Biological variations in plasma VEGF and VEGFR-1 may compromise their biomarker value in colorectal cancer.

INTRODUCTION:Vascular Endothelial Growth Factor (VEGF) plays a prominent role in tumor angiogenesis and plasma VEGF concentration may carry prognostic information in colorectal cancer. The VEGF receptor 1 (VEGFR-1) is a regulatory receptor which is shredded into plasma of patients with colorectal cancer. For both molecules, large biological variation and lack of standardization of assay procedures are major challenges. METHODS:We investigated pre-analytical, analytical, as well as short term and long term biological variation of plasma VEGF and VEGFR-1 in volunteers. In addition, we evaluated plasma VEGF and VEGFR-1 as markers of colorectal disease in a case-control study on four groups of 77 individuals undergoing bowel endoscopy. Groups were categorized as 'no findings', 'non-malignant findings', 'adenoma', or 'colorectal cancer'. RESULTS:In the studies on variation, temperature and delay before centrifugation significantly influenced plasma VEGF and, to a minor extent, plasma VEGFR-1 concentrations. In addition, we found large biological variations with CV up to 69.2% for VEGF and CV up to 35.9% for VEGFR-1. For both molecules the intra-subject variation exceeded the inter-subject variation. In the case control study neither plasma VEGF nor VEGFR-1 was able to differentiate between the four groups of individuals although plasma VEGFR-1 was significantly lower in patients with 'no findings'. CONCLUSION:There was no difference in plasma VEGF or VEGFR-1 between patients with no findings, benign disease, pre-malignant findings, and malignant findings after endoscopy. The poor discrimination between patients may be explained by the large inter- and intra-subject variations found for both molecules in volunteers.