismatch-binding protein","ui":"C094443","reg":"0"},{"n":"MLH1 protein, human","ui":"C501486","reg":"0"},{"n":"PMS2 protein, human","ui":"C094934","reg":"EC 3.6.1.-"},{"n":"Mismatch Repair Endonuclease PMS2","ui":"D000070976","reg":"EC 3.6.1.3"},{"n":"MutL Protein Homolog 1","ui":"D000070957","reg":"EC 3.6.1.3"}],"comments_corrections":null,"source_flags":5,"s2_open_access_pdf_url":null,"s2_open_access_landing_url":null,"s2_open_access_license":null,"s2_open_access_status":null,"pmc_open_access_pdf_url":null,"pmc_open_access_landing_url":null,"pmc_open_access_license":null,"pmc_open_access_status":null,"unpaywall_open_access_pdf_url":null,"unpaywall_open_access_landing_url":null,"unpaywall_open_access_license":null,"unpaywall_open_access_status":null,"abstract":"Screening for Lynch syndrome (LS) is routinely performed in patients with endometrial carcinoma. Currently, no screening recommendations exist for LS in precancerous lesions. The study goal was to determine the incidence of abnormal protein expression in endometrioid intraepithelial neoplasia/atypical hyperplasia (EIN/AH). We analyzed mismatch repair (MMR) protein expression by immunohistochemistry in EIN/AH concurrent with MMR-deficient endometrial carcinomas, and in endometrial biopsy/curettage specimens with EIN/AH from an unselected group of patients. Of 63 patients with MMR-deficient endometrial carcinoma, 34 demonstrated loss of MLH1/PMS2 expression; 1 showed loss of PMS2 alone; 12 showed loss of MSH2/MSH6, and 15 had loss of MSH6 alone. Genetic testing identified deleterious mutations in 14 cases (LS). 15 tumors demonstrated MLH1 promoter hypermethylation. Abnormal MMR expression in EIN/AH and adjacent carcinoma was concordant in 100% of LS cases and 71% of MLH1 promoter hypermethylation cases. Of 118 patients from the unselected group with EIN/AH, 4 (3%) cases demonstrated absent expression of one or more MMR proteins. Of these, 2 patients were later confirmed to have deleterious mutations in subsequent specimens with endometrial carcinoma. The prevalence of abnormal MMR expression in EIN/AH adjacent to carcinoma and in the unselected group of patients with EIN/AH is similar to the reported prevalence of LS in endometrial carcinoma. Identifying patients at high risk for LS through abnormal MMR expression in EIN/AH provides the benefit of early surveillance, treatment and timely diagnosis for the patient and affected family members.","claims":[{"public_id":"cl_f3e3b798a5ad91af643983bb0cf3fe73","status":"active","text":"Abnormal mismatch repair expression in EIN/AH and adjacent carcinoma was concordant in all Lynch syndrome cases and in 71% of MLH1 promoter hypermethylation cases.","confidence":0.97,"contributors":[{"id":1,"public_id":"12632b8b5f","public_label":"Anonymous (12632b8b5f)","roles":["extraction"],"url":"https://sah.borca.ai/u/12632b8b5f"}],"url":"https://sah.borca.ai/claims/cl_f3e3b798a5ad91af643983bb0cf3fe73"},{"public_id":"cl_3e64794950e5f464f4394d3def5f94dc","status":"active","text":"Abnormal mismatch repair protein expression in EIN/AH occurs at a prevalence similar to the reported prevalence of Lynch syndrome in endometrial 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