Comparison of Endometrial Serous and Gastric HER2 Immunohistochemistry Scoring Schemes in Endometrial Carcinomas With Aberrant p53 Expression: Reproducibility and In Situ Hybridization Correlation

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Austin McHenry

doi:10.1097/PGP.0000000000001115

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.

Comparison of Endometrial Serous and Gastric HER2 Immunohistochemistry Scoring Schemes in Endometrial Carcinomas With Aberrant p53 Expression: Reproducibility and In Situ Hybridization Correlation

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