Invasive oxygen measurements and pimonidazole labeling in human cervix carcinoma

Abstract

Purpose: This study was designed to compare tumor hypoxia assessed by invasive O 2 sensitive electrodes and pimonidazole labeling in primary human cervix carcinomas. Methods and Materials: Twenty-eight patients with primary cervix carcinomas (FIGO Stage Ib–IVa) were investigated. Both invasive pO 2 measurements and pimonidazole labeling were obtained in all patients. Before treatment, patients were given pimonidazole as a single injection (0.5 g/m 2 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 (pO 2) was evaluated as the median tumor pO 2 and the fraction of pO 2 values ≤ 10 mmHg (HF 10). 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 HF 10 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). Conclusion: Hypoxia measured in human uterine cervix carcinomas is heterogeneously expressed both within and between tumors when assessed by either invasive pO 2 measurements or pimonidazole binding. Despite a trend that tumors with high pO 2 values expressed less pimonidazole binding, no correlation was seen between the two assays in this preliminary report.