Original paper
Oxygen tension in human tumours measured with polarographic needle electrodes and its relationship to vascular density, necrosis and hypoxia

https://doi.org/10.1016/S0167-8140(97)01920-8Get rights and content

Abstract

Background and purpose: The use of polarographic needle electrodes for measurement of oxygen tension (pO2) in tumours requires documentation of the validity of the method. In the present work the pO2 values measured polarographically with the Eppendorf pO2 histograph in human tumours were compared with the histological appearance of the tumour tissue, i.e. vascular density, fraction of necrosis and fraction of hypoxic tissue, to investigate whether the measurements reflected the expected pO2.

Materials and methods: The pO2 was measured in cervix tumours in patients and in human melanoma xenografted tumours in athymic mice. Vascular density was determined in the cervix tumours by histological analysis of biopsies from the pO2 measurement tracks. Fraction of necrosis and fraction of hypoxic tissue, i.e. tissue binding the hypoxia marker pimonidazole, were determined in the melanomas by analysis of histological sections from the tumour planes in which the pO2 measurements were performed.

Results: The pO2 distributions showed large intratumour heterogeneity. In cervix tumours, tumour regions with vascular density (vascular length per unit tissue volume) in the range of 47–77 mm/mm3 showed higher pO2 than tumour regions with vascular density in the range of 20–47 mm/mm3, which in turn showed higher pO2 than tumour regions with vascular density in the range of 0–20 mm/mm3. In melanomas, tumour regions in which necrosis and hypoxia constituted more than 50% of the tissue showed lower pO2 than other tumour regions.

Conclusions: The pO2 measured in the tumours was consistent with the histological appearance of the tissue in which the measurements were performed, suggesting that reliable pO2 distributions of tumours can be obtained with polarographic needle electrodes.

References (35)

  • W. Fleckenstein et al.

    A comparison of pO2 histograms from rabbit hind-limb muscles obtained by simultaneous measurements with hypodermic needle electrodes and with surface electrodes

    Adv. Exp. Med. Biol.

    (1984)
  • J.F. Fowler

    The influence of recovery, repopulation and reoxygenation on radiosensitivity of tumors and normal tissues

  • D.G. Hirst et al.

    Changes in tumour morphology with alteration in oxygen availability: further evidence for oxygen as a limiting substrate

    Br. J. Cancer

    (1991)
  • M. Höckel et al.

    Association between tumor hypoxia and malignant progression in advanced cancer of the uterine cervix

    Cancer Res.

    (1996)
  • M. Höckel et al.

    Oxygenation of carcinomas of the uterine cervix: evaluation of computerized O2 tension measurements

    Cancer Res.

    (1991)
  • F. Kallinowski et al.

    Blood flow, metabolism, cellular microenvironment, and growth rate of human tumor xenografts

    Cancer Res.

    (1989)
  • A.A. Khalil et al.

    The importance of determining necrotic fraction when studying the effect of tumour volume on tissue oxygenation

    Acta Oncol.

    (1995)
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