OBJECTIVETo determine the relation between the vascular endothelial growth factor (VEGF), proliferating cell nuclear antigen (PCNA), and microvessel density (MVD) as well as the influence on portal vein thrombosis and transfer (PVTT) in hepatocellular carcinoma (HCC).

METHODSTumor specimens were collected in 36 patients (16 patients with PVTT, the other patients without PVTT and metastasis) undergoing resection of HCC and thrombectomy. PVTT specimens of 16 patients were named Group A1, and HCC of the same patients named Group A2. The other 20 patients belonged to Group B. In situ hybridization and immunohistochemistry were used to investigate VEGF, PCNA expression and MVD. The intensity was evaluated with a computer image analyzer-cell analysis system.

RESULTSVEGF mRNA expression was detected in the tumor cells. The expression rates in Group B, A2, and A1 were 30%, 100%, and 100%, respectively. Group A2 and A1 were higher than Group B (P<0.01). VEGF protein expression was often detected in the tumor cells, vascular endothelial cells, and fibroblast cells. Invasion was detected in the small vein in Group A2, and more tumor cell colony detected in Group A1. The expression rates of VEGF protein in Group B, A2, and A1 were the same as VEGF mRNA. The intensity of VEGF mRNA and protein were all lower in Group A2 than Group A1 (P<0.01). In Group B, A2, and A1, MVD and PCNA-LI were gradually elevated. PCNA reactive vascular endothelial cells were occasionally observed in Group A2, and often observed in Group A1. There was a statistically significant correlation between the intensity of VEGF expression, PCNA-LI and MVD in Group A2 and A1, and significant correlation between PCNA-LI and MVD in Group B, A2, and A1.

CONCLUSIONSOverexpression of VEGF could be an important factor of the high MVD and the highly proliferative activity of cancer cells in HCC and PVTT. High MVD and PCNA-LI associate very well with the formation of PVTT and metastasis in HCC.