肝细胞癌门静脉主干癌栓微血管形成和细胞增殖的关系

Relationship between the proliferative activity of cancer cells and microvessel density in portal vein thrombosis and transfer of hepatocellular carcinoma

目的 研究肝细胞癌血管内皮生长因子（vascular endothelial srowth factor,VEGF）、增殖细胞核抗原（proliferating cell nuclear antigen,PCNA）和微血管密度（micro—vessel density,MVD）的关系,及其对肝癌门静脉主干癌栓形成和转移的影响。方法 用原位杂交等技术检测16例肝癌PVTT（A1 组）、其原发癌A2 组）和 20例无转移肝癌（B组）VEGF、PCNA表达。结果 A1组、A2组VEGF mRNA和蛋白质阳性表达率均高于B组,A1组细胞平均吸光度高于A2组（t=8.83,P值均< 0.01）。B组、A2组、A1组PCNA阳性表达和MVD均呈升高趋势（P值均<0.01）。A1组、A2组VEGF mRNA、蛋白质表达与MVD、增殖细胞核抗原标记指数（PCNA-LI）有良好相关性,r在0.65～0.95范围,P值均< 0.01。在A1、A2、B组MVD、PCNA-LI之间存在良好的相关性,r在0.78～0.97范围,P值均<0.01。结论 VEGF过量表达是肝细胞癌微血管形成和癌细胞增生活跃的重要原因;丰富的微血管形成和癌细胞的快速生长是肝癌转移和门静脉主干癌栓形成的重要机制之一。

Objective To 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 hepatocellulat carcinoma (HCC). Methods Tumor specimens were collected in 36 patients (16 patients with PVTT, the other patients without PVTT and metastasis) undergoing resection of HCC and thrombectemy. 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. Results VEGF 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 Al (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. Conclusions Overexpression 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.