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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

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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.

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Acknowledgments

The authors appreciate the contributions of Dr. Dong-Ying Chen (Department of pathology, Sun-Yat-Sen Medical College, Sun-Yat-Sen University) for pathological support during the experiment.

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Correspondence to Shi-Qiang Shen.

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Chen, ZB., Shen, SQ., Ding, YM. et al. The angiogenic and prognostic implications of VEGF, Ang-1, Ang-2, and MMP-9 for hepatocellular carcinoma with background of hepatitis B virus. Med Oncol 26, 365–371 (2009). https://doi.org/10.1007/s12032-008-9130-7

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  • DOI: https://doi.org/10.1007/s12032-008-9130-7

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