胸苷磷酸化酶（血小板衍生内皮细胞生长因子）、微血管密度与肝细胞癌的临床预后

Thymidine phosphorylase (platelet-derived endothelial cell growth factor), microvessel density and clinical outcome in hepatocellular carcinoma.

作者信息

Yamamoto A, Dhar D K, El-Assal O N, Igarashi M, Tabara H, Nagasue N

机构信息

Second Department of Surgery, Shimane Medical University, Izumo, Japan.

出版信息

J Hepatol. 1998 Aug;29(2):290-9. doi: 10.1016/s0168-8278(98)80015-9.

DOI:10.1016/s0168-8278(98)80015-9

PMID:9722211

Abstract

BACKGROUND/AIMS: Angiogenesis plays an important role in tumor growth and metastasis. It is regulated by angiogenic factors. Thymidine phosphorylase (platelet-derived endothelial cell growth factor) is one such factor. Although the significance of platelet-derived endothelial cell growth factor has been studied for several types of tumor, the expression of platelet-derived endothelial cell growth factor and its correlation with microvessel density or clinicopathological factors in hepatocellular carcinoma are unknown. We evaluated microvessel density and platelet-derived endothelial cell growth factor expression in hepatocellular carcinoma to determine whether microvessel density and platelet-derived endothelial cell growth factor expression are correlated with the clinicopathological factors of hepatocellular carcinoma.

METHODS

Using immunohistochemical staining with anti-platelet-derived endothelial cell growth factor antibody and the ELISA method, we evaluated the correlation among platelet-derived endothelial cell growth factor expression, microvessel density and clinicopathological factors in 84 hepatocellular carcinoma patients. Microvessels were stained with anti-human von Willebrand factor (anti-Factor VIII) and anti-CD34.

RESULTS

In the surrounding liver, there was a significant correlation between microvessel density and platelet-derived endothelial cell growth factor expression (p=0.002), and hepatitis C virus-positive livers had higher microvessel densities than otherwise (p=0.003). However, this correlation was not found for hepatocellular carcinoma, but hepatitis C virus-positive tumors had higher expression of platelet-derived endothelial cell growth factor (p=0.018). Microvessel density in hepatocellular carcinoma obtained by Factor VIII staining inversely affected the recurrence-free survival rate (p=0.0416), but the microvessel density by CD34 staining was not a significant predictor.

CONCLUSIONS

This study indicates that platelet-derived endothelial cell growth factor may not be a major regulator of angiogenesis of hepatocellular carcinoma, but this enzyme may play an important role in hepatocarcinogenesis cooperating with hepatitis C virus. Also, the density, not of sinusoid-like vessels, but of larger vessels in hepatocellular carcinoma could be a prognostic factor for hepatocellular carcinoma.

摘要

背景/目的：血管生成在肿瘤生长和转移中起重要作用。它受血管生成因子调控。胸苷磷酸化酶（血小板衍生内皮细胞生长因子）就是这样一种因子。尽管已对几种类型的肿瘤研究了血小板衍生内皮细胞生长因子的意义，但肝细胞癌中血小板衍生内皮细胞生长因子的表达及其与微血管密度或临床病理因素的相关性尚不清楚。我们评估了肝细胞癌中的微血管密度和血小板衍生内皮细胞生长因子表达，以确定微血管密度和血小板衍生内皮细胞生长因子表达是否与肝细胞癌的临床病理因素相关。

方法

我们使用抗血小板衍生内皮细胞生长因子抗体进行免疫组织化学染色及酶联免疫吸附测定法，评估了84例肝细胞癌患者中血小板衍生内皮细胞生长因子表达、微血管密度和临床病理因素之间的相关性。微血管用抗人血管性血友病因子（抗因子VIII）和抗CD34染色。

结果

在周围肝组织中，微血管密度与血小板衍生内皮细胞生长因子表达之间存在显著相关性（p = 0.002），丙型肝炎病毒阳性的肝脏微血管密度高于其他情况（p = 0.003）。然而，在肝细胞癌中未发现这种相关性，但丙型肝炎病毒阳性肿瘤的血小板衍生内皮细胞生长因子表达较高（p = 0.018）。通过因子VIII染色获得的肝细胞癌微血管密度对无复发生存率有反向影响（p = 0.0416），但通过CD34染色的微血管密度不是一个显著的预测指标。