ArticleGynecologic oncology reports2025
Impact of molecular and immune signature on endometrial biopsies with atypical hyperplasia with and without concurrent endometroid carcinoma.
Article in Gynecologic oncology reports, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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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.
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