Jun B Expression Is Associated with Non-GC (Germinal Center) B Cell Differentiation Immunophenotype, and Jun B and Jun D with High Proliferation of Tumor Cells in DLBCL.
Alexandra Papoudou-Bai, Anna Batistatou, Eleftheria Hatzimichael, Aggeliki Dasoula, Panagiotis Kanavaros, Vasiliki Malamou-Mitsi. Medical School, University of Ioannina, Greece
Background: The Jun family includes c-Jun, Jun B and Jun D that are components of the activator protein-1 (AP-1) transcription factor complex involved in cell proliferation and apoptosis. Recent evidence suggests that c-Jun and Jun B are expressed in classical Hodgkin lymphomas and CD30+ non-Hodgkin lymphomas.
Design: Therefore, we investigated 130 cases of DLBCL for the expression of c-Jun, Jun B and Jun D, in relation to the B-cell differentiation phenotype, the cell cycle/proliferation profile and the apoptosis profile. 41 cases had a GC (Germinal Center) and 89 cases a non-GC B-cell differentiation phenotype. In a subset of cases with low Jun B expression, we performed MSP (methylation specific PCR) in order to investigate whether methylation of the JunB promoter correlates with silencing of the gene.
Results: Phospho-c-Jun, Jun B and Jun D expression was found in 59/103 (67%), 100/103 (97%) and 94/98 (97%) cases of DLBCL, respectively. Jun B expression was positively associated with Ki-67 (p=0.032), Cyclin A (p=0.042), Cyclin B (p=0.016), Cyclin D2 (p=0.037), Cyclin E (p=0.001), CD30 (p<0.005), MUM-1/IRF-4 (p<0.005), and non-GC phenotype (p=0.006), but negatively associated with CD10 (p<0.005). Jun D was positively associated with Ki-67 (p=0.01), Cyclin E (p=0.007) and Bcl-6 (p=0.03). Phospho-c-Jun was positively associated with CD30 (p=0.003) and MUM-1 (p=0.030). Methylation of the Jun B promoter was found in 17/20 of the cases with low Jun B expression.
Conclusions: On the basis of the association between Jun B and Jun D and high proliferation, we suggest that increased Jun B and Jun D expression may be involved in their pathogenesis by favoring tumor cell proliferation in DLBCL. The association between Jun B and non-GC phenotype may reflect NFk-B control of Jun B in view of previous findings that Jun B is under NFk-B control in Hodgkin lymphomas and NFk-B is activated in non-GC DLBCL. The association between Jun D and Bcl-6 expression is in line with data that Jun D is a major enhancer molecule of Bcl-6 in mouse GC B-cells. Aberrant methylation of the Jun B promoter may be the underlying mechanism in the cases with low Jun B expression.
Wednesday, March 2, 2011 1:00 PM
Poster Session VI # 208, Wednesday Afternoon