Thymidine phosphorylase (platelet-derived endothelial cell growth factor), microvessel density and clinical outcome in hepatocellular carcinoma

J Hepatol. 1998 Aug;29(2):290-9. doi: 10.1016/s0168-8278(98)80015-9.

Abstract

Background/aims: Angiogenesis plays an important role in tumor growth and metastasis. It is regulated by angiogenic factors. Thymidine phosphorylase (platelet-derived endothelial cell growth factor) is one such factor. Although the significance of platelet-derived endothelial cell growth factor has been studied for several types of tumor, the expression of platelet-derived endothelial cell growth factor and its correlation with microvessel density or clinicopathological factors in hepatocellular carcinoma are unknown. We evaluated microvessel density and platelet-derived endothelial cell growth factor expression in hepatocellular carcinoma to determine whether microvessel density and platelet-derived endothelial cell growth factor expression are correlated with the clinicopathological factors of hepatocellular carcinoma.

Methods: Using immunohistochemical staining with anti-platelet-derived endothelial cell growth factor antibody and the ELISA method, we evaluated the correlation among platelet-derived endothelial cell growth factor expression, microvessel density and clinicopathological factors in 84 hepatocellular carcinoma patients. Microvessels were stained with anti-human von Willebrand factor (anti-Factor VIII) and anti-CD34.

Results: In the surrounding liver, there was a significant correlation between microvessel density and platelet-derived endothelial cell growth factor expression (p=0.002), and hepatitis C virus-positive livers had higher microvessel densities than otherwise (p=0.003). However, this correlation was not found for hepatocellular carcinoma, but hepatitis C virus-positive tumors had higher expression of platelet-derived endothelial cell growth factor (p=0.018). Microvessel density in hepatocellular carcinoma obtained by Factor VIII staining inversely affected the recurrence-free survival rate (p=0.0416), but the microvessel density by CD34 staining was not a significant predictor.

Conclusions: This study indicates that platelet-derived endothelial cell growth factor may not be a major regulator of angiogenesis of hepatocellular carcinoma, but this enzyme may play an important role in hepatocarcinogenesis cooperating with hepatitis C virus. Also, the density, not of sinusoid-like vessels, but of larger vessels in hepatocellular carcinoma could be a prognostic factor for hepatocellular carcinoma.

MeSH terms

  • Antigens, CD / analysis
  • Antigens, CD34 / analysis
  • Carcinoma, Hepatocellular / blood supply
  • Carcinoma, Hepatocellular / enzymology
  • Carcinoma, Hepatocellular / mortality
  • Carcinoma, Hepatocellular / pathology*
  • Carcinoma, Hepatocellular / surgery*
  • Female
  • Hepatectomy
  • Humans
  • Immunohistochemistry
  • Liver Neoplasms / blood supply
  • Liver Neoplasms / enzymology
  • Liver Neoplasms / mortality
  • Liver Neoplasms / pathology*
  • Liver Neoplasms / surgery*
  • Male
  • Microcirculation / pathology*
  • Neovascularization, Pathologic*
  • Predictive Value of Tests
  • Prognosis
  • Regression Analysis
  • Retrospective Studies
  • Survival Analysis
  • Thymidine Phosphorylase / analysis*
  • Time Factors
  • Treatment Outcome
  • von Willebrand Factor / analysis

Substances

  • Antigens, CD
  • Antigens, CD34
  • von Willebrand Factor
  • Thymidine Phosphorylase