Tumor VEGF expression and serum VEGF levels are independent prognostic factors in curatively resected gastric cancer patients

Abstract

4021 Background: Increased serum and/or tumor vascular endothelial growth factor (VEGF) and urokinase-type plasminogen activator (uPA) have been shown to predict poor survival in several neoplasms, but their prognostic value in gastric cancer (GC) remains unknown. Methods: Serum VEGF (S-VEGF) and uPA concentrations were measured by commercially available ELISA in 20 healthy controls and 97 GC patients (70% I-II stages) before an R0 gastric resection. Tumor expression of VEGF and uPA were assessed by immunohistochemistry. Additional variables, including demographic, histological and therapeutic data were also evaluated. Univariate (Kaplan-Meier, log-rank test) and multivariate (Cox regression) analyses were performed to select prognostic factors regarding survival and tumor recurrence. Results: S-VEGF, but not uPA levels were significantly higher in GC patients than in controls. After a mean follow-up of 47 ± 3 months, the probability of cancer-related survival at 2, 5, and 10 years was 86%, 69% and 59%, respectively. Univariate analysis identified tumor VEGF expression (p=0.001) and high (> 289 pg/ml) S-VEGF levels (p=0.045), along with pTMN stage, grade of curability, perineural invasion, lymph node ratio, and extent of lymphadenectomy as variables associated with cancer-related survival. The mean disease-free survival was 20 ± 3 months, the probability of tumor recurrence being 78%, 62% and 62% at 2, 5 and 10 years, respectively. Prognostic variables for recurrence were the same as those identified for survival. Multivariate analysis identified tumor VEGF expression and high S-VEGF levels as independent prognostic survival factors. Conclusions: After a long follow-up, tumor VEGF expression and S-VEGF levels are independent prognostic factors for recurrence and survival in curatively resected gastric cancer patients. Such markers for increased angiogenic activity might help to identify patients at high risk of recurrence that could mostly benefit from adjuvant therapies. It is tempting to speculate that trials assessing the potential benefit of a.ntiangiogenic agents might be particularly warranted in patients with resected GC and a highly angiogenic phenotype. No significant financial relationships to disclose.