Stromal gene signatures in large-B-cell lymphomas.
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.
Lenz, G; Wright, G; Dave, SS; Xiao, W; Powell, J; Zhao, H; Xu, W; Tan, B; Goldschmidt, N; Iqbal, J; Vose, J; Bast, M; Fu, K; Weisenburger, DD; Greiner, TC; Armitage, JO; Kyle, A; May, L; Gascoyne, RD; Connors, JM; Troen, G; Holte, H; Kvaloy, S; Dierickx, D; Verhoef, G; Delabie, J; Smeland, EB; Jares, P; Martinez, A; Lopez-Guillermo, A; Montserrat, E; Campo, E; Braziel, RM; Miller, TP; Rimsza, LM; Cook, JR; Pohlman, B; Sweetenham, J; Tubbs, RR; Fisher, RI; Hartmann, E; Rosenwald, A; Ott, G; Muller-Hermelink, H-K; Wrench, D; Lister, TA; Jaffe, ES; Wilson, WH; Chan, WC; Staudt, LM; Lymphoma/Leukemia Molecular Profiling Project,
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