{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T11:02:51Z","timestamp":1791198171074,"version":"4.1.0"},"reference-count":103,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T00:00:00Z","timestamp":1791158400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Oncol."],"abstract":"<jats:p>As research in molecular biology continues to advance, the classification of endometrial cancer has gradually shifted from traditional histology toward risk stratification based on the integration of molecular subtyping with clinicopathologic factors. Molecular subtyping has not only transformed our understanding of the biological heterogeneity of endometrial cancer but also provided new evidence for prognostic assessment and treatment selection. However, the maturity of clinical evidence and the translational therapeutic value vary across molecular subtypes. This review systematically summarizes the molecular characteristics and clinical significance of the POLE ultramutated(POLE-mut)subtype, mismatch repair deficient (dMMR) subtype, p53 abnormal (p53-abn) subtype, and no specific molecular profile (NSMP) subtype, with a focus on evaluating whether different molecular features can be further translated from risk stratification into specific treatment decisions. Centering on key issues such as de-escalated therapy for the POLE-mut subtype, the predictive value of immunotherapy for the dMMR subtype, intensified therapy for the p53-abn subtype, and further risk stratification of the NSMP subtype, this review analyzes the clinical basis and limitations of existing evidence and further discusses the challenges that tumors with multiple molecular features pose for classification and treatment decision making. Building on this, the paper compares how major international guidelines integrate molecular information with clinical and pathologic factors and analyzes real world implementation barriers such as testing standardization, result interpretation, and healthcare accessibility. Finally, it outlines the potential value of emerging technologies, including liquid biopsy, artificial intelligence, and multiomics, in dynamic risk assessment and precision therapy. This review aims to trace the continuum of evidence from molecular discovery to clinical action, clarifying which clinical decisions can be supported by existing molecular markers and identifying questions that current evidence cannot yet answer, thereby providing guidance for the precise application and clinical translation of molecular subtyping in endometrial cancer.<\/jats:p>","DOI":"10.3389\/fonc.2026.1947939","type":"journal-article","created":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T10:44:33Z","timestamp":1791197073000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Endometrial cancer molecular classification: research advances and clinical application"],"prefix":"10.3389","volume":"16","author":[{"given":"Ya","family":"Liu","sequence":"first","affiliation":[{"name":"Department of Obstetrics and Gynecology, Wuhan Children\u2019s Hospital Graduate Joint Training Base, School of Medicine, Wuhan University of Science and Technology","place":["Wuhan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yueying","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Tianjin Medical University General Hospital","place":["Tianjin, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liping","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Gynecology, Wuhan Children\u2019s Hospital (Wuhan Maternal and Child Healthcare Hospital), Tongji Medical College, Huazhong University of Science & Technology","place":["Wuhan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,10,5]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.3322\/caac.70090","article-title":"Global cancer statistics 2024: GLOBOCAN estimates of incidence and mortality worldwide for 34 cancers in 186 countries","volume":"76","author":"Sung","year":"2026","journal-title":"CA Cancer J Clin"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2026.2248","article-title":"Endometrial cancer: a review","volume":"335","author":"Mager","year":"2026","journal-title":"JAMA"},{"key":"B3","doi-asserted-by":"publisher","first-page":"2593","DOI":"10.2217\/fon-2017-0217","article-title":"Endometrial cancer evolution: new molecular-biologic types and hormonal-metabolic shifts","volume":"13","author":"Berstein","year":"2017","journal-title":"Future Oncol"},{"key":"B4","doi-asserted-by":"publisher","first-page":"751","DOI":"10.1016\/j.ygyno.2012.03.032","article-title":"Insulin resistance: a significant risk factor of endometrial cancer","volume":"125","author":"Mu","year":"2012","journal-title":"Gynecol Oncol"},{"key":"B5","doi-asserted-by":"publisher","first-page":"256","DOI":"10.1016\/j.bulcan.2015.01.006","article-title":"Environmental and genetic risk factors for endometrial carcinoma","volume":"102","author":"S\u00e9n\u00e9chal","year":"2015","journal-title":"Bull Cancer"},{"key":"B6","doi-asserted-by":"publisher","first-page":"92","DOI":"10.1016\/j.anndiagpath.2019.02.003","article-title":"A potpourri of pathogenetic pathways in endometrial carcinoma with a focus on Lynch Syndrome","volume":"39","author":"Wadee","year":"2019","journal-title":"Ann Diagn Pathol"},{"key":"B7","doi-asserted-by":"publisher","first-page":"S93","DOI":"10.1097\/PGP.0000000000000524","article-title":"Pathologic Prognostic Factors in Endometrial Carcinoma (Other Than Tumor Type and Grade)","volume":"38","author":"Singh","year":"2019","journal-title":"Int J Gynecol Pathol"},{"key":"B8","doi-asserted-by":"publisher","first-page":"67","DOI":"10.1038\/nature12113","article-title":"Integrated genomic characterization of endometrial carcinoma","volume":"497","author":"Kandoth","year":"2013","journal-title":"Nature"},{"key":"B9","doi-asserted-by":"publisher","first-page":"299","DOI":"10.1038\/bjc.2015.190","article-title":"A clinically applicable molecular-based classification for endometrial cancers","volume":"113","author":"Talhouk","year":"2015","journal-title":"Br J Cancer"},{"key":"B10","doi-asserted-by":"publisher","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":"B11","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(25)00167-6","article-title":"ESGO-ESTRO-ESP guidelines for the management of patients with endometrial carcinoma: update 2025","volume":"26","author":"Concin","year":"2025","journal-title":"Lancet Oncol"},{"key":"B12","doi-asserted-by":"publisher","first-page":"3388","DOI":"10.1200\/JCO.20.00549","article-title":"Molecular Classification of the PORTEC-3 Trial for High-Risk Endometrial Cancer: Impact on Prognosis and Benefit From Adjuvant Therapy","volume":"38","author":"Le\u00f3n-Castillo","year":"2020","journal-title":"J Clin Oncol"},{"key":"B13","doi-asserted-by":"publisher","first-page":"23","DOI":"10.1016\/S1470-2045(25)00612-6","article-title":"Molecular profile-based adjuvant treatment for women with high-intermediate risk endometrial cancer (PORTEC-4a): results of a randomised, open-label, phase 3, multicentre, non-inferiority trial","volume":"27","author":"van den Heerik","year":"2026","journal-title":"Lancet Oncol"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1136\/ijgc-2022-004039","article-title":"Refining adjuvant treatment in endometrial cancer based on molecular features: the RAINBO clinical trial program","volume":"33","year":"2023","journal-title":"Int J Gynecol Cancer"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1016\/j.annonc.2024.05.546","article-title":"Overall survival in patients with endometrial cancer treated with dostarlimab plus carboplatin-paclitaxel in the randomized ENGOT-EN6\/GOG-3031\/RUBY trial","volume":"35","author":"Powell","year":"2024","journal-title":"Ann Oncol"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-025-03566-1","article-title":"Pembrolizumab plus chemotherapy in advanced or recurrent endometrial cancer: overall survival and exploratory analyses of the NRG GY018 phase 3 randomized trial","volume":"31","author":"Eskander","year":"2025","journal-title":"Nat Med"},{"key":"B17","doi-asserted-by":"publisher","first-page":"805613","DOI":"10.3389\/fonc.2022.805613","article-title":"Current Prognostic and Predictive Biomarkers for Endometrial Cancer in Clinical Practice: Recommendations\/Proposal from the Italian Study Group","volume":"12","author":"Zannoni","year":"2022","journal-title":"Front Oncol"},{"key":"B18","doi-asserted-by":"publisher","first-page":"5429","DOI":"10.3390\/cancers14215429","article-title":"Integrated Biomarker Analysis Reveals L1CAM as a Potential Stratification Marker for No Specific Molecular Profile High-Risk Endometrial Carcinoma","volume":"14","author":"Ravaggi","year":"2022","journal-title":"Cancers (Basel)"},{"key":"B19","doi-asserted-by":"publisher","first-page":"312","DOI":"10.1002\/path.5373","article-title":"Clinicopathological and molecular characterisation of 'multiple-classifier' endometrial carcinomas","volume":"250","author":"Le\u00f3n-Castillo","year":"2020","journal-title":"J Pathol"},{"key":"B20","doi-asserted-by":"publisher","first-page":"385","DOI":"10.1016\/j.clml.2011.01.001","article-title":"Translating trial-based molecular monitoring into clinical practice: importance of international standards and practical considerations for community practitioners","volume":"11","author":"Akard","year":"2011","journal-title":"Clin Lymphoma Myeloma Leuk"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2025.1685565","article-title":"Navigating tumour microenvironment in endometrial carcinoma: a comprehensive review integrating immunohistochemistry, single-cell RNA-sequencing and spatial transcriptomics","volume":"15","author":"Mondal","year":"2025","journal-title":"Front Oncol"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1016\/0090-8258(83)90111-7","article-title":"Two pathogenetic types of endometrial carcinoma","volume":"15","author":"Bokhman","year":"1983","journal-title":"Gynecol Oncol"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1111\/his.13977","article-title":"Revising the WHO classification: female genital tract tumours","volume":"76","author":"Cree","year":"2020","journal-title":"Histopathology"},{"key":"B24","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1007\/s00428-010-0939-z","article-title":"Does high-grade endometrioid carcinoma (grade 3 FIGO) belong to type I or type II endometrial cancer? A clinical-pathological and immunohistochemical study","volume":"457","author":"Zannoni","year":"2010","journal-title":"Virchows Arch"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1016\/j.ygyno.2016.12.010","article-title":"Bokhman redux: endometrial cancer types in the 21st century","volume":"144","author":"Suarez","year":"2017","journal-title":"Gynecol Oncol"},{"key":"B26","doi-asserted-by":"publisher","first-page":"S64","DOI":"10.1097\/PGP.0000000000000518","article-title":"Endometrial Carcinoma Diagnosis: Use of FIGO Grading and Genomic Subcategories in Clinical Practice: Recommendations of the International Society of Gynecological Pathologists","volume":"38","author":"Soslow","year":"2019","journal-title":"Int J Gynecol Pathol"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2023.1266485","article-title":"Pulmonary metastasis of stage I, low-grade endometrioid carcinoma: two case reports and the literature review","volume":"13","author":"Wang","year":"2023","journal-title":"Front Oncol"},{"key":"B28","doi-asserted-by":"publisher","first-page":"99","DOI":"10.1016\/j.ygyno.2024.01.018","article-title":"Prognosis of polymerase epsilon (POLE) mutation in high-grade endometrioid endometrial cancer: systematic review and meta-analysis","volume":"182","author":"Casanova","year":"2024","journal-title":"Gynecol Oncol"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(19)30020-8","article-title":"Lenvatinib plus pembrolizumab in patients with advanced endometrial cancer: an interim analysis of a multicentre, open-label, single-arm, phase 2 trial","volume":"20","author":"Makker","year":"2019","journal-title":"Lancet Oncol"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1016\/j.ygyno.2019.08.019","article-title":"TCGA molecular groups of endometrial cancer: pooled data about prognosis","volume":"155","author":"Raffone","year":"2019","journal-title":"Gynecol Oncol"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1093\/annonc\/mdy058","article-title":"Final validation of the ProMisE molecular classifier for endometrial carcinoma in a large population-based case series","volume":"29","author":"Kommoss","year":"2018","journal-title":"Ann Oncol"},{"key":"B32","doi-asserted-by":"publisher","first-page":"2820","DOI":"10.1093\/hmg\/ddt131","article-title":"DNA polymerase \u03b5 and \u03b4 exonuclease domain mutations in endometrial cancer","volume":"22","author":"Church","year":"2013","journal-title":"Hum Mol Genet"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1038\/nature12477","article-title":"Signatures of mutational processes in human cancer","volume":"500","author":"Alexandrov","year":"2013","journal-title":"Nature"},{"key":"B34","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1016\/j.ygyno.2014.05.006","article-title":"POLE exonuclease domain mutation predicts long progression-free survival in grade 3 endometrioid carcinoma of the endometrium","volume":"134","author":"Meng","year":"2014","journal-title":"Gynecol Oncol"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1097\/PAS.0000000000001020","article-title":"Molecular classification of grade 3 endometrioid endometrial cancers identifies distinct prognostic subgroups","volume":"42","author":"Bosse","year":"2018","journal-title":"Am J Surg Pathol"},{"key":"B36","doi-asserted-by":"publisher","first-page":"2409","DOI":"10.1002\/cncr.33516","article-title":"Evaluation of treatment effects in patients with endometrial cancer and POLE mutations: An individual patient data meta-analysis","volume":"127","author":"McAlpine","year":"2021","journal-title":"Cancer"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra012242","article-title":"Hereditary colorectal cancer","volume":"348","author":"Lynch","year":"2003","journal-title":"N Engl J Med"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.7759\/cureus.99364","article-title":"Mismatch repair deficiency profiling and its impact on management and prognosis in endometrial cancer patients: a comprehensive update","volume":"17","author":"Almperi","year":"2025","journal-title":"Cureus"},{"key":"B39","doi-asserted-by":"publisher","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":"B40","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijgc.2024.100048","article-title":"Clinicopathologic stratification demonstrates survival differences between endometrial carcinomas with mismatch repair deficiency and no specific molecular profile: a cohort study","volume":"35","author":"Loukovaara","year":"2025","journal-title":"Int J Gynecol Cancer"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejca.2024.113584","article-title":"Impact of molecular profile on prognosis and relapse pattern in low and intermediate risk endometrial cancer","volume":"200","author":"Lindemann","year":"2024","journal-title":"Eur J Cancer"},{"key":"B42","doi-asserted-by":"publisher","first-page":"1212","DOI":"10.1093\/jnci\/djab029","article-title":"Prevalence and prognosis of lynch syndrome and sporadic mismatch repair deficiency in endometrial cancer","volume":"113","author":"Post","year":"2021","journal-title":"J Natl Cancer Inst"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1016\/j.ygyno.2026.01.233","article-title":"Substratification of mismatch repair deficient endometrial cancers based on mechanism of MMR loss can provide prognostic and predictive refinement","volume":"205","author":"Jamieson","year":"2026","journal-title":"Gynecol Oncol"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1038\/s41379-022-01066-y","article-title":"Genomic landscape of endometrial carcinomas of no specific molecular profile","volume":"35","author":"Momeni-Boroujeni","year":"2022","journal-title":"Mod Pathol"},{"key":"B45","doi-asserted-by":"publisher","first-page":"423","DOI":"10.1007\/s00404-021-06385-0","article-title":"Prognostic significance of CTNNB1 mutation in early stage endometrial carcinoma: a systematic review and meta-analysis","volume":"306","author":"Travaglino","year":"2022","journal-title":"Arch Gynecol Obstet"},{"key":"B46","doi-asserted-by":"publisher","first-page":"584","DOI":"10.1016\/j.ajog.2025.09.041","article-title":"Prognostic role of immunohistochemical and molecular markers in no specific molecular profile endometrial cancer: a systematic review and meta-analysis","volume":"234","author":"Ferrari","year":"2026","journal-title":"Am J Obstet Gynecol"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.1038\/s41416-023-02141-0","article-title":"Prognostic refinement of NSMP high-risk endometrial cancers using oestrogen receptor immunohistochemistry","volume":"128","author":"Vermij","year":"2023","journal-title":"Br J Cancer"},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.1016\/j.modpat.2022.100085","article-title":"Grade and estrogen receptor expression identify a subset of no specific molecular profile endometrial carcinomas at a very low risk of disease-specific death","volume":"36","author":"Jamieson","year":"2023","journal-title":"Mod Pathol"},{"key":"B49","doi-asserted-by":"publisher","first-page":"59","DOI":"10.1016\/j.ygyno.2025.05.015","article-title":"Prognostic significance of estrogen receptor expression and estrogen signaling in endometrial carcinomas of no specific molecular profile: a comprehensive molecular and pathologic analysis","volume":"198","author":"Lam","year":"2025","journal-title":"Gynecol Oncol"},{"key":"B50","doi-asserted-by":"publisher","DOI":"10.1016\/j.ygyno.2023.05.062","article-title":"Prognostic significance of L1CAM expression in addition to ProMisE in endometrial cancer","volume":"174","author":"Kim","year":"2023","journal-title":"Gynecol Oncol"},{"key":"B51","doi-asserted-by":"publisher","DOI":"10.1016\/j.ygyno.2024.11.005","article-title":"Prognostic and therapeutic implication of molecular classification including L1CAM expression in high-risk endometrial cancer","volume":"192","author":"Kleppe","year":"2025","journal-title":"Gynecol Oncol"},{"key":"B52","doi-asserted-by":"publisher","DOI":"10.1136\/ijgc-2023-005111","article-title":"Prognostic role of transcription factor ARID1A in patients with endometrial cancer of no specific molecular profile (NSMP) subtype","volume":"34","author":"Onoprienko","year":"2024","journal-title":"Int J Gynecol Cancer"},{"key":"B53","doi-asserted-by":"publisher","first-page":"66","DOI":"10.1007\/s00432-026-06440-w","article-title":"The features and prognostic value of ARID1A mutation and protein expression in endometrial cancer of no specific molecular profile (NSMP) subtype: a retrospective study in a large Chinese cohort","volume":"152","author":"Yuan","year":"2026","journal-title":"J Cancer Res Clin Oncol"},{"key":"B54","doi-asserted-by":"publisher","first-page":"299","DOI":"10.1016\/j.ygyno.2024.10.026","article-title":"KRAS mutations in endometrial cancers: possible prognostic and treatment implications","volume":"191","author":"Kilowski","year":"2024","journal-title":"Gynecol Oncol"},{"key":"B55","doi-asserted-by":"publisher","DOI":"10.1111\/his.15531","article-title":"Endometrial carcinoma and immune escape: prognostic relevance of HLA class I loss in NSMP subtype","volume":"88","author":"Grillini","year":"2026","journal-title":"Histopathology"},{"key":"B56","doi-asserted-by":"publisher","DOI":"10.3390\/ijms231911684","article-title":"TCGA molecular prognostic groups of endometrial carcinoma: current knowledge and future perspectives","volume":"23","author":"Arciuolo","year":"2022","journal-title":"Int J Mol Sci"},{"key":"B57","doi-asserted-by":"publisher","first-page":"229","DOI":"10.1136\/ijgc-2023-004864","article-title":"Clinicopathological characteristics of multiple-classifier endometrial cancers: a cohort study and systematic review","volume":"34","author":"De Vitis","year":"2024","journal-title":"Int J Gynecol Cancer"},{"key":"B58","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2026.1800797","article-title":"Clinical and molecular heterogeneity in advanced-stage POLE-mutated endometrial carcinoma: a focus on aggressive subsets and co-mutations","volume":"16","author":"Cavasin","year":"2026","journal-title":"Front Oncol"},{"key":"B59","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejogrb.2026.115324","article-title":"Interpretation strategy of POLE, mismatch repair deficiency, and p53 in the multiple molecular classification of endometrial carcinoma and its clinical differences from single classification: a retrospective cohort study","volume":"325","author":"Xia","year":"2026","journal-title":"Eur J Obstet Gynecol Reprod Biol"},{"key":"B60","doi-asserted-by":"publisher","first-page":"836","DOI":"10.1038\/modpathol.2015.43","article-title":"Refining prognosis and identifying targetable pathways for high-risk endometrial cancer; a TransPORTEC initiative","volume":"28","author":"Stelloo","year":"2015","journal-title":"Mod Pathol"},{"key":"B61","doi-asserted-by":"publisher","first-page":"367","DOI":"10.1007\/s00432-024-05901-4","article-title":"Determination of endometrial cancer molecular subtypes using a whole exome-sequencing based single-method approach","volume":"150","author":"Mustea","year":"2024","journal-title":"J Cancer Res Clin Oncol"},{"key":"B62","doi-asserted-by":"publisher","first-page":"98","DOI":"10.1016\/j.humpath.2021.02.006","article-title":"Molecular subtype diagnosis of endometrial carcinoma: comparison of the next-generation sequencing panel and Proactive Molecular Risk Classifier for Endometrial Cancer classifier","volume":"111","author":"Huvila","year":"2021","journal-title":"Hum Pathol"},{"key":"B63","doi-asserted-by":"publisher","first-page":"162","DOI":"10.1186\/s13000-024-01584-0","article-title":"Prognostic factors and survival outcomes of immunohistochemically detection based-molecular subtypes of endometrial cancer-analysis of 576 clinical cases","volume":"19","author":"Wang","year":"2024","journal-title":"Diagn Pathol"},{"key":"B64","doi-asserted-by":"publisher","first-page":"103710","DOI":"10.1016\/j.esmoop.2024.103710","article-title":"Identification of molecular subtypes for endometrial carcinoma using a 46-gene next-generation sequencing panel: a retrospective study on a consecutive cohort","volume":"9","author":"Guo","year":"2024","journal-title":"ESMO Open"},{"key":"B65","doi-asserted-by":"publisher","first-page":"734","DOI":"10.1002\/jso.2797","article-title":"Molecular Classification of Endometrial Cancers Using an Integrative DNA Sequencing Panel","volume":"131","author":"Kim","year":"2025","journal-title":"J Surg Oncol"},{"key":"B66","doi-asserted-by":"publisher","DOI":"10.1002\/path.5372","article-title":"Interpretation of somatic POLE mutations in endometrial carcinoma","volume":"250","author":"Le\u00f3n-Castillo","year":"2020","journal-title":"J Pathol"},{"key":"B67","doi-asserted-by":"publisher","DOI":"10.1016\/j.annonc.2022.05.009","article-title":"Endometrial cancer: ESMO clinical practice guideline for diagnosis, treatment and follow-up","volume":"33","author":"Oaknin","year":"2022","journal-title":"Ann Oncol"},{"key":"B68","doi-asserted-by":"publisher","first-page":"1475","DOI":"10.1038\/s41379-022-01102-x","article-title":"p53 immunohistochemistry in endometrial cancer: clinical and molecular correlates in the PORTEC-3 trial","volume":"35","author":"Vermij","year":"2022","journal-title":"Mod Pathol"},{"key":"B69","volume-title":"NCCN Clinical Practice Guidelines in Oncology: Uterine Neoplasms, Version 3.2026","year":"2026"},{"key":"B70","doi-asserted-by":"publisher","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":"B71","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejca.2026.116739","article-title":"ESGO consensus statement on endometrial cancer prevention, risk reduction strategies, and management of women with Lynch syndrome","volume":"240","author":"Marchetti","year":"2026","journal-title":"Eur J Cancer"},{"key":"B72","doi-asserted-by":"publisher","first-page":"3932","DOI":"10.1002\/cncr.28933","article-title":"Performance characteristics of screening strategies for Lynch syndrome in unselected women with newly diagnosed endometrial cancer who have undergone universal germline mutation testing","volume":"120","author":"Ferguson","year":"2014","journal-title":"Cancer"},{"key":"B73","doi-asserted-by":"publisher","first-page":"1","DOI":"10.3310\/hta21510","article-title":"Molecular testing for Lynch syndrome in people with colorectal cancer: systematic reviews and economic evaluation","volume":"21","author":"Snowsill","year":"2017","journal-title":"Health Technol Assess"},{"key":"B74","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2019.00061","article-title":"A micro-costing study of screening for Lynch syndrome-associated pathogenic variants in an unselected endometrial cancer population: cheap as NGS chips","volume":"9","author":"Ryan","year":"2019","journal-title":"Front Oncol"},{"key":"B75","doi-asserted-by":"publisher","DOI":"10.1007\/s12094-022-02799-7","article-title":"SEOM-GEICO clinical guidelines on endometrial cancer (2021)","volume":"24","author":"Barretina-Ginesta","year":"2022","journal-title":"Clin Transl Oncol"},{"key":"B76","doi-asserted-by":"publisher","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":"B77","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.35596","article-title":"Challenges in implementation of molecular classification in early stage endometrial cancer: an NRG Oncology cooperative group mixed-methods study","volume":"131","author":"Wilson","year":"2025","journal-title":"Cancer"},{"key":"B78","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2026.1676000","article-title":"Recommendations for the treatment of endometrial cancer in settings with limited resources: report from the International Gynecological Cancer Society consensus meeting","volume":"16","author":"Maluf","year":"2026","journal-title":"Front Oncol"},{"key":"B79","doi-asserted-by":"publisher","first-page":"605","DOI":"10.1186\/s12905-023-02677-6","article-title":"Molecular-based classification of endometrial carcinoma in Northern Thailand: impact on prognosis and potential for implementation in resource-limited settings","volume":"23","author":"Dankai","year":"2023","journal-title":"BMC Womens Health"},{"key":"B80","doi-asserted-by":"publisher","first-page":"537","DOI":"10.1097\/PGP.0000000000000654","article-title":"Interlaboratory Concordance of ProMisE Molecular Classification of Endometrial Carcinoma Based on Endometrial Biopsy Specimens","volume":"39","author":"Plotkin","year":"2020","journal-title":"Int J Gynecol Pathol"},{"key":"B81","doi-asserted-by":"publisher","first-page":"53","DOI":"10.1016\/j.ygyno.2023.07.005","article-title":"Practical lessons learned from real-world implementation of the molecular classification for endometrial carcinoma","volume":"176","author":"Moreira","year":"2023","journal-title":"Gynecol Oncol"},{"key":"B82","doi-asserted-by":"publisher","first-page":"75","DOI":"10.1093\/ajcp\/aqae010","article-title":"Implementation of endometrial cancer molecular subtyping into a hybrid community-academic practice","volume":"162","author":"Ferreira","year":"2024","journal-title":"Am J Clin Pathol"},{"key":"B83","doi-asserted-by":"publisher","DOI":"10.1038\/s41571-024-00909-8","article-title":"Towards equitable AI in oncology","volume":"21","author":"Viswanathan","year":"2024","journal-title":"Nat Rev Clin Oncol"},{"key":"B84","volume-title":"Guidance for Human Genome Data Collection, Access, Use and Sharing","year":"2024"},{"key":"B85","doi-asserted-by":"publisher","first-page":"106","DOI":"10.1016\/j.ygyno.2017.12.009","article-title":"Racial disparities in molecular subtypes of endometrial cancer","volume":"149","author":"Dubil","year":"2018","journal-title":"Gynecol Oncol"},{"key":"B86","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-15-0057","article-title":"POLE proofreading mutations elicit an antitumor immune response in endometrial cancer","volume":"21","author":"van Gool","year":"2015","journal-title":"Clin Cancer Res"},{"key":"B87","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(25)00379-1","article-title":"Adjuvant chemoradiotherapy versus radiotherapy alone in women with high-risk endometrial cancer (PORTEC-3): 10-year clinical outcomes and post-hoc analysis by molecular classification from a randomised phase 3 trial","volume":"26","author":"Post","year":"2025","journal-title":"Lancet Oncol"},{"key":"B88","doi-asserted-by":"publisher","first-page":"145","DOI":"10.1016\/j.ygyno.2025.07.020","article-title":"The challenge of molecular stratification in No Specific Molecular Profile endometrial cancer","volume":"200","author":"Marchetti","year":"2025","journal-title":"Gynecol Oncol"},{"key":"B89","doi-asserted-by":"publisher","first-page":"48","DOI":"10.1016\/j.ygyno.2022.10.024","article-title":"Molecular testing for endometrial cancer: An SGO clinical practice statement","volume":"168","author":"Walsh","year":"2023","journal-title":"Gynecol Oncol"},{"key":"B90","doi-asserted-by":"publisher","first-page":"359","DOI":"10.2147\/OTT.S368050","article-title":"Targeted treatment of advanced endometrial cancer: focus on pembrolizumab","volume":"16","author":"El-Ghazzi","year":"2023","journal-title":"Onco Targets Ther"},{"key":"B91","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.23.02132","article-title":"Durvalumab plus carboplatin\/paclitaxel followed by maintenance durvalumab with or without olaparib as first-line treatment for advanced endometrial cancer: the phase III DUO-E trial","volume":"42","author":"Westin","year":"2024","journal-title":"J Clin Oncol"},{"key":"B92","doi-asserted-by":"publisher","DOI":"10.1172\/JCI84940","article-title":"Immune activation and response to pembrolizumab in POLE-mutant endometrial cancer","volume":"126","author":"Mehnert","year":"2016","journal-title":"J Clin Invest"},{"key":"B93","doi-asserted-by":"publisher","first-page":"1565","DOI":"10.1001\/jamaoncol.2016.0891","article-title":"Landscape of Phosphatidylinositol-3-Kinase Pathway Alterations Across 19\u202f784 Diverse Solid Tumors","volume":"2","author":"Millis","year":"2016","journal-title":"JAMA Oncol"},{"key":"B94","doi-asserted-by":"publisher","first-page":"23","DOI":"10.1007\/s11912-016-0507-z","article-title":"New targeted agents in endometrial cancer: are we really making progress","volume":"18","author":"Rodriguez-Freixinos","year":"2016","journal-title":"Curr Oncol Rep"},{"key":"B95","doi-asserted-by":"publisher","first-page":"47","DOI":"10.1200\/JCO.23.02005","article-title":"Efficacy and safety of trastuzumab deruxtecan in patients with HER2-expressing solid tumors: primary results from the DESTINY-PanTumor02 phase II trial","volume":"42","author":"Meric-Bernstam","year":"2024","journal-title":"J Clin Oncol"},{"key":"B96","doi-asserted-by":"publisher","first-page":"e65","DOI":"10.3802\/jgo.2026.37.e65","article-title":"Trastuzumab deruxtecan in HER2-expressing gynecologic cancers from DESTINY-PanTumor02: antitumor activity, safety, and exploratory biomarker analyses","volume":"37","author":"Lee","year":"2026","journal-title":"J Gynecol Oncol"},{"key":"B97","doi-asserted-by":"publisher","first-page":"6300","DOI":"10.1038\/s41467-022-33982-7","article-title":"Single-cell transcriptomic analysis highlights origin and pathological process of human endometrioid endometrial carcinoma","volume":"13","author":"Ren","year":"2022","journal-title":"Nat Commun"},{"key":"B98","doi-asserted-by":"publisher","first-page":"5029","DOI":"10.1038\/s41467-023-40271-4","article-title":"Spatial transcriptomics reveals distinct and conserved tumor core and edge architectures that predict survival and targeted therapy response","volume":"14","author":"Arora","year":"2023","journal-title":"Nat Commun"},{"key":"B99","doi-asserted-by":"publisher","first-page":"1404","DOI":"10.3390\/cells14171404","article-title":"Integrating Multi-Omics in Endometrial Cancer: From Molecular Insights to Clinical Applications","volume":"14","author":"Kim","year":"2025","journal-title":"Cells"},{"key":"B100","doi-asserted-by":"publisher","DOI":"10.3390\/cancers12082231","article-title":"Utility of circulating tumor DNA for detection and monitoring of endometrial cancer recurrence and progression","volume":"12","author":"Moss","year":"2020","journal-title":"Cancers (Basel)"},{"key":"B101","doi-asserted-by":"publisher","first-page":"71","DOI":"10.1038\/s41698-026-01280-w","article-title":"An interpretable deep learning model for predicting endometrial cancer molecular subtypes from H&E-stained slides","volume":"10","author":"Guo","year":"2026","journal-title":"NPJ Precis Oncol"},{"key":"B102","doi-asserted-by":"publisher","first-page":"112110","DOI":"10.1016\/j.ejrad.2025.112110","article-title":"Prediction of molecular subtypes of endometrial cancer patients on the basis of intratumoral and peritumoral radiomic features from multiparametric MR images","volume":"187","author":"Zhou","year":"2025","journal-title":"Eur J Radiol"},{"key":"B103","doi-asserted-by":"publisher","first-page":"102860","DOI":"10.1016\/j.ijgc.2025.102860","article-title":"Access to molecular classification in endometrial cancer recommended by ESGO-ESTRO-ESP guidelines: multi-national survey in Eastern Europe","volume":"36","author":"Abacjew-Chmylko","year":"2026","journal-title":"Int J Gynecol Cancer"}],"container-title":["Frontiers in Oncology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fonc.2026.1947939\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T10:44:35Z","timestamp":1791197075000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fonc.2026.1947939\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,10,5]]},"references-count":103,"alternative-id":["10.3389\/fonc.2026.1947939"],"URL":"https:\/\/doi.org\/10.3389\/fonc.2026.1947939","relation":{},"ISSN":["2234-943X"],"issn-type":[{"value":"2234-943X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,10,5]]},"article-number":"1947939"}}