Invasive oxygen measurements and pimonidazole labeling in human cervix carcinoma.
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.
Nordsmark
M
M
Department of Experimental Clinical Oncology, Danish Cancer Society, Aarhus University Hospital, Aarhus, Denmark. marianne@oncology.dk
Loncaster
J
J
Chou
S C
SC
Havsteen
H
H
Lindegaard
J C
JC
Davidson
S E
SE
Varia
M
M
West
C
C
Hunter
R
R
Overgaard
J
J
Raleigh
J A
JA
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*
D009593:Nitroimidazoles; D011838:Radiation-Sensitizing Agents; C033815:pimonidazole; D010100:Oxygen