Stromal gene signatures in large-B-cell lymphomas.

Authors

• G Lenz, National Institutes of Health, Bethesda, MD
• G Wright, National Institutes of Health, Bethesda, MD
• S S Dave, National Institutes of Health, Bethesda, MD
• W Xiao, National Institutes of Health, Bethesda, MD
• J Powell, National Institutes of Health, Bethesda, MD
• H Zhao, National Institutes of Health, Bethesda, MD
• W Xu, National Institutes of Health, Bethesda, MD
• B Tan, National Institutes of Health, Bethesda, MD
• N Goldschmidt, National Institutes of Health, Bethesda, MD
• Javeed Iqbal, University of Nebraska Medical CenterFollow
• Julie M. Vose, University of Nebraska Medical CenterFollow
• M Bast, University of Nebraska Medical CenterFollow
• Kai Fu, University of Nebraska Medical CenterFollow
• D D. Weisenburger, University of Nebraska Medical Center
• T C Greiner, University of Nebraska Medical CenterFollow
• James O. Armitage, University of Nebraska Medical CenterFollow
• A Kyle, British Columbia Cancer Agency
• L May, British Columbia Cancer Agency
• R D Gascoyne, British Columbia Cancer Agency
• J M Connors, British Columbia Cancer Agency
• G Troen, University of Oslo
• H Holte, University of Oslo
• S Kvaloy, University of Oslo
• D Dierickx, University of Leuven, Belgium
• G Verhoef, University of Leuven, Belgium
• J Delabie, University of Oslo
• E B Smeland, University of Oslo
• P Jares, University of Barcelona
• A Martinez, University of Barcelona
• A Lopez-Guillermo, University of Barcelona
• E Montserrat, University of Barcelona
• E Campo, University of Barcelona
• R M Braziel, Oregon Health and Science University
• T P Miller, Southwest Oncology Group
• L M Rimsza, Southwest Oncology Group
• J R Cook, Southwest Oncology Group
• B Pohlman, Cleveland Clinic Taussig Cancer Institute
• J Sweetenham, Cleveland Clinic Taussig Cancer Institute
• R R Tubbs, Southwest Oncology Group
• R I Fisher, Southwest Oncology Group
• E Hartmann, University of Würzburg
• A Rosenwald, University of Würzburg
• G Ott, University of Würzburg
• H-K Muller-Hermelink, University of Würzburg
• D Wrench, Bartholomew's Hospital, London
• T A Lister, Bartholomew's Hospital, London
• E S Jaffe, National Institutes of Health, Bethesda, MD
• W H Wilson, National Institutes of Health, Bethesda, MD
• W C. Chan, University of Nebraska Medical Center
• L M Staudt, National Institutes of Health, Bethesda, MD

Document Type

Article

Journal Title

The New England journal of medicine

Publication Date

Winter 11-27-2008

Volume

359

Abstract

BACKGROUND: The addition of rituximab to combination chemotherapy with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP), or R-CHOP, has significantly improved the survival of patients with diffuse large-B-cell lymphoma. Whether gene-expression signatures correlate with survival after treatment of diffuse large-B-cell lymphoma is unclear.

METHODS: We profiled gene expression in pretreatment biopsy specimens from 181 patients with diffuse large-B-cell lymphoma who received CHOP and 233 patients with this disease who received R-CHOP. A multivariate gene-expression-based survival-predictor model derived from a training group was tested in a validation group.

RESULTS: A multivariate model created from three gene-expression signatures--termed "germinal-center B-cell," "stromal-1," and "stromal-2"--predicted survival both in patients who received CHOP and patients who received R-CHOP. The prognostically favorable stromal-1 signature reflected extracellular-matrix deposition and histiocytic infiltration. By contrast, the prognostically unfavorable stromal-2 signature reflected tumor blood-vessel density.

CONCLUSIONS: Survival after treatment of diffuse large-B-cell lymphoma is influenced by differences in immune cells, fibrosis, and angiogenesis in the tumor microenvironment.

MeSH Headings

Antibodies, Monoclonal, Antibodies, Monoclonal, Murine-Derived, Antineoplastic Combined Chemotherapy Protocols, Cyclophosphamide, Disease Progression, Doxorubicin, Extracellular Matrix, Gene Expression, Gene Expression Profiling, Gene Expression Regulation, Neoplastic, Genes, MHC Class II, Germinal Center, Humans, Immunologic Factors, Kaplan-Meier Estimate, Lymphoma, Large B-Cell, Diffuse, Middle Aged, Multivariate Analysis, Neovascularization, Pathologic, Prednisone, Prognosis, Rituximab, Stromal Cells, Vincristine

DOI Link

10.1056/NEJMoa0802885

ISSN

1533-4406

Rights

From the New England Journal of Medicine, Lenz G, Wright G, Dave SS, et al. Stromal gene signatures in large-B-cell lymphomas, 359, 2313-2323 . Copyright © (2008) Massachusetts Medical Society. Reprinted with permission.

Recommended Citation

Lenz, G; Wright, G; Dave, S S; Xiao, W; Powell, J; Zhao, H; Xu, W; Tan, B; Goldschmidt, N; Iqbal, Javeed; Vose, Julie M.; Bast, M; Fu, Kai; Weisenburger, D D.; Greiner, T C; Armitage, James O.; Kyle, A; May, L; Gascoyne, R D; Connors, J M; Troen, G; Holte, H; Kvaloy, S; Dierickx, D; Verhoef, G; Delabie, J; Smeland, E B; Jares, P; Martinez, A; Lopez-Guillermo, A; Montserrat, E; Campo, E; Braziel, R M; Miller, T P; Rimsza, L M; Cook, J R; Pohlman, B; Sweetenham, J; Tubbs, R R; Fisher, R I; Hartmann, E; Rosenwald, A; Ott, G; Muller-Hermelink, H-K; Wrench, D; Lister, T A; Jaffe, E S; Wilson, W H; Chan, W C.; and Staudt, L M, "Stromal gene signatures in large-B-cell lymphomas." (2008). Journal Articles: Pathology and Microbiology. 32.
https://digitalcommons.unmc.edu/com_pathmicro_articles/32