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 prognosis. Complementary techniques for detecting hypoxia, cell growth, and metastases are required to study these relationships.


OBJECTIVE
The purpose of this study was to demonstrate the clinical feasibility of quantitative hypoxia detection with pimonidazole, a novel hypoxia marker, and to correlate hypoxia with S-phase markers of tumor proliferation.


METHODS
Pimonidazole binds to thiol-containing proteins specifically in hypoxic cells. Ten patients with cervical carcinoma received 0.5 g/m2 pimonidazole intravenously followed by biopsy of the cervical carcinoma the next day. Hypoxic cells were recognized by immunohistochemical detection of pimonidazole using a mouse monoclonal antibody. Cell proliferation was detected with a commercially available monoclonal antibody for proliferating cell nuclear antigen (PCNA). Assessment of hypoxia and cell proliferation was made qualitatively with light microscopy and quantitatively using point counting and image analysis software methods.


RESULTS
No clinical toxic effects were associated with pimonidazole administration. Immunostaining with pimonidazole antibody was observed in 9 of 10 tumors, suggesting that hypoxia is a common occurrence in cervical carcinoma. 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.


CONCLUSIONS
Pimonidazole can be used for qualitative and quantitative assessment of tumor hypoxia.
Varia
M A
MA
Department of Radiation Oncology, University of North Carolina, Chapel Hill, North Carolina, 27599, USA.
Calkins-Adams
D P
DP
Rinker
L H
LH
Kennedy
A S
AS
Novotny
D B
DB
Fowler
W C
WC
Raleigh
J A
JA
D015415:Biomarkers; D002455:Cell Division; D015687:Cell Hypoxia; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D009593:Nitroimidazoles / Q000494:pharmacology*; D018809:Proliferating Cell Nuclear Antigen / Q000032:analysis; D016196:S Phase; D002583:Uterine Cervical Neoplasms / Q000378:metabolism* / Q000473:pathology
D015415:Biomarkers; D009593:Nitroimidazoles; D018809:Proliferating Cell Nuclear Antigen; C033815:pimonidazole