The angiogenic and prognostic implications of VEGF, Ang-1, Ang-2, and MMP-9 for hepatocellular carcinoma with background of hepatitis B virus.
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.
Chen
Zu-Bing
ZB
Department of General Surgery, Renmin Hospital of Wuhan University, 430060 Wuhan, China.
Shen
Shi-Qiang
SQ
Ding
You-Ming
YM
Wang
Wei-Xing
WX
Tao
Jian-Ping
JP
Liang
Li-Jian
LJ
Hu
Wen-Jie
WJ
D000328:Adult; D000368:Aged; D042501:Angiogenic Proteins / Q000378:metabolism*; D042683:Angiopoietin-1 / Q000378:metabolism; D042702:Angiopoietin-2 / Q000378:metabolism; D018952:Antigens, CD34 / Q000378:metabolism; D006528:Carcinoma, Hepatocellular / Q000098:blood supply* / Q000378:metabolism / Q000473:pathology / Q000821:virology*; D018572:Disease-Free Survival; D006509:Hepatitis B / Q000150:complications / Q000378:metabolism*; D006514:Hepatitis B Surface Antigens / Q000378:metabolism; D006515:Hepatitis B virus / Q000302:isolation & purification*; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D008875:Middle Aged; D009389:Neovascularization, Pathologic / Q000378:metabolism / Q000821:virology; D011379:Prognosis; D016016:Proportional Hazards Models; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
D042501:Angiogenic Proteins; D042683:Angiopoietin-1; D042702:Angiopoietin-2; D018952:Antigens, CD34; D006514:Hepatitis B Surface Antigens; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D020780:Matrix Metalloproteinase 9