第10号染色体上缺失与张力蛋白同源的磷酸酯酶基因表达下调促进肝细胞癌血管生成拟态形成

Down - regulation of phosphatase and tensin homologue deleted on chromosometen promote vascu-logenic mimicry formation in hepatoceilular carcinoma

目的探讨磷酸酶第10号染色体上缺失与张力蛋白同源的磷酸酯酶基因（PTEN）表达与肝癌血管生成拟态（VM）形成的关系。方法收集85例肝细胞癌患者的组织标本及临床资料，过碘酸希夫（PAS）／CD31双重染色及免疫组织化学法观察肝癌组织中VM的存在和PTEN的表达，分析VM存在与临床预后指标及PTEN表达的相关性；三维细胞培养观察肝癌细胞株SMMC-7221及HepG2的VM形成，实时定量聚合酶链反应（Real-timePCR）检测PTENmRNA表达。结果85例肝癌标本中17例存在VM结构，VM阳性组门脉癌栓阳性率（52．9％）高于阴性组（17．6％），生存时间为（29．9±3．6）个月低于阴性组的（42．2±5．5）个月，差异有统计学意义（P〈0．05）；PTEN表达VM阳性组（35．3％）低于VM阴性组（63．2％），差异有统计学意义（P〈0．05）；三维培养体系中肝癌细胞株SMMC-7221能够形成VM结构，而HepG2不能；SMMC-7221中PTEN的表达低于HepG2，差异有统计学意义（P〈0．05）。结论肝细胞癌中PTEN表达与VM的形成及患者临床预后相关。

Objective To investigate the relations-hip between the expression of phosphatase and tensin homologue deleted on chromosometen （PTEN） gene and vasculogenic mimicry （VM） formation in hepatocellular carcinoma （HCC）. Methods HCC specimens and clinicopathologic data from 85 patients were collected. By immunohistochemical and Periodic Acid Schiff （PAS）/CD31 double -staining method, the presence of VM and expression of PTEN in usual paraffin sections of HCC tumor samples were studied. Relationships between VM and PTEN/clinicopathologic features were established using statistical tests. In addition, two kinds of HCC cell lines were cultured in 3D cell culture system. VM networks in vitro were observed with a microscope and mRNA expression of PTEN was detected by real - time quantitative poly- merase chain reaction （Real - time PCR）. Results The positive rate of VM was 20% （ 17/85 ） in the whole group. The survival time of VM presence [ （29. 9± 3.6） months ] was shorter than that of VM ab- sence [ （42. 2±5.5） months, P 〈 0. 05 ]. A negative correlation between presence of VM and expression of PTEN was found （ P 〈 0. 05 ）. VM network was observed in SMMC - 7221 culture system which had higher expression of PTEN mRNA. Conclusion PTEN may play an important role in the formation of VM in HCC and offers a potential molecular target for HCC antiangiogenesis therapy.