IB期3级子宫内膜样子宫内膜腺癌的治疗具有挑战性，实践多种多样。分子表征可能有助于确定阶段后的辅助治疗策略。我们旨在通过 ProMisE 分类、突变特征和常见突变基因来表征这些肿瘤，从而更好地了解这些肿瘤的分子特征。纳入了两个机构的 IB 期 3 级 EEC 患者。对存档的 FFPE 组织切片进行免疫组织化学和全外显子组测序以确定 ProMisE 分类。使用个人癌症基因组报告程序进行体细胞变异注释，并根据 COSMIC 单碱基替换突变特征生成突变特征。46 名患者接受了可变辅助治疗。 9 名患者复发（19.6%），大多数患有腹外疾病（n = 5，即 55.6%）。 10 名有 POLE 突变（21.7%），18 名有 MMR 缺陷（39.1%），6 名有异常 p53（13.0%），12 名有 p53 野生型（26.1%）。 POLE 亚组没有复发。在 38 名患者中发现显性突变特征：17 例 SBS5 特征（44.7%）、10 例 SBS15 或 SBS44 特征（26.3%）、7 例 SBS10a 或 SBS10b 特征（18.4%）、3 例 SBS14 特征（7.9%）和 1 例 SBS40 特征（2.6%）。复发的 6 名患者有 SBS5 签名。频繁突变的基因包括 ARID1A (n = 30, 65%)、PTEN (n = 28, 61%)、MUC16 (n = 27, 59%) 和 PIK3CA (n = 25, 54%)。 这项综合评估发现尽管组织学、分期和分级相同，但肿瘤的分子结构却不同。突变特征 SBS5 与高复发风险相关。子宫内膜癌分类的进一步细化可能会实现更精确的患者分层和个性化治疗方法。版权所有 © 2024 作者。由爱思唯尔公司出版。保留所有权利。

The treatment for stage IB grade 3 endometrioid endometrial adenocarcinoma is challenging with variable practice. Molecular characterization may help identify adjuvant therapy strategies beyond stage. We aimed to better understand the molecular features of these tumors by characterizing them by ProMisE classification, mutational signature, and commonly mutated genes.Patients with stage IB grade 3 EEC at two institutions were included. Immunohistochemistry and whole exome sequencing were performed on archival FFPE tissue sections to determine ProMisE classification. Personal Cancer Genome Reporter was used for somatic variant annotation, and mutational signatures were generated based on COSMIC single base substitution mutational signatures.46 patients were included with variable adjuvant treatment. Nine patients recurred (19.6%), most with extra-abdominal disease (n = 5, or 55.6%). 10 had POLE mutations (21.7%), 18 were MMR deficient (39.1%), 6 had abnormal p53 (13.0%), and 12 were p53 wildtype (26.1%). There were no recurrences in the POLE subgroup. A dominant mutational signature was identified in 38 patients: 17 SBS5 signature (44.7%), 10 SBS15 or SBS44 signature (26.3%), 7 SBS10a or SBS10b signature (18.4%), 3 SBS14 signature (7.9%), and 1 SBS40 signature (2.6%). The six patients that recurred had a SBS5 signature. Frequently mutated genes included ARID1A (n = 30, 65%), PTEN (n = 28, 61%), MUC16 (n = 27, 59%), and PIK3CA (n = 25, 54%).This comprehensive evaluation found a molecularly diverse cohort of tumors, despite the same histology, stage and grade. Mutational signature SBS5 correlated with a high risk of recurrence. Further refining of endometrial cancer classification may enable more precise patient stratification and personalized treatment approaches.Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.