Breast cancers presenting luminal B subtype features show higher discordant human epidermal growth factor receptor 2 results between immunohistochemistry and fluorescence in situ hybridization

Background: The aims of this study were to compare human epidermal growth factor receptor 2 (HER2) results between immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH), and to investigate the clinicopathological characteristics and outcomes according to their results. Methods: Using consecutive tissue microarrays, IHC and FISH were performed as guidelines in 950 invasive breast cancers treated between November 1999 and August 2005. Characteristics and outcomes were retrospectively analyzed using a chi-square test, the Kaplan-Meier method, and Cox's model. Results: FISH-positivity was observed in 2.6%, 4.8%, 28.1%, and 93.8% of IHC 0, 1+, 2+, and 3+, respectively, and the concordance rate between the 2 assays was 95.5%. IHC-positive or FISH-positive cases were associated with poorer differentiation, negative expression of hormone receptors, and higher proliferative index. Among IHC-equivocal or IHC-negative patients, positive FISH was negatively associated with survival in univariate and multivariate analyses. Among IHC-negative patients, tumors showing luminal B subtype features such as estrogen receptor (ER)-positive, grade II/III, and high Ki-67 presented discordantly high FISH-positivity. Among IHC-positive cases, FISH was not related to outcomes. Conclusions: The result of FISH is significantly related to prognosis of patients with IHC-negative or IHC-equivocal result. Therefore, FISH should be performed in IHC-equivocal cases. FISH assay might be considered for a selected group of patients with IHC-negative tumors showing luminal B subtype features of ER-positive, grade II/III, and high Ki-67 expression.