Submitted September 8, 2008
Accepted November 14, 2008
Diffuse large B cell lymphoma: reduced CD20 expression is associated with an inferior survival
Nathalie A Johnson, Merrill Boyle, Ali Bashashati, Stephen Leach, Angela Brooks-Wilson, Laurie H Sehn, Mukesh Chhanabhai, Ryan R Brinkman, Joseph M. Connors, Andrew P Weng, and Randy D Gascoyne*
Department of Pathology and Laboratory Medicine, British Columbia Cancer Agency, Vancouver, BC, Canada
Terry Fox Laboratory, British Columbia Cancer Research Center, Vancouver, BC, Canada
Canada's Michael Smith Genome Sciences Centre, British Columbia Cancer Agency and the University of British Columbia, Vancouver, BC, Canada
Department of Medical Oncology, British Columbia Cancer Agency and the University of British Columbia, Vancouver, BC, Canada
* Corresponding author; email: rgascoyn{at}bccancer.bc.ca.
CD19 and CD20 are B cell specific antigens whose expression is heterogeneous when analyzed by flow cytometry (FCM). We determined the association between CD20 expression and clinical outcome in patients with diffuse large B cell lymphoma (DLBCL). The mean fluorescence intensity (MFI) of CD20 and CD19 was determined by FCM and the cytoplasmic expression of CD20 was determined by immunohistochemistry (IHC) on 272 diagnostic DLBCL samples. Exon 5 of the MS4A1 gene coding for the extracellular component of the CD20 antigen was sequenced in 15 samples. 43/272 (16%) samples had reduced CD20 expression by FCM, of these 35 (13%) had bright CD19 expression. The latter had a markedly inferior survival when treated with CHOP or R-CHOP (median survival of 1.2 and 3.0 years versus not reached for the others, p = 0.00001 and p = 0.001), independent of the international prognostic index. 41/43 samples with reduced CD20 expression by FCM had strong staining for CD20 by IHC. There were no mutations in exon 5 of the MS4A1 gene to explain the discrepancy between FCM and IHC. CD20 and CD19 expression by FCM should be determined on all biopsies of patients with DLBCL because reduced CD20 expression cannot be reliably detected by IHC.
