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The angiogenic and prognostic implications of VEGF, Ang-1, Ang-2, and MMP-9 for hepatocellular carcinoma with background of hepatitis B virus.

Abstract
The objective of this study was to investigate the expressions of angiogenic factors and elucidate their angiogenic and prognostic roles in hepatocellular carcinoma (HCC) with background of hepatitis B virus (HBV). We evaluated microvessel density (MVD) of HCC, and investigated immunohistochemical expression of vascular endothelial growth factor (VEGF), angiopoietins (Ang-1 and Ang-2), and matrix metalloproteinases-9 (MMP-9) in 67 specimens of surgically resected HCC, which were all positive for hepatitis B surface antigen. We investigated the relationship between their expressions and clinicopathological factors or prognosis. The microvessel density (MVD) of tumor tissue and surrounding normal liver tissue was 93.1 +/- 43.8/mm2 and 30.4 +/- 14.8/mm2, respectively. The MVD of well-differentiated HCC was significantly less than that of poorly differentiated HCC. MVD was positively correlated with VEGF and Ang-2 expression (P = 0.0023 and 0.0265, respectively). There was less tumor recurrence in low Ang-2 and low MMP-9 group than high Ang-2 and/or high MMP-9 group (P = 0.002). In Cox regression model, portal vein thrombus and intrahepatic metastasis was the risk factors of tumor recurrence (P = 0.003 and 0.001, respectively). Our study showed that the expression of VEGF and Ang-2 were positively correlated with MVD. Ang-2 expression and/or MMP-9 expression might be a significant predictive factor for recurrence after resection in HCC patients with the background of HBV.
AuthorsZu-Bing Chen, Shi-Qiang Shen, You-Ming Ding, Wei-Xing Wang, Jian-Ping Tao, Li-Jian Liang, Wen-Jie Hu
JournalMedical oncology (Northwood, London, England) (Med Oncol) Vol. 26 Issue 3 Pg. 365-71 ( 2009) ISSN: 1357-0560 [Print] United States
PMID19082771 (Publication Type: Journal Article)
Chemical References
  • Angiogenic Proteins
  • Angiopoietin-1
  • Angiopoietin-2
  • Antigens, CD34
  • Hepatitis B Surface Antigens
  • VEGFA protein, human
  • Vascular Endothelial Growth Factor A
  • Matrix Metalloproteinase 9
Topics
  • Adult
  • Aged
  • Angiogenic Proteins (metabolism)
  • Angiopoietin-1 (metabolism)
  • Angiopoietin-2 (metabolism)
  • Antigens, CD34 (metabolism)
  • Carcinoma, Hepatocellular (blood supply, metabolism, pathology, virology)
  • Disease-Free Survival
  • Hepatitis B (complications, metabolism)
  • Hepatitis B Surface Antigens (metabolism)
  • Hepatitis B virus (isolation & purification)
  • Humans
  • Immunohistochemistry
  • Kaplan-Meier Estimate
  • Matrix Metalloproteinase 9 (metabolism)
  • Middle Aged
  • Neovascularization, Pathologic (metabolism, virology)
  • Prognosis
  • Proportional Hazards Models
  • Vascular Endothelial Growth Factor A (metabolism)

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