Metabolism-related proteins are differentially expressed according to the molecular subtype of invasive breast cancer defined by surrogate immunohistochemistry

Pathobiology. 2013;80(1):41-52. doi: 10.1159/000339513. Epub 2012 Jul 24.

Abstract

Objective: The purpose of this study was to investigate the expression of metabolism-related proteins such as Glut-1 and carbonic anhydrase IX (CAIX) according to breast cancer molecular subtype.

Methods: We generated a tissue microarray of 276 breast cancer patients and performed immunohistochemical staining for known metabolism-related proteins, which were evaluated according to the molecular subtype.

Results: The expression of IGF-1, MIF, and HIF-1α was correlated with the HER-2 type (p < 0.05). Glut-1 overexpression and CAIX expression were associated with TNBC type, especially with basal-like type, high histologic grade, estrogen receptor negativity, and progesterone receptor negativity (p < 0.05). The expression of Glut-1 and CAIX was correlated with statistical significance (p < 0.001).

Conclusion: We identified different patterns of expression of metabolism-related proteins according to the molecular subtypes of breast cancer defined by surrogate immunohistochemistry. Increased expression of HIF-1α, IGF-1, and MIF was noted in HER-2 type breast cancer and increased expression of Glut-1 and CAIX was noted in TNBC type breast cancer, especially in the basal-like subtype, which exhibited a glycolytic and acid-resistant tumor phenotype.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antigens, Neoplasm / metabolism*
  • Biomarkers, Tumor / metabolism*
  • Breast Neoplasms / metabolism*
  • Breast Neoplasms / mortality
  • Breast Neoplasms / pathology
  • Carbonic Anhydrase IX
  • Carbonic Anhydrases / metabolism*
  • Carcinoma, Ductal, Breast / metabolism*
  • Carcinoma, Ductal, Breast / mortality
  • Carcinoma, Ductal, Breast / pathology
  • Female
  • Gene Expression Regulation, Neoplastic
  • Glucose Transporter Type 1 / metabolism*
  • Glycolysis
  • Humans
  • Hypoxia-Inducible Factor 1, alpha Subunit / metabolism
  • Immunohistochemistry
  • Immunophenotyping
  • Intramolecular Oxidoreductases / metabolism
  • Macrophage Migration-Inhibitory Factors / metabolism
  • Middle Aged
  • Neoplasm Grading
  • Neoplasm Staging
  • Prognosis
  • Protein Serine-Threonine Kinases / metabolism
  • Pyruvate Dehydrogenase Acetyl-Transferring Kinase
  • Receptor, ErbB-2 / metabolism
  • Survival Rate
  • Tissue Array Analysis

Substances

  • Antigens, Neoplasm
  • Biomarkers, Tumor
  • Glucose Transporter Type 1
  • HIF1A protein, human
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • Macrophage Migration-Inhibitory Factors
  • Pyruvate Dehydrogenase Acetyl-Transferring Kinase
  • ERBB2 protein, human
  • Receptor, ErbB-2
  • Protein Serine-Threonine Kinases
  • CA9 protein, human
  • Carbonic Anhydrase IX
  • Carbonic Anhydrases
  • Intramolecular Oxidoreductases
  • MIF protein, human