A survey of immunohistochemical biomarkers for basal-like breast cancer against a gene expression profile gold standard

Mod Pathol. 2013 Nov;26(11):1438-50. doi: 10.1038/modpathol.2013.97. Epub 2013 May 24.

Abstract

Gene expression profiling of breast cancer delineates a particularly aggressive subtype referred to as 'basal-like', which comprises ∼15% of all breast cancers, afflicts younger women and is refractory to endocrine and anti-HER2 therapies. Immunohistochemical surrogate definitions for basal-like breast cancer, such as the clinical ER/PR/HER2 triple-negative phenotype and models incorporating positive expression for CK5 (CK5/6) and/or EGFR are heavily cited. However, many additional biomarkers for basal-like breast cancer have been described in the literature. A parallel comparison of 46 proposed immunohistochemical biomarkers of basal-like breast cancer was performed against a gene expression profile gold standard on a tissue microarray containing 42 basal-like and 80 non-basal-like breast cancer cases. Ki67 and PPH3 were the most sensitive biomarkers (both 92%) positively expressed in the basal-like subtype, whereas CK14, IMP3 and NGFR were the most specific (100%). Among biomarkers surveyed, loss of INPP4B (a negative regulator of phosphatidylinositol signaling) was 61% sensitive and 99% specific with the highest odds ratio (OR) at 108, indicating the strongest association with basal-like breast cancer. Expression of nestin, a common marker of neural progenitor cells that is also associated with the triple-negative/basal-like phenotype and poor breast cancer prognosis, possessed the second highest OR at 29 among the 46 biomarkers surveyed, as well as 54% sensitivity and 96% specificity. As a positively expressed biomarker, nestin possesses technical advantages over INPP4B that make it a more ideal biomarker for identification of basal-like breast cancer. The comprehensive immunohistochemical biomarker survey presented in this study is a necessary step for determining an optimized surrogate immunopanel that best defines basal-like breast cancer in a practical and clinically accessible way.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomarkers, Tumor / analysis*
  • Biomarkers, Tumor / genetics*
  • Breast Neoplasms / chemistry*
  • Breast Neoplasms / classification
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / pathology
  • Female
  • Gene Expression Profiling / standards*
  • Genetic Testing / standards*
  • Humans
  • Immunohistochemistry / standards*
  • Nestin / analysis
  • Phosphoric Monoester Hydrolases / analysis
  • Predictive Value of Tests
  • Prognosis
  • Tissue Array Analysis / standards

Substances

  • Biomarkers, Tumor
  • NES protein, human
  • Nestin
  • Phosphoric Monoester Hydrolases
  • phosphatidylinositol-3,4-bisphosphate 4-phosphatase