由于组织病理学相似，卵巢高级别子宫内膜样癌（HGEC）和高级别浆液性癌（HGSC）的诊断存在相当大的观察者间差异。虽然同源重组缺陷 (HRD) 与 HGSC 的药物敏感性相关，但 HGEC 的分子特征尚不清楚。 JGOG-TR2 队列中 15 个卵巢 HGEC 和 274 个卵巢 HGSC 的新鲜冷冻样本被提交进行靶向 DNA 测序、RNA 测序、 DNA甲基化阵列和SNP阵列。我们还分析了来自 TCGA-OV 的 555 个卵巢 HGSC 和来自 TCGA-UCEC 的 287 个子宫内膜高级别癌。使用拷贝数特征进行无监督聚类，确定了四个不同的肿瘤组（C1、C2、C3 和 C4）。 C1 (n = 41) 显示 CCNE1 扩增和较差的存活率。 C2 (n = 160) 和 C3 (n = 59) 分别表现出高 BRCA1/2 改变频率以及低倍性和中倍性。 C4 (n = 22) 的特点是良好的结果、较高的 HGEC 比例、无 BRCA1/2 改变或 CCNE1 扩增、HRD 评分、倍性、瘤内异质性、细胞增殖率和 WT1 基因表达水平较低。值得注意的是，C4 表现出正常的子宫内膜样 DNA 甲基化谱，因此被定义为“HGEC 型”肿瘤，在 TCGA-OV 和 TCGA-UCEC 中也被鉴定出。卵巢“HGEC 型”肿瘤呈现非 HRD 状态、良好的预后和子宫内膜分化，可能构成临床诊断的 HGSC 的一个子集。© 2024。作者，获得 Springer Nature Limited 的独家许可。

Considerable interobserver variability exists in diagnosis of ovarian high-grade endometrioid carcinoma (HGEC) and high-grade serous carcinoma (HGSC) due to histopathological similarities. While homologous recombination deficiency (HRD) correlates with drug sensitivity in HGSC, the molecular features of HGEC are unclear.Fresh-frozen samples from 15 ovarian HGECs and 274 ovarian HGSCs in the JGOG-TR2 cohort were submitted to targeted DNA sequencing, RNA sequencing, DNA methylation array, and SNP array. We additionally analyzed 555 ovarian HGSCs from TCGA-OV and 287 endometrial high-grade carcinomas from TCGA-UCEC.Unsupervised clustering using copy number signatures identified four distinct tumor groups (C1, C2, C3 and C4). C1 (n = 41) showed CCNE1 amplification and poor survival. C2 (n = 160) and C3 (n = 59) showed high BRCA1/2 alteration frequency with low and moderate ploidy, respectively. C4 (n = 22) was characterized by favorable outcome, higher HGEC proportion, no BRCA1/2 alteration or CCNE1 amplification, and low levels of HRD score, ploidy, intra-tumoral heterogeneity, cell proliferation rate, and WT1 gene expression. Notably, C4 exhibited a normal endometrium-like DNA methylation profile, thus, defined as "HGEC-type" tumors, which were also identified in TCGA-OV and TCGA-UCEC.Ovarian "HGEC-type" tumors present a non-HRD status, favorable prognosis, and endometrial differentiation, possibly constituting a subset of clinically diagnosed HGSCs.© 2024. The Author(s), under exclusive licence to Springer Nature Limited.