ERBB2 and cancer: Neither IHC nor ISH reliably detects the activating ERBB2 mutations, which may constitutively activate the receptor independently of HER2 protein abundance at the cell surface or gene copy number; identifying such mutations requires next-generation sequencing (NGS) or PCR-based molecular assays, which are becoming increasingly clinically relevant technologies for picking up on the extended genetic profiles of cancers as more targeted treatments are developed [26,27].