Endometrial cancer molecular classification: research advances and clinical application.
- 1Department of Obstetrics and Gynecology, Wuhan Children's Hospital Graduate Joint Training Base, School of Medicine, Wuhan University of Science and Technology, Wuhan, China.
- 2Department of Obstetrics and Gynecology, Tianjin Medical University General Hospital, Tianjin, China.
- 3Department of Gynecology, Wuhan Children's Hospital (Wuhan Maternal and Child Healthcare Hospital), Tongji Medical College, Huazhong University of Science & Technology, Wuhan, China.
Abstract
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.
Related
- Brain-computer interfaces in pediatric populations: research advances, application challenges, and future directions
- Beyond Molecular Classification: The Incremental Value of Prognostic Biomarkers in Endometrial Cancer
- Integrated Molecular Classification of Endometrial Cancer: Impact on Diagnosis, Prognosis, and Clinical Management—A Systematic Review
- Advances in Research on the Genotype–Phenotype Correspondence of Antibiotic Resistance in Helicobacter pylori and Its Molecular Mechanisms: A Narrative Review
- Advances in Multi-Omics Research on Post-Stroke Depression: From Molecular Mechanisms to Therapeutic Strategies.
BibTeX
@article{liu2026endometrial,
title = {{Endometrial cancer molecular classification: research advances and clinical application.}},
author = {Ya Liu and Yueying Li and Liping Zhang},
journal = {Frontiers in oncology},
year = {2026},
month = oct,
doi = {10.3389/fonc.2026.1947939},
url = {https://europepmc.org/article/MED/42898997},
note = {CC BY},
}
RIS
TY - JOUR
TI - Endometrial cancer molecular classification: research advances and clinical application.
AU - Ya Liu
AU - Yueying Li
AU - Liping Zhang
PY - 2026
DA - 2026/10/05
JO - Frontiers in oncology
DO - 10.3389/fonc.2026.1947939
UR - https://europepmc.org/article/MED/42898997
AB - 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.
SN - 2234-943X
ER -