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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。
Objective To investigate the existence of angiogenic mimicry (VM) and the relationship between VM, hypoxia inducible factor-1α (HIF-1) and vascular endothelial growth factor (VEGF) and the prognosis of gallbladder carcinoma. Methods The expression of HIF-1α and VEGF in gallbladder carcinoma was quantitatively analyzed by HE staining and CD31-PAS staining. Immunohistochemistry, computer image, receiver operating characteristic curve and high and low cut-off immunohistochemical score were used to evaluate the expression of HIF-1α , The relationship between the expression of VEGF and clinicopathological features and prognosis of patients with gallbladder carcinoma without VM and without VM. Results VM was found in 21.35% of gallbladder carcinomas, and was associated with gallbladder adenocarcinoma and liver metastasis (P <0.01). Patients with VM-positive gallbladder cancer had high expression of HIF-1α and low expression of VEGF (P <0.01). HIF-1alpha was associated with serosal invasion and differentiation (P <0.01) in VM patients with gallbladder carcinoma and Nevin staging, negative liver metastasis and serosal invasion, negative and positive lymph node metastasis (P <0.05) in VM subgroup. VEGF was associated with liver metastasis, differentiation degree (P <0.01) and VM subgroup Nevuli staging, negative liver metastasis and moderate differentiation (P <0.01). Multivariate analysis confirmed that VM, Nevin staging and HIF-1α were independent factors in gallbladder cancer patients. Conclusions There is VM in human gallbladder carcinoma. The expression of HIF-1α and VEGF is significantly correlated with VM and disease progression in patients with gallbladder carcinoma. VM and IF-1α are independent prognostic factors in gallbladder carcinoma.