Prognostic value of angiogenesis in patients following curative resection of gastric cancer (GC)

Abstract

9605 Background: Despite novel therapies in GC, long-term prognosis remains poor. Assessment of angiogenesis holds the promise of predicting outcome in an individual basis, as well as to identify novel therapeutic targets. This study was aimed at evaluating the prognostic significance of tumor angiogenesis assessed by the expression of angiogenic factors and proteases in patients undergoing curative (R0) GC resection. Methods: In 148 patients with R0 GC, tumor microvessel density and expression of VEGF, angiopoietin-2 (Ang2), cyclooxigenase-2 (COX2), p53, urokinase-type plasminogen activator and its inhibitor (PAI1), and matrix metalloproteinases (MMP)1 and 9 were assayed by immunohistochemistry. We also evaluated 12 clinico-pathological variables: age, sex, pTNM, degree of differentiation, Lauren’s classification, vascular, lymphatic and perineural invasion, lymph node ratio, type of surgery, extent of lymphadenectomy and adjuvant chemotherapy. Univariate and multivariate analyses were performed to select the independent prognostic factors, and to adjust results of the molecular study for any significant clinical variables. Results: After a mean follow-up of 56±4 months, the probability of overall survival at 2, 5, and 10 yrs was 66%, 49% and 31%, respectively. The univariate analysis identified VEGF (p=0.002), Ang2 (p=0.001), COX2 (p=0.04), PAI1 (p=0.0002), and MMP9 expression (p=0.01), along with pTMN, Lauren’s classification, lymphatic invasion, lymph node ratio, and extent of lymphadenectomy as variables associated with overall survival. The mean disease-free survival was 52±4 months, the probability of tumor recurrence being 67%, 51% and 45% at 2, 5 and 10 yrs, respectively. Predictive variables for recurrence were the same as those identified for overall survival. Furthermore, multivariate analysis identified VEGF, Ang2 and PAI1 as independent predictive factors, but adjusting for significant clinical variables, only VEGF expression maintained its independent prognostic value. Conclusions: After a long follow-up period, VEGF expression predicts both overall survival and tumor recurrence in patients with R0 GC. VEGF might be a tempting therapeutic target in GC. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration La Caixa