title: Invasive oxygen measurements and pimonidazole labeling in human cervix carcinoma.
abstract: OBJECTIVE
  This study was designed to compare tumor hypoxia assessed by invasive O2 sensitive electrodes and pimonidazole labeling in primary human cervix carcinomas.
  
  
  METHODS
  Twenty-eight patients with primary cervix carcinomas (FIGO Stage Ib-IVa) were investigated. Both invasive pO2 measurements and pimonidazole labeling were obtained in all patients. Before treatment, patients were given pimonidazole as a single injection (0.5 g/m2 i.v.). Ten to 24 h later, oxygenation measurements were done by Eppendorf histography, and after this procedure biopsies were taken for pimonidazole-binding analysis. Tumor oxygen partial pressure (pO2) was evaluated as the median tumor pO2 and the fraction of pO2 values < or = 10 mmHg (HF10). Biopsies were formalin fixed and paraffin embedded, and hypoxia was detected by immunohistochemistry using monoclonal antibodies directed against reductively activated pimonidazole. Pimonidazole binding was evaluated by a semiquantitative scoring system.
  
  
  RESULTS
  Both Eppendorf measurements and pimonidazole binding showed large intra-and intertumor variability. A comparison between pimonidazole binding expressed as the fraction of fields at the highest score and HF10 showed a trend for the most well-oxygenated tumors having a low fraction of fields; however, the correlation did not reach statistical significance (p = 0.43, r = 0.165; Spearman's rank correlation test).
  
  
  CONCLUSIONS
  Hypoxia measured in human uterine cervix carcinomas is heterogeneously expressed both within and between tumors when assessed by either invasive pO2 measurements or pimonidazole binding. Despite a trend that tumors with high pO2 values expressed less pimonidazole binding, no correlation was seen between the two assays in this preliminary report.
authors.affiliation: Department of Experimental Clinical Oncology, Danish Cancer Society, Aarhus University Hospital, Aarhus, Denmark. marianne@oncology.dk
authors.forename: M
authors.initials: M
authors.lastname: Nordsmark
authors.forename: J
authors.initials: J
authors.lastname: Loncaster
authors.forename: S C
authors.initials: SC
authors.lastname: Chou
authors.forename: H
authors.initials: H
authors.lastname: Havsteen
authors.forename: J C
authors.initials: JC
authors.lastname: Lindegaard
authors.forename: S E
authors.initials: SE
authors.lastname: Davidson
authors.forename: M
authors.initials: M
authors.lastname: Varia
authors.forename: C
authors.initials: C
authors.lastname: West
authors.forename: R
authors.initials: R
authors.lastname: Hunter
authors.forename: J
authors.initials: J
authors.lastname: Overgaard
authors.forename: J A
authors.initials: JA
authors.lastname: Raleigh
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002277:Carcinoma / Q000737:chemistry / Q000473:pathology / Q000503:physiopathology*; D015687:Cell Hypoxia; D005260:Female; D006801:Humans; D008875:Middle Aged; D009593:Nitroimidazoles / Q000378:metabolism; D010100:Oxygen / Q000032:analysis*; D010313:Partial Pressure; D011838:Radiation-Sensitizing Agents / Q000378:metabolism; D002583:Uterine Cervical Neoplasms / Q000737:chemistry / Q000473:pathology / Q000503:physiopathology*
chemical_list: D009593:Nitroimidazoles; D011838:Radiation-Sensitizing Agents; C033815:pimonidazole; D010100:Oxygen