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This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Gascoyne, R. D. Articles by Connors, J. M. Search for Related Content PubMed PubMed Citation Articles by Gascoyne, R. D. Articles by Connors, J. M. Related Collections Neoplasia Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Prognostic Significance of Bcl-2 Protein Expression and Bcl-2 Gene Rearrangement in Diffuse Aggressive Non-Hodgkin's Lymphoma Randy D. Gascoyne, Sheryle A. Adomat, Stanislaw Krajewski, Maryla Krajewska, Douglas E. Horsman, Anthony W. Tolcher, Susan E. O'Reilly, Paul Hoskins, Andrew J. Coldman, John C. Reed, and Joseph M. Connors From the Departments of Pathology, Medical Oncology, and Biostatistics, British Columbia Cancer Agency, University of British Columbia, Vancouver, BC, Canada; and The Burnham Institute, Cancer Research Center, La Jolla, CA. The prognostic significance of Bcl-2 protein expression and bcl-2 gene rearrangement in diffuse large cell lymphomas (DLCL) is controversial. Bcl-2 protein expression prevents apoptosis and may have an important role in clinical drug resistance. The presence of a bcl-2 gene rearrangement in de novo DLCL suggests a possible follicle center cell origin and perhaps a distinct clinical behavior more akin to low-grade non-Hodgkin's lymphoma (NHL). The purpose of this study was to determine the impact of Bcl-2 protein expression and bcl-2 gene rearrangement (mbr and mcr) on survival of a cohort of patients with DLCL who were uniformly evaluated and treated with effective chemotherapy. Patients included the original MACOP-B cohort (n = 121) and the initial 18 patients treated with the VACOP-B regimen (total = 139). All patients had advanced-stage disease, were 16 to 70 years old, and corresponded to Working Formulation categories F, G, or H. No patients had prior treatment, discordant lymphoma, or human immunodeficiency virus seropositivity. Paraffin sections from diagnostic biopsies were analyzed for bcl-2 gene rearrangement including mbr and mcr breakpoints by polymerase chain reaction and Bcl-2 protein expression by immunohistochemistry. With a median follow-up of 81 months, overall (OS), disease-free (DFS), and relapse-free survival (RFS) were measured to determine the prognostic significance of these parameters. Analyzable DNA was present in 118 of 139 (85%) cases, with 14 demonstrating a bcl-2 rearrangement (11 mbr, 3 mcr). All 14 of these bcl-2 gene rearrangement-positive cases were found in the 102 patients with a B-cell immunophenotype, but the presence of this rearrangement had no significant influence on survival. Bcl-2 protein expression was interpretable in 116 of 139 (83%) cases, with immunopositivity detected in 54 of 116 (47%). Using a cut-off of greater than 10% Bcl-2 immunopositive tumor cells for analysis, positive Bcl-2 protein expression was seen in 28 of 116 (24%) patients and the presence of this expression correlated with decreased 8-year OS (34% v 60%, P < .01), DFS (32% v 66%, P < .001), and RFS (25% v 59%, P < .001). Bcl-2 protein expression remained significant in multivariate analysis that included the clinical international prognostic index factors and immunophenotype (P < .02). In conclusion, although bcl-2 gene rearrangement status could not be shown to have an impact on outcome, Bcl-2 protein expression is a strong significant predictor of OS, DFS, and RFS in DLCLs. Blood, Vol. 90 No. 1 (July 1), 1997: pp. 244-251 © 1997 by The American Society of Hematology. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: D. Ennishi, H. Asai, Y. Maeda, K. Shinagawa, K. Ikeda, M. Yokoyama, Y. Terui, K. Takeuchi, T. Yoshino, K. Matsuo, et al. Statin-independent prognosis of patients with diffuse large B-cell lymphoma receiving rituximab plus CHOP therapy Ann. Onc., November 2, 2009; (2009) mdp490v1. [Abstract] [Full Text] [PDF] H.-W. Bernd, M. Ziepert, C. Thorns, W. Klapper, H.-H. Wacker, M. Hummel, H. Stein, M.-L. Hansmann, G. Ott, A. Rosenwald, et al. Loss of HLA-DR expression and immunoblastic morphology predict adverse outcome in diffuse large B-cell lymphoma - analyses of cases from two prospective randomized clinical trials Haematologica, November 1, 2009; 94(11): 1569 - 1580. 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