HER2 testing in multiple solid tumor types: concordance of immunohistochemistry scores between three HER2 scoring algorithms

Abstract Accurate human epidermal growth factor receptor 2 (HER2) immunohistochemistry (IHC) scoring is crucial to identify patients for HER2-directed therapy; however, validated HER2 scoring guidelines are lacking for non-breast/gastric solid tumors. We investigated concordance in IHC scores from independent pathologists using three different scoring algorithms in non-gastric/breast solid tumors. Whole-slide scans of HER2-stained tumor samples from DESTINY-PanTumor02 (NCT04482309) and a commercial pan-tumor sample set were scored by three independent, board-certified pathologists using American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) scoring algorithms for gastric (reference) and breast cancers, and a clinical trial-based algorithm for endometrial cancers (evaluated for endometrial tumors only). The pathologists evaluated 488 samples from multiple solid tumor types. Mean positive percentage agreement (PPA; across pathologists) between the breast and gastric algorithms was higher for samples scored as IHC 3 + or IHC 0 compared with IHC 2 + or IHC 1 + . Inter-pathologist PPA for each algorithm was greatest in samples scored as IHC 3 + and IHC 0. The majority of inter-pathologist pairwise comparisons had Cohen’s κ coefficient values > 0.4 when using the gastric or breast algorithm to determine IHC scores, indicating at least moderate agreement between pathologists; Cohen’s κ coefficient values were generally lower (range 0.17–0.43) for the endometrial algorithm. ASCO/CAP scoring algorithms for gastric and breast cancer were comparable for identifying HER2 IHC 3 + tumors; lower concordance was observed for IHC 2 + /1 + tumors. These findings highlight a real-world issue of inter-pathologist variability and emphasize a need for greater awareness of best scoring practices.