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文章:

子宫内膜癌的分子分型与临床结局:来自三级医疗中心的真实世界证据

Molecular Classification and Clinical Outcomes in Endometrial Cancer: Real-World Evidence from a Tertiary Care Center

原文发布日期:6 January 2026

DOI: 10.3390/cancers18020181

类型: Article

开放获取: 是

 

英文摘要:

Background:Molecular classification has reshaped prognostication and treatment in endometrial carcinoma (EC). However, real-world evidence from Asian populations remains scarce. This study evaluated clinicopathologic characteristics and survival outcomes across molecular subtypes of EC in a Thai tertiary care center.Methods:This retrospective cohort included patients with histologically confirmed EC who underwent primary surgery at Chiang Mai University Hospital between 2015 and 2023, and had at least one investigation for molecular classification, including immunohistochemistry (IHC) for mismatch repair (MMR) proteins and p53, as well as POLE sequencing using the Idylla™ POLE–POLD1 Mutation Assay with confirmatory Sanger sequencing. Final molecular subtype assignment followed established hierarchical algorithms. Clinicopathologic variables were analyzed using Chi-square and logistic regression. Progression-free survival (PFS) and overall survival (OS) were estimated with Kaplan–Meier and compared using the log-rank test.Results:Among 803 EC cases diagnosed during the study period, 184 met the inclusion criteria. Of 184 patients, molecular subtypes were classified as POLE-mutated in 2.2%, dMMR in 38.6%, p53-abnormal (p53-abn) in 45.1% and NSMP (1.6%). dMMR tumors occurred predominantly in older women and exhibited mainly endometrioid histology, whereas p53-abn tumors were largely non-endometrioid and high-risk in the vast majority. In multivariate analysis, histologic type was the only independent predictor of both MMR deficiency (adjusted OR = 15.22; 95% CI 4.99–46.37;p< 0.001) and p53 abnormality (adjusted OR = 79.42; 95% CI 10.60–595.05;p= 0.003). Survival outcomes varied by molecular class: POLE-mutated tumors had excellent prognosis with no recurrence or death, dMMR tumors had intermediate outcomes, and p53-abn tumors showed the poorest PFS and OS. Overall survival differed significantly among subtypes.Conclusions:Molecular classification provides strong prognostic discrimination in EC, even with selective testing. MMR and p53 IHC serve as practical frontline tools, while POLE sequencing should be prioritized for intermediate- and high-risk endometrioid tumors. Expanded molecular testing in Asian populations is essential to refine risk stratification and optimize individualized management.

 

摘要翻译: 

背景:分子分型重塑了子宫内膜癌(EC)的预后评估和治疗策略。然而,来自亚洲人群的真实世界证据仍然匮乏。本研究评估了泰国一家三级医疗中心子宫内膜癌不同分子亚型的临床病理特征和生存结局。 方法:本回顾性队列纳入了2015年至2023年间在清迈大学医院接受初次手术、并经组织学确诊为子宫内膜癌的患者,这些患者至少接受了一项分子分型检测,包括错配修复(MMR)蛋白和p53的免疫组织化学(IHC)检测,以及使用Idylla™ POLE–POLD1突变检测试剂盒进行POLE测序(并经Sanger测序验证)。最终分子亚型的判定遵循既定的分层算法。临床病理变量采用卡方检验和逻辑回归进行分析。采用Kaplan–Meier法估计无进展生存期(PFS)和总生存期(OS),并采用对数秩检验进行比较。 结果:在研究期间诊断的803例子宫内膜癌病例中,184例符合纳入标准。在184例患者中,分子亚型分类为:POLE突变型占2.2%,错配修复缺陷型(dMMR)占38.6%,p53异常型(p53-abn)占45.1%,非特异性分子谱型(NSMP)占1.6%。dMMR肿瘤主要发生于老年女性,且主要为子宫内膜样组织学类型;而p53-abn肿瘤绝大多数为非子宫内膜样类型且属于高危类型。在多变量分析中,组织学类型是MMR缺陷(校正后OR = 15.22;95% CI 4.99–46.37;p < 0.001)和p53异常(校正后OR = 79.42;95% CI 10.60–595.05;p = 0.003)的唯一独立预测因子。生存结局因分子类别而异:POLE突变型肿瘤预后极佳,无复发或死亡;dMMR肿瘤预后中等;p53-abn肿瘤的PFS和OS最差。各亚型间的总生存期存在显著差异。 结论:即使在选择性检测的情况下,分子分型也能为子宫内膜癌提供强有力的预后区分。MMR和p53免疫组化可作为实用的前线检测工具,而POLE测序应优先用于中高危的子宫内膜样肿瘤。在亚洲人群中扩大分子检测对于完善风险分层和优化个体化管理至关重要。

 

 

原文链接:

Molecular Classification and Clinical Outcomes in Endometrial Cancer: Real-World Evidence from a Tertiary Care Center

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