目的 观察食管鳞状细胞癌(esophageal squamous cell carcinoma,ESCC)组织中缺氧诱导因子-1α(hypoxia inducible factor-1α,HIF-1α)、组织蛋白酶D(cathepsin D,CTSD)的表达情况,分析两者表达与血管生成拟态(vasculogenic mimicry,VM)及ESCC临床病理特征的关系.方法 收集120例ESCC组织,采用CD34/PAS套染检测ESCC VM情况;免疫组化EnVision两步法检测ESCC中VM标志性分子血管内皮钙黏素(vascular endothelial cadherin,VE-cadherin)和血管内皮生长因子(vascular endothelial grow factor,VEGF)以及HIF-1α、CTSD的表达,分析HIF-1 α和CTSD与ESCC临床病理特征的关系及各指标之间相关性.结果 120例ESCC中HIF-1α和CTSD的表达与患者年龄、性别无关;与淋巴结转移、脉管癌栓形成、临床分期、病理分级等有关;120例ESCC中有25例存在VM;HIF-1 α和CTSD在有VM组阳性率明显高于无VM组,且均与VM表达呈正相关;CTSD在HIF-1 α阳性组的表达明显高于HIF-1 α阴性组,且两者表达呈正相关;VE-cadherin、VEGF在CTSD阳性组的表达率明显高于CTSD阴性组,且与CTSD表达均呈正相关,提示在ESCC中CTSD表达与VM的形成相关.结论 CTSD有可能通过HIF-1α参与ESCC中VM形成过程,另外HIF-1 α和CTSD高表达提示ESCC患者预后不良.%Purpose To investigate the expression of vasculogenic mimicry (VM) and hypoxia inducible factor-1 α (HIF-1α),cathepsin D (CTSD) in esophageal squamous cell carcinoma (ESCC) and its relationship with clinicopathological parameters.Methods 120 specimens of primary ESCC and their clinical data were collected.Dual staining of CD34 and PAS were performed to validate the existence of VM in ESCC.Immunohistochemical of EnVision two-step method was used to detect the expression of VM-related markers vascular endothelial cadherin (VE-cadherin) and vascular endothelial grow factor (VEGF),HIF-1α and CTSD in 120 cases of ESCC.The relationship between HIF-1α,CTSD and clinical pathological parameters were analyzed.Results The positive rate of HIF-1α,CTSD was correlated with infilatrating,lymph node metastasis,clinical stage and cancer embolus.VM existed in 25 of 120 cases.The expression of HIF-1α and CTSD in cases with VM was obviously higher than that without VM,the expression of HIF-1 α and CTSD was positively correlated with VM in ESCC.The expression of CTSD in case with HIF-1 α was obviously lower than that without HIF-1α,the expression of CTSD was positively correlated with HIF-1α in ESCC.The expression of VE-cadherin and VEGF in cases with CTSD was obviously higher than that without CTSD,the level of VE-cadherin and VEGF expression was positively correlated with CTSD in ESCC.Conclusion CTSD may promote VM formation in ESCC via HIF-1α.High expression of HIF-1α and CTSD indicate poor prognosis of ESCC patients.
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