我们旨在评估错配修复（MMR）状态对传统风险分层算法在预测大单一机构队列中淋巴结受累和复发方面的贡献。评估2014-2020年间的子宫内膜样式的子宫内膜癌（EC）病例。普遍进行MMR免疫组化检查（IHC）。使用Mayo标准评估的子宫因素用于根据淋巴传播的低风险或高风险对患者进行回顾性分类。使用GOG 99和PORTEC标准将患者分类为复发风险。使用卡方检验和T检验评估相关性，并使用Logistic回归模型评估贡献因素。评估了1,514个内膜样式的EC，其中392个（25.9％）是MMR缺陷，其中80.4％的MMR缺陷与MLH1的表观遗传沉默有关。根据Mayo标准，相对于MMR熟练的肿瘤，表观遗传MMR缺陷的肿瘤更有可能具有淋巴结转移高风险（74.9％与60.6％，p =＜0.001），并伴有LN转移（20.3 vs 10.5％，p=0.003）。使用GOG99和PORTEC标准将表观遗传MMR缺陷肿瘤分类为高或高中风险的可能性显着高于其他肿瘤。此外，将表观遗传MMR缺陷归类为低或低中风险的案例更有可能复发（GOG99 p = 0.013; PORTEC p = 0.008），并独立于较差的无病生存（DFS）。MMR状态被发现与更差的DFS有独立关联（HR 1.90; 95％ CI 1.34-2.70; p = 0.003），但与总体生存率无关。虽然MMR缺陷的EC已被先前报告与较差的预后特征相关，但我们证明只有表观遗传MMR缺陷才有更差的预后。在控制风险标准后，表观遗传MMR缺陷与淋巴结转移有独立关联。表观遗传MMR缺陷被发现是超出传统风险分层算法考虑的因素独立预测复发的因素。在传统风险分层算法中应考虑采用MMR状态和MLH1高甲基化，并在术前病理标本上进行MMR IHC检查，以帮助风险分层和患者咨询。 版权所有©2023 Riedinger、Brown、Haight、Backes、Cohn、Goodfellow和Cosgrove。

We sought to evaluate the contribution of mismatch repair (MMR) status to traditional risk stratification algorithms used to predict nodal involvement and recurrence in a large single-institution cohort.Endometrioid endometrial cancer (EC) cases from 2014-2020 were evaluated. MMR immunohistochemistry (IHC) was performed universally. Uterine factors assessed in the Mayo criteria were used to retrospectively classify patients as low or high risk for lymphatic spread. Patients were classified according to risk for recurrence using GOG 99 and PORTEC criteria. Associations were evaluated using chi-square and t-tests and contributing factors assessed using logistic regression models.1,514 endometrioid EC were evaluated; 392 (25.9%) were MMR (MMR) deficient of which 80.4% of MMR defects were associated with epigenetic silencing of MLH1. Epigenetic MMR defects were significantly more likely to be high risk for lymph node (LN) metastasis based on Mayo criteria (74.9% vs 60.6%, p=<0.001) and with the presence of LN metastasis (20.3 vs 10.5%, p=0.003) compared to MMR proficient tumors. Tumors with epigenetic MMR defects were significantly more likely to be classified as high or high intermediate risk using GOG99 and PORTEC criteria. Furthermore, cases with epigenetic MMR defects classified as low or low intermediate risk were significantly more likely to recur (GOG99 p=0.013; PORTEC p=0.008) and independently associated with worse disease-free survival (DFS). MMR status was found to be independently associated with worse DFS (HR 1.90; 95% CI 1.34-2.70; p=0.003) but not overall survival.While MMR deficient EC has been associated with poor prognostic features in prior reports; we demonstrate that only epigenetic MMR defects have poorer outcomes. Epigenetic MMR defect were independently associated with lymph node metastasis after controlling for risk criteria. Epigenetic MMR deficiency was found to be an independent predictor of recurrence beyond the factors considered in traditional risk stratification algorithms. Traditional uterine-based risk stratification algorithms may not fully reflect the risk for recurrence in MMR deficient tumors. Consideration should be given to implementing MMR status and MLH1 hypermethylation alongside traditional risk stratification algorithms. Performing MMR IHC on preoperative pathologic specimens may aid in risk stratification and patient counseling.Copyright © 2023 Riedinger, Brown, Haight, Backes, Cohn, Goodfellow and Cosgrove.