BRG1 Expression in Diffuse Large B Cell Lymphoma (DLBCL) Is Associated with Advanced Disease Stage

Background: BRG1 is a component of the highly conserved multisubunit, 2.0-MDa mammalian transcriptional coactivator complex SWI/SNF. This chromatin-remodeling complex is critical for the regulation of gene transcription, thereby controlling diverse cellular processes including differentiation, proliferation, tumorigenesis and DNA repair. BRG1 gene is frequently down regulated or conversely, in some cases, up regulated in cancer cell lines and tumors, implicating that BRG1 may regulate cancer proliferation and progression. BRG1 is currently considered a potential selective therapeutic target. BRG1 expression level has been related to cancer cell migration and invasion and studies have suggested that BRG1 may serve as a prognostic marker in certain cancers. Few studies exist on expression of BRG1 in lymphoproliferative disorders and diffuse large B cell lymphoma (DLBCL) in particular. Our study was aimed at determining the immunohistochemical expression of the BRG1 protein in DLBCL and its potential association with clinicopathologic variables.

Design: Formalin-fixed, paraffin embedded sections from 49 Diffuse Large B-cell Lymphomas (DLBCL), were immunostained by a manual method (DAKO LSAB+ System-HRP) using rabbit monoclonal BRG1 (Abcam, Cambridge, MA) antibody. Nuclear and cytoplasmic immunoreactivity was semiquantitatively assessed in all cases. Scoring was based on staining intensity (weak, moderate, intense) and percentage of positive tumor cells (focal <= 10%, regional 11-50%, diffuse >50%). Results were correlated with clinicopathologic variables.

Results: BRG1 immunoreactivity was predominately nuclear. Intense diffuse nuclear BRG1 overexpression was observed in 22/49 (45%) cases and correlated with tumor stage [73% stage 4 vs 63% stage 3 vs 40% stage 2 vs 13% stage 1, (p=0.005)]. There were no other correlations that reached statistical significance.

Conclusion: BRG1 nuclear expression is increased in DLBCL and is associated with advanced tumor stage. This association with an important adverse prognostic indicator warrants further study of BRG1 expression and its potential as a selective therapeutic target in DLBCL.