[1489] Genetic Instability in Diffuse Large B-Cell Lymphomas (DLBCLs): Comparison of AIDS-Related and Immunocompetent DLBCLs

S Mathew, E Cesarman, L Pasqualucci, K Merati, D M Knowles, A Chadburn. Weill Cornell Medical College, New York, NY; Columbia University, New York, NY; GenPath, Elmwood Park, NJ; Feinberg School of Medicine, Chicago, IL

Background: Although DLBCLs compose 40% of immunocompetent (IC) and AIDS-related (AR) B cell lymphomas, our analysis of 114 AR- and 151 IC-DLBCLs showed differences in histogeneic origin (AR-DLBCLs more often germinal center (GC) origin), antigen expression (85% IC vs. 60% AR-DLBCLs express BCL2) and viral content (40% AR vs 2% IC-DLBCLs EBV+). We now examine these cases to determine if genetic differences exist.
Design: FISH was performed on TMAs generated from 114 cases submitted to the AIDS and Cancer Specimen Resource and from 131 of 151 previously studied de novo DLBCLs diagnosed at New York Presbyterian Hospital using LSI BCL2 (18q21), BCL6 (3q27) and MYC (8q24) dual color break apart probes. p53 was analyzed by IHC. Any rearrangement/gain/loss by FISH or p53 positivity was scored as abnormal. Findings in the two clinical groups were compared with histogenic origin (Hans criteria; null=not GC, non-GC), proliferation rate (Ki67) and EBER (AR only).
Results: FISH was evaluable for 1 or more probes in 67/114 AR (46 GCs, 13 non-GCs, 8 null) and 74/131 IC-DLBCLs (31 GC, 36 non-GC, 7 null). p53 IHC was evaluable in 105 AR and 122 IC-DLBCLs. 39% of AR-DLBCLs were EBV positive.

Frequency of Genetic Abnormalities:
 AR-BCL6AR-MYCAR-p53IC-BCL6IC-MYCIC-p53
GC1/45 (2%)5/29 (17%)19/67 (28%)0/182/18 (11%)10/52 (19%)
non-GC1/13 (8%)1/6 (16%)3/25 (12%)2/25 (8%)1/17 (5%)13/52 (25%)
Null1/7 (4%)0/53/13 (23%)0/30/33/18 (17%)
Total3/65 (4%)6/40 (15%)25/105 (24%)2/46 (4%)3/38 (8%)26/122 (21%)


No AR and only 2 IC-DLBCLs had BCL2-abnormal. More AR (15%) vs. IC (8%) DLBCLs had MYC-abnormal; more AR GCs (28%) compared to IC GCs (19%) were p53 positive; the reverse was true for the non-GC cases (AR=12%; IC=25%). 52 cases had results for all 3 FISH probes and p53 IHC; 7/24 (29%) IC and 14/28 (50%) AR had one or more abnormality (p=0.15); 20/21 fully analyzed abnormal cases had a proliferation rate >70%. In the fully characterized AR-DLBCLs, 63% of EBV+ cases had an abnormality, compared to 42% of EBV- cases (p=0.29).
Conclusions: AR-DLBCLs tend to exhibit more genetic abnormalities than IC-DLBCLs with a higher percentage of genetically abnormal EBV positive compared to EBV negative AR-DLBCLs. These findings suggest the immune environment promoted by HIV may foster genetic instability thereby contributing to the higher rate of lymphoma in HIV+ patients.
Category: Hematopathology

Tuesday, March 20, 2012 1:00 PM

Poster Session IV # 191, Tuesday Afternoon

 

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