Serum vascular endothelial growth factor levels in pancreatic cancer patients correlate with advanced and metastatic disease and poor prognosis Anastasios J. Karayiannakis a, * , Helen Bolanaki a , Konstantinos N. Syrigos b , Byron Asimakopoulos c , Alexandros Polychronidis a , Stavros Anagnostoulis a , Constantinos Simopoulos a a Second Department of Surgery, Democritus University of Thrace, Medical School, 6 I. Kaviri Street, Alexandroupolis 68 100, Greece b Oncology Unit, Third Department of Medicine, University of Athens, Medical School, Athens 115 27, Greece c Department of Physiology, Democritus University of Thrace, Medical School, Alexandroupolis 68 100, Greece Received 21 August 2002; received in revised form 25 December 2002; accepted 3 January 2003 Abstract The serum concentrations of vascular endothelial growth factor (VEGF) were measured by an enzyme linked immunosorbent assay in 51 healthy controls and in 58 patients with pancreatic cancer before and 30 days after surgery. Pancreatic cancer patients had significantly higher serum VEGF levels compared with healthy controls with a significant association between serum VEGF levels, disease stage and the presence of both lymph node and distant metastases. Serum levels of VEGF decreased significantly after radical resection of the tumor. Elevated preoperative serum VEGF level was a significant prognostic factor, although not independent of stage, for patient survival. These findings suggest that serum VEGF concentrations may reflect pancreatic cancer progression and that their determination may be clinically useful. q 2003 Elsevier Science Ireland Ltd. All rights reserved. Keywords: Vascular endothelial growth factor; Pancreatic cancer; Prognosis; Soluble; Serum; Survival 1. Introduction Vascular endothelial growth factor (VEGF) is a potent angiogenic peptide with specific mitogenic activity on endothelial cells. It also enhances vascular permeability and promotes the extravasation of proteins thus providing a fibrin matrix that is necessary for the invasion of stromal cells into developing tumors [1]. VEGF exists in four isoforms generated by alternative mRNA splicing. The shorter isoforms (VEGF 121 and VEGF 165 ) are secreted peptides that may act as diffusible agents with VEGF 165 being the predominant soluble isoform, whereas the longer isoforms (VEGF 189 and VEGF 206 ) are bound to the extracellular matrix [2,3]. Previous studies provided evidence that VEGF plays a pivotal role in the angiogenic activity and the metastatic spread of solid tumors. Up-regulation of 0304-3835/03/$ - see front matter q 2003 Elsevier Science Ireland Ltd. All rights reserved. doi:10.1016/S0304-3835(03)00047-8 Cancer Letters 194 (2003) 119–124 www.elsevier.com/locate/canlet * Corresponding author. Tel.: þ 30-25510-76141; fax: þ 30- 25510-76142. E-mail address: akarayan@usa.net (A.J. Karayiannakis).