Department of Pathology, Herlev and Gentofte Hospital, Herlev, Denmark.
Department of Hematology, Herlev and Gentofte Hospital, Herlev, Denmark.
Eur J Haematol. 2019 May;102(5):395-406. doi: 10.1111/ejh.13219. Epub 2019 Mar 6.
In patients with large B-cell lymphoma (LBCL) according to WHO, the prognostic significance of MYC translocation is still not sufficiently clarified. We therefore aimed to investigate whether prognostication could be improved in patients with MYC translocation positive LBCL by additional stratification according to MYC and BCL2 protein expression levels or MYC translocation partner gene as well as concurrent BCL2 and/or BCL6 translocation (DH).
From an unselected consecutive cohort of >600 patients with LBCL investigated with fluorescent in situ hybridization (FISH), 64 patients were diagnosed with MYC translocation positive LBCL and included in the study. They were further investigated for supplemental translocations with FISH and MYC and BCL2 protein expression with immunohistochemistry (IHC).
MYC expression >75% was associated with both reduced progression-free survival (PFS) and overall survival (OS) (PFS: HR 6.8 (95% CI 1.5-31), P = 0.004. OS: HR 4.3 (95% CI 0.9-21), P = 0.05). Immunoglobulin (IG) MYC translocation partner gene was related to high MYC protein expression (P = 0.047) but was not prognostic for PFS (P = 0.8) or OS (P = 0.6). DH did not confer a worse outcome compared to MYC single hit (SH). These findings were confirmed in a comparable, independent validation cohort of 28 patients with MYC translocation positive LBCL. All patients included in the survival analyses were treated with R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) or R-CHOEP (R-CHOP + etoposide).
These findings suggest that in patients with LBCL stratification by MYC protein expression level significantly improves the prognostic impact associated with MYC translocation.
在世界卫生组织（WHO）定义的大 B 细胞淋巴瘤（LBCL）患者中，MYC 易位的预后意义仍未得到充分阐明。因此，我们旨在通过根据 MYC 和 BCL2 蛋白表达水平或 MYC 易位伙伴基因以及同时存在的 BCL2 和/或 BCL6 易位（DH）对 MYC 易位阳性 LBCL 患者进行进一步分层，来探讨是否可以改善预后。
从 >600 例经荧光原位杂交（FISH）检查的 LBCL 患者的未选择连续队列中，诊断出 64 例 MYC 易位阳性 LBCL 患者，并纳入本研究。他们进一步接受 FISH 检查以确定补充易位，以及通过免疫组织化学（IHC）检测 MYC 和 BCL2 蛋白表达。
MYC 表达 >75%与无进展生存期（PFS）和总生存期（OS）降低均相关（PFS：HR 6.8（95% CI 1.5-31），P=0.004。OS：HR 4.3（95% CI 0.9-21），P=0.05）。免疫球蛋白（IG）MYC 易位伙伴基因与高 MYC 蛋白表达相关（P=0.047），但与 PFS 无关（P=0.8）或 OS 无关（P=0.6）。DH 与 MYC 单打击（SH）相比并未导致更差的结局。在另一项 28 例 MYC 易位阳性 LBCL 患者的可比独立验证队列中证实了这些发现。所有纳入生存分析的患者均接受 R-CHOP（利妥昔单抗、环磷酰胺、多柔比星、长春新碱和泼尼松）或 R-CHOEP（R-CHOP+依托泊苷）治疗。
这些发现表明，在 LBCL 患者中，根据 MYC 蛋白表达水平进行分层可显著改善与 MYC 易位相关的预后影响。
