Vascular density and VEGF expression in hepatic lesions

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.

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.

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).

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.