肝癌内皮细胞包裹肿瘤细胞团与VEGF表达的意义

Clinical value of endothelium-coated tumor clusters and vascular endothelial growth factor in hepatocellular carcinoma

目的研究血管内皮细胞生长因子(VEGF)的表达与肝癌形成内皮细胞包裹的肿瘤细胞团(ECTC)的关系及其与肝癌复发预后的关系。方法选取根治性切除肝癌组织石蜡标本90例,采用免疫组化方法检测标本ECTC形成情况及VEGF表达情况,分析两者相关性及与预后关系;多因素分析影响肝癌预后的独立危险因素。结果 90例肝癌组织中42例(46.7%)存在ECTC结构,61例(67.8%)VEGF表达阳性。VEGF与形成ECTC具有明显相关性(rs=0.305,P=0.003),两者均与肿瘤复发相关(rs=0.269,rs=0.174)。按有/无ECTC及VEGF表达情况,将患者分为A组(ECTC-/VEGF-)、B组(ECTC+/VEGF-;ECTC-/VEGF+)、C组(ECTC+/VEGF+)。A组1、3、5年无瘤生存率分别是92.0%、72.0%和32.0%,B组分别为88.9%、51.9%和14.8%,C组分别为78.9%、15.8%和2.6%,差异有统计学意义(χ2=24.101,P<0.01)。A组的1、3、5年生存率分别是96.0%、80.0%和64.0%,B组分别为96.3%、77.8%和37.0%,C组分别为92.1%、36.8%和18.4%,差异有统计学意义(χ2=18.358,P<0.01)。多因素分析显示TNM分期、ECTC及VEGF是影响生存的独立危险因素。结论 VEGF与形成ECTC具有明显相关性,两者是影响肝癌长期生存的独立危险因素。

Objective To investigate the clinical value of endothelium-coated tumor clusters （ECTC） and vascular endothelial growth factor （VEGF） in hepatocellular carcinoma （HCC）. Methods Ninety consecutive HCC specimens were evaluated by immunohistochemical staining for VEGF and cluster of differentiation 34 （CD34）. Correlations between VEGF, ECTC and the recurrence of HCC were analyzed. Risk factors to long-term survival were analyzed by a Cox model. Results The presence of ECTCs in HCC was 46.7%, and positive staining of VEGF was 67.8%, respectively. The presence of ECTCs in HCC positively correlated to VEGF （rs=0.305, P=0.003） and both positively correlated to HCC recurrence （rs=0.269, rs=0.174）. The HCC patients were divided into three groups, according to presence of ECTC and VEGF： Group A, ECTC（-）/VEGF（-）; Group B, ECTC（-）/VEGF（＋）, or ECTC（＋）/VEGF（-）; Group C, ECTC（＋）/VEGF（＋）. The 1-, 3-, and 5-year tumor-free survival rates of Group A, Group B and Group C were 92.0%, 72.0%and 32.0%;88.9%, 51.9%and 14.8%;and 78.9%、15.8% and 2.6%, respectively. The difference was significant （χ2=24.101, P＆lt;0.01）. The 1-, 3-, and 5-year overall survival rates of Group A, Group B and Group C were 96.0%, 80.0%and 64.0%;96.3%, 77.8%and 37.0%;and 92.1%, 36.8%and 18.4%, respectively （χ2=18.358, P＆lt;0.01）. Multivariate analysis revealed that TNM classification, presence of ECTC and VEGF were independent risk factors to long-term survival. Conclusion VEGF positively correlated to the presence of ECTCs in HCC. Both could be regarded as valuable indicators for predicting recurrence （or metastasis） risk of HCC patients. The current results suggested that ECTCs and VEGF was predictor of a poor prognosis in patients with HCC.