Prognostic significance of angiogenesis in human pancreatic cancer

Br J Cancer. 1999 Mar;79(9-10):1553-63. doi: 10.1038/sj.bjc.6690248.

Abstract

To evaluate whether angiogenic factors are of clinical relevance to actual human pancreatic cancers, we studied the intratumoral microvessel density (IMD), and PD-ECGF, VEGF protein expression in 40 pancreatic cancers using immunohistochemistry. We also investigated PD-ECGF and VEGF gene expression using reverse transcriptase-PCR (RT-PCR). Of the 40 pancreatic cancers studied, 30 carcinomas (75.0%) were evaluated to be PD-ECGF-positive and 10 carcinomas (25.0%) were determined to be PD-ECGF-negative. In contrast, 27 carcinomas (67.5%) were evaluated to be VEGF-positive, whereas 13 carcinomas (32.5%) were VEGF-negative. VEGF gene expression was moderately associated with an increase in the IMD (r2 = 0.181, P = 0.006), but no significant relationship was found between PD-ECGF gene expression and the IMD (r2 = 0.093, P = 0.059). However, tumours with positive expression for both PD-ECGF and VEGF had a higher IMD (P = 0.027). The results of the immunohistochemistry agreed well with the results of the quantitative RT-PCR. The median survival time of the hypervascular group was significantly shorter than that of the hypovascular group (P < 0.0001). In comparing the survival according to PD-ECGF and VEGF gene expression, the median survival time of the patients with positive PD-ECGF expression was significantly shorter than those with negative PD-ECGF expression (P = 0.040). Furthermore, the median survival time of the patients with positive VEGF expression was significantly shorter than those with negative VEGF expression (P = 0.048). However, the Cox multivariate analysis indicated that the IMD and VEGF expression were independent prognostic factors of the various clinicopathologic variables in pancreatic cancer patients (P = 0.0021 and P = 0.0443, respectively).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Antigens, CD34 / analysis
  • Antigens, CD34 / genetics
  • Disease-Free Survival
  • Endothelial Growth Factors / analysis*
  • Endothelial Growth Factors / genetics
  • Female
  • Gene Expression
  • Humans
  • Immunohistochemistry
  • Lymphokines / analysis*
  • Lymphokines / genetics
  • Male
  • Microcirculation
  • Middle Aged
  • Neovascularization, Pathologic / metabolism
  • Neovascularization, Pathologic / mortality
  • Neovascularization, Pathologic / pathology*
  • Pancreatic Neoplasms / blood supply*
  • Pancreatic Neoplasms / metabolism
  • Pancreatic Neoplasms / mortality*
  • Pancreatic Neoplasms / pathology
  • Pancreatic Neoplasms / surgery
  • Prognosis
  • Reverse Transcriptase Polymerase Chain Reaction
  • Thymidine Phosphorylase / analysis*
  • Thymidine Phosphorylase / genetics
  • Vascular Endothelial Growth Factor A
  • Vascular Endothelial Growth Factors

Substances

  • Antigens, CD34
  • Endothelial Growth Factors
  • Lymphokines
  • Vascular Endothelial Growth Factor A
  • Vascular Endothelial Growth Factors
  • Thymidine Phosphorylase