Evaluating HER2 Scoring Criteria in Endometrial Carcinoma: Gynecologic Versus Gastric Guidelines for Trastuzumab and Trastuzumab-Deruxtecan Selection.
Gastric criteria reclassify nearly half of HER2-equivocal endometrial biopsies as positive.
Evaluating HER2 Scoring Criteria in Endometrial Carcinoma: Gynecologic Versus Gastric Guidelines for Trastuzumab and Trastuzumab-Deruxtecan Selection.
HER2 overexpression and/or amplification defines a molecularly distinct subset of endometrial carcinomas (endometrial carcinomas) that may benefit from HER2-targeted therapies.
HER2 immunohistochemistry (immunohistochemistry) and whole-slide fluorescence in situ hybridization (FISH) were interpreted by subspecialty breast and gynecologic pathologists, with HER2 immunohistochemistry performed on 494 tumor samples (2021-2025) and reflex FISH for equivocal cases.
Among equivocal cases, 28.2% (58/205) demonstrated ERBB2 amplification, yielding an overall HER2-positive rate of 27.5% (132/480).
Re-assessment with gastric scoring criteria demonstrated variability in HER2 classification, with high concordance in cytology specimens (100%) and resections (90.8%; K = 0.842, p < 0.001) but substantially lower concordance in biopsies (60.6%; K = 0.401, p < 0.001), mainly due to reclassification of equivocal cases.
These findings highlight the evolving nature of HER2 testing in endometrial carcinomas and demonstrate the significant impact of scoring methodology on HER2 interpretation.
Our results support the development of endometrial carcinomas-specific HER2 testing guidelines and a dual-reporting approach incorporating both ISGyP and gastric scoring criteria, with selective confirmatory FISH testing, to optimize patient selection for HER2-targeted therapies.