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

  • 摘要:
      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MUM1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。

     

    Abstract:
      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 CD10, BCL-6, MUM1, 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 andP = 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.

     

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