Stromal Gene Signatures in Large-B-Cell Lymphomas.
Lenz, G. M.D.; Wright, G. Ph.D.; Dave, S. S. M.D.; Xiao, W. Ph.D.; Powell, J. M.S.; Zhao, H. M.S.; Xu, W. M.S.; Tan, B. M.D.; Goldschmidt, N. M.D.; Iqbal, J. Ph.D.; Vose, J. M.D.; Bast, M. B.S.; Fu, K. M.D., Ph.D.; Weisenburger, D. D. M.D.; Greiner, T. C. M.D.; Armitage, J. O. M.D.; Kyle, A. Ph.D.; May, L. Ph.D.; Gascoyne, R. D. M.D.; Connors, J. M. M.D.; Troen, G. Ph.D.; Holte, H. M.D., Ph.D.; Kvaloy, S. M.D., Ph.D.; Dierickx, D. M.D.; Verhoef, G. M.D.; Delabie, J. M.D.; Smeland, E. B. M.D., Ph.D.; Jares, P. Ph.D.; Martinez, A. M.D.; Lopez-Guillermo, A. M.D.; Montserrat, E. M.D.; Campo, E. M.D.; Braziel, R. M. M.D.; Miller, T. P. M.D.; Rimsza, L. M. M.D.; Cook, J. R. M.D.; Pohlman, B. M.D.; Sweetenham, J. M.D.; Tubbs, R. R. M.D.; Fisher, R. I. M.D.; Hartmann, E. M.D.; Rosenwald, A. M.D.; Ott, G. M.D.; Muller-Hermelink, H. -K. M.D.; Wrench, D. M.D.; Lister, T. A. M.D.; Jaffe, E. S. M.D.; Wilson, W. H. M.D., Ph.D.; Chan, W. C. M.D.; Staudt, L. M. M.D., Ph.D.; the LymphomaLeukemia Molecular Profiling Project /
[Article]
New England Journal of Medicine.
359(22):2313-2323, November 27, 2008.
(Format: HTML, PDF)
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.
Copyright (C) 2008 Massachusetts Medical Society. All rights reserved.
