Measurements of hypoxia using pimonidazole and polarographic oxygen-sensitive electrodes in human cervix carcinomas.
OBJECTIVE
The measurement of tumour oxygenation using Eppendorf oxygen-sensitive needle electrodes can provide prognostic information but the method is limited to accessible tumours that are suitable for electrode insertion. In this paper the aim was to study the relationship between such physiological measurements of tumour hypoxia and the labelling of tumours with the hypoxia-specific marker pimonidazole.


METHODS
Assessment of tumour oxygen partial pressure (pO(2)) using an Eppendorf pO(2) histograph and immunohistochemical pimonidazole labelling was carried out in 86 patients with primary cervix carcinomas. Pimonidazole was given as a single injection (0.5 g/m(2) i.v.) and 10-24 h later pO(2) measurements were made and biopsies taken. Tumour oxygenation status was evaluated as the median tumour pO(2) and the fraction of pO(2) values </=10 mmHg (HP(10)), </=5 mmHg (HP(5)) and </=2.5 mmHg (HP(2.5)). Hypoxia was detected by immunohistochemistry using monoclonal antibodies directed against reductively activated pimonidazole. Pimonidazole binding was scored using a light microscope. Each tumour was evaluated by the relative area pimonidazole at highest score and the accumulated area of pimonidazole labelling from score 1 to 4. Necrosis was measured in HE stained sections.


CONCLUSIONS
The degree of hypoxia assessed by either pimonidazole binding or invasive electrode measurements varied significantly between tumours. There was a trend that the most hypoxic tumours measured by oxygen electrodes had the highest score of necrosis, and no or little pimonidazole binding. However, this observation was not consistent and there was no correlation between pimonidazole staining expressed in this way and oxygen electrode measurements of hypoxia.
Nordsmark
Marianne
M
Department of Experimental Clinical Oncology, Aarhus University Hospital, Aarhus, Denmark.
Loncaster
Juliette
J
Aquino-Parsons
Christina
C
Chou
Shu Chuan
SC
Ladekarl
Morten
M
Havsteen
Hanne
H
Lindegaard
Jacob C
JC
Davidson
Susan E
SE
Varia
Mahesh
M
West
Catharine
C
Hunter
Robin
R
Overgaard
Jens
J
Raleigh
James A
JA
D000293:Adolescent; D000328:Adult; D000704:Analysis of Variance; D002277:Carcinoma / Q000378:metabolism* / Q000473:pathology; D015687:Cell Hypoxia; D003196:Computer Graphics; D005260:Female; D006801:Humans; D008839:Microelectrodes; D009593:Nitroimidazoles; D010100:Oxygen / Q000032:analysis*; D011048:Polarography / Q000379:methods; D011838:Radiation-Sensitizing Agents; D012189:Retrospective Studies; D018709:Statistics, Nonparametric; D002583:Uterine Cervical Neoplasms / Q000378:metabolism* / Q000473:pathology
D009593:Nitroimidazoles; D011838:Radiation-Sensitizing Agents; C033815:pimonidazole; D010100:Oxygen