Tumor angiogenesis as a prognostic predictor in pancreatic cancer

The purpose of this study was to evaluate the role of angiogenesis, proliferative activity (assessed by Ki-67 expression), p53 and ras-oncogene (H-ras) expression, and conventional clinicopathologic factors in predicting overall survival rates in patients with pancreatic ductal adenocarcinoma. We followed-up 22 patients with ductal adenocarcinoma of the pancreas for a median of 19 months (range, 2 to 44 months). Angiogenesis was quantitated as vascular surface density (VSD) and the number of vessels per mm2 stroma (NVES) after microvessels were immunostained, using factor VIII-related antigen. p53, H-ras, and Ki-67 proteins were also determined immunohistochemically. VSD and NVES showed significant correlations with increased proliferative activity, poor tumor differentiation, and tumor size of 3 cm or more (P = 0.001, P = 0.013, and P = 0.047, respectively). The overall 2-year survival rate of 33.3% in patients with high VSD and NVES values was significantly worse than that of 66.6% estimated in patients with low microvessel count (log rank, 3.97; P = 0.046). In multivariate analysis using the Cox model, VSD was found to be an independent prognostic factor of survival (P = 0.039). H-ras and p53 expressions were not correlated with angiogenesis parameters. We conclude that, in pancreatic ductal adenocarcinoma, angiogenesis is closely related to tumor growth and patient survival.