Correlation of immunohistochemistry-equivocal (2+) human epidermal growth factor receptor 2 (HER2) with fluorescence in situ hybridization (FISH) gene status in invasive breast cancer: Is FISH necessary for all HER2 equivocal breast cancer cases?

Objectives: Identifying human epidermal growth factor receptor 2 (HER2) gene amplification status is mandatory in patients with breast cancer for predictive and prognostic purposes. It can be determined by different techniques including fluorescence in situ hybridization (FISH). This study aimed to identify the final gene amplification status by FISH for HER2 equivocal cases using immunohistochemistry (IHC). Design: Retrospective study Setting: Faculty of Pathology, King Saud University Medical Center, King Saud University, Riyadh, Saudi Arabia Subjects: All patients with suspected breast cancer and HER2 equivocal (2+) status examined using IHC between May 2017 and August 2019 were selected and reviewed. Interventions: FISH was performed to determine the amplification status of the HER2 gene. Main outcome measure: Amplification of the HER2 gene using FISH Results: The study identified 300 patients with invasive breast cancer, of whom 57 had HER2 equivocal (2+) status. FISH revealed that multiple copies of the HER2 gene were not detected in 52 patients (91.2%), while the remaining five (8.8%) had an amplified gene status. Conclusions: Even though nine of ten patients with breast cancer of equivocal HER2 identified with IHC had non-amplification of the HER2 gene, FISH must be performed on all the equivocal HER2 IHC cases despite the difficulties and cost associated with conducting the technique. The need to determine HER2 by FISH in HER2-IHC cases with a score of 2 is well recognized by pathologists and oncologists who diagnose and treat patients with breast cancer.