GLUT1 and CAIX expression profiles in breast cancer correlate with adverse prognostic factors and MCT1 overexpression

Histol Histopathol. 2011 Oct;26(10):1279-86. doi: 10.14670/HH-26.1279.

Abstract

The goal of the present work was to evaluate the correlation of glucose transporter 1 (GLUT1) and carbonic anhydrase IX (CAIX) with the monocarboxylate transporters 1 (MCT1) and 4 (MCT4) and their chaperone, CD147, in breast cancer. The clinico-pathological value of GLUT1 and CAIX was also evaluated. For that, we analysed the immunohistochemical expression of GLUT1 and CAIX, in a large series of invasive breast carcinoma samples (n=124), previously characterized for MCT1, MCT4 and CD147 expression. GLUT1 expression was found in 46% of the cases (57/124), while CAIX was found in 18% of the cases (22/122). Importantly, both MCT1 and CD147, but not MCT4, were associated with GLUT1 and CAIX expression. Also, GLUT1 and CAIX correlated with each other. Concerning the clinico-pathological values, GLUT1 was associated with high grade tumours, basal-like subtype, absence of progesterone receptor, presence of vimentin and high proliferative index as measured by Ki-67. Additionally, CAIX was associated with large tumour size, high histological grade, basal-like subtype, absence of estrogen and progesterone receptors and presence of basal cytokeratins and vimentin expression. Finally, patients with CAIX positive tumours had a significantly shorter disease-free survival. The association between MCT1 and both GLUT1 and CAIX may result from hypoxia-mediated metabolic adaptations, which confer a glycolytic, acid-resistant and more aggressive phenotype to cancer cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigens, Neoplasm / biosynthesis
  • Antigens, Neoplasm / genetics*
  • Biomarkers, Tumor / analysis
  • Biomarkers, Tumor / genetics*
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / pathology
  • Carbonic Anhydrase IX
  • Carbonic Anhydrases / biosynthesis
  • Carbonic Anhydrases / genetics*
  • Female
  • Gene Expression
  • Gene Expression Profiling*
  • Glucose Transporter Type 1 / biosynthesis
  • Glucose Transporter Type 1 / genetics*
  • Humans
  • Immunohistochemistry
  • Kaplan-Meier Estimate
  • Monocarboxylic Acid Transporters / biosynthesis
  • Monocarboxylic Acid Transporters / genetics*
  • Muscle Proteins / biosynthesis
  • Muscle Proteins / genetics
  • Neoplasm Staging
  • Prognosis
  • Symporters / biosynthesis
  • Symporters / genetics*
  • Tissue Array Analysis

Substances

  • Antigens, Neoplasm
  • Biomarkers, Tumor
  • Glucose Transporter Type 1
  • Monocarboxylic Acid Transporters
  • Muscle Proteins
  • SLC16A4 protein, human
  • SLC2A1 protein, human
  • Symporters
  • monocarboxylate transport protein 1
  • CA9 protein, human
  • Carbonic Anhydrase IX
  • Carbonic Anhydrases