组织微阵列研究VEGF在原发性肝癌中的表达及预后

HIGH-THROUGHPUT TISSUE MICROARRAY ANALYSISEXPRESSION OF VASCULAR ENDOTHELIAL GROWTHFACTIOR IN PRIMARY LIVER CANCER AND ITSRELATIONSHIP WITH PROGNOSIS

目的 探讨血管内皮细胞生长因子(vascularendothelial growth factor,VEGF)在原发性肝癌中的表达及其与预后的关系。方法 应用组织微阵列新技术(tissuemicroarray)和免疫组织化学染色方法回顾性研究165例行手术切除并经病理学证实的肝细胞肝癌标本中VEGF的表达情况,Log-rank法比较不同VEGF表达组间生存率和无瘤生存率的差别,COX回归模型进行单因素、多因素分析比较各有关因素对生存率的影响。结果VEGF表达主要见于肿瘤胞浆内,肿瘤VEGF表达与肝癌病人总生存和无瘤生存显著相关,VEGF表达强阳性患者的l、3、5年总生存率和无瘤生存率分别为51.69%、30.71%、11.08%和76.92%、38.46%、14.96%,P值分别为0.0000和0.0056。COX回归模型单因素分析肿瘤大小、数目、分化程度、癌栓和VEGF表达是影响肝癌病人生存的相关因素,仅肿瘤大小、VEGF表达与无瘤生存相关;多因素分析则发现肿瘤分化程度和VEGF表达是肝癌患者生存的影响因素,仅VEGF表达与无瘤生存相关。结论 组织微阵列技术为一种高效、快速的分子生物学研究方法。VEGF表达与肝癌复发及预后密切相关,可作为肝癌病人的独立的预后指标。

ve To study the expression of vascularendothelial growth factor in hepatocellular carcinoma and itsrelationship with prognosis.Methods The expression of vascularendothelial growth factor in 165 patients with hepatocellularcarcinoma(HCC)proven by surgery and pathology during 1995 to 1997 was analyzed retrospectively by high-throughput tissuemicroarray technology and histoimunochemistry. The overall andtumor-free survival rates of the groups with different expression of VEGF were calculated by Kaplan-Meire method,and statisticaldifferences were tested by log-rank method.Munivariate andmultivariate study with COX's proportional hazard model was used toevaluate the relative aspects.Results Expression of VEGF wasobserved mainly in cytoplasm of tumor cells,and it was significantlyassociated with the overall and tumor-free survival of the patients.The 1,3 and 5 year overall survival rates and tumor-free survivalrates of the patients with strongly positive expression of VEGF were5l.69%, 30.7l%, l1.08% and 76.92%, 38.46%, l4.96%respectively which were significantly lower than that in patients withpositive expression of VEGF(83.l5%, 62.86%, 46.43% and86.l5%,64.62%,48.87% respectively), and that in patients withnegative expression of VEGF(93.02%, 8l.33%, 78.l4% andl00%, 76.92%, 72.97% respectively). The univariate log-rankanalysis found a significant relationship between tumor size,tumornumber,tumor differentiation,cancer embolus,VEGF expressin andthe overall survival,but only a significant relationship between tumorsize,VEGF expression and the tumor-free survival was found.Amultivariate analysis indicated a significant association betweentumor differentiation,VEGF expression and the overall survival,butonly VEGF expression was significantly associated with the tumor-free survival.Conclusion Tissue microarray is an efficient andrapid technique of molecular biology.VEGF expression is closelycorrelated with recurrence and prognosis of HCC,and it seems to bean independent predictor of prognosis for HCC.