胆囊癌血管生成拟态,缺氧诱导因子-1α和血管内皮生长因子表达及其与临床预后的关系(英文)

Vasculogenic mimicry,HIF-1α and VEGF expression in gallbladder carcinoma:association with clinical outcomes and prognostic implications

目的探讨人胆囊癌是否存在血管生成拟态(VM)以及VM、缺氧诱导因子-1α(HIF-1)和血管内皮生长因子(VEGF)与胆囊癌预后的关系。方法应用HE和CD31-PAS染色观察胆囊癌VM,应用免疫组织化学、计算机图像、接收机操作特性曲线和高低免疫组化反应截止评分定量分析胆囊癌HIF-1α、VEGF表达;同时评估HIF-1α、VEGF表达与胆囊癌VM和无VM组病人临床病理学特征与预后的关系。结果 21.35%的胆囊癌存在VM,VM与胆囊腺癌和肝转移相关(P<0.01)。VM阳性胆囊癌病人存在HIF-1α高表达和VEGF低表达(P<0.01)。HIF-1α与胆囊癌VM病人的浆膜浸润、分化程度(P<0.01)和VM亚组病人的Nevin分期、阴性肝转移和浆膜浸润、阴性和阳性淋巴结转移(P<0.05)相关。VEGF则与胆囊癌VM病人的肝转移、分化程度(P<0.01)和VM亚组病人Nevin分期、阴性肝转移和中分化程度(P<0.01)相关。多因素分析证实,VM、Nevin分期和HIF-1α是胆囊癌病人的独立因素。结论人胆囊癌存在VM;HIF-1α和VEGF表达与胆囊癌病人的VM和疾病进展明显相关;VM和IF-1α是胆囊癌病人预后判断的独立因素。

Purpose To explore whether VM exists in human gallbladder carcinoma (GBC) and VM' correlation with HIF-1α,VEGF and prognosis of GBC patients.Methods HE and CD31-PAS staining were used to observe VM in GBC.Immunohistochemistry (IHC),computer-assisted image and receiver operating characteristic curve were used to analyze expression of HIF-1α and VEGF in GBC,IHC quantitative analysis and selection of the cut-off score for high or low IHC reactivity.Correlation of HIF-1α and VEGF expression with clinicopathologic features and prognosis of GBC patients with VM and non-VM was evaluated simultaneously.Results VM was observed in GBC (21.35%) and associated with adenocarcinoma and liver metastasis (both P<0.01).Over-expression of HIF-1α and reduced-expression of VEGF were observed in GBC patients with VM (both P<0.01).HIF-1α was correlated with serosal invasion,degree of differentiation in VM group (all P<0.01),and VM in the same subset of clinical-pathologic parameters including Nevin stage,negative liver metastasis and serosal invasion,negative and positive lymph node metastasis (all P<0.05).VEGF was associated with liver metastasis,degree of differentiation in VM group (all P<0.01),and VM in the same subset of clinicopathologic parameters including Nevin stage,negative liver metastasis and moderate degree of differentiation (all P<0.01).Multivariate analysis confirmed that VM,Nevin stage and HIF-1α were independent factors for GBC patients.Conclusions VM exists in human GBC.HIF-1α and VEGF expression is significantly associated with VM and advanced stage in GBC patients.VM and HIF-1α is independent factors for GBC patients.