Comparison of Endometrial Serous and Gastric HER2 Immunohistochemistry Scoring Schemes in Endometrial Carcinomas With...

In 2023, the College of American Pathologists (CAP) supported histotype-specific scoring for HER2 testing in endometrial serous carcinoma based on enrollment criteria for trastuzumab eligibility in the NCT01367002 clinical trial. However, in 2024, the DESTINY-PanTumor02 trial showed the benefit of trastuzumab-deruxtecan in patients with HER2-IHC 2+ and 3+ tumors using CAP gastric scoring, resulting in confusion about how these criteria relate. We compare the results of these scoring schemes by interobserver agreement and correlation with HER2/Chromosome 17 dual in situ hybridization (DISH). Six observers scored 44 HER2-IHC stained p53-abnormal endometrial carcinoma specimens in tissue microarray (TMA) format by endometrial serous (NCT01367002) and gastric systems. Interobserver agreement for HER2 scores (0, 1+, 2+, and 3+) was 81.5% (kappa=0.75) for endometrial serous and 84.6% (kappa=0.79) for gastric scoring. Eight specimens showed discordant HER2 endometrial serous and gastric scores: 4 endometrial serous 1+/gastric 0 and 4 endometrial serous 2+/gastric 3+. HER2-IHC-DISH discordance occurred in 4 specimens by gastric criteria (IHC 3+/DISH negative) and 1 specimen by endometrial serous criteria (IHC 3+/DISH negative). Endometrial serous and gastric HER2-IHC scoring schemes show similar interobserver agreement. In instances of minimal, faint HER2 staining, the endometrial serous score may be 1+ when the gastric score is 0. In instances of limited, strong HER2 staining, the endometrial serous score may be 2+ when the gastric score is 3+. The endometrial serous scheme appears more concordant with DISH results than the gastric scheme, which shows non-infrequent IHC 3+ cases without HER2-DISH amplification. We emphasize recognition of HER2-IHC therapy-specific scoring in endometrial carcinomas, as these scoring systems are similar but not identical.