Wang T T, Li S X, Xia B, Zhao H F, Xu W, Yang H L, Wang X F, Yu Y, Sun B C, Zhang Y Z
Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin's Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for Cancer, Tianjin 300060, China.
Zhonghua Yi Xue Za Zhi. 2017 May 16;97(18):1400-1405. doi: 10.3760/cma.j.issn.0376-2491.2017.18.010.
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. 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. 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-1R, 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(: 8.918, =0.020), and FOXP3 protein expression was the independent prognostic factor affecting the patients' 5-year PFS (: 0.122, <0.001). And EBV was an independent prognostic factor of PFS and OS in the CHL patients. 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.
观察经典型霍奇金淋巴瘤（CHL）患者中三种微环境相关预后因素，即程序性死亡1（PD-1）、叉头框蛋白3（FOXP3）和集落刺激因子1受体（CSF-1R）蛋白的表达情况，并探讨蛋白表达与患者预后之间的相关性。分析了2005年2月至2010年8月期间收治于天津医科大学肿瘤医院和中国人民解放军总医院的45例CHL患者，包括临床特征、预后因素及治疗方案。收集CHL患者的标本，采用免疫组织化学染色分析PD-1、FOXP3和CSF-1R蛋白的表达。通过原位杂交分析检测爱泼斯坦-巴尔病毒编码的mRNA（EBER）。结合临床和随访数据分析PD-1、FOXP3和CSF-1R蛋白表达与患者预后的关系。采用Kaplan-Meier法进行生存分析，用Cox比例风险模型进行多因素分析。在这45例CHL患者队列中，发现7例（15.6%）PD-1阳性，23例（51.1%）FOXP3高表达，18例（40.0%）CSF-1R阳性。单因素分析显示，FOXP3和CSF-1R的表达、国际预后指数（IPI）评分、Ann Arbor分期及EBER与患者的5年总生存（OS）相关；IPI评分、FOXP3的表达及EBER与患者的5年无进展生存（PFS）相关。多因素分析表明，CSF-1R蛋白表达是影响患者5年OS的独立预后因素（：8.918，=0.020），FOXP3蛋白表达是影响患者5年PFS的独立预后因素（：0.122，<0.001）。并且EBV是CHL患者PFS和OS的独立预后因素。微环境相关预后因素FOXP3、CSF-1R和EBV可能是CHL的独立预后因素，本研究可能为CHL的靶向治疗提供新策略。
