摘要目的 探讨多重基因异常在弥漫大B细胞淋巴瘤(DLBCL)中的发生情况及其与蛋白高表达之间的关系.方法 收集2012年1月至2016年12月确诊的DLBCL非特指型患者50例,采用免疫组织化学法检测c-myc、bcl-2及bcl-6蛋白表达情况,采用间期荧光原位杂交(I-FISH)方法检测3个基因异常情况.结果 50例DLBCL患者中,男性27例,女性23例;年龄3~85岁,中位年龄50岁.发病部位:淋巴结23例(46.00%),结外27例(54.00%),以胃肠道最为多见(13例,48.15%).免疫组织化学检测c-myc蛋白阳性率94.00%(47/50),阳性细胞超过40%者41例(82.00%);bcl-2蛋白阳性率84.00%(42/50),阳性细胞超过70%者38例(76.00%);18例(36.00%)同时高表达c-myc和bcl-2.FISH检测结果显示,7例(14.00%)c-myc断裂,2例(4.00%)扩增;6例(12.00%)bcl-2断裂,4例(8.00%)扩增;8例(16.00%)bcl-6断裂,3例(6.00%)扩增,1例(2.00%)同时断裂及扩增;4例(8.00%)检测到多重基因异常,其中1例(2.00%)c-myc合并bcl-2基因异常,2例(4.00%)c-myc合并bcl-6基因异常,为双重打击淋巴瘤(DHL),1例(2.00%)同时检测到c-myc、bcl-2及bcl-6基因异常,为三重打击淋巴瘤(THL).4例多重基因异常病例中,3例起源于生发中心B细胞(GCB),1例起源于非GCB.18例c-myc和bcl-2蛋白双高表达组仅有3例(16.67%)检测到多重基因异常,包括2例DHL和1例THL.结论 多重基因异常在DLBCL中的检出率为8.00%.基因异常与蛋白高表达之间无明显相关性,DHL的检出依赖于分子遗传学检测.

abstractsObjective To study the frequency of diffuse large B-cell lymphoma (DLBCL) with multi-genetic alteration, and its correlation with c-myc, bcl-2 and bcl-6 protein expression. Methods 50 cases diagnosed with DLBCL from January 2012 to December 2016 were collected. The expression of c-myc, bcl-2 and bcl-6 was analyzed by immunohistochemistry. Interphase fluorescence in situ hybridization (I-FISH) analysis was performed to identify the genetic alteration of c-myc, bcl-2 and bcl-6. Results In all cases, there were 27 males and 23 females with a median age of 50 years (range: 3-85 years). 23 (46.00 %) cases were defined as primary nodal DLBCL and 27 (54.00 %) cases were primary extra-nodal DLBCL, with gastrointestinal tract (48.15 %, 13/27) being the most common site of involvement. c-myc protein expression was detected in 94.00 % (47/50) cases, in which 82.00 % (41/47) cases exhibited high levels of c-myc expression with positive nuclear staining observed in over 40.00 % of tumor cells. The positive rate of bcl-2 protein was 84.00 % (42/50), 76 % (38/50) cases presented with high-level bcl-2 expression. Concurrent high expression of c-myc and bcl-2 were presented in 18 cases (36.00%). FISH analysis demonstrated c-myc gene rearrangement in 7 cases (14.00 %) and amplification in 2 cases (4.00 %). bcl-2 gene rearrangement was detected in 6 cases (12.00 %) and 4 cases (8.00 %) exhibited gene amplification. bcl-6 gene rearrangement was identified in 8 cases (16.00%), amplification in 3 cases (6.00%), and 1 case concomitantly harbored the rearrangement and amplification of bcl-6. Multi-genetic alterations were defined in 4 cases with 3 cases fulfilling the criteria for double-hit lymphoma (DHL) and 1 case for triple-hit lymphoma (THL). For the cases with concomitant high-level expression of c-myc and bcl-2 proteins, 3 cases (16.67 %) was detected with multi-genetic alterations, including 2 cases for DHL and 1 case for THL. Conclusions The proportion of DLBCL with multi-genetic alterations is 8.00 % in this study. The genetic alterations are not consistently correlated with the protein expression. The molecular genetic testing is reliable for the identification of DHL.