{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T18:40:08Z","timestamp":1790361608051,"version":"4.1.0"},"reference-count":202,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2026,1,28]],"date-time":"2026-01-28T00:00:00Z","timestamp":1769558400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Endometrial cancer is the most common gynaecologic malignancy in high-income countries, with a rising incidence largely driven by reproductive factors, obesity, and prolonged exposure to unopposed oestrogens. Although most cases are sporadic, approximately 2\u20135% are associated with hereditary cancer syndromes, of which Lynch syndrome represents the most important contributor. Lynch syndrome results from germline mutations in DNA mismatch repair (MMR) genes and is associated with a substantially increased lifetime risk of endometrial cancer, reaching up to 71% in carriers of MutS homologue 6 (MSH6) mutations. Hereditary cancer predisposition typically follows an autosomal dominant inheritance pattern and may be suspected based on clinical warning signs such as early disease onset, multiple primary malignancies, a strong family history, or the presence of microsatellite instability in tumour tissue. In addition to Lynch syndrome, rarer genetic conditions\u2014including Cowden syndrome (PTEN), Li\u2013Fraumeni syndrome (TP53), polymerase proofreading\u2013associated polyposis (POLE\/POLD1), and hereditary breast and ovarian cancer syndromes (BRCA1\/2)\u2014also contribute to hereditary endometrial cancer risk. Recognition of these genetic backgrounds is essential for accurate diagnosis, personalised surveillance, and the implementation of targeted preventive and therapeutic strategies. Despite major advances in molecular diagnostics, hereditary endometrial cancer remains frequently underdiagnosed, leading to missed opportunities for cancer prevention among affected individuals and their families. This comprehensive review summarises current evidence on hereditary predispositions to endometrial cancer, with a particular emphasis on Lynch syndrome, and discusses underlying genetic mechanisms, inheritance patterns, diagnostic strategies, and clinical implications for screening, genetic counselling, and treatment optimisation.<\/jats:p>","DOI":"10.3390\/ijms27031304","type":"journal-article","created":{"date-parts":[[2026,1,28]],"date-time":"2026-01-28T15:04:46Z","timestamp":1769612686000},"page":"1304","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Hereditary Endometrial Cancer: Lynch Syndrome, Mismatch Repair Deficiency, and Emerging Genetic Predispositions\u2014A Comprehensive Review with Clinical and Laboratory Guidelines"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7008-114X","authenticated-orcid":false,"given":"Andrzej","family":"Kluk","sequence":"first","affiliation":[{"name":"Department of Pathomorphology, Poznan University of Medical Sciences, 60-355 Poznan, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-7928-1702","authenticated-orcid":false,"given":"Hanna","family":"Gryczka","sequence":"additional","affiliation":[{"name":"Department of Pathomorphology, Poznan University of Medical Sciences, 60-355 Poznan, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0347-4829","authenticated-orcid":false,"given":"Ma\u0142gorzata","family":"Braszka","sequence":"additional","affiliation":[{"name":"Cairns Base Hospital, Cairns, QLD 4870, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-5346-4526","authenticated-orcid":false,"given":"Rafa\u0142","family":"A\u0142tyn","sequence":"additional","affiliation":[{"name":"IT Department, Poznan University of Medical Sciences, 61-701 Poznan, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-2548-0552","authenticated-orcid":false,"given":"Hanna","family":"Markiewicz","sequence":"additional","affiliation":[{"name":"Department of Histology and Embryology, Faculty of Medicine, Medical University of Warsaw, 02-004 Warsaw, Poland"},{"name":"Department of Methodology, Faculty of Medicine, Medical University of Warsaw, 02-004 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-1777-213X","authenticated-orcid":false,"given":"Jan K.","family":"\u015al\u0119\u017cak","sequence":"additional","affiliation":[{"name":"Department of Pathomorphology, Poznan University of Medical Sciences, 60-355 Poznan, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2872-7987","authenticated-orcid":false,"given":"Ewa","family":"Dwojak","sequence":"additional","affiliation":[{"name":"Department of Pathomorphology, Poznan University of Medical Sciences, 60-355 Poznan, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-4033-6645","authenticated-orcid":false,"given":"Joanna","family":"Czerniak","sequence":"additional","affiliation":[{"name":"Centre of Experimental Medicine, Poznan University of Medical Sciences, 60-806 Poznan, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8552-2566","authenticated-orcid":false,"given":"Pawe\u0142","family":"Zieli\u0144ski","sequence":"additional","affiliation":[{"name":"Department of Pathomorphology, Poznan University of Medical Sciences, 60-355 Poznan, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5579-5101","authenticated-orcid":false,"given":"Bartosz J.","family":"P\u0142achno","sequence":"additional","affiliation":[{"name":"Institute of Botany, Faculty of Biology, Jagiellonian University, 30-387 Cracow, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5134-0975","authenticated-orcid":false,"given":"Paula","family":"Dobosz","sequence":"additional","affiliation":[{"name":"Department of Pathomorphology, Poznan University of Medical Sciences, 60-355 Poznan, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,1,28]]},"reference":[{"key":"ref_1","unstructured":"Mahdy, H., Vadakekut, E.S., and Crotzer, D. (2025, November 15). Endometrial cancer, StatPearls [Internet], Available online: https:\/\/www.ncbi.nlm.nih.gov\/books\/NBK525981\/."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"D\u00f6rk, T., Hillemanns, P., Tempfer, C., Breu, J., and Fleisch, M.C. (2020). Genetic susceptibility to endometrial cancer: Risk factors and clinical management. Cancers, 12.","DOI":"10.3390\/cancers12092407"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"2167","DOI":"10.1038\/s41436-019-0536-8","article-title":"The proportion of endometrial cancers associated with Lynch syndrome: A systematic review and meta-analysis","volume":"21","author":"Ryan","year":"2019","journal-title":"Genet. Med."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Garutti, M., Foffano, L., Mazzeo, R., Michelotti, A., Da Ros, L., Viel, A., Miolo, G., Zambelli, A., and Puglisi, F. (2023). Hereditary cancer syndromes: A comprehensive review with a visual tool. Genes, 14.","DOI":"10.3390\/genes14051025"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"40","DOI":"10.5306\/wjco.v14.i2.40","article-title":"Hereditary cancer syndromes","volume":"14","author":"Imyanitov","year":"2023","journal-title":"World J. Clin. Oncol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"695","DOI":"10.6004\/jnccn.2024.0061","article-title":"Genetic\/familial high-risk assessment: Colorectal, endometrial, and gastric, version 3.2024, NCCN Clinical Practice Guidelines in Oncology","volume":"22","author":"Hodan","year":"2024","journal-title":"J. Natl. Compr. Cancer Netw."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"3353","DOI":"10.1038\/s41467-020-16483-3","article-title":"Assessment of polygenic architecture and risk prediction based on common variants across fourteen cancers","volume":"11","author":"Zhang","year":"2020","journal-title":"Nat. Commun."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1733","DOI":"10.1002\/cncr.35267","article-title":"A tale of two pathways: Immune checkpoint inhibitors in mismatch repair\u2013deficient and microsatellite instability\u2013high endometrial cancers","volume":"130","author":"Liu","year":"2024","journal-title":"Cancer"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1038\/nature12634","article-title":"Mutational landscape and significance across 12 major cancer types","volume":"502","author":"Kandoth","year":"2013","journal-title":"Nature"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"2509","DOI":"10.1056\/NEJMoa1500596","article-title":"PD-1 blockade in tumors with mismatch-repair deficiency","volume":"372","author":"Le","year":"2015","journal-title":"N. Engl. J. Med."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"752","DOI":"10.1200\/JCO.21.01874","article-title":"Pembrolizumab in patients with microsatellite instability\u2013high advanced endometrial cancer: KEYNOTE-158","volume":"40","author":"Bariani","year":"2022","journal-title":"J. Clin. Oncol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"383","DOI":"10.1002\/ijgo.14923","article-title":"FIGO staging of endometrial cancer: 2023","volume":"162","author":"Berek","year":"2023","journal-title":"Int. J. Gynaecol. Obstet."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"e423","DOI":"10.1016\/S1470-2045(25)00167-6","article-title":"ESGO\u2013ESTRO\u2013ESP guidelines for the management of patients with endometrial carcinoma: Update 2025","volume":"26","author":"Concin","year":"2025","journal-title":"Lancet Oncol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"2304","DOI":"10.1001\/jama.2011.743","article-title":"Cancer risks associated with germline mutations in MLH1, MSH2 and MSH6 genes in Lynch syndrome","volume":"305","author":"Bonadona","year":"2011","journal-title":"JAMA"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"7810","DOI":"10.1158\/0008-5472.CAN-06-1114","article-title":"Screening for Lynch syndrome among endometrial cancer patients","volume":"66","author":"Hampel","year":"2006","journal-title":"Cancer Res."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"404","DOI":"10.1158\/1055-9965.EPI-16-0693","article-title":"Prevalence and penetrance of major genes and polygenes for colorectal cancer","volume":"26","author":"Win","year":"2017","journal-title":"Cancer Epidemiol. Biomarkers Prev."},{"key":"ref_17","first-page":"15","article-title":"Cancer risks by gene, age, and gender in carriers of pathogenic mismatch repair variants","volume":"22","author":"Sampson","year":"2020","journal-title":"Genet. Med."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1016\/j.ygyno.2009.03.003","article-title":"Current and emerging trends in Lynch syndrome identification in women with endometrial cancer","volume":"114","author":"Resnick","year":"2009","journal-title":"Gynecol. Oncol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"2247","DOI":"10.1200\/JCO.2010.32.9979","article-title":"Testing women with endometrial cancer to detect Lynch syndrome","volume":"29","author":"Kwon","year":"2011","journal-title":"J. Clin. Oncol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1093\/jnci\/djh034","article-title":"Revised Bethesda guidelines for hereditary nonpolyposis colorectal cancer and microsatellite instability","volume":"96","author":"Umar","year":"2004","journal-title":"J. Natl. Cancer Inst."},{"key":"ref_21","unstructured":"Bhattacharya, P., Leslie, S.W., and McHugh, T.W. (2025, November 15). Lynch syndrome (hereditary nonpolyposis colorectal cancer), StatPearls [Internet], Available online: https:\/\/www.ncbi.nlm.nih.gov\/books\/."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1023\/A:1011590617833","article-title":"Cancer risk in mismatch repair gene mutation carriers","volume":"1","author":"Watson","year":"2001","journal-title":"Fam. Cancer"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1362","DOI":"10.18203\/2320-6012.ijrms20250715","article-title":"The Lynch syndrome\u2014A tip of an iceberg: A review of articles","volume":"13","author":"Modi","year":"2025","journal-title":"Int. J. Res. Med. Sci."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"350309","DOI":"10.1155\/2012\/350309","article-title":"Clinicopathological features and management of cancers in Lynch syndrome","volume":"2012","author":"Aarnio","year":"2012","journal-title":"Pathol. Res. Int."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1177\/107327480901600103","article-title":"Endometrial cancer and Lynch syndrome: Clinical and pathologic considerations","volume":"16","author":"Meyer","year":"2009","journal-title":"Cancer Control"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1080","DOI":"10.1136\/jmg-2024-110231","article-title":"Lynch syndrome diagnostic testing pathways in endometrial cancers: A nationwide English registry-based study","volume":"61","author":"Loong","year":"2024","journal-title":"J. Med. Genet."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1186\/1897-4287-7-17","article-title":"Cancer risk in MLH1, MSH2 and MSH6 mutation carriers: Different risk profiles may influence clinical management","volume":"7","author":"Ramsoekh","year":"2009","journal-title":"Hered. Cancer Clin. Pract."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1704","DOI":"10.21037\/atm-20-1582","article-title":"Ovarian cancer risk assessment in the era of next-generation sequencing","volume":"8","author":"Bonadio","year":"2020","journal-title":"Ann. Transl. Med."},{"key":"ref_29","unstructured":"Idos, G., and Valle, L. (2025, November 16). Lynch syndrome, GeneReviews\u00ae [Internet], Available online: https:\/\/www.ncbi.nlm.nih.gov\/books\/NBK1211\/."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"481","DOI":"10.1016\/j.gastrohep.2015.11.009","article-title":"Hereditary gastric and pancreatic cancer predisposition syndromes","volume":"39","author":"Leoz","year":"2016","journal-title":"Gastroenterol. Hepatol. (Engl. Ed.)"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1008","DOI":"10.1002\/ags3.12809","article-title":"High risk of multiple gastric cancers in Japanese individuals with Lynch syndrome","volume":"8","author":"Kanaya","year":"2024","journal-title":"Ann. Gastroenterol. Surg."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1501","DOI":"10.1097\/PAS.0000000000000321","article-title":"Lynch syndrome screening should be considered for all patients with newly diagnosed endometrial cancer","volume":"38","author":"Mills","year":"2014","journal-title":"Am. J. Surg. Pathol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1007\/s13669-012-0029-0","article-title":"Hereditary endometrial cancer: Lynch syndrome","volume":"2","author":"Banno","year":"2013","journal-title":"Curr. Obstet. Gynecol. Rep."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1111\/tog.12706","article-title":"Lynch syndrome for the gynaecologist","volume":"23","author":"Ryan","year":"2021","journal-title":"Obstet. Gynaecol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1016\/j.dnarep.2015.11.019","article-title":"DNA mismatch repair and the DNA damage response","volume":"38","author":"Li","year":"2016","journal-title":"DNA Repair."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1200\/PO.17.00073","article-title":"Landscape of microsatellite instability across 39 cancer types","volume":"1","author":"Bonneville","year":"2017","journal-title":"JCO Precis. Oncol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"816","DOI":"10.1126\/science.8484122","article-title":"Microsatellite instability in cancer of the proximal colon","volume":"260","author":"Thibodeau","year":"1993","journal-title":"Science"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"558","DOI":"10.1038\/363558a0","article-title":"Ubiquitous somatic mutations in simple repeated sequences reveal a new mechanism for colonic carcinogenesis","volume":"363","author":"Ionov","year":"1993","journal-title":"Nature"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"820","DOI":"10.1073\/pnas.68.4.820","article-title":"Mutation and cancer: Statistical study of retinoblastoma","volume":"68","author":"Knudson","year":"1971","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1186\/s13053-022-00243-z","article-title":"The prospective Lynch syndrome database: Background, design, and main results","volume":"20","year":"2022","journal-title":"Hered. Cancer Clin. Pract."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1417","DOI":"10.1007\/s12253-020-00811-5","article-title":"Diagnostic accuracy of immunohistochemistry for mismatch repair proteins as a surrogate of MSI testing in endometrial cancer","volume":"26","author":"Raffone","year":"2020","journal-title":"Pathol. Oncol. Res."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"2145","DOI":"10.1056\/NEJMoa2216334","article-title":"Dostarlimab for primary advanced or recurrent endometrial cancer","volume":"388","author":"Mirza","year":"2023","journal-title":"N. Engl. J. Med."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"3506","DOI":"10.1093\/hmg\/ddu058","article-title":"New insights into POLE and POLD1 germline mutations in familial colorectal cancer","volume":"23","author":"Valle","year":"2014","journal-title":"Hum. Mol. Genet."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1016\/j.mad.2008.02.012","article-title":"DNA mismatch repair: Molecular mechanism, cancer, and ageing","volume":"129","author":"Hsieh","year":"2008","journal-title":"Mech. Ageing Dev."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"26395","DOI":"10.1074\/jbc.R115.660142","article-title":"Mismatch repair","volume":"290","author":"Fishel","year":"2015","journal-title":"J. Biol. Chem."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"324","DOI":"10.1038\/ng.318","article-title":"Genome-wide association study identifies a new breast cancer susceptibility locus at 6q25.1","volume":"41","author":"Zheng","year":"2009","journal-title":"Nat. Genet."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1016\/j.jmoldx.2010.11.011","article-title":"Frequency of EPCAM deletions in MSH2-associated Lynch syndrome","volume":"13","author":"Rumilla","year":"2011","journal-title":"J. Mol. Diagn."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"3098","DOI":"10.1158\/0008-5472.CAN-09-3290","article-title":"Somatic hypermethylation of MSH2 is a frequent event in Lynch syndrome colorectal cancers","volume":"70","author":"Nagasaka","year":"2010","journal-title":"Cancer Res."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"697","DOI":"10.1056\/NEJMoa064522","article-title":"Inheritance of a cancer-associated MLH1 germ-line epimutation","volume":"356","author":"Hitchins","year":"2007","journal-title":"N. Engl. J. Med."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1186\/s13148-023-01511-y","article-title":"Identifying primary and secondary MLH1 epimutation carriers displaying low-level constitutional MLH1 methylation using droplet digital PCR and genome-wide DNA methylation profiling of colorectal cancers","volume":"15","author":"Joo","year":"2023","journal-title":"Clin. Epigenetics"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"743","DOI":"10.6004\/jnccn.2023.7020","article-title":"Constitutional MLH1 methylation is a major contributor to mismatch repair\u2013deficient, MLH1-methylated colorectal cancer in patients aged 55 years and younger","volume":"21","author":"Hitchins","year":"2023","journal-title":"J. Natl. Compr. Cancer Netw."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"264","DOI":"10.1136\/jclinpath-2020-207281","article-title":"DNA mismatch repair proteins: Scientific update and practical guide","volume":"74","author":"Bateman","year":"2021","journal-title":"J. Clin. Pathol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"314","DOI":"10.1002\/gcc.23015","article-title":"Mismatch repair deficiency: The what, how and why it is important","volume":"61","author":"Olave","year":"2022","journal-title":"Genes. Chromosomes Cancer"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1007\/s10689-016-9882-8","article-title":"Update on Lynch syndrome genomics","volume":"15","year":"2016","journal-title":"Fam. Cancer"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"2587","DOI":"10.1093\/emboj\/20.10.2587","article-title":"Replication slippage involves DNA polymerase pausing and dissociation","volume":"20","author":"Viguera","year":"2001","journal-title":"EMBO J."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"726","DOI":"10.1038\/s41416-022-02059-z","article-title":"Lynch syndrome: Molecular mechanisms and variant classification","volume":"128","author":"Abildgaard","year":"2023","journal-title":"Br. J. Cancer"},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"Favier, A., Varinot, J., Uzan, C., Duval, A., Brocheriou, I., and Canlorbe, G. (2022). Immunohistochemistry markers in mismatch repair\u2013deficient endometrial cancer: A systematic review. Cancers, 14.","DOI":"10.3390\/cancers14153783"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1016\/j.ygyno.2023.08.015","article-title":"Differential outcomes and immune checkpoint inhibitor response among endometrial cancer patients with MLH1 hypermethylation versus MLH1 \u201cLynch-like\u201d mismatch repair gene mutation","volume":"177","author":"Toboni","year":"2023","journal-title":"Gynecol. Oncol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"312","DOI":"10.1158\/2159-8290.CD-22-0686","article-title":"Distinct mechanisms of mismatch-repair deficiency delineate two modes of response to anti\u2013PD-1 immunotherapy in endometrial carcinoma","volume":"13","author":"Chow","year":"2023","journal-title":"Cancer Discov."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"591","DOI":"10.1586\/14737159.2016.1156533","article-title":"Mismatch repair deficiency testing in clinical practice","volume":"16","author":"Buza","year":"2016","journal-title":"Expert. Rev. Mol. Diagn."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1002\/ijc.33763","article-title":"Endometrial cancer in Lynch syndrome","volume":"150","author":"Zhao","year":"2022","journal-title":"Int. J. Cancer"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"953","DOI":"10.1097\/IGC.0000000000000985","article-title":"Clinicopathologic characteristics of endometrial cancer in Lynch syndrome","volume":"27","author":"Rossi","year":"2017","journal-title":"Int. J. Gynecol. Cancer"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"4473","DOI":"10.1158\/1078-0432.CCR-16-2655","article-title":"Immune microenvironment in microsatellite-instable endometrial cancers: Hereditary or sporadic origin matters","volume":"23","author":"Pakish","year":"2017","journal-title":"Clin. Cancer Res."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"e32572","DOI":"10.1097\/MD.0000000000032572","article-title":"Clinical and genetic diagnosis of Cowden syndrome: A case report of a rare PTEN germline variant and diverse clinical presentation","volume":"102","author":"Arai","year":"2023","journal-title":"Medicine"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"428","DOI":"10.1053\/j.seminoncol.2007.07.009","article-title":"Cowden syndrome","volume":"34","author":"Gustafson","year":"2007","journal-title":"Semin. Oncol."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1002\/(SICI)1098-2264(199801)21:1<2::AID-GCC2>3.0.CO;2-5","article-title":"Molecular alterations in the TP53 gene of peripheral blood cells of patients with chronic myeloid leukemia","volume":"21","author":"Peller","year":"1998","journal-title":"Genes Chromosomes Cancer"},{"key":"ref_67","first-page":"e67241","article-title":"Cowden syndrome: A case series highlighting cutaneous and systemic diversity","volume":"16","author":"Rossi","year":"2024","journal-title":"Cureus"},{"key":"ref_68","unstructured":"Yehia, L., and Eng, C. (2025, October 10). PTEN hamartoma tumor syndrome, GeneReviews\u00ae [Internet], Available online: https:\/\/www.ncbi.nlm.nih.gov\/books\/NBK1488\/."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"2023","DOI":"10.23922\/jarc.2023-028","article-title":"Clinical guidelines for diagnosis and management of Cowden syndrome\/PTEN hamartoma tumor syndrome in children and adults: Secondary publication","volume":"7","author":"Takayama","year":"2023","journal-title":"J. Anus Rectum Colon."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"85","DOI":"10.5946\/ce.2013.46.1.85","article-title":"Autosomal dominant inherited Cowden\u2019s disease in a family","volume":"46","author":"Ha","year":"2013","journal-title":"Clin. Endosc."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1136\/jmg.38.3.159","article-title":"Male breast cancer in Cowden syndrome patients with germline PTEN mutations","volume":"38","author":"Fackenthal","year":"2001","journal-title":"J. Med. Genet."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1016\/j.gynor.2012.10.006","article-title":"Endometrial cancer in a 15-year-old girl: A complication of Cowden syndrome","volume":"3","author":"ElNaggar","year":"2013","journal-title":"Gynecol. Oncol. Case Rep."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"400","DOI":"10.1158\/1078-0432.CCR-11-2283","article-title":"Lifetime cancer risks in individuals with germline PTEN mutations","volume":"18","author":"Tan","year":"2012","journal-title":"Clin. Cancer Res."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"876","DOI":"10.1111\/j.1447-0756.2012.02052.x","article-title":"Endometrial cancer in a 14-year-old girl with Cowden syndrome: A case report","volume":"39","author":"Baker","year":"2013","journal-title":"J. Obstet. Gynaecol. Res."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1016\/j.ygyno.2021.08.008","article-title":"Diagnosis and management of an endometrial cancer patient with Cowden syndrome","volume":"163","author":"Gatius","year":"2021","journal-title":"Gynecol. Oncol."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"77","DOI":"10.6004\/jnccn.2021.0001","article-title":"Genetic\/familial high-risk assessment: Breast, ovarian, and pancreatic, version 2.2021","volume":"19","author":"Daly","year":"2021","journal-title":"J. Natl. Compr. Cancer Netw."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1007\/s40291-013-0020-0","article-title":"Tumor protein p53 (TP53) testing and Li-Fraumeni syndrome","volume":"17","author":"Sorrell","year":"2013","journal-title":"Mol. Diagn. Ther."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"a026187","DOI":"10.1101\/cshperspect.a026187","article-title":"Inherited TP53 mutations and the Li\u2013Fraumeni syndrome","volume":"7","author":"Guha","year":"2017","journal-title":"Cold Spring Harb. Perspect. Med."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"1250","DOI":"10.1200\/JCO.2008.16.6959","article-title":"Beyond Li-Fraumeni syndrome: Clinical characteristics of families with p53 germline mutations","volume":"27","author":"Gonzalez","year":"2009","journal-title":"J. Clin. Oncol."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1016\/j.soc.2008.08.006","article-title":"Li-Fraumeni syndrome: The genetics and treatment considerations for the sarcoma and associated neoplasms","volume":"18","author":"Upton","year":"2009","journal-title":"Surg. Oncol. Clin. N. Am."},{"key":"ref_81","unstructured":"Schneider, K., Zelley, K., Nichols, K.E., Schwartz Levine, A., and Garber, J. (2025, October 12). Li-Fraumeni syndrome, GeneReviews\u00ae [Internet], Available online: https:\/\/www.ncbi.nlm.nih.gov\/books\/NBK1311\/."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"258","DOI":"10.1097\/PGP.0000000000000792","article-title":"Endometrial carcinoma as the presenting malignancy in a teenager with a pathogenic TP53 germline mutation: A case report and literature review","volume":"41","author":"Irshaid","year":"2022","journal-title":"Int. J. Gynecol. Pathol."},{"key":"ref_83","doi-asserted-by":"crossref","unstructured":"Ye, Q.L., Qi, Y., Liu, J.J., Hu, Y.X., Lv, Y., and Lin, B. (2023). First case of endometrial cancer after yolk sac tumor in a patient with Li-Fraumeni syndrome. BMC Womens Health, 23.","DOI":"10.1186\/s12905-023-02426-9"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"545","DOI":"10.1007\/s13244-015-0425-x","article-title":"Do hereditary syndrome-related gynecologic cancers have any specific features?","volume":"6","author":"Neto","year":"2015","journal-title":"Insights Imaging"},{"key":"ref_85","unstructured":"Casaubon, J.T., Kashyap, S., and Regan, J.P. (2025, November 02). BRCA1 and BRCA2 mutations, StatPearls [Internet], Available online: https:\/\/www.ncbi.nlm.nih.gov\/books\/."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1126\/science.7545954","article-title":"A strong candidate for the breast and ovarian cancer susceptibility gene BRCA1","volume":"266","author":"Miki","year":"1994","journal-title":"Science"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"433","DOI":"10.1016\/S0092-8674(00)80936-8","article-title":"BRCA1, BRCA2, and DNA damage response: Collision or collusion?","volume":"92","author":"Zhang","year":"1998","journal-title":"Cell"},{"key":"ref_88","first-page":"5485","article-title":"Nuclear location and cell cycle regulation of the BRCA2 protein","volume":"57","author":"Bertwistle","year":"1997","journal-title":"Cancer Res."},{"key":"ref_89","unstructured":"National Comprehensive Cancer Network (2025, October 23). Genetic\/Familial High-Risk Assessment: Breast, Ovarian, Pancreatic, and Prostate (NCCN Guidelines\u00ae, ID 1545). Version 2.2026. Available online: https:\/\/www.nccn.org\/guidelines\/guidelines-detail?category=2&id=1545."},{"key":"ref_90","doi-asserted-by":"crossref","unstructured":"Zakerinasab, F., Behfar, Q., Parsaee, R., Hossein Zadeh, R., Foroughi, E., Amirbeik, A., Mirzaie, M., Ghaffari, P., Najafi, S., and Farzaneh, P. (2024). BRCA1\/2 mutations and risk of uterine cancer: A systematic review and meta-analysis. BMC Genom. Data, 25.","DOI":"10.1186\/s12863-024-01189-y"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"1203","DOI":"10.1093\/jnci\/djab036","article-title":"Endometrial cancer risk in women with germline BRCA1 or BRCA2 mutations: Multicenter cohort study","volume":"113","author":"Jenner","year":"2021","journal-title":"J. Natl. Cancer Inst."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"698","DOI":"10.1002\/cncr.31842","article-title":"Uterine cancer in Jewish Israeli BRCA1\/2 mutation carriers","volume":"125","author":"Laitman","year":"2019","journal-title":"Cancer"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"1434","DOI":"10.1001\/jamaoncol.2016.1820","article-title":"Uterine cancer after risk-reducing salpingo-oophorectomy without hysterectomy in women with BRCA mutations","volume":"2","author":"Shu","year":"2016","journal-title":"JAMA Oncol."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"650","DOI":"10.1097\/IGC.0000000000000402","article-title":"Endometrial cancers in mutation carriers from hereditary breast ovarian cancer syndrome kindreds","volume":"25","author":"Casey","year":"2015","journal-title":"Int. J. Gynecol. Cancer"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"114","DOI":"10.1016\/j.ejca.2017.07.004","article-title":"Risk of uterine cancer for BRCA1 and BRCA2 mutation carriers","volume":"84","author":"Lee","year":"2017","journal-title":"Eur. J. Cancer"},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1016\/j.ejca.2020.05.030","article-title":"BRCA1 and BRCA2 pathogenic variant carriers and endometrial cancer risk: A cohort study","volume":"136","author":"Kitson","year":"2020","journal-title":"Eur. J. Cancer"},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"572","DOI":"10.1038\/modpathol.2012.169","article-title":"Endometrium is not the primary site of origin of pelvic high-grade serous carcinoma in BRCA1 or BRCA2 mutation carriers","volume":"26","author":"Reitsma","year":"2013","journal-title":"Mod. Pathol."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1093\/jnci\/djx159","article-title":"Risk of serous endometrial carcinoma in women with pathogenic BRCA1\/2 variant after risk-reducing salpingo-oophorectomy","volume":"110","author":"Saule","year":"2018","journal-title":"J. Natl. Cancer Inst."},{"key":"ref_99","first-page":"1033","article-title":"Risk of endometrial cancer after RRSO in BRCA1\/2 carriers: A multicentre cohort study","volume":"26","author":"Pardo","year":"2024","journal-title":"Clin. Transl. Oncol."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1016\/j.ejca.2016.11.028","article-title":"Linking uterine serous carcinoma to BRCA1\/2-associated cancer syndrome: A meta-analysis and case report","volume":"72","author":"Mooyaart","year":"2017","journal-title":"Eur. J. Cancer"},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"1080","DOI":"10.1038\/ejhg.2014.242","article-title":"Germline variants in POLE are associated with early onset mismatch repair deficient colorectal cancer","volume":"23","author":"Lsayed","year":"2015","journal-title":"Eur. J. Hum. Genet."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1186\/s13073-023-01234-y","article-title":"Recommendations for the classification of germline variants in the exonuclease domain of POLE and POLD1","volume":"15","author":"Mur","year":"2023","journal-title":"Genome Med."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1038\/gim.2015.75","article-title":"POLE and POLD1 mutations in 529 kindred with familial colorectal cancer and\/or polyposis","volume":"18","author":"Bellido","year":"2016","journal-title":"Genet. Med."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1038\/s41698-022-00258-8","article-title":"Collision of germline POLE and PMS2 variants in a young patient treated with immune checkpoint inhibitors","volume":"6","author":"Berrino","year":"2022","journal-title":"NPJ Precis. Oncol."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"555","DOI":"10.1007\/s00438-023-02000-w","article-title":"Characterization of POLE c.1373A>T p.(Tyr458Phe), causing high cancer risk","volume":"298","author":"Rocque","year":"2023","journal-title":"Mol. Genet. Genom."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"1827","DOI":"10.1002\/humu.23655","article-title":"Matchbox: An open-source tool for patient matching via the Matchmaker Exchange","volume":"39","author":"Arachchi","year":"2018","journal-title":"Hum. Mutat."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"216","DOI":"10.1186\/s13046-022-02422-1","article-title":"POLE\/POLD1 mutation and tumor immunotherapy","volume":"41","author":"Ma","year":"2022","journal-title":"J. Exp. Clin. Cancer Res."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"1381","DOI":"10.1038\/modpathol.2016.135","article-title":"Germline multi-gene hereditary cancer panel testing in an unselected endometrial cancer cohort","volume":"29","author":"Ring","year":"2016","journal-title":"Mod. Pathol."},{"key":"ref_109","doi-asserted-by":"crossref","unstructured":"Anca-Stanciu, M.B., Manu, A., Olinca, M.V., Coroleuc\u0103, C., Comanda\u0219u, D.E., Coroleuca, C.A., Mogo\u0219, D., M\u0103rginean, C.O., Niculescu, A.M., and Popescu, M.F. (2025). Comprehensive review of endometrial cancer: New molecular and FIGO classification and recent treatment changes. J. Clin. Med., 14.","DOI":"10.3390\/jcm14041385"},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"3145","DOI":"10.1002\/cncr.31534","article-title":"Universal screening of both endometrial and colon cancers increases the detection of Lynch syndrome","volume":"124","author":"Adar","year":"2018","journal-title":"Cancer"},{"key":"ref_111","doi-asserted-by":"crossref","unstructured":"Stewart, A. (2013). Genetic testing strategies in newly diagnosed endometrial cancer patients aimed at reducing morbidity or mortality from Lynch syndrome in the index case or her relatives. PLoS Curr., 16.","DOI":"10.1371\/currents.eogt.b59a6e84f27c536e50db4e46aa26309c"},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"2390","DOI":"10.1038\/s41436-019-0489-y","article-title":"The Manchester International Consensus Group recommendations for the management of gynecological cancers in Lynch syndrome","volume":"21","author":"Crosbie","year":"2019","journal-title":"Genet. Med."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1016\/j.path.2016.01.004","article-title":"Lynch syndrome","volume":"9","author":"Mills","year":"2016","journal-title":"Surg. Pathol. Clin."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"1308","DOI":"10.1053\/j.gastro.2014.08.041","article-title":"Colon and endometrial cancers with mismatch repair deficiency can arise from somatic, rather than germline, mutations","volume":"147","author":"Haraldsdottir","year":"2014","journal-title":"Gastroenterology"},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1093\/annonc\/mdw542","article-title":"Practical guidance for mismatch repair-deficiency testing in endometrial cancer","volume":"28","author":"Stelloo","year":"2017","journal-title":"Ann. Oncol."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"3667","DOI":"10.31557\/APJCP.2024.25.10.3667","article-title":"Simplifying mismatch repair deficiency screening in endometrial adenocarcinoma: Immunohistochemistry with two-antibody panel (PMS2 and MSH6)","volume":"25","author":"Panyavaranant","year":"2024","journal-title":"Asian Pac. J. Cancer Prev."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"409","DOI":"10.3109\/00313025.2010.493871","article-title":"Immunohistochemistry for PMS2 and MSH6 alone can replace a four antibody panel for mismatch repair deficiency screening in colorectal adenocarcinoma","volume":"42","author":"Hall","year":"2010","journal-title":"Pathology"},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"1775","DOI":"10.1038\/s41379-022-01149-w","article-title":"Validity of a two-antibody testing algorithm for mismatch repair deficiency testing in cancer: A systematic literature review and meta-analysis","volume":"35","author":"Aiyer","year":"2022","journal-title":"Mod. Pathol."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"78","DOI":"10.5858\/arpa.2022-0280-RA","article-title":"Practical updates and diagnostic challenges in endometrial carcinoma","volume":"148","author":"Turashvili","year":"2024","journal-title":"Arch. Pathol. Lab. Med."},{"key":"ref_120","doi-asserted-by":"crossref","unstructured":"Addante, F., d\u2019Amati, A., Santoro, A., Angelico, G., Inzani, F., Arciuolo, D., Ricciardi, E., Montironi, R., Maiorana, A., and Tonini, G. (2024). Mismatch repair deficiency as a predictive and prognostic biomarker in endometrial cancer: A review on immunohistochemistry staining patterns and clinical implications. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25021056"},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1016\/j.humpath.2017.10.022","article-title":"Universal screening for Lynch syndrome in endometrial cancers: Frequency of germline mutations and identification of patients with Lynch-like syndrome","volume":"70","author":"Dillon","year":"2017","journal-title":"Hum. Pathol."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"473","DOI":"10.1038\/s41586-024-07810-5","article-title":"Substrate binding and inhibition mechanism of norepinephrine transporter","volume":"633","author":"Ji","year":"2024","journal-title":"Nature"},{"key":"ref_123","doi-asserted-by":"crossref","unstructured":"Reitsam, N.G., M\u00e4rkl, B., Dintner, S., Waidhauser, J., Vlasenko, D., and Grosser, B. (2022). Concurrent loss of MLH1, PMS2 and MSH6 immunoexpression in digestive system cancers indicating a widespread dysregulation in DNA repair processes. Front. Oncol., 12.","DOI":"10.3389\/fonc.2022.1019798"},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1158\/1940-6207.CAPR-10-0345","article-title":"The search for unaffected individuals with Lynch syndrome: Do the ends justify the means?","volume":"4","author":"Hampel","year":"2011","journal-title":"Cancer Prev. Res."},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1016\/j.ygyno.2024.01.032","article-title":"The emerging and challenging role of PD-L1 in patients with gynecological cancers: An updating review with clinico-pathological considerations","volume":"184","author":"Santoro","year":"2024","journal-title":"Gynecol. Oncol."},{"key":"ref_126","doi-asserted-by":"crossref","unstructured":"Joder, C., Gm\u00fcr, A., Solass, W., Christe, L., Rabaglio, M., Fluri, M., Tschan, M.P., Perren, A., Herrmann, C., and Fr\u00fch, M. (2024). Real-world data on institutional implementation of screening for mismatch repair deficiency and Lynch syndrome in endometrial cancer patients. Cancers, 16.","DOI":"10.3390\/cancers16030671"},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"e000688","DOI":"10.1136\/bmjonc-2024-000688","article-title":"Mismatch in testing: A retrospective analysis of mismatch repair testing in endometrial cancer and Lynch syndrome diagnosis in multiple specialist centres in the UK and Ireland","volume":"4","author":"Ryan","year":"2025","journal-title":"BMJ Oncol."},{"key":"ref_128","doi-asserted-by":"crossref","unstructured":"Chung, Y., Nam, S.K., Chang, H.E., Lee, C., Kang, G.H., Lee, H.S., Kim, J.W., Park, S.Y., Choi, C.H., and Bae, D.S. (2023). Evaluation of an eight marker-panel including long mononucleotide repeat markers to detect microsatellite instability in colorectal, gastric, and endometrial cancers. BMC Cancer, 23.","DOI":"10.1186\/s12885-023-11607-6"},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"130","DOI":"10.1016\/j.ygyno.2024.12.020","article-title":"Pembrolizumab in microsatellite instability-high\/mismatch repair deficient (MSI-H\/dMMR) and non\u2013MSI-H\/non\u2013dMMR advanced endometrial cancer: Phase 2 KEYNOTE-158 study results","volume":"193","author":"Bariani","year":"2025","journal-title":"Gynecol. Oncol."},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1007\/s10689-017-0043-5","article-title":"Screening for germline mutations in mismatch repair genes in patients with Lynch syndrome by next generation sequencing","volume":"17","author":"Soares","year":"2018","journal-title":"Fam. Cancer"},{"key":"ref_131","doi-asserted-by":"crossref","unstructured":"Guo, Y., Yan, G., Zhang, P., Liu, Y., Zhao, C., and Zeng, X. (2024). The clinical utility of next generation sequencing in endometrial cancer: Focusing on molecular subtyping and Lynch syndrome. Front. Genet., 15.","DOI":"10.3389\/fgene.2024.1440971"},{"key":"ref_132","doi-asserted-by":"crossref","unstructured":"Plotkin, A., Olkhov-Mitsel, E., and Nofech-Mozes, S. (2023). MLH1 methylation testing as an integral component of universal endometrial cancer screening\u2014A critical appraisal. Cancers, 15.","DOI":"10.3390\/cancers15215188"},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"216","DOI":"10.3892\/ol.2023.13802","article-title":"Germline multigene panel testing of patients with endometrial cancer","volume":"25","author":"Kral","year":"2023","journal-title":"Oncol. Lett."},{"key":"ref_134","doi-asserted-by":"crossref","unstructured":"American College of Obstetricians and Gynecologists (2019). Committee Opinion No. 793: Hereditary cancer syndromes and risk assessment. Obstet. Gynecol., 134, e143\u2013e149. Available online: https:\/\/www.acog.org\/clinical\/clinical-guidance\/committee-opinion\/articles\/2019\/09\/hereditary-cancer-syndromes-and-risk-assessment.","DOI":"10.1097\/AOG.0000000000003562"},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"727","DOI":"10.1016\/j.jmoldx.2024.05.005","article-title":"Open-source bioinformatic pipeline to improve PMS2 genetic testing using short-read NGS data","volume":"26","author":"Blanco","year":"2024","journal-title":"J. Mol. Diagn."},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1038\/s41525-025-00461-z","article-title":"Whole genome sequencing completes the molecular genetic testing workflow of patients with Lynch syndrome","volume":"10","author":"Bozsik","year":"2025","journal-title":"NPJ Genom. Med."},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"156","DOI":"10.1186\/s40364-024-00701-x","article-title":"State of the art CRISPR-based strategies for cancer diagnostics and treatment","volume":"12","author":"Sorrentino","year":"2024","journal-title":"Biomark. Res."},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"424","DOI":"10.1007\/BF02053699","article-title":"The International Collaborative Group on Hereditary Non-Polyposis Colorectal Cancer (ICG-HNPCC)","volume":"34","author":"Vasen","year":"1991","journal-title":"Dis. Colon. Rectum"},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"1453","DOI":"10.1016\/S0016-5085(99)70510-X","article-title":"New clinical criteria for hereditary nonpolyposis colorectal cancer (HNPCC, Lynch syndrome) proposed by the International Collaborative Group on HNPCC","volume":"116","author":"Vasen","year":"1999","journal-title":"Gastroenterology"},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"1555","DOI":"10.1001\/jama.2012.13088","article-title":"Identification of Lynch syndrome among patients with colorectal cancer","volume":"308","author":"Moreira","year":"2012","journal-title":"JAMA"},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"2751","DOI":"10.1056\/NEJMoa053493","article-title":"Identification and survival of carriers of mutations in DNA mismatch-repair genes in colon cancer","volume":"354","author":"Barnetson","year":"2006","journal-title":"N. Engl. J. Med."},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1186\/s13053-023-00266-0","article-title":"Diagnosis of patients with Lynch syndrome lacking the Amsterdam II or Bethesda criteria","volume":"21","year":"2023","journal-title":"Hered. Cancer Clin. Pract."},{"key":"ref_143","doi-asserted-by":"crossref","unstructured":"Fanale, D., Corsini, L.R., Brando, C., Dimino, A., Filorizzo, C., Magrin, L., Bivona, L., Di Marco, F., Caruso, S., and Cognetti, F. (2022). Impact of different selection approaches for identifying Lynch syndrome-related colorectal cancer patients: Unity is strength. Front. Oncol., 12.","DOI":"10.3389\/fonc.2022.827822"},{"key":"ref_144","doi-asserted-by":"crossref","unstructured":"Gallon, R., Gawthorpe, P., Phelps, R.L., Hayes, C., Borthwick, G.M., Santibanez-Koref, M., Taylor, J.C., Thomas, H.J., Barrow, S., and Dunlop, M.G. (2021). How should we test for Lynch syndrome? A review of current guidelines and future strategies. Cancers, 13.","DOI":"10.3390\/cancers13030406"},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"djv308","DOI":"10.1093\/jnci\/djv308","article-title":"Comparison of prediction models for Lynch syndrome among individuals with colorectal cancer","volume":"108","author":"Kastrinos","year":"2016","journal-title":"J. Natl. Cancer Inst."},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"999","DOI":"10.1016\/j.gim.2022.01.012","article-title":"Universal tumor screening in a population with MSH6- and PMS2-associated Lynch syndrome","volume":"24","author":"Einarsson","year":"2022","journal-title":"Genet. Med."},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"806","DOI":"10.1001\/jamaoncol.2018.0104","article-title":"Assessment of tumor sequencing as a replacement for Lynch syndrome screening and current molecular tests for patients with colorectal cancer","volume":"4","author":"Hampel","year":"2018","journal-title":"JAMA Oncol."},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"1","DOI":"10.3310\/hta25420","article-title":"Testing strategies for Lynch syndrome in people with endometrial cancer: Systematic reviews and economic evaluation","volume":"25","author":"Stinton","year":"2021","journal-title":"Health Technol. Assess."},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1126\/science.aan6733","article-title":"Mismatch repair deficiency predicts response of solid tumors to PD-1 blockade","volume":"357","author":"Le","year":"2017","journal-title":"Science"},{"key":"ref_150","doi-asserted-by":"crossref","unstructured":"Cancer Genome Atlas Research Network, Kandoth, C., Schultz, N., Cherniack, A.D., Akbani, R., Liu, Y., Shen, H., Robertson, A.G., Pashtan, I., and Shen, R. (2013). Integrated genomic characterization of endometrial carcinoma. Nature, 497, 67\u201373.","DOI":"10.1038\/nature12113"},{"key":"ref_151","doi-asserted-by":"crossref","unstructured":"Leclerc, J., Vermaut, C., and Buisine, M.P. (2021). Diagnosis of Lynch syndrome and strategies to distinguish Lynch-related tumors from sporadic MSI\/dMMR tumors. Cancers, 13.","DOI":"10.3390\/cancers13030467"},{"key":"ref_152","doi-asserted-by":"crossref","first-page":"472","DOI":"10.1016\/j.jmoldx.2015.06.001","article-title":"Targeted next-generation sequencing for hereditary cancer syndromes","volume":"17","author":"Tafe","year":"2015","journal-title":"J. Mol. Diagn."},{"key":"ref_153","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1007\/s10689-024-00374-3","article-title":"Challenges and opportunities for Lynch syndrome cascade testing in the United States","volume":"23","author":"Passero","year":"2024","journal-title":"Fam. Cancer"},{"key":"ref_154","doi-asserted-by":"crossref","first-page":"67","DOI":"10.2147\/CMAR.S283668","article-title":"A focused clinical review of Lynch syndrome","volume":"15","author":"Georgiou","year":"2023","journal-title":"Cancer Manag. Res."},{"key":"ref_155","doi-asserted-by":"crossref","first-page":"1330","DOI":"10.1038\/s41591-024-02942-7","article-title":"Nivolumab for mismatch-repair-deficient or hypermutated gynecologic cancers: A phase 2 trial with biomarker analyses","volume":"30","author":"Friedman","year":"2024","journal-title":"Nat. Med."},{"key":"ref_156","doi-asserted-by":"crossref","first-page":"e35","DOI":"10.3802\/jgo.2025.36.e35","article-title":"A phase II study of induction PD-1 blockade (nivolumab) in patients with surgically completely resectable mismatch repair deficient endometrial cancer (NIVEC)","volume":"36","author":"Lee","year":"2025","journal-title":"J. Gynecol. Oncol."},{"key":"ref_157","doi-asserted-by":"crossref","first-page":"4685","DOI":"10.1158\/1078-0432.CCR-21-0327","article-title":"FDA approval summary: Pembrolizumab for the treatment of tumor mutational burden\u2013high solid tumors","volume":"27","author":"Marcus","year":"2021","journal-title":"Clin. Cancer Res."},{"key":"ref_158","doi-asserted-by":"crossref","first-page":"2930","DOI":"10.1172\/JCI91190","article-title":"IFN-\u03b3\u2013related mRNA profile predicts clinical response to PD-1 blockade","volume":"127","author":"Ayers","year":"2017","journal-title":"J. Clin. Investig."},{"key":"ref_159","doi-asserted-by":"crossref","first-page":"188","DOI":"10.1158\/2159-8290.CD-16-1223","article-title":"Primary resistance to PD-1 blockade mediated by JAK1\/2 mutations","volume":"7","author":"Shin","year":"2017","journal-title":"Cancer Discov."},{"key":"ref_160","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1056\/NEJMoa052627","article-title":"Prophylactic surgery to reduce the risk of gynecologic cancers in the Lynch syndrome","volume":"354","author":"Schmeler","year":"2006","journal-title":"N. Engl. J. Med."},{"key":"ref_161","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1007\/s10151-010-0666-0","article-title":"Prophylactic surgery in Lynch syndrome","volume":"15","author":"Celentano","year":"2011","journal-title":"Tech. Coloproctol."},{"key":"ref_162","doi-asserted-by":"crossref","first-page":"e34375","DOI":"10.1016\/j.heliyon.2024.e34375","article-title":"Effect of genetic profiling on surgical decisions at hereditary colorectal cancer syndromes","volume":"10","author":"Goudarzi","year":"2024","journal-title":"Heliyon"},{"key":"ref_163","first-page":"1","article-title":"Current surgical concepts in Lynch syndrome and familial adenomatous polyposis","volume":"39","author":"Horisberger","year":"2023","journal-title":"Viszeralmedizin"},{"key":"ref_164","unstructured":"U.S. National Library of Medicine (2025, October 17). A Clinical Trial of Pembrolizumab (MK-3475) Evaluating Predictive Biomarkers in Subjects with Advanced Solid Tumors (KEYNOTE-158). Identifier: NCT02628067, Available online: https:\/\/clinicaltrials.gov."},{"key":"ref_165","unstructured":"U.S. National Library of Medicine (2025, October 17). Study of Induction PD-1 Blockade in Subjects with Locally Advanced Mismatch Repair Deficient Rectal Adenocarcinoma. Identifier: NCT04165772, Available online: https:\/\/clinicaltrials.gov."},{"key":"ref_166","unstructured":"U.S. National Library of Medicine (2025, October 18). Phase II Study of Talazoparib with Androgen Deprivation Therapy and Abiraterone in Castration-Sensitive Prostate Cancer. Identifier: NCT04734730, Available online: https:\/\/clinicaltrials.gov."},{"key":"ref_167","unstructured":"U.S. National Library of Medicine (2025, October 20). Phase 3 Randomized Double-Blind Multicenter Study of Dostarlimab Plus Carboplatin-Paclitaxel Versus Placebo Plus Carboplatin-Paclitaxel in Patients with Recurrent or Primary Advanced Endometrial Cancer. Identifier: NCT03981796, Available online: https:\/\/clinicaltrials.gov."},{"key":"ref_168","doi-asserted-by":"crossref","first-page":"e103","DOI":"10.3802\/jgo.2024.35.e103","article-title":"Unveiling pembrolizumab effectiveness in diverse subtypes of MSI-high endometrial cancers","volume":"35","author":"Ozawa","year":"2024","journal-title":"J. Gynecol. Oncol."},{"key":"ref_169","doi-asserted-by":"crossref","first-page":"484","DOI":"10.1002\/bjs.11902","article-title":"European guidelines from the EHTG and ESCP for Lynch syndrome: An updated third edition of the Mallorca guidelines","volume":"108","author":"Latchford","year":"2021","journal-title":"Br. J. Surg."},{"key":"ref_170","doi-asserted-by":"crossref","unstructured":"Capasso, I., Santoro, A., Lucci Cordisco, E., Perrone, E., Tronconi, F., Catena, U., Marini, M., Rossi, F., De Stefano, V., and Bianchi, P. (2023). Lynch syndrome and gynecologic tumors: Incidence, prophylaxis, and management of patients with cancer. Cancers, 15.","DOI":"10.3390\/cancers15051400"},{"key":"ref_171","doi-asserted-by":"crossref","first-page":"150","DOI":"10.4254\/wjh.v11.i2.150","article-title":"Colorectal liver metastases: An update on multidisciplinary approach","volume":"11","author":"Chow","year":"2019","journal-title":"World J. Hepatol."},{"key":"ref_172","doi-asserted-by":"crossref","first-page":"2207","DOI":"10.1056\/NEJMoa2017699","article-title":"Pembrolizumab in microsatellite-instability\u2013high advanced colorectal cancer","volume":"383","author":"Shiu","year":"2020","journal-title":"N. Engl. J. Med."},{"key":"ref_173","doi-asserted-by":"crossref","first-page":"520","DOI":"10.1111\/den.13702","article-title":"Colorectal cancer screening in Lynch syndrome: Indication, techniques and future perspectives","volume":"33","author":"Perrod","year":"2021","journal-title":"Dig. Endosc."},{"key":"ref_174","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1111\/codi.12778","article-title":"Colonoscopy screening compliance and outcomes in patients with Lynch syndrome","volume":"17","author":"Newton","year":"2015","journal-title":"Colorectal Dis."},{"key":"ref_175","doi-asserted-by":"crossref","first-page":"453","DOI":"10.1053\/j.gastro.2021.04.010","article-title":"Gene-specific variation in colorectal cancer surveillance strategies for Lynch syndrome","volume":"161","author":"Kastrinos","year":"2021","journal-title":"Gastroenterology"},{"key":"ref_176","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1136\/gutjnl-2019-319915","article-title":"Guidelines for the management of hereditary colorectal cancer from the British Society of Gastroenterology, Association of Coloproctology of Great Britain and Ireland and United Kingdom Cancer Genetics Group","volume":"69","author":"Monahan","year":"2020","journal-title":"Gut"},{"key":"ref_177","doi-asserted-by":"crossref","unstructured":"American College of Obstetricians and Gynecologists, and Society of Gynecologic Oncology (2014). Practice bulletin no. 147. Obstet. Gynecol., 124, 1042\u20131054.","DOI":"10.1097\/01.AOG.0000456325.50739.72"},{"key":"ref_178","doi-asserted-by":"crossref","first-page":"1558","DOI":"10.1093\/annonc\/mdz233","article-title":"Hereditary gastrointestinal cancers: ESMO clinical practice guidelines for diagnosis, treatment and follow-up","volume":"30","author":"Stjepanovic","year":"2019","journal-title":"Ann. Oncol."},{"key":"ref_179","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1038\/ajg.2014.435","article-title":"ACG clinical guideline: Genetic testing and management of hereditary gastrointestinal cancer syndromes","volume":"110","author":"Syngal","year":"2015","journal-title":"Am. J. Gastroenterol."},{"key":"ref_180","doi-asserted-by":"crossref","first-page":"775","DOI":"10.1093\/jnci\/djad074","article-title":"The scope of colorectal cancer screening in Lynch syndrome: Is there an optimal interval?","volume":"115","author":"Biller","year":"2023","journal-title":"J. Natl. Cancer Inst."},{"key":"ref_181","doi-asserted-by":"crossref","unstructured":"Underkofler, K.A., and Ring, K.L. (2023). Updates in gynecologic care for individuals with Lynch syndrome. Front. Oncol., 13.","DOI":"10.3389\/fonc.2023.1127683"},{"key":"ref_182","doi-asserted-by":"crossref","first-page":"264","DOI":"10.5694\/mja2.52227","article-title":"Screening and prevention of ovarian cancer","volume":"220","author":"Sideris","year":"2024","journal-title":"Med. J. Aust."},{"key":"ref_183","doi-asserted-by":"crossref","first-page":"909","DOI":"10.3892\/mco.2014.397","article-title":"Features of ovarian cancer in Lynch syndrome","volume":"2","author":"Nakamura","year":"2014","journal-title":"Mol. Clin. Oncol."},{"key":"ref_184","doi-asserted-by":"crossref","first-page":"646","DOI":"10.1136\/ijgc-2021-003132","article-title":"Screening and risk-reducing surgery for endometrial or ovarian cancers in Lynch syndrome: A systematic review","volume":"32","author":"Lim","year":"2022","journal-title":"Int. J. Gynecol. Cancer"},{"key":"ref_185","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1200\/OP.21.00382","article-title":"Risk-reducing bilateral salpingo-oophorectomy for ovarian cancer: A review and clinical guide for hereditary predisposition genes","volume":"18","author":"Liu","year":"2022","journal-title":"JCO Oncol. Pract."},{"key":"ref_186","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1186\/s13053-015-0031-4","article-title":"Decisions about prophylactic gynecologic surgery: A qualitative study of the experience of female Lynch syndrome mutation carriers","volume":"13","author":"Etchegary","year":"2015","journal-title":"Hered. Cancer Clin. Pract."},{"key":"ref_187","unstructured":"National Institute for Health and Care Excellence (NICE) (2024). Ovarian Cancer: Identifying and Managing Familial and Genetic Risk, NICE. Available online: https:\/\/www.nice.org.uk\/guidance\/ng103."},{"key":"ref_188","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1055\/s-0032-1313780","article-title":"Endometrial and ovarian cancer in Lynch syndrome","volume":"25","author":"Crispens","year":"2012","journal-title":"Clin. Colon. Rectal Surg."},{"key":"ref_189","unstructured":"PDQ Cancer Genetics Editorial Board (2002). Cancer Genetics Risk Assessment and Counseling (PDQ\u00ae): Health Professional Version, National Cancer Institute."},{"key":"ref_190","doi-asserted-by":"crossref","first-page":"e040613","DOI":"10.1136\/bmjopen-2020-040613","article-title":"Are prolonged sitting and sleep restriction a dual curse for the modern workforce? a randomised controlled trial protocol","volume":"10","author":"Vincent","year":"2020","journal-title":"BMJ Open"},{"key":"ref_191","doi-asserted-by":"crossref","first-page":"e000821","DOI":"10.1136\/bmjonc-2025-000821","article-title":"Bridging the gap between guidelines and practice in Lynch syndrome screening for endometrial cancer","volume":"4","author":"Yoshida","year":"2025","journal-title":"BMJ Oncol."},{"key":"ref_192","doi-asserted-by":"crossref","first-page":"5783","DOI":"10.1200\/JCO.2008.17.5950","article-title":"Feasibility of screening for Lynch syndrome among patients with colorectal cancer","volume":"26","author":"Hampel","year":"2008","journal-title":"J. Clin. Oncol."},{"key":"ref_193","doi-asserted-by":"crossref","first-page":"423","DOI":"10.1007\/s10689-016-9893-5","article-title":"Genetic Counseling and Cascade Genetic Testing in Lynch Syndrome","volume":"15","author":"Hampel","year":"2016","journal-title":"Fam. Cancer"},{"key":"ref_194","doi-asserted-by":"crossref","unstructured":"Ryan, N.A.J., McMahon, R., Tobi, S., Snowsill, T., Esquibel, S., Wallace, A.J., Bunstone, S., Squirrell, E., Evans, D.G., and Crosbie, E.J. (2020). The proportion of endometrial tumours associated with Lynch syndrome (PETALS): A prospective cross-sectional study. PLoS Med., 17.","DOI":"10.1371\/journal.pmed.1003263"},{"key":"ref_195","doi-asserted-by":"crossref","unstructured":"Ryan, N.A.J., Davison, N.J., Payne, K., Cole, A., Evans, D.G., and Crosbie, E.J. (2019). A micro-costing study of screening for Lynch syndrome\u2013associated pathogenic variants in an unselected endometrial cancer population: Cheap as NGS chips?. Front. Oncol., 9.","DOI":"10.3389\/fonc.2019.00061"},{"key":"ref_196","doi-asserted-by":"crossref","first-page":"e184","DOI":"10.2196\/resprot.8138","article-title":"Cancer predisposition cascade screening for hereditary breast\/ovarian cancer and Lynch syndromes in Switzerland: Study protocol","volume":"6","author":"Katapodi","year":"2017","journal-title":"JMIR Res. Protoc."},{"key":"ref_197","doi-asserted-by":"crossref","unstructured":"Snowsill, T.M., Ryan, N.A.J., and Crosbie, E.J. (2020). Cost-effectiveness of the Manchester approach to identifying Lynch syndrome in women with endometrial cancer. J. Clin. Med., 9.","DOI":"10.3390\/jcm9061664"},{"key":"ref_198","doi-asserted-by":"crossref","first-page":"453","DOI":"10.1016\/j.ygyno.2016.10.008","article-title":"Cost-effectiveness of routine screening for Lynch syndrome in endometrial cancer patients up to 70 years of age","volume":"143","author":"Goverde","year":"2016","journal-title":"Gynecol. Oncol."},{"key":"ref_199","doi-asserted-by":"crossref","first-page":"218","DOI":"10.3390\/jpm4020218","article-title":"Knowledge, attitudes and referral patterns of Lynch syndrome: A survey of clinicians in Australia","volume":"4","author":"Tan","year":"2014","journal-title":"J. Pers. Med."},{"key":"ref_200","doi-asserted-by":"crossref","first-page":"e1937","DOI":"10.1002\/jgc4.1937","article-title":"Investigating genetic counselors\u2019 communication with Lynch syndrome patients about cascade testing: Barriers, facilitators, and strategies","volume":"34","author":"Zhong","year":"2025","journal-title":"J. Genet. Couns."},{"key":"ref_201","doi-asserted-by":"crossref","first-page":"2568","DOI":"10.1200\/JCO.2016.71.9260","article-title":"Multigene panel testing provides a new perspective on Lynch syndrome","volume":"35","author":"Espenschied","year":"2017","journal-title":"J. Clin. Oncol."},{"key":"ref_202","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1016\/j.ygyno.2023.02.017","article-title":"MLH1-methylated endometrial cancer under 60 years of age as the \u201csentinel\u201d cancer in female carriers of high-risk constitutional MLH1 epimutation","volume":"171","author":"Hitchins","year":"2023","journal-title":"Gynecol. Oncol."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/3\/1304\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,28]],"date-time":"2026-01-28T15:07:26Z","timestamp":1769612846000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/3\/1304"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1,28]]},"references-count":202,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2026,2]]}},"alternative-id":["ijms27031304"],"URL":"https:\/\/doi.org\/10.3390\/ijms27031304","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1,28]]}}}