title: Diffuse large B-cell lymphoma: reduced CD20 expression is associated with an inferior survival.
abstract: 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 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. A total of 43 of 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 cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) or rituximab-CHOP (R-CHOP; median survival of 1.2 and 3.0 years vs not reached for the others, P < .001 and P = .001), independent of the International Prognostic Index. A total of 41 of 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.
authors.affiliation: Department of Pathology and Laboratory Medicine, British Columbia Cancer Agency, Vancouver, Canada.
authors.forename: Nathalie A
authors.initials: NA
authors.lastname: Johnson
authors.forename: Merrill
authors.initials: M
authors.lastname: Boyle
authors.forename: Ali
authors.initials: A
authors.lastname: Bashashati
authors.forename: Stephen
authors.initials: S
authors.lastname: Leach
authors.forename: Angela
authors.initials: A
authors.lastname: Brooks-Wilson
authors.forename: Laurie H
authors.initials: LH
authors.lastname: Sehn
authors.forename: Mukesh
authors.initials: M
authors.lastname: Chhanabhai
authors.forename: Ryan R
authors.initials: RR
authors.lastname: Brinkman
authors.forename: Joseph M
authors.initials: JM
authors.lastname: Connors
authors.forename: Andrew P
authors.initials: AP
authors.lastname: Weng
authors.forename: Randy D
authors.initials: RD
authors.lastname: Gascoyne
mesh_terms: D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D058846:Antibodies, Monoclonal, Murine-Derived; D018941:Antigens, CD19 / Q000096:biosynthesis; D018951:Antigens, CD20 / Q000096:biosynthesis*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage; D003520:Cyclophosphamide / Q000008:administration & dosage; D018572:Disease-Free Survival; D004317:Doxorubicin / Q000008:administration & dosage; D005260:Female; D005434:Flow Cytometry; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D016403:Lymphoma, Large B-Cell, Diffuse / Q000188:drug therapy / Q000378:metabolism* / Q000401:mortality* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000096:biosynthesis*; D011241:Prednisone / Q000008:administration & dosage; D012189:Retrospective Studies; D000069283:Rituximab; D015996:Survival Rate; D014750:Vincristine / Q000008:administration & dosage
chemical_list: D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D018941:Antigens, CD19; D018951:Antigens, CD20; D009363:Neoplasm Proteins; D000069283:Rituximab; D014750:Vincristine; D004317:Doxorubicin; D003520:Cyclophosphamide; D011241:Prednisone