Evaluation of HER2 Gene Amplification using CISH in Patients with HER2 2+ (equivocal) Breast Carcinoma based on Immunohistochemistry in Imam Khomeini Cancer Institute from 2016 to 2018

Background: Human epidermal growth factor 2 (HER2) is known to be an important prognostic factor in breast cancer. Numerous studies have shown HER2+ breast cancers have reduced overall survival and recovery time, as well as the efficacy of anti-HER2 therapies along with chemotherapy in improving disease outcomes. For this reason, it is recommended that all patients with breast cancer should be evaluated for HER2 status. This study aimed to assess the HER2 gene amplification by the CISH method in evaluating the HER2 status in patients with immunohistochemistry (IHC) 2+ (equivocal) results. Methods: This retrospective cross-sectional study examined HER2 status based on the Chromogenic in situ hybridization (CISH) method in 280 breast carcinoma samples with an initial 2+ (equivocal) score in IHC. The relationship between HER2 amplification and hormone receptors (estrogen and progesterone) and Ki67 level was also investigated. Results: In sixty samples (21.4%), the HER2 gene was amplified based on the CISH method. The majority (215, 76.8%) of the samples were negative and 5 (1.8%) samples were indeterminate. No significant relationship was observed between HER2 amplification, estrogen receptor (p=0.143), and ki.67 protein level (p=0.977). There was a significant inverse relationship between HER2 amplification and progesterone receptor positivity (p=0.007). Conclusion: These results demonstrate that CISH is a helpful method to assess HER2 status in equivocal breast cancer and is positive (amplified) in about 21.4% of them.