子宫内膜癌分子分型与精准诊疗进展

Progress in Molecular Classification and Precision Diagnosis and Treatment of Endometrial Cancer

摘要: 目的：综述子宫内膜癌分子分型从The Cancer Genome Atlas (TCGA)多组学研究、Proactive Molecular Risk Classifier for Endometrial Cancer (ProMisE)临床转化至International Federation of Gynecology and Obstetrics (FIGO) 2023分期整合的发展脉络，探讨其在预后评估、辅助治疗、免疫治疗及个体化管理中的应用价值。方法：围绕子宫内膜癌、分子分型、TCGA、ProMisE、FIGO 2023、精准治疗、免疫治疗和保留生育功能等主题，检索并梳理近年国内外代表性文献、指南和专家共识。结果：TCGA将子宫内膜癌分为DNA polymerase epsilon (POLE)超突变型、微卫星不稳定高突变型、拷贝数低型和拷贝数高型，为精准分层奠定基础。ProMisE通过POLE测序、错配修复蛋白免疫组化和p53免疫组化建立了适合临床推广的分型流程。FIGO 2023分期进一步将分子特征纳入分期体系，使分子分型逐步成为影响诊断、预后和治疗决策的重要工具。结论：子宫内膜癌分子分型已成为精准诊疗的重要基础。未来应进一步推动标准化检测、真实世界验证、多组学整合及基层医院可及性建设。

Abstract: Objective: To review the development of molecular classification of endometrial cancer from The Cancer Genome Atlas (TCGA) integrated genomic analysis and the Proactive Molecular Risk Classifier for Endometrial Cancer (ProMisE) to the incorporation of molecular features into the 2023 International Federation of Gynecology and Obstetrics (FIGO) staging system, and to summarize its clinical value in prognostic evaluation, adjuvant therapy, immunotherapy and individualized management. Methods: A narrative review was conducted based on representative domestic and international studies, guidelines and expert consensuses related to endometrial cancer, molecular classification, TCGA, ProMisE, FIGO 2023 staging, precision treatment, immunotherapy and fertility preservation. The biological characteristics, clinical implications and application scenarios of different molecular subtypes were summarized. Results: The TCGA study di-vided endometrial cancer into four major molecular subgroups, including DNA polymerase epsilon (POLE) ultramutated, microsatellite instability hypermutated, copy-number low and copy-number high tumors. This classification revealed the molecular heterogeneity hidden behind traditional histopathological categories and provided a new framework for risk stratification. ProMisE simplified the TCGA classification into a clinically applicable algorithm based on POLE mutation testing, mismatch repair protein immuno-histochemistry and p53 immunohistochemistry, making molecular classification feasible in routine pathology practice. The 2023 FIGO staging system further integrated molecular features into endometrial cancer staging. Molecular classification also provides important information for adjuvant therapy selection, treatment de-escalation or escalation, immune checkpoint inhibitor use, fertility-preserving treatment and clinical trial design. Conclusion: Molecular classification has changed the diagnostic and therapeutic landscape of endometrial cancer. It is increasingly important for pathological diagnosis, FIGO staging, prognostic assessment and precision treatment. Future work should focus on standardized testing procedures, cost-effective implementation, real-world validation, integration of multi-omics data and improvement of accessibility in primary hospitals.