Mise M, Arii S, Higashituji H, Furutani M, Niwano M, Harada T, Ishigami S, Toda Y, Nakayama H, Fukumoto M, Fujita J, Imamura M
First Department of Surgery, Faculty of Medicine, Kyoto University, Japan.
Hepatology. 1996 Mar;23(3):455-64. doi: 10.1053/jhep.1996.v23.pm0008617424.
Hepatocellular carcinoma (HCC) is a typical hypervascular tumor. However, the relationship between the vascularity of HCC and the expression of angiogenic factors has not been investigated. In addition, no detailed studies have examined the possible involvement of angiogenic factors in the grade of malignancy of HCC. The aim of this study was to determine which angiogenic factors regulate tumor angiogenesis and contribute to the invasive ability of liver tumors, especially of HCC. Northern blot analysis was used to examine the transcriptional expression of vascular endothelial growth factor (VEGF), basic fibroblast growth factor (FGF), and acidic FGF in resected surgical specimens (20 HCC and 9 metastatic liver tumors). Correlations between messenger RNA (mRNA) expression and arteriographic findings, as well as histopathological findings, were evaluated. Immunohistochemistry was performed to identify the localization of cells expressing VEGF in HCC. Higher levels of VEGF mRNA were observed in 12 of 20 HCC and 2 of 9 metastatic liver tumors than in corresponding nontumorous tissues. The degree of VEGF mRNA expression was significantly correlated with the intensity of tumor staining in angiograms (P<.01). On immunohistochemical observation, VEGF protein was intensely detected in HCC cells. Furthermore, basic FGF mRNA was detected in 9 of 20 HCC and was related to the capsular infiltration of cancer cells (P<.05). In contrast, no significant difference was observed in the very low levels of acidic FGF mRNA found in the tumorous and nontumorous portions of the liver. In conclusion, these results suggest that VEGF contributes to angiogenesis of liver tumors, whereas basic FGF may be involved in the invasion of HCC into the surrounding tissues.
肝细胞癌（HCC）是一种典型的富血管肿瘤。然而，HCC的血管生成与血管生成因子表达之间的关系尚未得到研究。此外，尚无详细研究探讨血管生成因子是否可能参与HCC的恶性程度。本研究的目的是确定哪些血管生成因子调节肿瘤血管生成并促进肝肿瘤尤其是HCC的侵袭能力。采用Northern印迹分析检测20例HCC手术切除标本和9例肝转移瘤手术切除标本中血管内皮生长因子（VEGF）、碱性成纤维细胞生长因子（FGF）和酸性FGF的转录表达。评估信使核糖核酸（mRNA）表达与血管造影结果以及组织病理学结果之间的相关性。进行免疫组织化学以确定HCC中表达VEGF的细胞的定位。在20例HCC中的12例和9例肝转移瘤中的2例中观察到VEGF mRNA水平高于相应的非肿瘤组织。VEGF mRNA表达程度与血管造影中肿瘤染色强度显著相关（P<0.01）。免疫组织化学观察发现，HCC细胞中强烈检测到VEGF蛋白。此外，在20例HCC中的9例中检测到碱性FGF mRNA，且与癌细胞的包膜浸润有关（P<0.05）。相比之下，在肝肿瘤和非肿瘤部分中检测到的酸性FGF mRNA水平极低，未观察到显著差异。总之，这些结果表明VEGF促进肝肿瘤血管生成，而碱性FGF可能参与HCC向周围组织的侵袭。
