MYC, BCL6 and BCL2 Genetic Alterations and Associated Phenotypes of AIDS-Related (AR) Diffuse Large B Cell Lymphomas (DLBCLs) Suggest Biologic Differences with Immunocompetent (IC) DLBCLs
S Mathew, S Gogineni, E Cesarman, DM Knowles, A Chadburn. Weill Cornell Medical College, New York, NY; Northwestern University Feinberg School of Medicine, Chicago, IL
Background: DLBCLs comprise 40% of IC and AIDS NHLs. It has been shown that IC-DLBCLs are equally of germinal center (GC) and non-GC type, 70% BCL2+, >95% EBV negative; in contrast most of AR-DLBCLs are of GC origin, <50% BCL2+ and 40% EBV+. Previously reported studies showed by FISH, 30% of IC-DLBCLs with BCL6 translocations (t), 20-40% BCL2-t/extra gene copies and <10% MYC-t. 60% of IC MYC-t cases are GC origin, 2/3 BCL2 + and 60% have >80% proliferation rate (PFR). However, the incidence of BCL2, BCL6 and MYC gene aberrations in phenotypically well-characterized AR-DLBCLs has not been determined.
Design: FISH was performed on paraffin embedded TMAs (AIDS and Cancer Specimen Resource) containing 114 AR-DLBCLs using LSI BCL2 (18q21), BCL6 (3q27) and MYC (8q24) dual color break apart probes (Abbott Vysis, Inc). The cases were evaluated for translocations (t) and extra gene copies (E). The findings were compared to reported FISH results of IC-DLBCL MYC, BCL6, BCL2 analysis and AR/IC-DLBCL GC/non-GC origin, EBV status, BCL2 protein expression (IHC) and proliferation.
Results: 67 (59%) of 114 AR-DLBCLs had results with 1 or more probes including 8 cases with9 t/E (BCL2-0/36, BCL6-3/64, MYC-6/41; 1 MYC-t/BCL6-t). Of the 6 MYC-t cases, 5 were GC origin, 5 BCL2 IHC+, 1 EBV+; Ki67 was >80% in all. AR-DLBCLs with BCL6-t (1 GC, 1 non-GC) or E (1 not GC or non-GC) were all BCL2 IHC+ and EBV negative. Only 1/8 (13%) t/E positive compared to 20/59 (34%) t/E negative AR-DLBCLs were EBV+ (p=0.2). Incidence of AR-BCL6 (5%)/BCL2-t/E (0%) is less than reported BCL6-t (30%)/BCL2-t/E (30%) in IC-DLBCLs, while MYC-t are higher (AR-15%; IC-10%). More AR MYC-t cases are of GC origin (83%), BCL2 IHC+ (83%) and have a PFR >80% (100%) than IC MYC-t cases (60%, 67%, 60%, respectively).
Conclusions: The AR-DLBCLs more often (1) lack BCL6/BCL2-t/E, (2) are MYC-t positive, and, (3) in the MYC-t cases, have aggressive phenotypic features (BCL2 IHC+, high proliferation rate) than the IC-DLBCLs implying biologic differences. In addition, the lack of MYC-t/ BCL6-t/E in EBV+ AR-DLBCLs suggest that at least some of these lesions are EBV-driven.
Wednesday, March 24, 2010 9:30 AM
Poster Session V # 175, Wednesday Morning