A Clinical Study of Hypoxia Using Endogenous Hypoxic Markers and Polarographic Oxygen Electrodes

Abstract

To examine various kinds of endogenous hypoxia markers' expression in the tissues of uterine cervix cancer and to elucidate the characteristics and pitfalls when they are used as a hypoxia marker, by comparing these expressions with tumor oxygen partial pressure (pO2) values. Assessment of pO2 using polarographic oxygen electrodes was performed in 69 patients with cervix carcinomas. Biopsies were taken from the region of electrode measurements. Expression of endogenous hypoxic markers in biopsy specimens such as vascular endothelial growth factor, glucose transporter-1 (GLUT-1), involucrin, and osteopontin was detected by immunohistochemistry. A double immunolabeling technique with GLUT-1 and MIB-1 as a marker of proliferation was also performed. There was no significant correlation between expression of endogenous hypoxic markers and pO2. The only significant association seen was between the fraction of necrosis and pO2. A significant but weak correlation was found among expression of endogenous hypoxic markers. The levels of necrosis were related negatively with levels of expression of endogenous hypoxic markers. The double immunolabeling technique with GLUT-1 and MIB-1 indicated that there were about 20% MIB-1-positive tumor cells without GLUT-1 expression in tissues adjacent to areas of necrosis. The existence of necrosis affected the expression of endogenous hypoxic markers. Some hypoxic tumor cells without expressions of hypoxia markers can maintain clonogenicity and influence the treatment results. The combined use of hypoxic markers is recommended because their expression is influenced by factors other than hypoxia.