Investigation of possible endogenous hypoxia markers in colorectal cancer

Int J Radiat Biol. 2013 Jan;89(1):9-15. doi: 10.3109/09553002.2012.715789. Epub 2012 Aug 24.

Abstract

Objective: We evaluated the potential of some recently proposed hypoxia markers, being monocarboxylic acid transporter 1 (MCT1), MCT4 and prolyl hydroxylase 2 (PHD2); and a more established hypoxia marker, glucose transporter-1 (GLUT-1), by testing the association with the exogenous marker pimonidazole.

Materials and methods: Paraffin embedded tumour sections of 20 colorectal cancer patients were stained for blood vessels together with either pimonidazole or carbonic anhydrase-IX (CA-IX) and single stained for MCT1, MCT4, GLUT-1, and PHD2. Expression of all markers was compared with expression of pimonidazole and micro-vessel density (MVD) and with disease-free survival (DFS) and overall survival (OS).

Results: No correlation was found between the different intrinsic hypoxia markers tested and pimonidazole. A trend for high MCT1 expression in biopsies with low CA-IX expression was found (R = -0.45, p = 0.06) and also the expression of MCT1 was higher in tumours with a high MVD (R = 0.49, p = 0.04). The more advanced tumours showed a higher expression of GLUT-1 (p = 0.03). A low CA-IX expression in the tumour correlated with better DFS (p = 0.03) and related to better OS (p = 0.07).

Conclusion: Although none of the tested intrinsic hypoxia markers correlated with pimonidazole staining, we confirmed the important role of both GLUT-1 and CA-IX for a more advanced pTNM (pathological tumour-node-metastasis) stage and DFS respectively.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / metabolism*
  • Cell Hypoxia / drug effects
  • Colorectal Neoplasms / blood supply
  • Colorectal Neoplasms / metabolism*
  • Colorectal Neoplasms / pathology*
  • Female
  • Glucose Transporter Type 1 / metabolism
  • Humans
  • Hypoxia-Inducible Factor-Proline Dioxygenases
  • Male
  • Microvessels / drug effects
  • Microvessels / metabolism
  • Middle Aged
  • Monocarboxylic Acid Transporters / metabolism
  • Nitroimidazoles / pharmacology
  • Procollagen-Proline Dioxygenase / metabolism
  • Radiation-Sensitizing Agents / pharmacology
  • Survival Analysis

Substances

  • Biomarkers, Tumor
  • Glucose Transporter Type 1
  • Monocarboxylic Acid Transporters
  • Nitroimidazoles
  • Radiation-Sensitizing Agents
  • pimonidazole
  • EGLN1 protein, human
  • Procollagen-Proline Dioxygenase
  • Hypoxia-Inducible Factor-Proline Dioxygenases