Association of serum vascular endothelial growth factor-C (VEGF-C) with lymph node metastasis and prognosis in pancreatic adenocarcinoma

Abstract

4620 Background: Accurate staging and prognostic information is essential for treatment planning in pancreatic adenocarcinoma (PA). Current methods include endoscopic ultrasound, CT scanning, and serum CA 19–9 levels. Despite these, many patients considered resectable experience early relapse and die from their disease and within this group nodal status correlates with overall survival. For patients metastatic at presentation the prognosis is often variable with limited treatment options. Vascular endothelial growth factor- C (VEGF-C) plays a crucial role in lymphangiogenesis and has been implicated in promoting lymph node metastasis in PA. Prior studies demonstrate diagnostic utility of serum levels of VEGF-C in determining nodal involvement and prognosis in lung, gastric, and cervical cancer. We investigated if serum VEGF-C levels would predict nodal involvement or prognosis in pancreatic cancer. Methods: Pretreatment serum VEGF-C levels were measured in 40 PA patients who were node-negative (N0 =12), node-positive (N1=14) or metastatic (M1=14) at diagnosis using ELISA. Diagnostic accuracy was compared to conventional methods. Kaplan-Meier survival analysis was done for all patients and longitudinal samples were evaluated in 15 patients who were without disease or with early or late relapse. Results: Serum VEGF-C levels were significantly higher in node positive versus node negative disease (p=0.03) or controls (p=0.03). Serum VEGF-C levels correlated with overall survival across all stages regardless of treatment (p=0.04) and there was a prognostic trend seen within stages and on longitudinal sampling. The positive predictive value for nodal involvement was higher for serum VEGF-C than conventional imaging (73% versus 60%) as was the negative predictive value (60% versus 35%). CA 19–9 levels were unrelated to nodal status or survival. Conclusions: Serum VEGF-C levels appear useful in nodal staging and prognosis in pancreatic cancer. The finding that serum VEGF-C was elevated in N1 and M1 subjects, but not in N0 subjects, is consistent with a mechanism in which VEGF-C contributes to disease progression through increased metastasis. Therapeutic agents blocking VEGF-C may have clinical benefit in pancreatic cancer. No significant financial relationships to disclose.