Since the establishment of 4 molecular subgroups of endometrial carcinoma (EC), there has been significant interest in understanding molecular classification in the context of histologic features and diagnoses. ECs with undifferentiated, spindle, and/or sarcomatous components represent a diagnostically challenging subset of tumors with overlapping clinical and histologic features. We examined the clinicopathologic, morphologic, immunohistochemical, and molecular features of these tumors identified in our institutions' pathology databases using immunohistochemistry and targeted sequencing. Disease-specific survival (DSS) and progression-free survival (PFS) were analyzed using Kaplan-Meier curves and log-rank tests. One hundred sixty-two ECs were included: carcinosarcomas (UCS; n=96), dedifferentiated/undifferentiated EC (DDEC/UDEC; n=49), and grade 3 endometrioid EC with spindled growth (GR3spEEC) (n=17). All molecular subgroups were represented in all histologic subtypes and included 12 (7%) POLE-mutated (POLEmut), 43 (27%) mismatch repair-deficient (MMRd), 77 (48%) p53-abnormal (p53abn), and 30 (19%) no specific molecular profile (NSMP) tumors. However, the molecular classification (irrespective of histologic diagnosis) was a significant predictor for both DSS (P=0.008) and P≤0.0001). POLEmut EC showed an excellent prognosis with no recurrences or deaths from the disease. MMRd tumors also showed better outcomes relative to NSMP and p53abn tumors. In conclusion, molecular classification provides better prognostic information than histologic diagnosis for high-grade EC with undifferentiated and sarcomatous components. Our study strongly supports routine molecular classification of these tumors, with emphasis on molecular group, rather than histologic subtyping, in providing prognostication.

中文翻译：

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在预测具有未分化和肉瘤成分的高级别子宫内膜癌时，分子分类优于组织学分类。


自从子宫内膜癌 (EC) 的 4 个分子亚组建立以来，人们对在组织学特征和诊断的背景下理解分子分类产生了浓厚的兴趣。具有未分化、梭形和/或肉瘤成分的 EC 代表了具有重叠临床和组织学特征的诊断上具有挑战性的肿瘤子集。我们使用免疫组织化学和靶向测序检查了我们机构病理学数据库中鉴定的这些肿瘤的临床病理学、形态学、免疫组织化学和分子特征。使用 Kaplan-Meier 曲线和对数秩检验分析疾病特异性生存期 (DSS) 和无进展生存期 (PFS)。包括 162 个 EC：癌肉瘤 (UCS；n=96)、去分化/未分化 EC (DDEC/UDEC；n=49) 和梭形生长的 3 级子宫内膜样 EC (GR3spEEC) (n=17)。所有分子亚组均代表所有组织学亚型，包括 12 个 (7%) POLE 突变 (POLEmut)、43 个 (27%) 错配修复缺陷 (MMRd)、77 个 (48%) p53 异常 (p53abn) 和 30 个(19%) 无特定分子谱 (NSMP) 肿瘤。然而，分子分类（无论组织学诊断）是 DSS 的显着预测因子（P=0.008）和 P≤0.0001）。 POLEmut EC 显示出良好的预后，没有复发或死亡。相对于 NSMP 和 p53abn 肿瘤，MMRd 肿瘤也表现出更好的结果。总之，对于具有未分化和肉瘤成分的高级别 EC，分子分类比组织学诊断提供了更好的预后信息。 我们的研究强烈支持这些肿瘤的常规分子分类，在提供预后时强调分子组，而不是组织学亚型。