弥漫性大 B 细胞淋巴瘤中 MYC、BCL2 和/或 BCL6 额外拷贝的预后影响：与双/三打击淋巴瘤和双表达淋巴瘤的比较。
Prognostic impact of diffuse large B-cell lymphoma with extra copies of MYC, BCL2 and/or BCL6: comparison with double/triple hit lymphoma and double expressor lymphoma.
机构信息
Department of Pathology, Peking University First Hospital, 8 Xishiku Street, Xicheng District, Beijing, 100034, China.
Department of Pathology, Peking University Health Science Center, Beijing, 100191, China.
出版信息
Diagn Pathol. 2019 Jul 17;14(1):81. doi: 10.1186/s13000-019-0856-7.
BACKGROUND
The poor outcome of high-grade B-cell lymphoma, with rearrangements of MYC, BCL2 and/or BCL6, also known as double-hit lymphoma or triple-hit lymphoma (DHL or THL), has been well documented, while the clinical significance of extra copies of MYC, BCL2 or BCL6 are still less well known.
METHODS
In total, 130 cases of diffuse large B-cell lymphoma, not otherwise specified (DLBCL-NOS) were included in our study. Fluorescence in situ hybridization and immunohistochemistry were performed in all cases to evaluate the genetic status and protein expression levels of MYC, BCL2 and BCL6.
RESULTS
Among the 130 cases of DLBCL, the prevalence rates of extra copies of MYC, BCL2 and BCL6 were 10.8, 20.0 and 14.6%, respectively, and the corresponding rates of gene rearrangement were 10.0, 14.6 and 16.9%, respectively. In total, 7.7% (10/130) of patients were DHL/THL; 9.2% (12/130) of patients were DLBCL with MYC and BCL2 and/or BCL6 gene abnormalities including rearrangements or extra copies, while excluded DHL/THL. The positive protein expression rates of MYC, BCL2 and BCL6 were 46.9% (61), 75.4% (98) and 70.0% (91), respectively. Among the 51 cases with MYC/BCL2 co-expression, 14 cases showed concurrence of MYC, BCL2 and/or BCL6 genetic abnormalities, and the remaining 37 cases were classified as double-expressor lymphoma (DEL). MYC and BCL2 rearrangement and BCL2 extra copies were all associated with upregulated protein expression. Cases with concurrence of MYC, BCL2 and/or BCL6 genetic abnormalities were both associated with MYC/BCL2 co-expression. Patients with concurrence of MYC, BCL2 and/or BCL6 genetic abnormalities excluded DHL/THL had shorter OS (P < 0.001) than patients with DLBCL with no genetic change, and showed no statistical different with patients with DHL/THL (P = 0.419). Extra copies of MYC was independent prognostic factors for DLBCL.
CONCLUSIONS
Patients with MYC and BCL2 and/or BCL6 gene extra copies might show a trend towards poor prognosis, and the detection of extra copies of MYC, BCL2 and BCL6 might deserve more attention.
背景
具有 MYC、BCL2 和/或 BCL6 重排的高级别 B 细胞淋巴瘤（也称为双打击淋巴瘤或三打击淋巴瘤[DHL 或 THL]）的预后较差，这一点已得到充分证实，而 MYC、BCL2 或 BCL6 额外拷贝的临床意义仍知之甚少。
方法
我们的研究共纳入 130 例未分类弥漫性大 B 细胞淋巴瘤（DLBCL-NOS）患者。所有病例均行荧光原位杂交和免疫组化检查，以评估 MYC、BCL2 和 BCL6 的遗传状态和蛋白表达水平。
结果
在 130 例 DLBCL 中，MYC 额外拷贝、BCL2 额外拷贝和 BCL6 额外拷贝的发生率分别为 10.8%、20.0%和 14.6%，相应的基因重排率分别为 10.0%、14.6%和 16.9%。总共有 7.7%（10/130）的患者为 DHL/THL；9.2%（12/130）的患者为 MYC 和 BCL2 基因异常的 DLBCL，包括重排或额外拷贝，但排除 DHL/THL。MYC、BCL2 和 BCL6 的阳性蛋白表达率分别为 46.9%（61 例）、75.4%（98 例）和 70.0%（91 例）。在 51 例 MYC/BCL2 共表达的患者中，有 14 例同时存在 MYC、BCL2 和/或 BCL6 遗传异常，其余 37 例被归类为双表达淋巴瘤（DEL）。MYC 和 BCL2 重排以及 BCL2 额外拷贝均与蛋白表达上调有关。同时存在 MYC、BCL2 和/或 BCL6 遗传异常的病例均与 MYC/BCL2 共表达有关。同时存在 MYC、BCL2 和/或 BCL6 遗传异常的患者排除 DHL/THL 后，其总生存（OS）明显短于无基因改变的 DLBCL 患者（P<0.001），但与 DHL/THL 患者相比，差异无统计学意义（P=0.419）。MYC 额外拷贝是 DLBCL 的独立预后因素。
结论
存在 MYC 和 BCL2 和/或 BCL6 基因额外拷贝的患者可能预后较差，检测 MYC、BCL2 和 BCL6 的额外拷贝可能值得进一步关注。
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