Ng I O, Poon R T, Lee J M, Fan S T, Ng M, Tso W K
Department of Pathology, University of Hong Kong, Queen Mary Hospital, Pokfulam.
Am J Clin Pathol. 2001 Dec;116(6):838-45. doi: 10.1309/FXNL-QTN1-94FH-AB3A.
Assessment of angiogenesis may yield important information for an effective antiangiogenic treatment for hepatocellular carcinoma (HCC) because HCC is characteristically hypervascular We examined the relationship of microvessel density (MVD), vascular endothelial growth factor (VEGF), and VEGF receptors Flt-1 and Flk-1/KDR in 50 patients with HCC and in 3 hepatoma cell lines. VEGF messenger RNA (mRNA) was overexpressed in 26 tumors (52%), and the 3 VEGF isoforms (121, 165, and 189) were present in high frequencies. Flt-1 mRNA was overexpressed in 34 tumors (68%), with levels significantly increased in HCCs compared with the nontumorous livers. Tumor Flt-1 mRNA significantly correlated with tumor VEGF mRNA levels. Within the group of tumors 8.5 cm or less in diameter, tumors with intrahepatic metastasis in the form of tumor microsatellite formation had significantly higher VEGF mRNA levels. MVD assessed by immunohistochemical analysis with CD34 antibody was inversely related to tumor size. Angiogenesis as assessed by MVD and tumor VEGF expression seems to have a more important role in tumor growth and intrahepatic metastasis in smaller HCCs. The differential up-regulation of Flt-1 suggests that it may have an important role in angiogenesis in HCC.
由于肝细胞癌（HCC）具有血管丰富的特征，评估血管生成可能为HCC的有效抗血管生成治疗提供重要信息。我们检测了50例HCC患者和3种肝癌细胞系中微血管密度（MVD）、血管内皮生长因子（VEGF）以及VEGF受体Flt-1和Flk-1/KDR之间的关系。26例肿瘤（52%）中VEGF信使核糖核酸（mRNA）过度表达，3种VEGF亚型（121、165和189）出现频率较高。34例肿瘤（68%）中Flt-1 mRNA过度表达，与非肿瘤肝脏相比，HCC中其水平显著升高。肿瘤Flt-1 mRNA与肿瘤VEGF mRNA水平显著相关。在直径8.5 cm及以下的肿瘤组中，以肿瘤微卫星形式出现肝内转移的肿瘤VEGF mRNA水平显著更高。用CD34抗体通过免疫组织化学分析评估的MVD与肿瘤大小呈负相关。通过MVD和肿瘤VEGF表达评估的血管生成似乎在较小的HCC的肿瘤生长和肝内转移中起更重要的作用。Flt-1的差异上调表明它可能在HCC的血管生成中起重要作用。
