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

Cancer. 2012 Feb 15;118(4):914-23. doi: 10.1002/cncr.26406. Epub 2011 Jul 28.

Abstract

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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Biomarkers, Tumor / metabolism*
  • Breast Neoplasms / metabolism*
  • Breast Neoplasms / mortality
  • Breast Neoplasms / pathology*
  • Cell Differentiation
  • Cell Proliferation
  • Chi-Square Distribution
  • Female
  • Humans
  • Immunohistochemistry / methods*
  • In Situ Hybridization, Fluorescence / methods*
  • Kaplan-Meier Estimate
  • Middle Aged
  • Prognosis
  • Proportional Hazards Models
  • Receptor, ErbB-2 / metabolism*
  • Receptors, Estrogen / metabolism
  • Retrospective Studies
  • Survival Rate

Substances

  • Biomarkers, Tumor
  • Receptors, Estrogen
  • ERBB2 protein, human
  • Receptor, ErbB-2