Necessity of In Situ Hybridization Test of Human Epidermal Growth Factor Receptor 2 (HER2) Status in Breast Cancer Patients with Equivocal HER2 Immunohistochemistry Results

ABSTRACT

PURPOSE: Accurate human epidermal growth factor receptor 2 (HER2) status is important in predicting prognosis and providing treatment for HER2-positive breast cancer patients. However, performing in situ hybridization (ISH) can be an economic burden on developing countries. This study aimed to find an alternative to the ISH test by predicting the HER2 status in patients with equivocal immunohistochemistry (IHC) results. METHODS: We retrospectively reviewed the clinical data of 15,535 patients who underwent curative surgery for invasive breast cancer between February 2005 and April 2015 at the Samsung Medical Center. Equivocal HER2 IHC results were obtained for 461 patients. Logistic regression analysis using stepwise selection was performed to identify the clinicopathological factors related to silver in situ hybridization (SISH) status. We analyzed the data by dividing the estrogen receptor and progesterone receptor (PR) into three groups according to Allred score. RESULTS: Multivariable analysis identified poorly differentiated histological grade, lower PR score, higher expression of Ki-67 and p53, and lower expression of cytokeratin 5/6 and epidermal growth factor receptor as predictors of SISH-positive results. The area under the curve for the receiver-operating characteristic curve was 0.74. CONCLUSION: We identified factors related to a positive HER2 status by SISH. However, there was insufficient power in the prediction model for diagnosis and evaluation. Therefore, the SISH test is essential in determining the HER2 status of breast cancer patients when the IHC result is equivocal.