title: Investigation of possible endogenous hypoxia markers in colorectal cancer.
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.
  
  
  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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Radiation Oncology, UH Gasthuisberg, Leuven, Belgium. maud.verstraete@med.kuleuven.be
authors.forename: Maud
authors.initials: M
authors.lastname: Verstraete
authors.forename: Annelies
authors.initials: A
authors.lastname: Debucquoy
authors.forename: Ellen
authors.initials: E
authors.lastname: Devos
authors.forename: Xavier
authors.initials: X
authors.lastname: Sagaert
authors.forename: Freddy
authors.initials: F
authors.lastname: Penninckx
authors.forename: Adrian
authors.initials: A
authors.lastname: Begg
authors.forename: Karin
authors.initials: K
authors.lastname: Haustermans
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism*; D015687:Cell Hypoxia / Q000187:drug effects; D015179:Colorectal Neoplasms / Q000098:blood supply / Q000378:metabolism* / Q000473:pathology*; D005260:Female; D051272:Glucose Transporter Type 1 / Q000378:metabolism; D006801:Humans; D064799:Hypoxia-Inducible Factor-Proline Dioxygenases; D008297:Male; D055806:Microvessels / Q000187:drug effects / Q000378:metabolism; D008875:Middle Aged; D027501:Monocarboxylic Acid Transporters / Q000378:metabolism; D009593:Nitroimidazoles / Q000494:pharmacology; D011393:Procollagen-Proline Dioxygenase / Q000378:metabolism; D011838:Radiation-Sensitizing Agents / Q000494:pharmacology; D016019:Survival Analysis
chemical_list: D014408:Biomarkers, Tumor; D051272:Glucose Transporter Type 1; D027501:Monocarboxylic Acid Transporters; D009593:Nitroimidazoles; D011838:Radiation-Sensitizing Agents; C033815:pimonidazole; C490190:EGLN1 protein, human; D011393:Procollagen-Proline Dioxygenase; D064799:Hypoxia-Inducible Factor-Proline Dioxygenases