Abstract

Recently we experienced three cases of human epidermal growth factor receptor 2 (HER2)-amplified invasive breast carcinomas associated with co-amplification or gain of chromosome 17 centromere (CEP17) in silver-enhanced in situ hybridization (SISH) analysis. These cases revealed 2+ or 3+ staining for HER2 immunohistochemistry and >6 HER2 copies per cell on SISH analyses. However, the calculated HER2/CEP17 ratios were low (<2.2) and did not fit within the HER2-positive category. We interpreted those cases as HER2-positive tumors based on the number of HER2 copies per cell. There is a potential for misinterpretation of SISH analysis in cases showing increased CEP17 copy number, based on the criterion used for HER2 positivity (HER2 copies >6 per cell vs HER2/CEP17 ratio>2.2). We recommend reporting raw SISH or fluorescence in situ hybridization data, including number of cells counted, average numbers of HER2 and CEP17 signals, and the calculated HER2/CEP17 ratio to prevent underreporting of HER2 amplification.

• Keywords: Breast neoplasms;HER2;Amplification;Chromosome 17;Polysomy