Endometrial Carcinomas with POLE Exonuclease Domain Mutations Have a Favorable Prognosis
Endometrial Carcinomas with POLE Exonuclease Domain Mutations Have a Favorable Prognosis
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DOI：
10.1158/1078-0432.ccr-15-2233
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发表时间：
2016-06-15
影响因子：
11.5
通讯作者：
McAlpine, Jessica N.
中科院分区：
文献类型：
--
作者：
McConechy, Melissa K.;Talhouk, Aline;McAlpine, Jessica N.
目的：本研究的目的是确认POLE外切酶结构域突变（EDM）在子宫内膜癌患者中的预后意义。此外，还评估了对pole突变肿瘤的治疗效果。实验设计：对496例子宫内膜癌患者进行了回顾性研究，确定了POLE外切酶结构域的靶向测序，产生了406例可评估的肿瘤。进行单变量和多变量分析，以确定极点突变状态对无进展生存（PFS）、疾病特异性生存（DSS）和总生存（OS）的影响。结合8项研究的meta分析结果，我们计算了PFS、DSS和OS的HR。结果：406例子宫内膜癌中有39例（9.6%）检测到POLE edm。pole突变子宫内膜癌的女性更年轻，I期（92%）肿瘤，3级（62%），子宫内膜样组织学（82%）和频繁的淋巴血管侵犯（49%）。在单变量分析中，与无EDMs的PFS、DSS和OS患者相比，pole突变的子宫内膜癌的预后显著改善。在多变量分析中，POLE edm仅与改善的PFS显著相关。辅助治疗对pole突变病例的影响尚不能确定；然而，治疗和未治疗的POLE edm患者均有良好的预后。荟萃分析显示，POLE EDMs与改善的PFS和DSS之间的关联，合并hr分别为0.34[95%可信区间（CI）， 0.15-0.73]和0.35 （95% CI, 0.13-0.92）。结论：POLE edm是子宫内膜癌患者预后良好的预后指标。需要进一步调查以最终确定对这组妇女是否有必要进行治疗。(c) 2016年aacr。
Purpose: The aim of this study was to confirm the prognostic significance of POLE exonuclease domain mutations (EDM) in endometrial carcinoma patients. In addition, the effect of treatment on POLE-mutated tumors was assessed.Experimental Design: A retrospective patient cohort of 496 endometrial carcinoma patients was identified for targeted sequencing of the POLE exonuclease domain, yielding 406 evaluable tumors. Univariable and multivariable analyses were performed to determine the effect of POLE mutation status on progression-free survival (PFS), disease-specific survival (DSS), and overall survival (OS). Combining results from eight studies in a meta-analysis, we computed pooled HR for PFS, DSS, and OS.Results: POLE EDMs were identified in 39 of 406 (9.6%) endometrial carcinomas. Women with POLE-mutated endometrial carcinomas were younger, with stage I (92%) tumors, grade 3 (62%), endometrioid histology (82%), and frequent (49%) lymphovascular invasion. In univariable analysis, POLE-mutated endometrial carcinomas had significantly improved outcomes compared with patients with no EDMs for PFS, DSS, and OS. In multivariable analysis, POLE EDMs were only significantly associated with improved PFS. The effect of adjuvant treatment on POLE-mutated cases could not be determined conclusively; however, both treated and untreated patients with POLE EDMs had good outcomes. Meta-analysis revealed an association between POLE EDMs and improved PFS and DSS with pooled HRs 0.34 [95% confidence interval (CI), 0.15-0.73] and 0.35 (95% CI, 0.13-0.92), respectively.Conclusions: POLE EDMs are prognostic markers associated with excellent outcomes for endometrial carcinoma patients. Further investigation is needed to conclusively determine if treatment is necessary for this group of women. (C) 2016 AACR.