摘要目的 观察3种微环境相关的预后因子程序性死亡1(PD-1)、叉头转录因子3(FOXP3)、集落刺激因子1受体(CSF-1R)蛋白在经典型霍奇金淋巴瘤(CHL)患者中的表达,并探讨其与患者预后的相关性.方法 分析2005年2月至2010年8月天津医科大学肿瘤医院、解放军总医院共45例CHL患者的临床资料,包括临床特征、预后因素及治疗方案等.收集45例CHL患者的标本,采用免疫组织化学染色法检测相关蛋白PD-1、FOXP3、CSF-1R的表达,并采用原位杂交技术检测EB病毒(EBV)及EBV编码的小mRNA(EBER).结合患者临床及随访资料分析PD-1、FOXP3、CSF-1R蛋白表达与预后的相关性.采用Kaplan-Meier法进行生存分析,Cox比例风险模型进行多因素分析.结果 45例CHL患者中PD-1阳性者7例(15.6％),FOXP3高表达者23例(51.1％),CSF-1R阳性者18例(40.0％).单因素分析结果显示,FOXP3、CSF-1R蛋白的表达、国际预后指数(IPI)评分、Ann Arbor分期以及EBER是影响患者5年总生存(OS)的预后因素;IPI评分、FOXP3蛋白的表达以及EBER是影响患者5年无进展生存(PFS)的预后因素.多因素分析结果则显示,CSF-1R蛋白的表达是影响患者5年OS的独立预后因素(HR:8.918,P=0.020),FOXP3蛋白的表达是影响患者5年PFS的独立预后因素(HR:0.122,P＜0.001),且EBV是影响CHL患者PFS、OS的独立预后因素.结论 微环境相关的预后因子FOXP3和CSF-1R及EBV均与CHL患者的预后相关,对CHL患者的预后起一定判断作用,同时也为CHL的靶向治疗提供了新思路和理论依据.

abstractsObjective To observe the expression of three microenvironment related prognostic factors,i.e.programmed death 1 (PD-1),forkhead box protein 3 (FOXP3) and colony-stimulating factor 1 receptor(CSF-1R) protein in classical Hodgkin's lymphoma (CHL) patients,and to explore the correlation between the protein expression and the prognosis of the patients.Methods A total of 45 cases of CHL patients,who had been admitted to the Tianjin Medical University Cancer Institute and Hospital and Chinese PLA General Hospital from February 2005 to August 2010 were analyzed,including clinical features,prognostic factors,and treatment regimens.CHL patients' specimens were collected and the expression of PD-1,FOXP3,and CSF-1R proteins analyzed by immunohistochemical staining.Epstein-Barr virus encoded mRNA (EBER) was detected by in situ hybridization analysis.The relationship between the protein expression of PD-1,FOXP3 and CSF-1R and the patients' outcome was analyzed with clinical and follow-up data.Survival analysis was performed by Kaplan-Meier method,the Cox proportional hazard model was used to perform multivariate analysis.Results In this cohort of 45 CHL patients,PD-1 positive was found in 7 cases (15.6％),FOXP3 high expression in 23 cases (51.1％),CSF-1R positive in 18 cases (40.0％).In the univariate analysis,the expression of FOXP3 and CSF-1 R,International Prognostic Index (IPI) score,Ann Arbor stage and EBER were related with the patients' 5-year overall survival (OS);IPI score,the expression of FOXP3 and EBER were related with the patients' 5-year progress-free survival (PFS).Multivariate analysis indicated that CSF-1R protein expression was the independent prognostic factor affecting the patients' 5-year OS (HR:8.918,P=0.020),and FOXP3 protein expression was the independent prognostic factor affecting the patients' 5-year PFS (HR:0.122,P ＜0.001).And EBV was an independent prognostic factor of PFS and OS in the CHL patients.Conclusion Microenvironment related prognostic factors FOXP3,CSF-1R and EBV may be independent prognostic factors of CHL and this study may provide novel strategies for targeted therapy of CHL.