Agreement Between Medical Laboratory Technologists and Pathologists’ Assessment of ERBB2 (HER2) Fluorescence In Situ Hybridization Across Breast and Gastric Scoring Criteria

ERBB2 (HER2) fluorescence in situ hybridization (FISH) guides therapy selection for solid tumors, including breast and gastric cancers. While laboratory technologists typically perform the initial enumeration of HER2 FISH, laboratories differ in the extent of pathologist review, ranging from full slide reassessment to review of representative captured images. By performing a retrospective analysis of ∼10,000 HER2 FISH cases scored using breast and gastric criteria, the objective was to define decision boundaries at which technologists' and pathologists' interpretations converge, enabling a data-driven approach to triaging HER2 FISH sign-out. Results showed that agreement between technologists' and pathologists' interpretations was highest when technologists' counts were well beyond the diagnostic cutoffs for the HER2/CEP17 ratio and the number of HER2 signals per cell. Conversely, cases near diagnostic thresholds showed increased discordance, emphasizing the need for full review of the FISH slide in this subset. Individual technologists differed in their percent discordance with pathologists' final results; however, this was not explained by case volume (experience) alone and did not consistently improve over time. In summary, distinct HER2 FISH technologists HER2/CEP17 ratio and HER2 signal number per cell values were identified where concordance with pathologists results exceeded 99%, suggesting cases in these ranges may require only limited pathologist slide review, potentially allowing for more efficient triaging and sign-out of HER2 FISH.