人肝细胞癌血管生成拟态的实验研究

Vasculogenic mimicry in human hepatocellular carcinoma

目的探讨血管生成拟态（vasculogenic mimicry，VM）在原发肝细胞癌（hepatocellular carcinoma，HCC）中的表达及生物学和临床意义。方法42例患者共47个原发中心结节HCC的根治性手术切除肿瘤组织标本，42例患者分为2组，VM阳性组（16例）和VM阴性组（31例）。应用CD31和PAS双重染色检测VM表达及形态结构。RT．PCR检测VE．cadherin、EPHA2和MMP-2基因的表达情况及相关性。结果42例HCC患者标本中，有16例（38．1％）存在VM结构。VM结构为由肿瘤细胞围成的无内皮细胞衬附的管道样结构或PAS染色阳性的网络样结构。VM的生成与HCC的Edmondson病理学分级、肝内转移、术后复发时间比较差异有统计学意义（P〈0．05）。HCC中VM阳性的VE-cadherin、EPHA2和MMP-2基因表达高于VM阴性（P〈0．05），其基因表达与VM形成具有相关性。结论HCC中存在VM。HCC恶性程度越高形成VM的能力越强。VM阳性的HCC更容易发生肝内转移，并且有较高的术后复发率，预后较差。

Objective To detect the existence of vasculogenic mimicry in hepatocellular carcinoma （HCC）. Methods In this study 42 patients with a total of 47 HCC nodules underwent radical resection. Histological and immunohistochemical double staining of CD31 and PAS were applied to observe the existence of vasculogenic mimicry （VM）. Reverse tanscription PCR （RT-PCR） were applied to study the expression of VE-cadherin, EPHA2 and MMP-2 genes. Results VM was found in 16 of the 42 （38. 1% ） HCC cases. The typical forms of VM in the microscope are vessel-like structure formed by tumor ceils, without endothelial cells and the PAS-positive looping pattern. The existence of VM in HCC correlates to a higher Edmondson grade, higher capacity of intrahepatic disseminating and poorer tumor-free survival time （P 〈 0. 05）. Comparing the difference of VE-cadherin gene, EPHA2 gene and MMP-2 gene expression between VM positive nodes and in VM negative nodes by RT-PCR method demonstrated that VE-cadherin gene, EPHA2 gene and MMP-2 gene have a more intense expression in VM positive nodes than in VM negative nodes （ P 〈 0. 05 ）. Conclusion VM exists in human hepatocellular carcinoma. VM occurred more frequently in higher malignant HCC and predicts a higher rate of tumor recurrence and poorer prognosis.