Department Obstetrics and Gynaecology, Radboud University Medical Center, Nijmegen, the Netherlands; Department of Obstetrics and Gynaecology, Canisius-Wilhelmina Hospital, Nijmegen, the Netherlands.
Department of Pathology, Canisius-Wilhelmina Hospital, Nijmegen, the Netherlands.
Gynecol Oncol. 2019 Jul;154(1):124-130. doi: 10.1016/j.ygyno.2019.03.097. Epub 2019 May 15.
Mismatch repair (MMR) deficiency is found in 20 to 40% of endometrial cancers (ECs) and was recently identified as a discerning feature of one of the four prognostic subgroups identified by The Cancer Genome Atlas. There is accumulating evidence that MMR proteins are involved in the DNA repair processes following radiotherapy. We investigated the predictive value of MMR status for response to adjuvant radiotherapy in patients with stage IB/II, grade 3 endometrioid endometrial cancer (EEC).
A retrospective multicenter cohort study was performed to compare patients with histopathologically confirmed stage IB/II grade 3 EEC with and without adjuvant radiotherapy. Patients were classified according to the Proactive Molecular Risk Classifier for Endometrial Cancer (ProMisE) identifying ECs as either MMR-deficient, POLE, p53abn or p53wt. Multivariable Cox regression analysis explored associations between adjuvant treatment and outcome.
A total of 128 patients were analyzed, including 57 patients (43.0%) with MMR-deficient EECs. Baseline characteristics were comparable, except a higher proportion of MMR-deficient EECs were stage II (36.8% vs. 15.5%, p = 0.006). Eighty-two patients (64.1%) received adjuvant radiotherapy (external beam [n = 55], vaginal brachytherapy [n = 27]). In multivariable analysis, adjuvant radiotherapy was associated with improved disease-specific survival in patients with MMR-deficient EECs (hazard ratio 0.19, 95%-CI 0.05-0.77), but not in patients with MMR-proficient EECs (hazard ratio 0.92, 95%-CI 0.37-2.31).
Adjuvant radiotherapy improved survival in patients with MMR-deficient EECs. MMR status could be used as a predictive biomarker to select patients that benefit most from adjuvant radiotherapy.
错配修复（MMR）缺陷在 20%至 40%的子宫内膜癌（ECs）中发现，最近被确定为癌症基因组图谱（The Cancer Genome Atlas）确定的四个预后亚组之一的鉴别特征。有越来越多的证据表明，MMR 蛋白参与放射治疗后的 DNA 修复过程。我们研究了 MMR 状态对接受辅助放疗的 Ib/II 期、G3 子宫内膜样子宫内膜癌（EEC）患者的预测价值。
进行了一项回顾性多中心队列研究，比较了组织病理学证实的 Ib/II 期 G3 EEC 伴或不伴辅助放疗的患者。患者根据 Proactive Molecular Risk Classifier for Endometrial Cancer（ProMisE）进行分类，将 ECs 分为 MMR 缺陷型、POLE 型、p53abn 型或 p53wt 型。多变量 Cox 回归分析探讨了辅助治疗与结局之间的关系。
共分析了 128 例患者，其中 57 例（43.0%）为 MMR 缺陷型 EEC。基线特征无差异，除 MMR 缺陷型 EEC 分期较高（36.8%比 15.5%，p=0.006）外。82 例（64.1%）患者接受了辅助放疗（外照射放疗[n=55]，阴道近距离放疗[n=27]）。多变量分析显示，在 MMR 缺陷型 EEC 患者中，辅助放疗与疾病特异性生存改善相关（风险比 0.19，95%CI 0.05-0.77），但在 MMR 功能正常的 EEC 患者中则无相关性（风险比 0.92，95%CI 0.37-2.31）。
辅助放疗可改善 MMR 缺陷型 EEC 患者的生存。MMR 状态可作为预测生物标志物，用于选择最受益于辅助放疗的患者。
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