Pimonidazole: A novel hypoxia marker for complementary study of tumor hypoxia and cell proliferation in cervical carcinoma

Background. Tumor hypoxia may be associated with treatment resistance, cell proliferation, and metastatic potential, which contribute to poor prognosi s. Complementary techniques for detecting hypoxia, cell growth, and metasta ses are required to study these relationships. Objectives. The purpose of this study was to demonstrate the clinical feasi bility of quantitative hypoxia detection with pimonidazole, a novel hypoxia marker, and to correlate hypoxia with S-phase markers of tumor proliferati on. Methods. Pimonidazole binds to thiol-containing proteins specifically in hy poxic cells. Ten patients with cervical carcinoma received 0.5 g/m(2) pimon idazole intravenously followed by biopsy of the cervical carcinoma the next day. Hypoxic cells were recognized by immunohistochemical detection of pim onidazole using a mouse monoclonal antibody. Cell proliferation was detecte d with a commercially available monoclonal antibody for proliferating cell nuclear antigen (PCNA). Assessment of hypoxia and cell proliferation was ma de qualitatively with light microscopy and quantitatively using point count ing and image analysis software methods. Results. No clinical toxic effects were associated with pimonidazole admini stration. Immunostaining with pimonidazole antibody was observed in 9 of 10 tumors, suggesting that hypoxia is a common occurrence in cervical carcino ma. Quantitatively, tumors that had large numbers of hypoxic cells had the greatest percentage of S-phase cells, but some tumors with smaller amounts of hypoxia also had substantial numbers of S-phase cells. Conclusion. Pimon idazole can be used for qualitative and quantitative assessment of tumor hy poxia. (C) 1998 Academic Press.