Tumor hypoxia and systemic levels of vascular endothelial growth factor (VEGF) in head and neck cancers

Background: Hypoxia is the most important stimulus for the up-regulation of vascular endothelial growth factor (VEGF), one of the key cytokines for angiogenesis. We have investigated the possible relationship between tumor hypoxia and systemic levels of VEGF. Patients and Methods: 56 patients with head and neck cancers underwent measurement of tumor volume (pretreatment CT scans), tumor oxygenation (pO₂ histography) and serum levels of VEGF. The hemoglobin level ranged from 9.1 to 16 g/dl. The absolute amount of hypoxic tumor (hypoxic tumor volume) was determined as the product of the absolute tumor volume and the relative frequency of hypoxic (< 5 mm Hg) measurements in the pO₂ histography. Results: The serum VEGF levels in the 56 head and neck cancer patients ranged from 102 to 1699 pg/ml (median 405 pg/ml, mean 527 ± 396 pg/ml). Elevated serum-VEGF levels (> 700 pg/ml) were found in 14/56 patients (25%). Serum-levels of VEGF were significantly and independently correlated with hypoxic tumor volume (R² = 0.63, p < 0.001), but also with total tumor volume, hemoglobin levels, platelet counts and tumor hypoxia. There was no correlation with T and N category, histological grading, and age. Conclusions: The strong and independent impact of the hypoxic tumor volume on systemic VEGF Levels suggests that the absolute amount of hypoxia within a tumor represents the most important stimulus for up-regulation of angiogenesis. Anemia acts as a cofactor via worsening of tumor tissue oxygenation.