Gene Expression Profiling of Diffuse Large B-Cell Lymphomas Supervised by CD21 Expression.

Abstract

We have reported that CD21 expression in tumor cells is a favorable prognostic factor in diffuse large B-cell lymphomas (DLBCLs)(Ogawa S, et al. Br J Haematol , 2004; 125: 180–86). In the present study, we investigated the relationship between CD21 expression and the groups of germinal center B-cell-like (GCB) DLBCLs and activated B-cell-like (ABC) DLBCLs. The diagnosis of DLBCL was made according to the WHO Classification. CD21 in tumor cells was examined by means of immunohistochemistry using frozen sections. Forty cases of DLBCLs were investigated using Agilent 44K human oligo-microarrays (Agilent Technologies, Palo Alto, CA). GCB and ABC DLBCLs were identified based on Rosenwald's gene set (Rosenwald A, et al. N Engl J Med , 2002; 346: 1937–47). Four cases (10 %) of 40 DLBCLs were found to be GCB DLBCLs, and 36 cases ABC DLBCLs. Incidence of CD21-positive cases was 50% (2/4) in GCB DLBCLs and 39% (14/36) in ABC DLBCLs. Overall survival of 36 patient with ABC DLBCLs were shown in Fig.1. [Display omitted] Signature genes to distinguish between CD21-positive and CD21-negative DLBCLs were as follows; IgM (P=0.00017), CCR6 (P=0.0011), IL7 (P=0.0017), IgK (P=0.0037), EBI2 (P=0.0066), CD24 (P=0.0099) etc. were overexpressed in CD21-negative DLBCLs, and CR2 (CD21) (P=0.0010), MKNK2 (P=0.0028), LMO2 (P=0.00478), CDKN2A (P=0.0059), PDE8B (P=0.0066) etc. were overexpressed in CD21-positive DLBCLs. In 40 cases of DLBCLs, overall survival of patients with sIgM-positive DLBCL was significantly worse than that of patients with sIgM-negative DLBCL (P=0.023). Furthermore, in 216 consecutive cases of DLBCLs analyzed by immunohistochemistry using frozen sections from 1987 to 2004, overall survival according to sIgM expression was significantly different (P=0.013).In conclusion,CD21 expression was a favorable prognostic factor in ABC DLBCLs.A top feature gene to distinguish between CD21-positive and CD21-negative DLBCLs was IgM. CD21 expression seemed to be related to the differentiation level of lymphoma cells.sIgM expression itself was a poor prognostic factor in ABC DLBCLs and in whole DLBCLs.