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 an giogenesis. We have investigated the possible relationship between tumor hy poxia and Systemic Levels of VEGF. Patients and Methods: 56 patients with head and neck cancers underwent meas urement of tumor volume (pretreatment CT scans), tumor oxygenation (pO(2) h istography) 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 fr equency of hypoxic (< 5 mm Hg) measurements in the pO(2) histography. Results: The serum VEGF Levels in the 56 head and neck cancer patients rang ed from 102 to 1699 pg/ml (median 405 pg/ml, mean 527 +/- 396 pg/ml). Eleva ted serum-VEGF Levels (> 700 pg/ml) were found in 14/56 patients (25%). Ser um-levels of VEGF were Significantly and independently correlated with hypo xic tumor volume (R-2 = 0,63, p < 0.001), but also with total tumor volume, hemoglobin Levels, platelet counts and tumor hypoxia. There was no correla tion 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 angiog enesis. Anemia acts as a cofactor via worsening of tumor tissue oxygenation .