Prognostic Significance of POLE Exonuclease Domain Mutations in High-Grade Endometrioid Endometrial Cancer on Survival and Recurrence: A Subanalysis.
Prognostic Significance of POLE Exonuclease Domain Mutations in High-Grade Endometrioid Endometrial Cancer on Survival and Recurrence: A Subanalysis.
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DOI：
10.1097/igc.0000000000000681
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发表时间：
2016-06
期刊：
影响因子：
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通讯作者：
Goodfellow PJ
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文献类型：
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作者：
Billingsley CC;Cohn DE;Mutch DG;Hade EM;Goodfellow PJ
高级别子宫内膜样子宫内膜癌 (EEC) 中的 POLE 突变与生存率的提高有关。我们试图通过对先前描述的 544 名 EEC 患者队列中患有高级别 EEC 的女性进行亚分析，研究 POLE 肿瘤突变的患病率及其对结果和临床应用的预后意义，其中评估了 POLE 突变状态和生存结果。 PCR 扩增和 Sanger 测序用于检测 72 个肿瘤中的 POLE 突变。使用 Cox 比例风险模型研究 POLE 突变、人口统计学和临床病理特征与生存之间的关联。 POLE 突变在 7/72 (9.7%) 3 级 EEC 中被发现。没有发现 POLE 突变患者和没有 POLE 突变患者的临床病理特征存在显着差异。调整年龄后，POLE 突变患者的复发风险降低（aHR=0.37，95%CI 0.09-1.55），死亡风险也降低（aHR=0.19，95%CI 0.03-1.42）。患有 3 级 EEC 的女性肿瘤中的 POLE 突变与较低的复发和死亡风险相关，但由于这些估计值的高度变异性，在统计上并不显着。这些发现与最近发表的综合分析一致，支持 POLE 突变状态作为一个值得注意的预后标志物，并可能有利于改变 3 级 EEC 女性的治疗方法，特别是对于那些患有早期疾病的女性，其中省略辅助治疗和减少监测可能是适当的。
POLE mutations in high grade endometrioid endometrial cancer (EEC) have been associated with improved survival. We sought to investigate the prevalence of POLE tumor mutation and its prognostic significance on outcomes and clinical applications in a sub-analysis of women with high grade EEC from a previously described cohort of 544 EEC patients in which POLE mutation status and survival outcomes was assessed. PCR amplification and Sanger sequencing was used to test for POLE mutations in 72 tumors. Associations between POLE mutation, demographic and clinicopathologic features and survival were investigated with Cox proportional hazard models. POLE mutations were identified in 7/72 (9.7%) grade 3 EECs. No significant differences in the clinicopathologic features between those with POLE mutations and those without were identified. Adjusted for age, a decreased risk of recurrence was suggested in patients with a POLE mutation (aHR=0.37, 95%CI 0.09-1.55), as well as decreased risk of death (aHR=0.19, 95% CI 0.03-1.42). POLE mutations in tumors of women with grade 3 EEC are associated with a lower risk of recurrence and death, though not statistically significant due to high variability in these estimates. These findings, consistent with recently published combined analyses, support POLE mutation status as a noteworthy prognostic marker and may favor a change in the treatment of women with grade 3 EECs, particularly in those with early stage disease, in which omission of adjuvant therapy and decreased surveillance could possibly be appropriate.