Division of Genome Biology, National Cancer Center Research Institute, Tokyo 104-0045, Japan; Department of Gynecology, National Cancer Center Hospital, Tokyo 104-0045, Japan.
Division of Genome Biology, National Cancer Center Research Institute, Tokyo 104-0045, Japan; Department of Obstetrics and Gynecology, Juntendo University Faculty of Medicine, Tokyo 113-8421, Japan.
Gynecol Oncol. 2024 Nov;190:139-145. doi: 10.1016/j.ygyno.2024.08.016. Epub 2024 Aug 26.
The 2023 International Federation of Gynecology and Obstetrics classification with molecular classification shows superior discriminatory ability compared to staging systems lacking molecular data. However, the accuracy of endometrial biopsy data in molecular classification remains uncertain. This study aimed to assess the concordance of molecular classifications between preoperative biopsy and hysterectomy to predict prognosis before surgical staging.
Endometrial biopsies and corresponding hysterectomy specimens were collected at the National Cancer Center Hospital between 2012 and 2023. Immunohistochemistry for p53 and mismatch repair (MMR) proteins and next-generation sequencing of all exons of polymerase epsilon (POLE) were performed. Given the limited number of POLE mut cases in prior studies, we prepared a POLE mut-enriched cohort. Cohen's kappa estimates were used to determine concordance for molecular and clinicopathological subgroup assignments.
Among 70 patients classified into four molecular subtype groups, 33 exhibited POLE mutations, 15 showed loss of MMR protein expression, 13 had p53-abnormality, and 9 had no specific molecular profile. Concordance between biopsy and hysterectomy specimens was 100% (κ = 1.000). In contrast, histological types and grades between biopsy and surgical specimens showed moderate and substantial agreement (κ = 0.420 and κ = 0.780, respectively).
Molecular subtypes were completely consistent with those derived from surgical specimens, demonstrating high concordance between preoperative and postoperative molecular classifications. This suggests that endometrial biopsies could reliably predict prognosis. Future studies should investigate how biopsy-based molecular profiling influences treatment planning and patient outcomes.
2023 年国际妇产科联盟（FIGO）分类联合分子分类较缺乏分子数据的分期系统具有更好的鉴别能力。然而，子宫内膜活检数据在分子分类中的准确性仍不确定。本研究旨在评估术前活检和子宫切除术之间的分子分类一致性，以预测手术分期前的预后。
2012 年至 2023 年期间，在国家癌症中心医院收集子宫内膜活检和相应的子宫切除术标本。进行 p53 和错配修复（MMR）蛋白的免疫组织化学染色以及聚合酶 epsilon（POLE）所有外显子的下一代测序。鉴于先前研究中 POLE 突变病例数量有限，我们准备了一个 POLE 突变富集队列。使用 Cohen's kappa 估计来确定分子和临床病理亚组分配的一致性。
在 70 名被分为四个分子亚型组的患者中，33 名存在 POLE 突变，15 名表现出 MMR 蛋白表达缺失，13 名存在 p53 异常，9 名没有特定的分子特征。活检和子宫切除术标本之间的一致性为 100%（κ=1.000）。相比之下，活检和手术标本的组织学类型和分级显示出中度和显著的一致性（κ=0.420 和 κ=0.780）。
分子亚型与来自手术标本的亚型完全一致，表明术前和术后的分子分类具有高度一致性。这表明子宫内膜活检可以可靠地预测预后。未来的研究应探讨基于活检的分子谱分析如何影响治疗计划和患者结局。
