Concordance between gastric HER2 scores for endometrial sampling versus hysterectomy specimens in endometrial cancer

Gastric HER2 scoring criteria, which are often extrapolated to endometrial cancer, differentiate between biopsy and resection specimens. The objective of this study was to evaluate concordance between gastric HER2 scores of endometrial sampling versus hysterectomy specimens among patients with high grade endometrial cancer.

Patients with high grade endometrial cancer with matched sampling and hysterectomy specimens from 11/2022 to 10/2025 were identified from an institutional clinical genomics database. Each specimen was assigned a HER2 score of 0, 1+, 2+, or 3+ using gastric criteria for biopsy or resection as applicable. Clinical characteristics, responses to HER2-directed therapies, and select genomic profiling results were abstracted. The primary outcome was concordance between HER2 scores for sampling versus hysterectomy specimens as assessed with matrix correlation coefficients.

Twenty-nine patients with high grade endometrial cancer were identified including 20 (69%) with serous histology. For both the sampling and hysterectomy specimens, 44.8% were HER2 low (0 or 1+) and 55.2% HER2 high (2+ or 3+). Sampling and hysterectomy scores were concordant for 15/29 (51.7%) patients (r = 0.68, p < 0.0001). Of the 14 discordant cases, 10 would have changed treatment eligibility based on current guidelines. There was an even greater discordance when internal HER2 scores were compared to Caris HER2 scores with only 10/29 (34.5%) in agreement (r = 0.31, p = 0.10). Only 4 tumors had ERBB2 amplification (13.8%).

There was a clinically significant discordance between gastric HER2 scores for endometrial sampling versus hysterectomy specimens. Determining HER2 score based on only one of these specimens is insufficient in high grade endometrial cancer.