Targeted anti–human epidermal growth factor receptor 2 (HER2) therapy has recently become the standard for advanced-stage and recurrent HER2-positive endometrial serous carcinoma (ESC) in the United States, and an endometrial carcinoma–specific HER2 testing algorithm has been proposed. However, comprehensive studies on the specific features of HER2 gene amplification in these tumors are lacking.


To evaluate the characteristics of HER2 amplification in ESC in the context of breast and gastric HER2 fluorescence in situ hybridization (FISH) guidelines.


Ninety-four ESCs with available HER2 immunohistochemistry (IHC) and FISH were included. HER2 IHC was scored according to the proposed endometrial carcinoma–specific algorithm and FISH was evaluated by using the 2018 ESC clinical trial criteria, the American Society of Clinical Oncology/College of American Pathologists (ASCO/CAP) 2016 gastric criteria, and ASCO/CAP 2013 and 2018 breast criteria.


Most tumors (90.4%; 85 of 94) had a 2+ HER2 IHC score. Polysomy of chromosome 17 was present in 16% (15 of 94) and monosomy 17 was seen in 2% (2 of 94) of tumors. HER2 FISH interpretation per the clinical trial criteria (HER2/CEP17 ratio ≥ 2.0) showed 99% concordance with the current gastric and breast HER2 FISH interpretations.


Our results support the clinical trial criteria for HER2 FISH in ESC with a modification to include HER2 IHC 2+ and HER2/CEP17 ratio less than 2.0 and average HER2 copy number of 6.0 or greater in the HER2-positive category. Future prospective clinical investigations are necessary to assess the correlation between specific HER2 FISH result categories and therapeutic response.

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Author notes

The authors have no relevant financial interest in the products or companies described in this article.