El-Assal O N, Yamanoi A, Soda Y, Yamaguchi M, Igarashi M, Yamamoto A, Nabika T, Nagasue N
Second Department of Surgery, Shimane Medical University, Izumo, Japan.
Hepatology. 1998 Jun;27(6):1554-62. doi: 10.1002/hep.510270613.
As in other tumors, the assessment of microvessel density (MVD) in hepatocellular carcinoma (HCC) may be essential to perform an effective anti-angiogenic therapy for this tumor. The relationship between vascular endothelial growth factor (VEGF) and MVD of HCC as well as the surrounding liver remains to be elucidated. In 71 patients who had undergone curative hepatic resection for HCC, MVD and VEGF expressions were evaluated for HCC and the liver by quantitative reverse-transcription polymerase chain reaction (RT-PCR) and/or immunostaining. The intensity and extent of VEGF immunoreactivity were evaluated using a computer image analyzer-cell analysis system (CAS). Angiographic data were re-evaluated and compared with MVD in 50 tumors. Tumoral MVD was significantly correlated with tumor capsule formation (t test, P = .0016). Small HCCs (< or = 2 cm) had a significantly lower MVD compared with moderate-sized HCCs (2-5 cm) (t test, P = .016), and the MVD of large HCCs was relatively lower than that of moderate tumors. Tumor vascularity on angiography was not correlated with the MVD. Neither VEGF mRNA levels nor protein expression in HCC were correlated with the tumoral MVD or any histopathological features of the tumor. However, cirrhotic livers had significantly higher MVD and VEGF expressions compared with noncirrhotic livers (t test, P = .0015 and P = .047, respectively). Only the MVD of tumor was significantly correlated with intrahepatic recurrence (t test, P = .0048) and disease-free survival (DFS) rates (log rank test, P = .0035). Moreover, the MVD was an independent predictor for DFS by multivariate analysis (chi2 test, P = .03). In conclusion, the MVD in HCC may be involved in the dismal prognosis of this tumor, and VEGF may be associated with the angiogenic process of the cirrhotic liver, but not with the angiogenesis of HCC.
与其他肿瘤一样，评估肝细胞癌（HCC）中的微血管密度（MVD）对于对该肿瘤实施有效的抗血管生成治疗可能至关重要。血管内皮生长因子（VEGF）与HCC以及周围肝脏的MVD之间的关系仍有待阐明。在71例因HCC接受根治性肝切除的患者中，通过定量逆转录聚合酶链反应（RT-PCR）和/或免疫染色评估了HCC和肝脏的MVD及VEGF表达。使用计算机图像分析仪 - 细胞分析系统（CAS）评估VEGF免疫反应性的强度和范围。对50个肿瘤的血管造影数据进行重新评估并与MVD进行比较。肿瘤MVD与肿瘤包膜形成显著相关（t检验，P = 0.0016）。小肝癌（≤2 cm）的MVD明显低于中等大小肝癌（2 - 5 cm）（t检验，P = 0.016），大肝癌的MVD相对低于中等大小肿瘤。血管造影上的肿瘤血管与MVD无关。HCC中的VEGF mRNA水平和蛋白表达均与肿瘤MVD或肿瘤的任何组织病理学特征无关。然而，与非肝硬化肝脏相比，肝硬化肝脏的MVD和VEGF表达明显更高（t检验，分别为P = 0.0015和P = 0.047）。只有肿瘤的MVD与肝内复发（t检验，P = 0.0048）和无病生存率（DFS）显著相关（对数秩检验，P = 0.0035）。此外，通过多变量分析，MVD是DFS 的独立预测因子（卡方检验，P = 0.03）。总之，HCC中的MVD可能与该肿瘤的不良预后有关，VEGF可能与肝硬化肝脏的血管生成过程有关，但与HCC的血管生成无关。
