{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,15]],"date-time":"2026-06-15T01:09:59Z","timestamp":1781485799935,"version":"3.54.1"},"reference-count":48,"publisher":"American Society of Clinical Oncology (ASCO)","issue":"3","content-domain":{"domain":["ascopubs.org"],"crossmark-restriction":true},"short-container-title":["JCO Glob Oncol"],"published-print":{"date-parts":[[2026,3]]},"abstract":"<jats:sec>\n                    <jats:title>PURPOSE<\/jats:title>\n                    <jats:p>Geographical and racial diversity may influence endometrial cancer (EC) prognosis, yet its impact remains underexplored. In South Africa (SA), the rising incidence of EC underscores the need to investigate potential biologic differences. Molecular classification of EC offers valuable prognostic insights that could help address disparities and improve care. This study evaluated the prevalence and prognostic significance of molecular subtypes in a South African high-intermediate and high-risk EC cohort.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>MATERIALS AND METHODS<\/jats:title>\n                    <jats:p>We included 133 patients with high-intermediate and high-risk EC diagnosed in SA between January 2017 and December 2021. Clinical, demographic (including self-identified race), and follow-up data were collected. Central pathology review assessed histotype, grade, lymphovascular space invasion, and International Federation of Gynecology and Obstetrics 2009 stage. Molecular subtyping followed the WHO 2020 algorithm using targeted next-generation sequencing and immunohistochemistry for p53, mismatch repair (MMR) proteins, and ER. Shallow whole-genome sequencing (sWGS) assessed genome-wide copy number alterations.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>\n                      Among 131 patients with complete molecular classification, the most common subtype was p53-abnormal (p53abn, n = 71; 54.2%), followed by MMR-deficient (MMRd, n = 30; 22.9%), no specific molecular profile (NSMP, n = 21; 16.0%), and\n                      <jats:italic toggle=\"yes\">POLE<\/jats:italic>\n                      -ultramutated (\n                      <jats:italic toggle=\"yes\">POLE<\/jats:italic>\n                      mut, n = 9; 6.9%). Nonendometrioid EC (NEEC) predominated (n = 82; 61.7%). High-grade endometrioid EC and NEEC were more frequent in non-White patients (\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      = .030). Molecular subtypes were significantly associated with overall recurrence (\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      = .029), with no recurrences in\n                      <jats:italic toggle=\"yes\">POLE<\/jats:italic>\n                      mut ECs and the worst outcomes in p53abn ECs. sWGS revealed higher CN burdens in p53abn ECs, with recurrent focal alterations involving\n                      <jats:italic toggle=\"yes\">CCNE1<\/jats:italic>\n                      amplification and\n                      <jats:italic toggle=\"yes\">RB1<\/jats:italic>\n                      loss.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSION<\/jats:title>\n                    <jats:p>To our knowledge, this study is the first to demonstrate the prognostic value of EC molecular classification in a South African cohort. These findings support the global relevance of molecular EC subtyping. The urgent need for access to molecular diagnostics or cost-effective alternatives in resource-limited settings is highlighted.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1200\/go-25-00407","type":"journal-article","created":{"date-parts":[[2026,3,19]],"date-time":"2026-03-19T19:59:11Z","timestamp":1773950351000},"update-policy":"https:\/\/doi.org\/10.1200\/crossmark","source":"Crossref","is-referenced-by-count":1,"title":["Prognostic Relevance of Molecular Classification in Endometrial Cancer: Insights From a South African Cohort"],"prefix":"10.1200","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2981-4724","authenticated-orcid":true,"given":"Rubina","family":"Razack","sequence":"first","affiliation":[{"name":"Division of Anatomical Pathology, Department of Pathology, Tygerberg Hospital, National Health Laboratory Service and Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2739-6124","authenticated-orcid":true,"given":"Ezgi Dicle","family":"Serbes","sequence":"additional","affiliation":[{"name":"Department of Pathology, Van Research and Training Hospital, Van, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michelle Cara","family":"Bryan-Mc Innes","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynaecology, Tygerberg Hospital, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6535-1245","authenticated-orcid":true,"given":"Jennifer L.","family":"Butt","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynaecology, Tygerberg Hospital, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7399-6804","authenticated-orcid":true,"given":"Claire. 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H.","family":"Kramer","sequence":"additional","affiliation":[{"name":"Department of Pathology, Leiden University Medical Center, Leiden, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natalja T.","family":"ter Haar","sequence":"additional","affiliation":[{"name":"Department of Pathology, Leiden University Medical Center, Leiden, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8581-4753","authenticated-orcid":true,"given":"Nanda","family":"Horeweg","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, Leiden University Medical Center, Leiden, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6046-1453","authenticated-orcid":false,"given":"Matthys H.","family":"Botha","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynaecology, Tygerberg Hospital, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6881-8437","authenticated-orcid":true,"given":"Tjalling","family":"Bosse","sequence":"additional","affiliation":[{"name":"Department of Pathology, Leiden University Medical Center, Leiden, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"233","reference":[{"key":"e_1_3_6_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ygyno.2021.01.036"},{"key":"e_1_3_6_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(22)00323-3"},{"key":"e_1_3_6_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijgc.2025.101910"},{"key":"e_1_3_6_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.path.2019.02.003"},{"key":"e_1_3_6_6_2","doi-asserted-by":"publisher","DOI":"10.1136\/ijgc-2022-003772"},{"key":"e_1_3_6_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/S2214-109X(19)30374-2"},{"key":"e_1_3_6_8_2","unstructured":"International Agency for Research on Cancer: World Health Organization. https:\/\/www.iarc.who.int\/"},{"key":"e_1_3_6_9_2","unstructured":"South African National Cancer Registry Annual 2020 report. 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