弥漫性大B细胞淋巴瘤t(14;18)易位及bcl-2基因扩增的检测  

Detection of t(14; 18)translocation and bc1-2 amplification in diffuse large B-cell lymphoma

作　　者：蒋会勇[1] 李慧灵[1] 胡海[1] 何滢[1] 赵彤[1] 

机构地区：[1]南方医科大学附属南方医院病理科

出　　处：《中华病理学杂志》2007年第2期84-89,共6页Chinese Journal of Pathology

基　　金：广东省社会发展攻关基金(B30301);广州市科技计划基金(2002Z34061)

摘　　要：目的探讨弥漫性大 B 细胞淋巴瘤(DLBCL)t(14;18)染色体异位及 bcl-2基因扩增在其分类及临床分期、疗效评估中的作用。方法先对60例 DLBCL 的标本进行显微切割,获取相对比较纯的肿瘤组织,再使用细胞核芯片荧光原位杂交(FISH)对标本进行 t(14;18)易位及 bcl-2基因扩增检测,采用免疫组织化学 SP 法在组织微阵列上同步观测 CD20、CD10、bcl-6、MUM1的表达,进行生发中心样(GCB)和非生发中心样(non-GCB)分类;通过病例分析得出治疗效果及临床分期的信息,并统计分析以上各因素之间的关系。结果在60例 DLBCL 中,10例 bcl-2/IgH 阳性,18例 bcl-2基因扩增;GCB 29例(48.3%),non-GCB 31例(51.7%)。经 FISH 检测 t(14;18)阳性10例中,GCB 8例,non-GCB 2例,差异有统计学意义(P=0.031)。t(14;18)阳性及 bcl-2基因扩增的病例 bcl-2表达均增高。在36例正规 CHOP 治疗的病例中,bcl-2扩增13例,无扩增23例,bcl-2扩增的13例之治疗结果显效、部分有效、无效率分别为3例(23.1%)、4例(30.8%)和6例(46.2%);临床分期情况为Ⅰ～Ⅱ期1例(7.7%),Ⅲ～Ⅳ期12例(92.3%),这两项指标与 bcl-2不扩增的相比差异均有统计学意义(P=0.019、0.046)。结论 t(14;18)易位及 bcl-2基因扩增均是引起 DLBCL 之 bcl-2蛋白表达的原因,bcl-2阳性者与预后有关的原因难以确定,可能是由于引起其阳性表达的原因不同所致;bcl-2基因扩增与治疗效果较差及临床分期较晚有关;FISH 检测 t(14;18)染色体易位可用于 DLBCL 的分类。Objective To investigate the role of t （14; 18 ） chromosomal translocation and bcl-2 amplification in classification, clinical staging and prognostic evaluation of diffuse large B cell lymphoma （DLBCL）. Methods Sixty cases of DLBCL were included in this investigation. Microdissection of the lymphoma tissue was performed. Tissue microarray and in-situ fluorescence hybridization technique were used to detect t（ 14; 18 ） and bcl-2 amplification. The phenotypes of either germinal center B-cell-like （GCB） or non-germinal center B-cell-like （non-GCB） were determined by immunohistochemistry including CD20,CD10,bcl-6 and MUM1 （S-P method） using the tissue microarray format. Clinical staging and therapeutic response were obtained by medical record review. The relationships among different parameters were analyzed by appropriate statistical methods. Results Among 60 cases of DLBCL, bcl-2/IgH was positive in 10 cases and bcl-2 gene amplification was detected in 18 cases. Overall, 29（48.3% ） cases were GCB and 31 （51.7% ） cases were non-GCB. The t （ 14 ; 18 ） was seen in 8 （ 80. 0% ） cases of GCB and 2 （ 20. 0% ） of non-GCB. The difference was statistical significance （ P = 0. 031 ）. Over-expression of bcl-2 was seen in all cases having both t （ 14; 18 ） and bcl-2 gene amplification. Of thirty-six patients who underwent routine CHOP treatment, bcl-2 gene amplification was seen in 13 cases. In these cases, the rates of complete remission, partial remission and no change were 3 （ 23.1% ）, 4 （ 30. 8% ） and 6 （ 46. 2% ） respectively, and the clinical stages were stage Ⅰ - Ⅱ （ 1 case, 7.7% ） and stage Ⅲ - Ⅳ （ 12 cases,92. 3% ）. The clinical stages and therapeutic response were significantly different between the bcl-2 amplification cases and those without （P=0.046 and P=0.019, respectively）. Conclusions T（14;18） and/or bcl-2 gene amplification can lead to an over-expression of bcl-2 protein. The bcl-2 gene amplification correlates with worse t

关 键 词：淋巴瘤 大细胞 弥漫性 基因 BCL-2 基因扩增 易位 遗传 微阵列分析 显微切割 

分 类 号：R733.1[医药卫生—肿瘤]