人肝细胞癌中血管内皮生长因子、微血管密度的定量分析及其临床病理特征

Quantitative analysis of vascular endothelial growth factor, microvascular density and their clinicopathologic features in human hepatocellular carcinoma.

作者信息

Yao Deng-Fu, Wu Xin-Hua, Zhu Yong, Shi Gong-Sheng, Dong Zhi-Zhen, Yao Deng-Bing, Wu Wei, Qiu Li-Wei, Meng Xian-Yong

机构信息

Research Center of Clinical Molecular Biology, Affiliated Hospital of Nantong University, Nantong 226001, China.

出版信息

Hepatobiliary Pancreat Dis Int. 2005 May;4(2):220-6.

PMID:15908319

Abstract

BACKGROUND

Angiogenesis is known to be essential to the survival, growth, invasion, and metastasis of tumor cells. Vascular endothelial growth factor (VEGF) are an important angiogenic factor regulating tumor angiogenesis, but its significance and tumor pathologic features are unclear in hepatocellular carcinoma (HCC). In the present study, we analyzed expression of tissue VEGF, alteration of microvascular density (MVD) in microvessel angiogenesis, development and metastasis of HCC, and level of serum VEGF in differential diagnosis of benign and malignant liver diseases.

METHODS

Tumor specimens were prospectively collected from HCC patients undergoing resection. Total RNAs were extracted and the expression levels were detected from different parts of HCC tissues. The cellular distributions of VEGF and MVD of liver tumors and their paracancerous and distal cancerous tissues were investigated by streptavidin peroxidase (S-P) immunohistochemistry, respectively. The VEGF levels of circulating blood and hepatoma tissues were measured by enzyme-linked immunosorbent assay.

RESULTS

The incidence of VEGF expression was 63.9% in HCCs (23/36 cases), 78.3% in non-encapsulated HCCs (18/23), and 90.9% in HCCs with extrahepatic metastasis (10/11), respectively. The VEGF expression was tightly correlated with MVD (P<0.01). The MVD in HCC with metastasis, low differentiation or non-encapsulation was significantly higher than that in HCC with intact capsule, high differentiation, or no metastasis. No significant difference was found between VEGF, MVD, tumor size, and hepatitis virus infection. The level of total RNA in HCC tissues was significantly lower but the VEGF level significantly higher than those in paracancerous or distal cancerous ones (P<0.01). The abnormal expression levels of VEGF in sera of HCC patients were directly correlated with the metastasis and recurrence of tumors.

CONCLUSION

The high expression of VEGF and abnormality of tissue MVD are useful predictors for vascular invasion and metastasis of liver tumors.

摘要

背景

血管生成对于肿瘤细胞的存活、生长、侵袭和转移至关重要。血管内皮生长因子（VEGF）是调节肿瘤血管生成的重要血管生成因子，但其在肝细胞癌（HCC）中的意义及与肿瘤病理特征的关系尚不清楚。在本研究中，我们分析了组织VEGF的表达、微血管生成中微血管密度（MVD）的变化、HCC的发生发展及转移情况，以及血清VEGF水平在良恶性肝脏疾病鉴别诊断中的作用。

方法

前瞻性收集接受手术切除的HCC患者的肿瘤标本。提取总RNA并检测HCC组织不同部位的表达水平。分别采用链霉亲和素过氧化物酶（S-P）免疫组化法研究肝肿瘤及其癌旁和远处癌组织中VEGF的细胞分布及MVD。采用酶联免疫吸附测定法检测循环血液和肝癌组织中的VEGF水平。

结果

HCC中VEGF表达发生率分别为63.9%（23/36例），无包膜HCC中为78.3%（18/23），肝外转移HCC中为90.9%（10/11）。VEGF表达与MVD密切相关（P<0.01）。有转移、低分化或无包膜的HCC中的MVD显著高于有完整包膜、高分化或无转移的HCC。VEGF、MVD、肿瘤大小及肝炎病毒感染之间无显著差异。HCC组织中的总RNA水平显著低于癌旁或远处癌组织，而VEGF水平显著高于癌旁或远处癌组织（P<0.01）。HCC患者血清中VEGF的异常表达水平与肿瘤的转移和复发直接相关。