Justification of the change from 10% to 30% for the immunohistochemical HER2 scoring criterion in breast cancer

Abstract

We compared the American Society of Clinical Oncology/College of American Pathologists (ASCO/CAP) immunohistochemical scoring criterion (30%) for determining HER2 status and the Food and Drug Administration criterion (10%) with fluorescence in situ hybridization (FISH), the HER2 gene amplification method in 328 cases of breast cancer. Of 294 tumor samples successfully analyzed simultaneously by FISH and immunohistochemically, 178 of 196 cases scored 3+ using the 10% and the 30% criteria. Using FISH as the reference, the number of false-positives was reduced from 24 to 9 after application of the 30% criterion. The specificity of immunohistochemical analysis was higher with the 30% (92.0%) vs the 10% (78.8%) criterion. The κ coefficient between FISH and immunohistochemical analysis was increased to 0.850 (almost perfect agreement; P