HER2-testing in 538 consecutive breast cancer cases using FISH and immunohistochemistry

HER2 is amplified and overexpressed in up to 20% of all breast carcinomas, and accurate assessment of the HER2-status is essential for the appropriate use of anti-HER2 therapies, including trastuzumab. Here, we have evaluated the accuracy of two commercially available and commonly used HER2 antibodies (antibody A0485 and HercepTest), followed by FISH-test, in 538 consecutive breast cancers, to identify a reliable procedure for the determination of HER2-status. Immunohistochemical (IHC) analysis revealed that 282 cases (52.2%) were positive (2+/3+) for antibody A0485, while only 179 cases (33.3%) were positive (2+/3+) for HercepTest (81.2% concordance between A0485 and HercepTest). FISH-analysis of the 103 IHC discordant cases revealed 89.3% concordance with HercepTest. The results of the present study, which is the largest in Scandinavia, revealed a significantly higher concordance rate between HercepTest and HER2 copy number status than between antibody A0485 and HER2 copy number status. Eleven cases (11% of 103 discordant cases) with HER2-amplification were positive for antibody A0485 and false negative for HercepTest. Our findings indicate that HercepTest is a reliable and accurate IHC-assay and that in the absence of clinical outcome data for IHC-positive/FISH-negative and IHC-negative/FISH-positive patients, FISH-analysis should be performed on all IHC 2+ and 3+ cases.