219例弥漫性大B细胞淋巴瘤免疫表型及遗传学特征分析

Immunophenotypes and Cytogenetic Alterations in 219 Cases of Diffuse Large B-cell Lymphoma

目的:探讨国内弥漫性大B细胞淋巴瘤(DLBCL)免疫表型分型及BCL-2和BCL-6基因异常的分布情况。方法:应用组织芯片和免疫组织化学法及FISH技术对219例DLBCL的免疫表型及BCL-2和BCL-6基因异常进行检测,根据Hans法进行分型;并收集国内7家相关研究报道,进行综合分析。结果:本组研究结果:219例DLBCL中,非GCB型(165例,75.3%)显著高于GCB型(54例,24.7%)(P<0.001)。BCL-2基因异常共49例(25.8%),其中t(14;18)5例(2.6%)均为GCB型;BCL-2基因扩增44例(23.2%),GCB型4例(8.5%),非GCB型40例(28.0%),有显著性差异(P=0.013)。BCL-6基因重排共42例(22.1%),GCB型7例(14.9%),非GCB型35例(24.5%),差异无统计学意义(P=0.189)。BCL-2基因扩增和BCL-6基因重排呈显著负相关(r=-0.180,P=0.013) 8组综合分析:1 259例中非GCB型(879例,69.8%)明显高于GCB型(380例,30.2%)(P<0.001);免疫表型中CD10和MUMl阳性率组间差异较小(P=0.047和P=0.048),而BCL-6及BCL-2阳性率组间存在明显差异(P<0.001)。结论:我国DLBCL患者在主要免疫表型和遗传学特征方面具有独特性,对此值得进行深入研究。

Objective： To investigate the immunophenotypes, subtypes based on Hans algorithm, and alterations of Bcl-2 and Bcl-6 gene in diffuse large B-cell lymphoma （ DLBCL ） from Chinese patients. Methods： The expression of CDI0, BCL-6, MUM 1, BCL-2, Ki67 and other markers were detected by immunohistochemistry in tissue microarrays of 219 DLBCL cases. Hans algorithm was applied to classify DLBCL into GCB and non-GCB subtypes. Interphase fluorescence in situ hybridization （ FISH ） was used to detect the incidence of Bcl-2 and Bcl-6 gene alterations. Other seven studies published in the last two years on DLBCL from China were collected and analyzed. Results： （1） This study： ① of 219 DLBCL cases, non-GCB subtype （ 165 cases, 75.3 % ） was significantly more common than GCB subtype （ 54 cases, 24.7 % ） （ P 〈 0.001 ）. ② Bcl-2 gene alteration was detected in 49 cases （ 25.8 % ）, including 5 cases with the t （ 14 ; 18 ） （ 2.6 % ） which all existed in GCB subtype, and 44 cases of Bcl-2 amplification （ 23.2 % ） which existed in GCB subtype in 4 cases （ 8.5 % ） and in non-GCB subtype in 40 cases （ 28.0 % ） （ P = 0.013）. ③ Bcl-6 gene rearrangement was detected in 42 cases （ 22.1% ）, which was in GCB in 7 cases （ 14.9 % ） and was in non-GCB in 35 cases （ 24.5 % ） （ P = 0.189）. ④ a significant negative correlation between Bcl-2 gene amplification and Bcl-6 gene rearrangement was seen （ r = - 0.179 6, P = 0.016 8 ）. Amongst 5 cases having the t （ 14 ; 18 ） translocation, 2 cases accompanied by Bcl-6 gene rearrangement. Forty-nine cases with Bcl-2 gene alterations including translocation and amplification were all but one expressing BCL-2 protein, and there was no significant association between Bcl-6 gene rearrangement and BCL-6 protein expression （ P = 0.726 ）. ⑤ there was no significant difference between nodal and extranodal DLBCLs in immunophenotypes, subtypes based on Hans algorithm, and Bcl-2 and Bcl-6 gene alterations （ P = 0.462, P = 0.426 and P = 0.167 ）. （2） Comprehensive analysis of eight studies：of the total 1,259 cases, non-GCB subtype （ 879 cases, 69.8 % ） was significantly more common than GCB subtype （ 380 cases, 30.2 % ） （ P 〈 0.001 ）. Conclusion： There are some distinctive features on immunophenotypes and cytogenetic alterations in DLBCL of Chinese patients, which need elucidation by more studies.