Impact of molecular and immune signature on endometrial biopsies with atypical hyperplasia with and without concurrent endometroid carcinoma

IF 1.3 Q3 OBSTETRICS & GYNECOLOGY

Gynecologic Oncology Reports Pub Date : 2025-09-19 DOI:10.1016/j.gore.2025.101959

Terrence Wong , Joellen Fresia , Nicholas Adzibolosu , Logan Corey , Sharon Wu , Larissa Mattei , Joanne Xiu , Kurt Hodges , Matthew Oberley , Premal H. Thaker , Rami Musallam , Mira Kheil , Sudeshna Bandyopadhyay , Ira Winer , Robert Morris , Rouba Ali-Fehmi

{"title":"Impact of molecular and immune signature on endometrial biopsies with atypical hyperplasia with and without concurrent endometroid carcinoma","authors":"Terrence Wong , Joellen Fresia , Nicholas Adzibolosu , Logan Corey , Sharon Wu , Larissa Mattei , Joanne Xiu , Kurt Hodges , Matthew Oberley , Premal H. Thaker , Rami Musallam , Mira Kheil , Sudeshna Bandyopadhyay , Ira Winer , Robert Morris , Rouba Ali-Fehmi","doi":"10.1016/j.gore.2025.101959","DOIUrl":null,"url":null,"abstract":"<div><h3>Objective</h3><div>Patients with a biopsy diagnosis of atypical endometrial hyperplasia (AEH) or endometrial intraepithelial neoplasia (EIN) have a significant underlying risk of concurrent endometrial cancer (EC). We sought to determine whether molecular and/or immune signatures can be utilized to differentiate between pre-operative, premalignant lesions with and without concurrent occult endometrioid adenocarcinoma.</div></div><div><h3>Methods</h3><div>A single-institution database was queried for patients diagnosed with AEH/EIN on pre-operative sampling who then underwent subsequent hysterectomy. Whole exome and whole transcriptome sequencing of tissue samples were performed by CARIS Life Sciences. Quantification of immune cells from RNA sequencing data was estimated using quanTIseq.</div></div><div><h3>Results</h3><div>We identified 34 patients with matched pre-operative and hysterectomy specimens: 19 patients (56 %) with AEH/EIN only and 15 patients (44 %) with EC. Forty-four pathologic specimens (65 %) were successfully profiled. The most frequent genomic alterations in the EC cohort were PTEN (83.3 %), MSI-H (22.2 %), PIK3R1 (22.2 %), and CTNNB1 (16.7 %). There were no MSI-H or CTNNB1 alterations in the AEH/EIN cohort. Median expression of all ten immune checkpoint genes analyzed (CD80, CD86, CD274, CTLA4, HAVCR2/TIM3, IFNG, IDO1, LAG3, PDCD1, PDCD1LG2) were numerically higher for pre-operative biopsies in the EC cohort. Infiltrates of pro-tumorigenic regulatory T cells (+2.42 %) and tumor-suppressing neutrophils (+11.75 %) and CD8 + T cells (+2.39 %) trended higher (p < 0.05) in this same cohort – absolute fractions of tumor-suppressing NK cells and M1 macrophages were also greater.</div></div><div><h3>Conclusions</h3><div>Pre-operative AEH/EIN biopsy specimens exhibit different molecular and immune profiles depending on the coexistence of concurrent EC. Further characterization of these signatures may lead to advances in diagnostic precision and prognostic capability.</div></div>","PeriodicalId":12873,"journal":{"name":"Gynecologic Oncology Reports","volume":"61 ","pages":"Article 101959"},"PeriodicalIF":1.3000,"publicationDate":"2025-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Gynecologic Oncology Reports","FirstCategoryId":"1085","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S2352578925001845","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"OBSTETRICS & GYNECOLOGY","Score":null,"Total":0}

引用次数: 0

Abstract

Objective

Patients with a biopsy diagnosis of atypical endometrial hyperplasia (AEH) or endometrial intraepithelial neoplasia (EIN) have a significant underlying risk of concurrent endometrial cancer (EC). We sought to determine whether molecular and/or immune signatures can be utilized to differentiate between pre-operative, premalignant lesions with and without concurrent occult endometrioid adenocarcinoma.

Methods

A single-institution database was queried for patients diagnosed with AEH/EIN on pre-operative sampling who then underwent subsequent hysterectomy. Whole exome and whole transcriptome sequencing of tissue samples were performed by CARIS Life Sciences. Quantification of immune cells from RNA sequencing data was estimated using quanTIseq.

Results

We identified 34 patients with matched pre-operative and hysterectomy specimens: 19 patients (56 %) with AEH/EIN only and 15 patients (44 %) with EC. Forty-four pathologic specimens (65 %) were successfully profiled. The most frequent genomic alterations in the EC cohort were PTEN (83.3 %), MSI-H (22.2 %), PIK3R1 (22.2 %), and CTNNB1 (16.7 %). There were no MSI-H or CTNNB1 alterations in the AEH/EIN cohort. Median expression of all ten immune checkpoint genes analyzed (CD80, CD86, CD274, CTLA4, HAVCR2/TIM3, IFNG, IDO1, LAG3, PDCD1, PDCD1LG2) were numerically higher for pre-operative biopsies in the EC cohort. Infiltrates of pro-tumorigenic regulatory T cells (+2.42 %) and tumor-suppressing neutrophils (+11.75 %) and CD8 + T cells (+2.39 %) trended higher (p < 0.05) in this same cohort – absolute fractions of tumor-suppressing NK cells and M1 macrophages were also greater.

Conclusions

Pre-operative AEH/EIN biopsy specimens exhibit different molecular and immune profiles depending on the coexistence of concurrent EC. Further characterization of these signatures may lead to advances in diagnostic precision and prognostic capability.

查看原文本刊更多论文

分子和免疫特征对不典型增生伴或不伴子宫内膜样癌的子宫内膜活检的影响

活检诊断为非典型子宫内膜增生（AEH）或子宫内膜上皮内瘤变（EIN）的患者具有并发子宫内膜癌（EC）的显著潜在风险。我们试图确定分子和/或免疫特征是否可以用于区分术前、癌前病变伴和不伴隐匿性子宫内膜样腺癌。方法对术前抽样诊断为AEH/EIN并行子宫切除术的患者进行单机构数据库查询。组织样本的全外显子组和全转录组测序由CARIS生命科学公司进行。利用quanTIseq从RNA测序数据中估计免疫细胞的定量。结果我们确定了34例术前和子宫切除术标本相匹配的患者：19例（56%）仅患有AEH/EIN， 15例（44%）患有EC。44例病理标本（65%）被成功分析。EC队列中最常见的基因组改变是PTEN（83.3%）、MSI-H（22.2%）、PIK3R1（22.2%）和CTNNB1（16.7%）。在AEH/EIN队列中没有MSI-H或CTNNB1的改变。在EC队列中，术前活检分析的所有10个免疫检查点基因（CD80、CD86、CD274、CTLA4、HAVCR2/TIM3、IFNG、IDO1、LAG3、PDCD1、PDCD1LG2）的中位表达量均较高。在同一队列中，促肿瘤调节性T细胞（+ 2.42%）、肿瘤抑制中性粒细胞（+ 11.75%）和CD8 + T细胞（+ 2.39%）的浸润率呈上升趋势（p < 0.05），肿瘤抑制NK细胞和M1巨噬细胞的绝对比例也更高。结论术前AEH/EIN活检标本表现出不同的分子和免疫特征，这取决于并发EC的共存。这些特征的进一步表征可能导致诊断精度和预后能力的进步。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Gynecologic Oncology Reports OBSTETRICS & GYNECOLOGY-

CiteScore

2.00

自引率

0.00%

发文量

183

审稿时长

41 days

期刊介绍： Gynecologic Oncology Reports is an online-only, open access journal devoted to the rapid publication of narrative review articles, survey articles, case reports, case series, letters to the editor regarding previously published manuscripts and other short communications in the field of gynecologic oncology. The journal will consider papers that concern tumors of the female reproductive tract, with originality, quality, and clarity the chief criteria of acceptance.