BCL3 rearrangement, amplification and expression in diffuse large B-cell lymphoma

Aim of the study is to investigate diffuse large B-cell lymphoma (DLBCL) for the presence of BCL3 gene rearrangement and protein expression and to correlate these with immunophenotypic subsets of DLBCL. We aimed to investigate the pathogenetic implication of BCL3 in DLBCL.

Tissue microarray sections from 78 DLBCLs were evaluated for BCL3 protein expression using immunohistochemistry and for BCL3 and IGH rearrangement using Fluorescent in situ hybridisation (FISH) with split-apart probes. BCL3 expression was positive in 36/78 cases, of which BCL3 rearrangement was seen seen in one case. Three additional cases showed evidence of trisomy of BCL3/chromosome 19, and two of these three cases showed BCL3 expression. The four cases with FISH-detectable abnormalities showed MUM1 expression and had a non-germinal center (GC) phenotype. The median [and inter-quartile range (IQR)] percentage of BCL3-positive cells in MUM1-positive and MUM1-negative subsets was 65% (5-85%) and 5% (0-20%), respectively (P < 0.001). The median (IQR) percentage of BCL3-positive cells among GC and non-GC subsets of DLBCLs was 12% (12-81%) and 60% (6-87%), respectively (P = 0.022).

Rearrangement or amplification involving the BCL3 gene is a rare event in DLBCL but is likely to play a role in the pathogenesis of a minority of de novo DLBCL. BCL3 over-expression is more frequent and occurs in the absence of rearrangement or amplification and is a feature of the non-GC subset of DLBCL.