{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,23]],"date-time":"2026-06-23T06:49:51Z","timestamp":1782197391700,"version":"3.54.5"},"reference-count":26,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2026,6,22]],"date-time":"2026-06-22T00:00:00Z","timestamp":1782086400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Background\/Objectives: HER2 overexpression and\/or amplification defines a molecularly distinct subset of endometrial carcinomas (ECs) that may benefit from HER2-targeted therapies. However, HER2 testing algorithms remain non-standardized and vary across institutions. This study is a large single-institution audit of EC HER2 testing practices, using both gynecologic (ISGyP) and gastric cancer-specific scoring algorithms at a major academic center with a reference gynecologic oncology service and biomarker laboratory. Methods: HER2 immunohistochemistry (IHC) and whole-slide fluorescence in situ hybridization (FISH) were interpreted by subspecialty breast and gynecologic pathologists, with HER2 IHC performed on 494 tumor samples (2021\u20132025) and reflex FISH for equivocal cases. Results: Using ISGyP criteria, 15.0% (74\/494) of tumors were HER2 IHC 3+, 44.5% (220\/494) equivocal (2+), and 40.5% (200\/494) were negative (0\/1+). 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 &lt; 0.001) but substantially lower concordance in biopsies (60.6%; K = 0.401, p &lt; 0.001), mainly due to reclassification of equivocal cases. Notably, 47.9% (n = 34) of ISGyP-equivocal biopsy specimens were reclassified as HER2 IHC 3+ using gastric biopsy criteria, potentially expanding eligibility for T-DXd therapy. Conclusions: These findings highlight the evolving nature of HER2 testing in EC and demonstrate the significant impact of scoring methodology on HER2 interpretation. Our results support the development of EC-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.<\/jats:p>","DOI":"10.3390\/cancers18122009","type":"journal-article","created":{"date-parts":[[2026,6,23]],"date-time":"2026-06-23T06:13:37Z","timestamp":1782195217000},"page":"2009","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Evaluating HER2 Scoring Criteria in Endometrial Carcinoma: Gynecologic Versus Gastric Guidelines for Trastuzumab and Trastuzumab-Deruxtecan Selection"],"prefix":"10.3390","volume":"18","author":[{"given":"Sharon","family":"Nofech-Mozes","sequence":"first","affiliation":[{"name":"Precision Diagnostics and Therapeutics Program, Division of Anatomic Pathology, Department of Laboratory Medicine and Molecular Diagnostics, Sunnybrook Health Sciences Centre, Toronto, ON M4N 3M5, Canada"},{"name":"Department of Laboratory Medicine and Pathobiology, Temerty Faculty of Medicine, University of Toronto, Toronto, ON M5S 3G9, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ekaterina","family":"Olkhov-Mitsel","sequence":"additional","affiliation":[{"name":"Precision Diagnostics and Therapeutics Program, Division of Anatomic Pathology, Department of Laboratory Medicine and Molecular Diagnostics, Sunnybrook Health Sciences Centre, Toronto, ON M4N 3M5, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fang-I","family":"Lu","sequence":"additional","affiliation":[{"name":"Precision Diagnostics and Therapeutics Program, Division of Anatomic Pathology, Department of Laboratory Medicine and Molecular Diagnostics, Sunnybrook Health Sciences Centre, Toronto, ON M4N 3M5, Canada"},{"name":"Department of Laboratory Medicine and Pathobiology, Temerty Faculty of Medicine, University of Toronto, Toronto, ON M5S 3G9, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-3604-9645","authenticated-orcid":false,"given":"Weei-Yuarn","family":"Huang","sequence":"additional","affiliation":[{"name":"Precision Diagnostics and Therapeutics Program, Division of Anatomic Pathology, Department of Laboratory Medicine and Molecular Diagnostics, Sunnybrook Health Sciences Centre, Toronto, ON M4N 3M5, Canada"},{"name":"Department of Laboratory Medicine and Pathobiology, Temerty Faculty of Medicine, University of Toronto, Toronto, ON M5S 3G9, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-9216-8500","authenticated-orcid":false,"given":"Anna","family":"Plotkin","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine and Pathobiology, Temerty Faculty of Medicine, University of Toronto, Toronto, ON M5S 3G9, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,6,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2225","DOI":"10.1002\/cncr.32802","article-title":"Annual report to the nation on the status of cancer, part I: National cancer statistics","volume":"126","author":"Henley","year":"2020","journal-title":"Cancer"},{"key":"ref_2","first-page":"229","article-title":"Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries","volume":"74","author":"Bray","year":"2024","journal-title":"CA Cancer J. 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