POLE 基因突变在高级别子宫内膜样腺癌中的预后：系统评价和荟萃分析。
Prognosis of polymerase epsilon (POLE) mutation in high-grade endometrioid endometrial cancer: Systematic review and meta-analysis.
机构信息
Gynecologic Oncology Unit, Hospital da Luz Lisboa, Lisboa, Portugal; Department of Obstetrics and Gynecology, LUZ SAÚDE, Hospital da Luz Lisboa, Lisboa, Portugal.
Laboratory of Clinical Pharmacology and Therapeutics, Faculty of Medicine, University of Lisbon, Lisboa, Portugal; Hospital da Luz Lisboa, Lisboa, Portugal.
出版信息
Gynecol Oncol. 2024 Mar;182:99-107. doi: 10.1016/j.ygyno.2024.01.018. Epub 2024 Jan 22.
BACKGROUND
POLE mutated endometrial carcinomas may represent a subspecific type of tumors harboring a more favorable prognosis. Grade 3 (G3 or high-grade) endometrioid endometrial carcinomas remain a clinical dilemma, with some tumors behaving as the low-grade counterparts and others presenting a more aggressive behavior.
OBJECTIVES
To determine the association between POLE mutational status and the overall-survival (OS) and progression-free-survival (PFS) of patients with G3 endometrioid endometrial cancer (EC). We also aimed to determine the prevalence of POLE mutations in G3 endometrioid EC.
METHODS
We conducted a systematic review in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines (PROSPERO No: CRD4202340008). We searched the following electronic databases: PubMed/Medline, EMBASE, Cochrane Library, Scopus, and Web of Science. For time-to-event data, the effect of POLE mutation in G3 EC was described using hazard ratios (HRs) and corresponding 95% confidence intervals (CIs). Individual patient data for each study was investigated if available from the study authors. If individual patient data were not available, information regarding time-to-event outcomes was extracted using an appropriate methodology. OS and PFS were analyzed using both one-stage and two-stage approaches, the Kaplan-Meier method, and Cox-proportional hazards models.
RESULTS
This systematic review and meta-analysis included 19 studies with 3092 patients who had high-grade endometrioid EC. Patients with POLE mutations had lower risks of death (HR = 0.36, 95% CI 0.26 to 0.50, I = 0%, 10 trials) and disease progression (HR = 0.31, 95% CI 0.17 to 0.57, I = 33%, 10 trials). The pooled prevalence of POLE mutation was 11% (95% CI 9 to 13, I = 68%, 18 studies).
CONCLUSION
POLE mutations in high-grade endometrioid EC are associated with a more favorable prognosis with increased OS and PFS.
背景
POLE 突变的子宫内膜癌可能代表一种预后较好的亚特异性肿瘤类型。3 级（G3 或高级别）子宫内膜样子宫内膜癌仍然是一个临床难题，一些肿瘤表现为低级别肿瘤的特征，而另一些则表现出更具侵袭性的行为。
目的
确定 POLE 突变状态与 G3 子宫内膜样子宫内膜癌（EC）患者的总生存（OS）和无进展生存（PFS）之间的关联。我们还旨在确定 G3 子宫内膜样 EC 中 POLE 突变的患病率。
方法
我们按照系统评价和荟萃分析的首选报告项目（PRISMA）指南（PROSPERO 编号：CRD4202340008）进行了系统综述。我们搜索了以下电子数据库：PubMed/Medline、EMBASE、Cochrane 图书馆、Scopus 和 Web of Science。对于生存时间数据，使用风险比（HRs）和相应的 95%置信区间（CIs）描述 G3 EC 中 POLE 突变的影响。如果可从研究作者处获得每个研究的个体患者数据，则对其进行研究。如果无法获得个体患者数据，则使用适当的方法从研究中提取关于生存时间结局的信息。使用 Kaplan-Meier 方法和 Cox 比例风险模型分析 OS 和 PFS。
结果
这项系统评价和荟萃分析包括 19 项研究，共纳入了 3092 名患有高级别子宫内膜样 EC 的患者。POLE 突变患者的死亡风险（HR=0.36，95%CI 0.26 至 0.50，I=0%，10 项试验）和疾病进展风险（HR=0.31，95%CI 0.17 至 0.57，I=33%，10 项试验）均较低。POLE 突变的合并患病率为 11%（95%CI 9 至 13，I=68%，18 项研究）。
结论
高级别子宫内膜样 EC 中的 POLE 突变与 OS 和 PFS 增加相关，预后更好。
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