Causes and consequences of BCL2 overexpression in diffuse large B-cell lymphoma

We investigated the frequency of bcl-2 protein overexpression in 80 diffuse large B-cell lymphoma (DLBCL) patients using both Western blotting and imm unohistochemistry (IHC). Fifty-nine percent of the DLBCLs overexpressed bcl -2 protein by Western blot and 52% by IHC. The two methods usually gave con cordant results (p=0.005), but 14 (21 %) out of the 67 cases that were anal yzed by both methods were positive by Western blot and negative by IHC, and 8 (12%) cases vice versa. Bcl-2 overexpression by IHC was associated with poor response to chemotherapy and poor survival, whereas these associations were not found when bcl-2 overexpression was determined by Western blottin g. The molecular mechanisms leading to bcl-2 overexpression were evaluated by PCR, karyotype analysis, and comparative genomic hybridization (CGH). Wh en studied by PCR and/or karyotype analysis, 12 (15%) of the 80 cases had t ranslocation (14;18)(q32;q21). All 12 lymphomas with (14;18)(q32;q21) trans location had bcl-2 overexpression by Western blot as compared with 35 (51 % ) of the 68 lymphomas without translocation (p=0.001). Ten (29%) out of 34 cases that were analyzed by CGH showed amplification of chromosome 18 in wh ich the BCL2 gene is located, and all cases showed bcl-2 overexpression by both Western blot and IHC. The results suggest that gene amplification and translocation are at least equally common mechanisms causing bcl-2 protein overexpression in DLBCL. Bcl-2 protein overexpression as determined by IHC is associated with poor response to chemotherapy and poor survival.