Division of Gynecologic Oncology, Princess Margaret Cancer Centre, University Health Network/Sinai Health Systems, Toronto, Ontario, Canada; Department of Obstetrics and Gynaecology, University of Toronto, Toronto, Canada.
Division of Gynecologic Oncology, Princess Margaret Cancer Centre, University Health Network/Sinai Health Systems, Toronto, Ontario, Canada.
Gynecol Oncol. 2021 Apr;161(1):221-227. doi: 10.1016/j.ygyno.2021.01.002. Epub 2021 Jan 19.
Findings on impact of mismatch repair deficiency (MMRd) on patient outcomes in endometrial cancer (EC) have been inconsistent to date. The objective of this study was to compare the oncologic outcomes and recurrence patterns between MMRd and MMR-intact (MMRi) endometrioid EC (EEC).
Between 2015 and 2018, we prospectively recruited 492 EEC cases from three cancer centers in Ontario, Canada. Tumors were reflexively assessed for MMR protein expression by immunohistochemistry (IHC). Clinicopathological, survival and recurrence patterns were compared between MMRd and MMRi cases.
Of 492 EEC, 348 were MMRi (71%) and 144 were MMRd (29%) with median follow-up of 16.8 months (0-69.6). MMRd tumors tended to be grade 2 or 3 (56% vs. 29%, p < 0.001), with propensity for lymphovascular space invasion (28% vs. 18%, p = 0.024), lymph node involvement (7% vs. 5%, p < 0.001) and received more adjuvant treatment (46% vs. 33%, p = 0.027). This group also had significantly lower 3-year recurrence-free survival (78% vs. 90%, p = 0.014) although there was no difference in OS (p = 0.603). MMRd cases were more likely to recur in retroperitoneal lymph nodes (p = 0.045). Upon subgroup analysis, MLH1 methylated tumors had the worst prognostic features and survival outcomes.
MLH1 methylated EECs exhibit more aggressive features compared to other MMRd and MMRi EECs. This may indicate an inherent difference in tumor biology, suggesting the importance of individualized management based on EC molecular phenotype.
目前，关于错配修复缺陷（MMRd）对子宫内膜癌（EC）患者结局的影响的研究结果并不一致。本研究的目的是比较 MMRd 和 MMR 完整（MMRi）子宫内膜样 EC（EEC）的肿瘤学结局和复发模式。
2015 年至 2018 年期间，我们从加拿大安大略省的三个癌症中心前瞻性招募了 492 例 EEC 病例。通过免疫组织化学（IHC）对肿瘤进行反射性 MMR 蛋白表达评估。比较 MMRd 和 MMRi 病例的临床病理特征、生存和复发模式。
在 492 例 EEC 中，348 例为 MMRi（71%），144 例为 MMRd（29%），中位随访时间为 16.8 个月（0-69.6）。MMRd 肿瘤往往为 2 级或 3 级（56% vs. 29%，p<0.001），具有倾向于淋巴血管空间侵犯（28% vs. 18%，p=0.024）、淋巴结受累（7% vs. 5%，p<0.001）和接受更多辅助治疗（46% vs. 33%，p=0.027）的趋势。这组患者的 3 年无复发生存率也显著降低（78% vs. 90%，p=0.014），尽管在 OS 方面没有差异（p=0.603）。MMRd 病例更有可能在后腹膜淋巴结中复发（p=0.045）。亚组分析显示，MLH1 甲基化肿瘤具有更差的预后特征和生存结果。
与其他 MMRd 和 MMRi EEC 相比，MLH1 甲基化 EEC 表现出更具侵袭性的特征。这可能表明肿瘤生物学存在内在差异，提示基于 EC 分子表型进行个体化管理的重要性。
