Ongoing debates in the assessment of the HER2 status in breast cancer: A comparative analysis by immunohistochemistry and FISH using original FDA and ASCO/CAP guidelines

ABSTRACT Background and aims: HER2 status should be precisely evaluated in breast cancer to ensure appropriate patient management. Method: We evaluated HER2 status in 755 breast cancers including 92 consecutively resected cases by immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH). Results: For the 92 consecutive cases, the positive rate of HER2 IHC (2+ and 3+) was 25.0%, and HER2 amplification (HER2/CEP17 ratio ≥ 2.0) was observed in 21.7%. Of the 755 cases, 88% of IHC 3+ cases; 57% of IHC 2+ cases; 15% of IHC 1+ cases; and 1% of IHC 0 cases showed HER2 amplification. Notably, 20 (2.6%) of the 755 cases exhibited a HER2/CEP17 ratio between 1.8 and 2.2, which was recently classified equivocal by the ASCO/CAP. Most of them revealed HER2 high polysomy with an average copy number per cell between 3.29 and 7.24. Immunohistochemically, 4 of the 20 cases were luminal A, 12 were luminal B, and 3 were HER2 subtype. Conclusions: The relatively high rate of HER2 amplification among IHC 1+ or 2+ cases at our institute emphasizes the importance of validating HER2 testing in different laboratories and the need for complementary HER2 FISH in IHC 1+ patients. Most patients equivocal for HER2 amplification had HER2 high polysomy and expressed hormone receptor.