title: Hypoxia-related molecules HIF-1α, CA9, and osteopontin : predictors of survival in patients with high-grade glioma.
abstract: OBJECTIVE
  A high expression of hypoxia-inducible factor-1 alpha (HIF)-1α, carbonic anhydrase 9 (CA9), and osteopontin appears to be a strong prognostic indicator in many malignancies; however, their role is unclear in high-grade gliomas.
  
  
  METHODS
  HIF-1α, CA9, and osteopontin levels in tissue specimens of 92 patients with high-grade glioma were evaluated by immunohistochemistry.
  
  
  RESULTS
  Patients with a high expression of cytoplasmic and nuclear HIF-1α, CA9, and osteopontin had significantly shorter overall survival. The expression results of these markers were combined to form a hypoxic profile, and high hypoxic scores (expression of two or three markers) were significantly correlated to poorer overall survival. In multivariate analysis, high hypoxic score-1 (cytoplasmic HIF-1α, CA9, and osteopontin) was the only independent negative prognostic factor for survival (p = 0.028).
  
  
  CONCLUSIONS
  Our results showed that a combination of hypoxic markers is more robust than a single marker for predicting survival in high-grade glioma. It may be necessary to utilize the hypoxic score in selecting patients for targeted therapy in the future.
authors.affiliation: Department of Radiation Oncology, Medical School of Gazi University, Ankara, Turkey. petektater@yahoo.com
authors.forename: O P
authors.initials: OP
authors.lastname: Erpolat
authors.forename: P U
authors.initials: PU
authors.lastname: Gocun
authors.forename: M
authors.initials: M
authors.lastname: Akmansu
authors.forename: G
authors.initials: G
authors.lastname: Ozgun
authors.forename: G
authors.initials: G
authors.lastname: Akyol
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000951:Antigens, Neoplasm / Q000032:analysis*; D014408:Biomarkers, Tumor / Q000032:analysis*; D001932:Brain Neoplasms / Q000175:diagnosis / Q000378:metabolism / Q000401:mortality*; D000071231:Carbonic Anhydrase IX; D002256:Carbonic Anhydrases / Q000032:analysis*; D015687:Cell Hypoxia; D005260:Female; D005910:Glioma / Q000175:diagnosis / Q000378:metabolism / Q000401:mortality*; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000032:analysis*; D008297:Male; D008875:Middle Aged; D053495:Osteopontin / Q000032:analysis*; D015995:Prevalence; D015203:Reproducibility of Results; D012307:Risk Factors; D012680:Sensitivity and Specificity; D016019:Survival Analysis; D015996:Survival Rate; D014421:Turkey / Q000453:epidemiology; D055815:Young Adult
chemical_list: D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D053495:Osteopontin; C089226:CA9 protein, human; D000071231:Carbonic Anhydrase IX; D002256:Carbonic Anhydrases