title: Expression of hypoxia-inducible factor-1alpha in cervical carcinomas: correlation with tumor oxygenation.
abstract: OBJECTIVE
  To investigate the relations between hypoxia-inducible factor-1 (HIF-1), tumor oxygenation, and clinical correlates in patients with locally advanced carcinoma of the uterine cervix.
  
  
  METHODS
  Biopsies from 42 patients with invasive cervical carcinoma and previous polarographic O2 measurements were assessed for the expression of HIF-1alpha using digitized microscopic imaging and analysis.
  
  
  RESULTS
  The HIF-1alpha expression levels ranged from <0.1% to 10.7% of the total tumor area; the positive staining was localized exclusively to the nuclei. Three distinct arrangement patterns of HIF-1alpha-positive cells in relation to blood vessels were identified using spatial image mapping: (1) most HIF-1alpha-positive cells were located within the typical oxygen diffusion distance in tissue (< or =150 microm to the nearest blood vessel); (2) most HIF-1alpha-positive cells were located in the vicinity (< or =60 microm) of the blood vessels; and (3) no apparent spatial relationship was found between HIF-1alpha-positive cells and blood vessels. A statistically significant association was found between HIF-1alpha expression and tumor oxygenation (Spearman correlation coefficient = 0.4, p <0.01), as determined with the Eppendorf pO2 histograph. No correlation was found between the level of HIF-1alpha expression and patient outcome, using disease-free survival as the end point.
  
  
  CONCLUSIONS
  Our results suggest that HIF-1alpha expression may represent a useful biologic marker for hypoxia in uterine cervical cancer.
authors.affiliation: Department of Medical Biophysics, Ontario Cancer Institute/Princess Margaret Hospital, Toronto, Ontario, Canada.
authors.forename: Hans Kristian
authors.initials: HK
authors.lastname: Haugland
authors.forename: Vojislav
authors.initials: V
authors.lastname: Vukovic
authors.forename: Melania
authors.initials: M
authors.lastname: Pintilie
authors.forename: Anthony W
authors.initials: AW
authors.lastname: Fyles
authors.forename: Michael
authors.initials: M
authors.lastname: Milosevic
authors.forename: Richard P
authors.initials: RP
authors.lastname: Hill
authors.forename: David W
authors.initials: DW
authors.lastname: Hedley
mesh_terms: D000368:Aged; D002277:Carcinoma / Q000378:metabolism*; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D000860:Hypoxia; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D007091:Image Processing, Computer-Assisted; D007150:Immunohistochemistry; D008875:Middle Aged; D010100:Oxygen / Q000378:metabolism*; D013997:Time Factors; D014157:Transcription Factors / Q000378:metabolism*; D002583:Uterine Cervical Neoplasms / Q000378:metabolism*
chemical_list: C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D014157:Transcription Factors; D010100:Oxygen