PDF(Sci-hub)
Abstract：
POLE-mutated endometrial cancer (EC) frequently shows high-grade endometrioid histology, which represents heterogeneity in the dualistic classification of EC. This study aimed to assess the clinicopathology and pathogenesis of POLE-mutated EC due to the scarcity of related information for Asian women. POLE variants were sequenced in tissues of Japanese women with EC. The tumor mutation burden (TMB) was assessed in tissues with a POLE variant of unknown significance. In the POLE-mutated EC tissues, the immunostaining expression of CD8, hormonal receptors, and p53 was evaluated, and the POLE variants in cancer and atypical endometrial hyperplasia (AEH) lesions were assessed by laser-capture microdissection. POLE variants were identified in five patients (3.9%) with high-grade endometrioid carcinoma among 127 patients with EC (S459F in two tissues and P441P in three tissues with a high TMB). The five cancer tissues coexisted with normal endometrium and/or AEH. Both AEH and cancer cells showed hormonal receptor positivity and harbored the same POLE mutation. Two patients showed a subclonal overexpression pattern of p53 in cancer and AEH lesions. In conclusion, POLE-mutated EC progresses through the type I pathway, even though it frequently shows high-grade endometrioid morphology. The common POLE mutation sites in EC might vary among races.
摘要：
POLE突变子宫内膜癌（EC）经常显示高级别子宫内膜样组织学，这代表了EC二元分类中的异质性。本研究旨在评估亚洲女性POLE突变EC的临床病理和发病机制。在患有EC的日本女性的组织中对POLE变体进行了测序。在具有未知显著性的POLE变体的组织中评估肿瘤突变负荷(TMB)。在POLE突变的EC组织中，CD8，激素受体的免疫染色表达，对p53进行了评估，通过激光捕获显微切割评估癌症和非典型子宫内膜增生（AEH）病变中的POLE变异。在127例EC患者中，有5例（3.9％）患有高级别子宫内膜样癌的患者中发现了POLE变体（两种组织中的S459F和三种TMB高的组织中的P441P）。五种癌组织与正常子宫内膜和/或AEH共存。AEH和癌细胞均显示激素受体阳性，并具有相同的POLE突变。两名患者在癌症和AEH病变中显示出p53的亚克隆过表达模式。总之,POLE突变的EC通过I型途径进行，即使它经常显示高度子宫内膜样形态。EC中常见的POLE突变位点可能因种族而异。
