Endometrial cancer with a POLE mutation progresses frequently through type I pathway despite its high-grade endometrioid morphology: a cohort study at a single institution in Japan
Endometrial cancer with a POLE mutation progresses frequently through type I pathway despite its high-grade endometrioid morphology: a cohort study at a single institution in Japan
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具有 POLE 突变的子宫内膜癌尽管具有高级子宫内膜样形态，但经常通过 I 型途径进展：日本一家机构的队列研究
DOI：
10.1007/s00795-020-00273-3
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发表时间：
2021
期刊：
影响因子：
--
通讯作者：
Mahina Monsur
中科院分区：
文献类型：
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作者：
Yoshihara H;Sugiura-Ogasawara M;Kitaori T;Ozaki Y.;Mahina Monsur
POLE突变的子宫内膜癌（EC）经常表现出高级别子宫内膜样组织学，这代表了EC二元分类的异质性。由于亚洲女性缺乏相关信息，本研究旨在评估 POLE 突变 EC 的临床病理学和发病机制。对日本患有 EC 的女性组织中的 POLE 变异进行了测序。在具有未知意义的 aPOLE 变体的组织中评估肿瘤突变负荷（TMB）。在 POLE 突变的 EC 组织中，评估了 CD8、激素受体和 p53 的免疫染色表达，并通过激光捕获显微切割评估了癌症和不典型子宫内膜增生 (AEH) 病变中的 POLE 变异。 在 127 名 EC 患者中，在 5 名高级别子宫内膜样癌患者 (3.9%) 中鉴定出 POLE 变异（2 份组织中为 S459F，3 份组织中为 P441P）具有较高的 TMB）。这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 病变中表现出 p53 的亚克隆过度表达模式。总之，POLE 突变的 EC 通过 I 型途径进展，尽管它经常表现出高级子宫内膜样形态。 EC 中常见的 POLE 突变位点可能因种族而异。
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 ofPOLE-mutated EC due to the scarcity of related information for Asian women.POLEvariants were sequenced in tissues of Japanese women with EC. The tumor mutation burden (TMB) was assessed in tissues with aPOLEvariant of unknown significance. In thePOLE-mutated EC tissues, the immunostaining expression of CD8, hormonal receptors, and p53 was evaluated, and thePOLEvariants in cancer and atypical endometrial hyperplasia (AEH) lesions were assessed by laser-capture microdissection.POLEvariants 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 samePOLEmutation. 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 commonPOLEmutation sites in EC might vary among races.