Comparison of HER2 Scoring Systems in Endometrial Cancer: Toward Optimization of HER2-Directed Therapies

Endometrial carcinomas (EC) show variable HER2 protein expression or gene amplification and may be eligible for HER2-directed therapy (trastuzumab or antibody-drug conjugates (ADCs) such as trastuzumab-deruxtecan). HER2 testing is currently recommended in advanced-stage/recurrent serous carcinomas and carcinosarcomas. However, no universally adopted reporting guidelines exist, and institutional practices vary. We aimed to analyze our experience with HER2 testing and compare gynecologic (GyC), gastric (GaC), and breast (BrC) criteria. We identified ECs with available HER2 immunohistochemistry (IHC) and fluorescence in-situ hybridization (FISH) results where applicable. HER2 IHC was reassessed using GyC, GaC, and BrC. The overall HER2-positivity rates were 31% by GyC and BrC, and 35.7% by GaC. The scoring systems significantly differed, with 69.8% concordance between GaC and GyC ( P <0.001) and 99.2% concordance between BrC and GyC. Our results emphasize the importance of using the appropriate HER2 scoring criteria depending on the type of intended HER2-directed therapy as well as comprehensive yet perspicuous reporting of HER2 status to ensure optimal clinical outcomes in EC patients.