How to Improve HER2 testing Accuracy: Incorporating the 2018 ASCO/CAP Focused Update

The mechanism of HER2 protein expression in tumors is primarily gene amplification, primarily enabled via the process of dimerization of HER2 receptors. Anytime there is a discrepancy, which is exceedingly rare, between protein and gene status, we rely more on the protein status rather than gene status for treatment purposes because the drug doesn’t target the gene. There are common misconceptions that low grade tumors, lobular, mucinous “tubular” tumors and tumors with incomplete membranous signal are always HER2 negative. Additionally, there is the misconception that most HER2-positive tumors are high grade. ASCO/CAP 2018 update moved closer to performing Immunohistochemistry (IHC) & FISH (Fluorescence) on all tumors and recommends the use of dual-probe instead of single-probe IHC assays. 2018 Guidelines swing the pendulum in the “negative results” direction. As this will not solve the dilemma of the “gray zone” group, we propose a 3-tier scoring of HER2 status as either positive, negative or low as this will not solve the dilemma of the “gray zone” group. Our QA program includes tumor analysis, nuclear score, tumor histological grade, IHC score and FISH score. Correlation with IHC and tumor histopathology and performing metrics is mandatory in order to improve HER2 testing accuracy.

Learning Objectives:

• Understand the impact of HER2 between the protein and gene status
• Understand the role of IHC & FISH in breast cancer diagnosis