Prognostic impact of matched preoperative plasma and serum VEGF in patients with primary colorectal carcinoma

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Abstract
In serum, the major part of vascular endothelial growth factor derives from in vitro degranulation of granulocytes and platelets. Therefore, plasma may be preferred for vascular endothelial growth factor measurements. However, which specimen is the best predictor of survival is still debated. The present study analyzed the prognostic value of matched preoperative serum and plasma vascular endothelial growth factor concentrations in patients with colorectal cancer. To establish the reference range among healthy people, vascular endothelial growth factor was analyzed in 50 matched EDTA-plasma and serum samples from healthy blood donors. Preoperatively, in 524 patients with colorectal cancer, matched plasma and serum vascular endothelial growth factor concentrations were analyzed. In the colorectal cancer patients, the median plasma vascular endothelial growth factor concentration (44 pg ml−1) was significantly (P=0.01) higher than the median plasma vascular endothelial growth factor concentration (30 pg ml−1) in the healthy blood donors. In serum, no significant (P=0.30) difference in the median vascular endothelial growth factor concentration was found between colorectal cancer patients (268 pg ml−1) and healthy blood donors (220 pg ml−1). The preoperative vascular endothelial growth factor concentrations were dichotomized by the 95th percentile of the healthy blood donors (plasma=112 pg ml−1, serum=533 pg ml−1). In univariate survival analyses, both high plasma vascular endothelial growth factor (>112 pg ml−1) and high serum vascular endothelial growth factor (>533 pg ml−1) predicted a reduced survival. In multivariate survival analyses, high serum vascular endothelial growth factor (>533 pg ml−1) independently predicted a reduced survival (HR=1.65, P=0.015), while high plasma vascular endothelial growth factor (>112 pg ml−1) did not (HR=1.27, P=0.23). This study indicates that preoperative serum vascular endothelial growth factor apparently is a better predictor of overall survival than the preoperative plasma vascular endothelial growth factor.