Cyclin D1 Positive Diffuse Large B-Cell Lymphomas Feature a Post-Germinal Center – Immunophenotype and Lack Alterations in the CCND1 Gene Locus
P Adam, T Vela-Chavez, M Cremer, K Bink, JA Ferry, F Fend, E Jaffe, L Quintanilla-Martinez. University of Tubingen, Tubingen, Germany; Technical University, Munich, Germany; Massachusetts Genaral Hospital, Boston; National Institutes of Health (NIH), Bethesda
Background: Diffuse large B-cell lymphomas (DLBCL) are a heterogeneous group of aggressive lymphomas and are generally believed to be cyclin D1 negative. However, in the last years there have been some reports of DLBCLs expressing cyclin D1. The association of cyclin D1 expression with specific histological subtypes of DLBCLs and/or in the setting of Richter´s transformation has not been studied systematically. The aims of this study were to analyse the incidence of cyclin D1 overexpression in DLBCLs and Richters transformation (RT) cases and to elucidate the possible molecular mechanism.
Design: Seventy-six cases of DLBCLs, including 67 de novo DLBCL and 9 RT cases were included in this study. Immunohistochemical stainings for CD20, CD5, CD30, BCL-2, BCL-6, CD10, MUM1, cyclin D1and Ki.67 were performed and complemented by immunofluorescence double stainings. CCND1 and c-MYC gene loci were analyzed by FISH.
Results: Of the 67 de novo DLBCLs, 13 cases (19.4%) were cyclin D1+ in >10% of the neoplastic cells. Immunofluorescence double stainings demonstrated cyclin D1 positivity in CD20+ tumor cells. Only one case of RT was cyclin D1+ (11%). To better characterize the cyclin D1+ DLBCL, seven cyclin D1+ DLBCL from other institutions were included in the analysis. The 21 cyclin D1+ DLBCL cases (20 de novo and 1 RT) displayed heterogeneous morphological patterns. All cases were negative for CD10. Bcl-6 was positive in 20 of 21 cases and MUM1 was positive in 11/14 cases. Only two cases were partially CD5+. No CCND1 gene locus alterations were identifed by FISH analysis, except for one case. No c-MYC translocations were identified.
Conclusions: 1) Cyclin D1 expression in DLBCL is not associated with a particular morphology but consistently shows a post-germinal or activated B-cell phenotype (CD10-, BCL-6+, MUM1+). 2) The abnormal expression of cyclin D1 is not associated with a t(11;14) or alterations in chromosome 11, suggesting an alternative mechanism of cyclin D1 deregulation.
Wednesday, March 24, 2010 9:30 AM
Poster Session V # 193, Wednesday Morning