Platelet activation and vascular endothelial growth factor 165 release in hepatocellular cancer

Background: Vascular endothelial growth factor (VEGF(165)) is stored, transported and released by platelets. Platelet functional abnormalities have been described in patients with hepatocellular carcinoma (HCC). Thus, this study was designed to investigate the behavior of VEGF(165) with respect to platelet activation in HCC. Methods: Plasma and serum VEGF(165) and plasma sP-selectin levels were analyzed in patients with HCC (n=70) or cirrhosis (n=45) and control subjects (n=70). Given the thrombocytopenia that characterizes both HCC and cirrhotic patients, plasma VEGF(165) and sP-selectin as well as serum VEGF (plt-VEGF(165)-load) levels were normalized by platelet counts. Results: Median concentrations of plasma VEGF(165)/platelet (p=0.002) and sP-selectin/platelet (p<0.0001) were higher in HCC or cirrhotic patients compared to controls. Moreover, sP-selectin/platelet was the only independent variable predictive of plasma VEGF(165)/platelet at multivariate analysis (p<0.0001). Conversely, plt-VEGF(165)-load correlated with tumor diameter (p<0.05) but not with sP-selectin/platelet and was an independent predictor for 5 year overall survival (p=0.012). Conclusions: The results obtained are suggestive for VEGF(165) release by tumor in HCC. It is plt-VEGF(165)-load, but not plasma VEGF(165) or serum VEGF(165) that is an independent predictor for overall survival of HCC patients. (C) 2010 Elsevier B.V. All rights reserved.