ArticleJournal of gynecologic oncology2026
Evaluation of HER2 status in endometrial carcinoma using endometrial, gastric, and breast cancer criteria: focus on HER2-low.
Article in Journal of gynecologic oncology, 2026. 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
objectiveTo evaluate human epidermal growth factor receptor 2 (HER2) status in endometrial carcinoma (EC) using 3 different criteria, assess its association with clinicopathological and molecular characteristics, and investigate intertumoral heterogeneity and prognostic significance, focusing on HER2-low.
methodsHER2 immunohistochemistry was performed on whole-slide sections from 365 EC and interpreted using EC, gastric cancer (GC), and breast cancer (BC) criteria. Silver in situ hybridization was performed for 2+/3+ cases. Intertumoral heterogeneity was assessed in 30 matched primary and recurrent/metastatic tumors.
resultsAmong 365 ECs, HER2-positive tumors (2.0%) were strongly associated with serous histology, high-grade, and the p53-abnormal (p53-abn) subgroup (p<0.001). HER2-low (45.7% by EC criteria and 18% by GC/BC criteria) was associated with advanced stage (p=0.045) and high-grade tumors (p=0.009), respectively. HER2-expression was enriched in p53-abn (60.4%, 37.7%), high-/advanced-risk (56.2%, 60.0%), and International Federation of Gynecology and Obstetrics III-IV (60.0%, 62.5%) tumors. Intertumoral heterogeneity was substantial (40.0%, 30.0%), reflecting dynamic changes, particularly in serous histology (p=0.018) and high-grade tumors (p=0.034). Based on GC/BC criteria, HER2-low status was an independent prognostic factor for recurrence in high- and advanced-risk groups compared with HER2-0 (p=0.040).
conclusionHER2 status in EC varies across scoring criteria, supporting the need for standardized interpretation. HER2 expression, including HER2-low, was more prevalent in biologically aggressive subsets, and HER-low showed prognostic relevance in high-/advanced-risk patients, supporting its potential value as a therapeutic target for antibody-drug conjugate therapy. The dynamic nature of HER2 across disease progression further supports the need for reassessment in recurrent or metastatic lesions.
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