Vascular density and VEGF expression in hepatic lesions.
BACKGROUND
Hepatocellular carcinoma (HCC) is the fifth most common malignant tumor worldwide and the third most common cause of cancer-related death. HCC is a hypervascular tumor expressing several angiogenic factors. The correlation between plasma levels of Vascular Endothelial Growth Factor (VEGF) and the survival of patients with HCC was demonstrated earlier. However, a relationship between the expression of VEGF and vascular density in the HCC and non-malignant hepatic parenchyma has not been investigated.


METHODS
We studied the expression of VEGF and vascular density in normal hepatic parenchyma, cirrhosis and HCC using a computer-based analysis of immunohistochemical stainings and confirmed it by Western Blot.


RESULTS
The vascular density in the areas of HCC and internodular fibrotic tissue in cirrhotic liver was significantly higher (185%; 146% respectively) than in non-neoplastic hepatic parenchyma. Additionally, cirrhotic nodules were characterized by significantly lower vascularization (71%) compared with normal liver. There was a strong correlation between the levels of VEGF expression in tissue and the number of vessels (r=0.98, R2=0.9696).


CONCLUSIONS
Cirrhosis and HCC are characterized by different degrees of vascularization, which has been quantitated by a novel computer-based analysis of immunohistochemical stainings. One of the major stimuli for angiogenesis in these liver diseases could be VEGF, as the VEGF expression was higher in HCC and diminished in cirrhotic nodules, thus strongly correlating with the degree of vascularization. Our findings demonstrate that angiogenesis may play an important role in the pathogenesis of these conditions.
Brodsky
Sergey V
SV
Department of Pathology, Renal Research Institute, BSB, R-C21 Valhalla, NY 10595 USA. sergey_brodsky@nymc.edu
Mendelev
Natalia
N
Melamed
Myron
M
Ramaswamy
Gita
G
D015153:Blotting, Western; D006528:Carcinoma, Hepatocellular / Q000098:blood supply / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D007150:Immunohistochemistry; D008099:Liver / Q000098:blood supply* / Q000378:metabolism; D008103:Liver Cirrhosis / Q000378:metabolism / Q000473:pathology*; D008113:Liver Neoplasms / Q000098:blood supply / Q000378:metabolism / Q000473:pathology*; D009389:Neovascularization, Pathologic / Q000378:metabolism / Q000473:pathology*; D012720:Severity of Illness Index; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis*
D042461:Vascular Endothelial Growth Factor A