Prognostic significance of estrogen receptor expression and estrogen signaling in endometrial carcinomas of no specific molecular profile: A comprehensive molecular and pathologic analysis Journal Article

  

Authors:	Lam, C.; Zhou, Q.; Aghajanian, C.; Abu-Rustum, N. R.; Mueller, J. J.; Ellenson, L. H.; Green, A. K.; Weigelt, B.; Jungbluth, A. A.; Momeni-Boroujeni, A.
Article Title:	Prognostic significance of estrogen receptor expression and estrogen signaling in endometrial carcinomas of no specific molecular profile: A comprehensive molecular and pathologic analysis
Abstract:	Introduction: Copy number-low (CNL) endometrial cancer (EC), also known as no specific molecular profile (NSMP), is the most heterogeneous molecular subtype. In this study, we evaluated the prognostic significance of estrogen receptor (ER) and PTEN expression in primary untreated CNL/NSMP ECs across all histologic subtypes to further refine risk stratification within this heterogeneous group. Methods: We identified a total of 1835 CNL/NSMP ECs that underwent clinical sequencing of 410–468 cancer-related genes. Of these, we randomly selected 100 CNL/NSMP ECs and evaluated ER and PTEN expression by immunohistochemistry. We recorded clinicopathological data regarding tumor histology and estrogen signaling sources, including ovarian volume, menopausal status, body mass index, exogenous sources of estrogen, and hotspot mutations in ESR1. We used Cox regression models to evaluate the prognostic value of these variables. Results: We observed ER positivity in 85 % of CNL/NSMP ECs, with absence of ER expression significantly associated with adverse progression-free (HR, 3.75; 95 % CI, 1.78–7.9) and overall survival (HR, 6; 95 % CI, 2.39–15.1). We observed PTEN loss of expression in 59 % of CNL/NSMP ECs, but it was not associated with survival outcomes. Multivariate analysis identified high-grade histology (HR, 6.75; 95 % CI, 2.5–17.9), lack of ER expression (HR, 3.46; 95 % CI, 1.2–9.7), and absence of any estrogen signaling sources (HR, 3.87; 95 % CI, 1.4–10.7) as significant prognostic factors for poor overall survival. Conclusion: ER positivity is associated with more favorable survival outcomes in CNL/NSMP EC. These data support dividing patients with CNL/NSMP EC into two distinct prognostic subgroups based on ER immunohistochemistry. © 2025
Keywords:	endometrial carcinoma; tumor heterogeneity; estrogen receptor expression
Journal Title:	Gynecologic Oncology
Volume:	198
ISSN:	0090-8258
Publisher:	Elsevier Inc.
Date Published:	2025-07-01
Start Page:	59
End Page:	65
Language:	English
DOI:	10.1016/j.ygyno.2025.05.015
PROVIDER:	scopus
PUBMED:	40414144
DOI/URL:	https://www.scopus.com/inward/record.uri?eid=2-s2.0-105005763151&doi=10.1016%2fj.ygyno.2025.05.015&partnerID=40&md5=d77c7e09eb516af2c2375c74d34856b9
Notes:	The MSK Cancer Center Support Grant (P30 CA008748) is acknowledge in the PDF -- Corresponding authors is MSK author: Amir Momeni-Boroujeni -- Source: Scopus

https://synapse.mskcc.org/synapse/works/has_related_data_chk/225447