Evaluation of Immunohistochemistry Technique in Detecting HER2 Overexpression in Invasive Ductal Breast Carcinoma Using Fluorescence in-situ Hybridization Method

Breast cancer is the most common cancer among women. HER2 gene is a proto-oncogene that encodes the receptor of tyrosine kinase from epidermal growth factor receptor (EFGR) family. It is an important prognostic factor with a determinant role in treatment of breast cancer. There is no globally accepted method for determining the status of this gene and the method of choice is still a matter of debate. We aimed to evaluate the validity of immunohistochemistry (IHC) method in predicting HER2 status using fluorescence in-situ hybridization (FISH) method and also, to investigate some clinicopathological variables associated with HER2 amplification. In this cross-sectional study, 190 formalin-fixed and paraffin-embedded tissue specimens of invasive breast carcinoma with HER2 of ++ and +++ in IHC evaluation were enrolled. FISH method was performed on all these samples and the relationship of HER2 status and clinicopathological variables was evaluated. The studied population included 160 specimens of ++ and 30 specimens of +++ HER2 in IHC evaluation. The estrogen and progesterone receptors (ER and PR) were expressed in 64.2% and 74.2% of the specimens, respectively. HER2 amplification on FISH method was found in 27.5% and 83.3% of specimens of ++ and +++ HER2 in IHC evaluation, respectively. Tumors with HER2 amplification were more likely to be negative for estrogen (52.2% vs. 26.4%, P < 0.001) and progesterone (39.1% vs. 18.2 %, P = 0.013) receptors. This study showed that immunohistochemistry is not a good method for evaluating HER2 status and decision making about trastuzumab therapy even in patients with +++ HER2.