Prognostic Impact of Germinal Center-associated Proteins and Chromosomal Breakpoints in Poor-risk Diffuse Large B-cell Lymphoma.
From: Department of Hematology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands. g.w.van.imhoff@int.umcg.nl
Journal of clinical oncology : official journal of the American Society of Clinical Oncology
- Publish Date: Sep 2006
- ISSN: 1527-7755
- Volume: 24
- Issue: 25
- Pages: 4135-42
- Medium: Internet
- Language: English
- Citation (JAMA): van Imhoff Gustaaf W, Boerma Evert-Jan G, van der Holt Bronno, et al. Prognostic Impact of Germinal Center-associated Proteins and Chromosomal Breakpoints in Poor-risk Diffuse Large B-cell Lymphoma.. J. Clin. Oncol. Sep 2006;24:4135-42
Abstract
PURPOSE: Outcome of diffuse large B-cell lymphoma (DLBCL) with a germinal center B-cell (GCB) expression profile is superior to that of non-GCB DLBCL. This conclusion is mainly derived from patients with mixed international prognostic index (IPI) risk profiles treated with CHOP-like therapy (cyclophosphamide, doxorubicin, vincristine, and prednisone). We wondered whether the prognostic impact of the expression profile would hold out in a homogeneous cohort of poor-risk DLBCL patients treated with high-dose sequential therapy (HDT) and autologous stem-cell transplantation (ASCT) as first-line therapy. PATIENTS AND METHODS: DLBCL from 66 newly diagnosed poor-risk patients, treated in two sequential prospective Dutch Hemato-Oncology Association (HOVON) trials, were studied retrospectively for expression of CD10, bcl6, MUM1/IRF4, bcl2, Ki67, and CD21+ follicular dendritic cells (FDC) by immunohistochemistry, and for the breakpoints of BCL2, BCL6, and MYC by fluorescent in situ hybridization (FISH). Lymphomas with any follicular component were excluded. RESULTS: A GCB immunophenotype profile was found in 58% and non-GCB immunophenotype profile in 42% of the tumors. Clinical characteristics of both groups were similar. Complete response (CR) rate was higher in patients with CD10+ tumors (58% v 30%; P = .03). A GCB immunophenotype profile, its constituting markers CD10 more than 30% and MUM1 less than 70%, and bcl2 less than 10% were each associated with a better overall survival (OS). FDC networks, equally present in GCB and non-GCB tumors, had superior CR (73% v 31%; P = .01), but disease-free survival rates were lower and there was no difference in OS rates. None of the breakpoints had a prognostic impact on outcome. CONCLUSION: Also in patients with poor-risk DLBCL treated with HDT and ASCT, the GCB immunophenotype and bcl2 expression retained a major impact on survival.
Mesh Headings (Keywords): Adolescent, Adult, Aged, Chromosome Breakage, DNA-Binding Proteins, Female, Germinal Center, Humans, Immunohistochemistry, Immunophenotyping, Interferon Regulatory Factors, Ki-67 Antigen, Lymphoma, B-Cell, Lymphoma, Large B-Cell, Diffuse, Male, Middle Aged, Neoplasm Proteins, Neoplasm Staging, Neprilysin, Predictive Value of Tests, Prognosis, Receptors, Complement 3d, Retrospective Studies, Risk Factors, Survival Analysis, Tumor Markers, Biological, bcl-Associated Death Protein
Check for Full Text / PubMed Unique Identifier (PMID): 16943530
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