摘要
目的弥漫大B细胞淋巴瘤(diffuse large B cell lymphoma,DLBCL)是一组具有明显异质性的大细胞淋巴瘤,通过多种检查手段早期识别DLBCL预后较差的亚群,对于预后判断和治疗选择具有重要作用。本研究选择了几种相对少见免疫表型表达的DLBCL类型(C-myc/Bcl-2共表达、NF-κB/p65阳性、CD5阳性及CD30阳性的DLBCL)和EB病毒(epstein-barr virus,EBV)阳性的DLBCL病例进行研究,通过检测肿瘤微环境细胞中程序性死亡受体-1(programmed death receptor-1,PD-1)表达情况,探讨PD-1表达相关的影响因素及其表达对相应DLBCL发生和发展的影响。方法收集贵州医科大学附属医院2010-01-01-2018-08-31诊断的120例DLBCL患者资料,通过普通免疫组化染色(C-myc、Bcl-2、NF-κB/p65和CD30)、免疫组化双标(CD5、PAX5)及EBER原位杂交检测筛选出上述特殊类型的病例并分组,普通免疫组化染色检测肿瘤微环境中PD-1蛋白表达情况。收集临床病理资料并随访,对实验数据进行统计学分析。结果120例DLBCL患者中,PD-1肿瘤浸润淋巴细胞(tumor infiltraling lymphoeytes,TILs)阳性病例共有63例(52.5%,63/120);其中C-myc/Bcl-2共表达组中PD-1(+)-TILs病例27例(69.25%,27/39),NF-κB/p65阳性组30例(68.2%,30/44),CD30阳性组17例(73.9%,17/23),CD5阳性组14例(77.8%,14/18),EBV阳性组中为5例(55.6%,5/9)。PD-1(+)-TILs与PD-1(-)-TILs组病例之间IPI评分(χ^2=4.514,P=0.034)和Ann Arbor分期(χ^2=4.760,P=0.029)差异有统计学意义,PD-1(+)-TILs组分期晚、IPI指数高;PD-1-TILs表达在阳性组C-myc/Bcl-2共表达(χ^2=6.485,P=0.011)、NF-κB/p65(χ^2=6.851,P=0.009)、CD30(χ^2=5.232,P=0.022)、CD5(χ^2=5.426,P=0.040)表达率明显高于阴性组,差异有统计学意义;PD-1-TILs表达在EBV阳性组与阴性组之间差异无统计学意义,χ^2=0.001,P=0.970。生存分析98例随访病例中,PD-1(+)-TILs组病例的总生存率(overall survival,OS)明显低于PD-1(-)-TILs组患者,χ^2=14.652,P<0.001;在C-myc/Bcl-2共表达(χ^2=4.071,P=0.049)、NF-κB/p65的核表达(χ^2=4.833,P=0.025)及CD30阳性DLBCL(χ^2=5.207,P=0.024)中PD-1(+)-TILs组的生存状况也明显较PD-1(-)-TILs组病例差;多因素回归分析显示,PD-1(+)-TILs是DLBCL的独立危险因素,HR=38.170,P=0.036。结论PD-1表达在C-myc/Bcl-2共表达阳性、NF-κB/p65阳性、CD30阳性和CD5阳性的DLBCL中明显增高,在EBV阳性的DLBCL中增加不明显,PD-1在肿瘤微环境细胞中的表达可能是(C-myc/Bcl-2共表达阳性、NF-κB/p65阳性和CD30阳性)DLBCL不良预后评估的相关因素。
OBJECTIVE The diffuse large B cell lymphoma(DLBCL)is a group of large cell lymphomas with significant heterogeneity.Early identification of subgroups of DLBCL with poor prognosis via a variety of examination methods plays an important role in predicting prognosis and treatment options.Several DLBCL types(DLBCL with C-myc/Bcl-2 co-expression,positive NF-κB/p65,positive CD5 and positive CD30)with relatively rare immunophenotypic expression and DLBCL cases with positive Epstein-Barr Virus(EBV)were selected in the present study.The influencing factors related to PD-1 expression and the effect of PD-1 expression on the occurrence and development of DLBCL were investigated by testing the expression of PD-1 in tumor microenvironment cells.METHODES The patients diagnosed with DLBCL in the Affiliated Hospital of Guizhou Medical University from January 1,2010 to August 31,2018 were enrolled in the study.The above special types of patients were screened out and divided into groups via general immunohistochemical staining(C-myc,Bcl-2,NF-κB/p65 and CD30),immunohistochemical double-labeling(CD5 and PAX5)and EBER in situ hybridization.The expression of PD-1 protein in the tumor microenvironment was detected by general immunohistochemical staining.The clinicopathological data were collected and followed up,and the experimental data were statistically analyzed.RESULTS Of the 120 DLBCL patients,there were 63 patients(52.5%,63,120)with PD-1(+)-TILs total positive rate.Twenty-seven patients(69.25%,27/39)with PD-1(+)-TILs in the C-myc/Bcl-2 co-expression group,30 patients(68.2%,30/44)with PD-1(+)-TILs in the p65 nuclear positive group,17 patients(73.9%,17/23)with PD-1(+)-TILs in the CD30 positive group,14 patients(77.8%,14/18)with PD-1(+)-TILs in the CD5 positive group,and 5 patients(55.6%,5/9)with PD-1(+)-TILs in the EBV positive group.There were statistically significant differences in IPI score and Ann Arbor staging between PD-1(+)-TILs and PD-1(-)-TILs groups(χ^2=4.514,P=0.034;χ^2=4.760,P=0.029).The stage was advanced and the IPI index was high in the positive group.The co-expression of C-myc/Bcl-2 and expressions of NF-κB/p65,CD30 and CD5 were compared between the positive group and negative group.There was statistically significant difference(Pvalues were 0.011,0.009,0.022 and 0.040,χ^2 values were 6.485,6.851,5.232 and5.426,respectively)in expression of PD-1-TILs.The expression rate was significantly increased in the positive group.The difference in the expression of PD-1-TILs was not significant(P=0.970,χ^2=0.001)between the EBV positive group and negative group.Among 98 patients followed up for survival analysis,the overall survival(OS)of PD-1(+)-TILs group was significantly lower than that of PD-1(-)-TILs group,χ^2=14.652,P<0.001;In C-myc/Bcl-2 co-expression(χ^2=4.071,P=0.049),NF-κB/p65 nuclear expression(χ^2=4.833,P=0.025)and CD30 positive DLBCL(χ^2=5.207,P=0.024)group was also significantly worse than those in PD-1(-)-TILs group;.Multivariate regression analysis:PD-1(+)-TILs is an independent risk factor for DLBCL(HR=38.170,P=0.036).CONCLUSIONS The expression of PD-1 in tumor microenvironment cells increased significantly in four special types(C-myc/Bcl-2 co-expression,NF-κB/p65 positive,CD30 positive and CD5 positive),and not significant in the DLBCL with EBV positive.The expression of PD-1 in tumor microenvironment cells may be a related(C-myc/Bcl-2 co-expression positive,NF-κB/p65 positive,CD30 positive)factor in the evaluation of poor prognosis of DLBCL.
作者
周杰
杨文秀
王平
ZHOU Jie;YANG Wen-xiu;WANG Ping(Department of Pathology,Guizhou Medical University,Guiyang 550004,P.R.China;Department of Pathology,Affliated Hospital of Guizhou Medical University,Guijyang 550004.P.R.China)
出处
《中华肿瘤防治杂志》
CAS
北大核心
2020年第7期526-532,共7页
Chinese Journal of Cancer Prevention and Treatment
基金
贵阳市科技局贵州医科大学联合基金(GY2016-4)。
