Comparative Analysis of HER2 Immunohistochemistry (IHC) and Brightfield Dual-Color In Situ Hybridization (DISH) in Lymph Node Metastasized Breast Cancer

Abstract Background The human epidermal growth factor receptor 2 (HER2) gene encodes a tyrosine kinase receptor, implicated in 15–20% of breast cancers. HER2 amplification is both prognostic and predictive of response to HER2-targeted therapy. IHC is the preferred initial test due to its cost-effectiveness and simplicity. While FISH is the gold standard test for HER2 amplification, it has several limitations, prompting consideration of DISH as an alternative. This study aims to evaluate the concordance between HER2 IHC and DISH in lymph node metastasized breast cancer and compares the results to existing data on HER2 IHC and FISH. Methods This retrospective study included 1,307 cases of pathologically confirmed lymph node metastasized invasive breast carcinoma with HER2 IHC scores of 2+ (481 cases) and 3+ (826 cases). Interpretation of HER2 IHC was performed using the 2023 ASCO/CAP guideline. HER2 DISH was conducted and evaluated by the HER2/Chromosome 17 signals ratio. Results HER2 amplification was detected in 933 cases, including 92% (760) of IHC 3 + cases and 36% (173) of IHC 2 + cases. Comparison with the meta-analysis data of IHC and FISH showed no significant differences, indicating that DISH is a reliable alternative to FISH. Conclusion Our study demonstrates no significant difference in the positive rates of HER2 IHC to DISH when compared with prior data of IHC to FISH, reaffirming the use of HER2 DISH as an effective and more accessible alternative to FISH in breast cancer. The high concordant rate between HER2 IHC and DISH in the IHC 3 + group and low positive rate in the IHC 2 + group support the recommendation to proceed with HER2-targeted therapy in IHC 3 + cases and to perform ISH in IHC 2 + cases.