应用细胞芯片荧光原位杂交技术检测弥漫性大B细胞淋巴瘤3q27重排  

Detection of 3q27 chromosomal abnormality in diffuse large B cell lymphoma using FISH on cell mlcroarray

作　　者：蒋会勇[1,2] 李慧灵[1] 赵彤[1] 

机构地区：[1]南方医科大学附属南方医院病理科,广州510515 [2]中国人民解放军沈阳军区总医院普通外科,沈阳110001

出　　处：《中华医学遗传学杂志》2008年第1期73-77,共5页Chinese Journal of Medical Genetics

基　　金：广东省社会发展攻关项目（B30301）;广州市科技计划项目（2002Z3-E4061）

摘　　要：目的研究3q27染色体断裂及bcl-6基因扩增与弥漫性大B细胞淋巴瘤（diffuse large B-cell lymphoma, DLBCL）与其分子分类及治疗效果、临床分期的关系。方法用细胞芯片荧光原位杂交（fluomscence in situ hybridization, FISH）技术对60例DLBCL的标本进行3q27染色体断裂及bcl-6扩增检测；采用免疫组化S-P法在组织微阵列上同步观测CD20、CD10、bel-6、MUM1的表达，进行生发中心样（genninat center B-cell-like，GCB）和非生发中心样（non-germinal center B-cell．like，non-GCB）分子分类；通过对临床病例的分析得出与治疗效果及临床分期的信息；统计分析以上各因素之间的关系。结果在60例DLBCL中，GCB占48．3％（29／60），non-GCB占51．7％（31／60）。FISH结果显示，3q27断裂阳性15例，bcl-6基因扩增阳性22例。存在3q27染色体断裂的15例中BCL-6蛋白表达阳性3例（20．0％），阴性12例（80．0％），与无3q27染色体断裂者相比其BCL-6蛋白表达率降低（P=0．017）。在60例DLBCL中，bcl-6扩增22例，其中GCB5例（22．7％），non-GCB17例（77．3％），与无bcl-6扩增者相比差异有统计学意义（P=0．003）。在36例经正规CHOP治疗的DLBCL中，bcl-6扩增15例，其治疗效果显效、部分有效、无效分别为4（26．7％）、4（26．7％）、7（46．7％），与无bcl-6扩增的病例比差异有统计学意义（P=0．016）。bcl-6扩增与BCL-6蛋白表达及临床分期的关系差异无统计学。BCL-6蛋白表达阳性组、阴性组与治疗效果及临床分期关系差异无统计学意义。结论存在bcl-6基因断裂的病例，其BCL-6蛋白表达率低。存在bcl-6基因扩增的DLBCL多数为non-GCB，并且治疗效果差，临床分期较晚，可能与DLBCL晚期染色体呈多倍体增加的趋势有关。Objective To investigate the association of 3q27 chromosome rearrangement with bcl-6 gene amplification and the molecular classification, therapeutic egicacies, and clinical stages in diffuse large B cell lymphoma （DL- BC）. Methods The newly invented cell microarray was used to detect 3q27 chromosome rearrangement andbcl-6 gene amplification in 60 cases of DLBCL by fluorescence/n situ hybridization （FISH）. The molecular classification of germinal center B-cell-like （GCB） and non-germinal center B-cell-like （non-GCB） was investigated by analyzing the expression of CD20,CD10,bcl-6 and MUM1 simultaneously by immunohistochemieal S-P method and tissue mieroarray. The information of therapeutic efficacies and clinical stages was obtained by analyzing clinical cases. The relationships among the factors were analyzedby statistics. Results In60 cases of DLBCL, 48.3%（29/60） wereGCBand51.7%（31/60） were non-GCB. The 3q27 chromosome rearrangement and bcl-6 gene amplification were present in 15 and 22 cases respectively. In 15 cases with 3q27 rearrangement, bcl-6 protein expression was positive in 3（20.0%）, which was significantly different from that in cases without 3q27 rearrangement （ P =0.017）. In 60 cases of DLBCL, bcl-6 gene amplification was present in 22 cases, in which 5 （22.7 % ） were GCB and 17（77.3 % ） were non-GCB, which was significantly different from that in cases without bcl-6 gene amplification （ P = 0.003）. In 36 cases undergoing the normal CHOP program treatment, bcl-6 gene amplification was present in 15 cases and the rates of the complete remission, partial remission and no change were 4（26.7%）, 4（26.7%） and 7（46.7%） respectively, and again it was significantly different from that in cases without bcl-6 gene amplification （P = 0.016）. There were no statistical significances among bcl-6 gene, BCL- 6 protein expression, and clinical stages. Cases with BCL-6 protein positive mM negative expression were not correlated with therapeutic eltlcacies and

关 键 词：弥漫性大B细胞淋巴瘤 BCL-6基因 染色体断裂 基因扩增 细胞核阵列分析 

分 类 号：R733.1[医药卫生—肿瘤]