Prognostic impact of “MYC/BCL-2 double expressors” in diffuse large B-cell lymphoma

Background: The presence of MYC and BCL2 and/or BCL6 rearrangements (double-/tripe-hit lymphoma) in DLBCL seems to be associated with a dismal bad prognosis On the other hand, immunohistochemical (IHC) analysis has revealed that concurrent protein expression of MYC and BCL2 in DLBCL (“so-called double expressors”) could have a prognostic impact asssociated with a nongerminal center phenotype. Objectives: The aim of this study was to clarify the clinical prognostic value of immunostaining and chromosomal translocation of MYC, BCL2, and BCL6 in a series of 102 adults consecutively diagnosed of DLBCL in our institution from 2001 to 2015. Patients and Methods: One hundred and two patients were included. MYC, BCL2, and BCL6 rearrangements were detected by FISH, and expressions of MYC, BCL2, and BCL6 proteins were investigated by IHC. Some of them were analyzed retrospectively in tissue microarray (TMA). Dual positivity for MYC (cutoff >40%) and BCl2 (cutoff >50%) proteins identified a double protein expressor (DE) phenotype. Cell of origin (COO) classification was achieved using the Hans algorithm. Overall survival (OS) and time to progression (TTP) were estimated by the Kaplan-Meier method. Results: Median age of the series was 67 years (range 26-89) with a slight male predominance 53 (52%). Median follow-up period was 78 months (range, 0-168). All patients were treated with immunochemotherapy schedules, mostly R-CHOP and some cases methotrexate/cytarabine based. COO determination revealed 43 (42,6%) cases to be GCB subtype and 57 (57,4%) cases ABC. The main clinical characteristics are detailed in Table 1. Only 10 of cases (10,2%) had MYC and BCL2 rearrangements (DHIT). No differences in terms of OS and TTP between DHIT patients (P = ,57 and P = ,61). MYC protein overexpression occurred in 32 (31,4%) patients and 20 (19,6%) of them overexpressed both MYC and BCL2. As had been reported before, DE cases appear more common in the ABC subtype (75%). DE patients had significantly worse 5-year OS and TTP at 5 years than non-DE (47% versus 66%, P = .015 and 64% vs 84%, P = ,055, log-rank test), as shown in Figure 1. Eleven DE patients needed a minimum of two lines of treatment, and three of them (15%) received an autologous transplant consolidation. A total of 75% of DE patients belonged to the nongerminal center group. Stratifying all patients into GCB and non-GCB subtypes, only ABC had significantly worse both OS and PFS. Keywords: “double-hit” lymphomas; activated B-cell–like (ABC)