摘要
目的:检测C-Myc、Bcl-2和Bcl-6基因重排在伴有C-Myc/Bcl-2蛋白共表达的弥漫大B细胞性淋巴瘤(diffuse large B cell lymphoma,DLBCL)(DLBCL with C-Myc/Bcl-2),又称双表达淋巴瘤(double expression lymphoma,DEL)中的发生情况,并探讨上述3种基因重排与DEL患者临床病理特征的相关性,以及对预后的影响。方法:收集2010年1月1日—2018年12月31日由贵州医科大学附属医院病理科确诊为DLBCL的病例资料,采用免疫组织化学法检测C-Myc和Bcl-2蛋白表达的情况,从中筛选出39例C-Myc和Bcl-2蛋白双表达的病例作为研究对象。免疫组织化学法检测p65蛋白的表达水平,荧光原位杂交技术(fluorescence in situ hybridization,FISH)检测C-Myc、Bcl-2和Bcl-6基因的重排情况,普通原位杂交法检测EB病毒编码的小分子RNA(Epstein-Barr virus encode RNA,EBER)的表达水平。收集临床病理及随访资料。根据FISH检测的基因重排结果进行分组,分为C-Myc、Bcl-2和Bcl-6基因重排阳性组和阴性组及双打击淋巴瘤(double hit lymphoma,DHL)和三打击淋巴瘤(triple hit lymphoma,THL)组,对实验数据进行Fisher精确检验,采用Kaplan-Meier法绘制患者的总生存(overall survival,OS)时间曲线,生存分析采用对数秩检验(log-rank)比较生存曲线,预后因素分析使用COX比例风险回归模型。结果:根据免疫组织化学检测结果,共39例C-Myc和Bcl-2蛋白双表达的病例被纳入研究。3种基因重排检测结果显示,发生C-Myc,Bcl-2及Bcl-6基因重排者检出率依次为23.08%(9/39)、23.08%(9/39)及30.77%(12/39)。C-Myc基因重排与Bcl-2或Bcl-6重排同时检出者(即DHL)3例,3种基因重排同时检出者(即THL)2例,高级别B细胞淋巴瘤(high grade B cell lymphoma,HGBL)(包括DHL及THL)占12.80%。39例DEL中,Bcl-2及Bcl-6基因重排在生发中心细胞型双表达淋巴瘤(germinal center B-cell like double expression lymphoma,GCB-DEL)的发生率明显高于非生发中心细胞型双表达淋巴瘤(non-germinal center B-cell like double expression lymphom,non-GCB-DEL)(P<0.05);HGBL也主要发生在non-GCB-DEL中。C-Myc基因重排和HGBL检出率在<60岁的病例中明显高于≥60岁的病例;蛋白检测结果显示,核因子-κB(nuclear factor-κB,NF-κB)(p65)的阳性表达率为53.84%(21/39),在non-GCB-DEL(16/23)中的阳性表达率显著高于GCB-DEL(5/16)(P<0.05),而在C-Myc基因重排、Bcl-2基因重排和Bcl-6基因重排阳性组以及阴性组DEL之间,p65阳性表达无明显差异。39例DEL中,Bcl-6基因重排阳性患者的生存状况明显差于阴性者,而C-Myc和Bcl-2基因重排阳性与阴性组之间、HGBL与其余的DEL之间的生存状况无明显差异。C-Myc与Bcl-2基因重排阳性与阴性组之间、HGBL与其余的DEL之间的临床分期、性别、原发部位、骨髓累及、IPI指数、血清乳酸脱氢酶(lactate dehydrogenase,LDH)及EBER表达水平均未见统计学差异。结论:DEL病例中有较高的C-Myc、Bcl-2和Bcl-6基因重排发生率,而且与患者年龄和Hans分型有关,不同的基因重排发生与DEL的临床过程和预后有一定影响,Bcl-6重排与DEL的不良预后有关,应该常规进行3种基因重排的检测为临床治疗方案的确定和预后评估提供依据。
Objective:To detect the C-Myc,Bcl-2 and Bcl-6 gene rearrangements in diffuse large B cell lymphoma with C-Myc/Bcl-2 co-expression,also known as double expression Lymphoma(DEL),and explore the correlation between the above three gene rearrangements and the clinicopathological characteristics of DEL patients,as well as the impact on the prognosis.Methods:Patients diagnosed as DLBCL by the Department of Pathology of affiliated Hospital of Guizhou Medical University from January 1,2010 to December 31,2018 were collected.Immunohistochemical(IHC)staining was used to detect the C-Myc and Bcl-2 expression,and 39 cases were screened out for the study.The expression of p65 was detected by immunohistochemical staining,gene rearrangements of C-Myc,Bcl-2 and Bcl-6 were detected by fluorescence in situ hybridization,and the expression of Epstein-Barr Virus encode RNA(Eber)was detected by ordinary hybridization in situ.Clinicopathological and follow-up data were collected.According to the results of gene rearrangement detected by FISH,these cases were divided into C-Myc,Bcl-2 and Bcl-6 gene rearrangement positive group,negative group and DHL/THL group.Fisher’s exact test was performed on the experimental data,the Kaplan-Meier method was used to draw the overall survival(OS)curve of the patients,and the log-rank test was used for survival analysis.The survival curves were compared,and the prognostic factors were analyzed using the COX proportional hazards regression model.Results:According to the results of IHC,39 cases with double expression of C-Myc and Bcl-2 protein were included in the study.The detection results of the three gene rearrangements showed that the detection rates of C-Myc,Bcl-2 and Bcl-6 gene rearrangements were 23.08%(9/39),23.08%(9/39)and 30.77%(12/39).C-Myc gene rearrangement was detected at the same time as Bcl-2 or Bcl-6 rearrangement(double-hit lymphoma,DHL)in 3 cases,3 gene rearrangements were detected at the same time(triple-hit lymphoma,THL)in 2 cases,high-grade B-cell lymphoma(high grade B cell lymphoma,HGBL)(including DHL and THL)accounted for 12.80%.In 39 cases of DEL,the incidence of Bcl-2 and Bcl-6 gene rearrangement in germinal center B-cell-like double expression lymphoma(GCB-DEL)was significantly higher than that of non-germinal center B-cell like double expression lymphoma(non-GCB-DEL)(P<0.05);HGBL also mainly occurred in non-GCB-DEL.Among 39 cases of DEL,the detection rate of C-Myc gene rearrangement and HGBL was significantly higher in cases under 60 years old(<60 years old)was significantly higher than in cases over 60 years old(≥60 years old).The positive expression rateof nuclear factor-κB(nuclear factor-κB,NF-κB)(p65)was 53.84%(21/39),p65 positive expression rate in the non-GCB-DEL(16/23)was significantly higher than in GCB-DEL(5/16)(P<0.05).There was no statistically significant difference in p65 positive expression between the C-Myc gene rearrangement,Bcl-2 gene and Bcl-6 gene rearrangement positive group and the negative group DEL.Among 39 cases of DEL,the survival status of Bcl-6 gene rearrangement positive cases was significantly worse than that of negative cases,while there was no statistically significant difference in survival status between the positive and negative groups of C-Myc and Bcl-2 gene rearrangement,and between HGBL and other DEL cases.There was no statistically significant difference in clinical stage,gender,primary site,bone marrow,IPI score,serum lactate dehydrogenase(LDH)and EBER expression between the positive and negative groups of C-Myc and Bcl-2 gene rearrangement,and between HGBL and other DEL cases.Conclusion:There is a higher incidence of C-Myc,Bcl-2 and Bcl-6 gene rearrangements in DEL cases,and it is related to the patient’s age and Hans classification.The occurrence of different gene rearrangements has a certain impact on the clinical process and prognosis of DEL,Bcl-6 rearrangement is associated with poor prognosis of DEL,and the detection of three gene rearrangements should be routinely performed to provide a basis for the determination of clinical treatment plans and prognostic evaluation.
作者
许娟
杨文秀
冯江龙
濮珍红
杨光
沈丹丹
XU Juan;YANG Wenxiu;FENG Jianglong;PU Zhenhong;YANG Guang;SHEN Dandan(Department of Pathology,Guizhou Medical University,Guiyang 550004,Guizhou Province,China;Department of Pathology,Guizhou Medical University Hospital,Guiyang 550004,Guizhou Province,China)
出处
《肿瘤》
CAS
CSCD
北大核心
2021年第4期257-267,共11页
Tumor
基金
贵阳市科技计划项目[编号:筑科合同(2019)9-1-6号]。
关键词
淋巴瘤
大B细胞
弥漫性
基因重排
原位杂交
荧光
双表达淋巴瘤
预后
Lymphoma,large B-Cell,diffuse
Gene Rearrangement
In situ hybridization,fluorescence
Double-expression lymphoma
Prognosis
