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Abstract
Introduction To further subclassify copy number-low endometrial carcinomas (CNL-EC) based on immunohistochemistry (IHC) with prognostic implications.
Methods We compiled EC patients who received their primary treatment at our institution from 2014 to 2022, and who had CNL-EC based on a surrogate of The Cancer Genome Atlas (TCGA) prognostic EC molecular subtype. Estrogen receptor (ER) and PTEN IHC was performed.
Results A total of 104 patients with CNL-EC were included. Eighty eight of 104 (84.6%) were ER positive by IHC, with 86 of 88 (97.7%) with endometrioid morphology. ER-positivity was found in conjunction with PTEN mutation, identified by genomic profiling, in 81.8[EL1]%. After combining histology and grade into a single variable (low-grade vs high-grade endometrioid or non-endometrioid (NE)) multivariate analysis demonstrated that only ER IHC status and the combined histology/grade variable are significant contributors to overall survival (HR=8.6 and 9.8, respectively, P=0.02 and P=0.002, respectively). Of the 14 deaths documented in this cohort, all but three had either high-grade and/or NE, or ER-negative tumors.
Conclusion/Implications These data highlight the importance of ER-IHC testing in CNL-EC and supports subclassify CNL tumors into 2 prognostic groups: a higher-risk group including FIGO grade 3, ER-negative endometrioid tumors and/or non-endometrioid features, and a more favorable group (FIGO grade 1/2 endometrioid ER positive carcinomas). Utilizing ER-IHC with histology and FIGO grade allows for better risk-stratification of patients with CNL-EC.
