Prediction of Survival in Follicular Lymphoma Based on Molecular Features of Tumor-Infiltrating Immune Cells
Sandeep S. Dave, M.D., George Wright, Ph.D., Bruce Tan, M.D., Andreas Rosenwald, M.D., Randy D. Gascoyne, M.D., Wing C. Chan, M.D., Richard I. Fisher, M.D., Rita M. Braziel, M.D., Lisa M. Rimsza, M.D., Thomas M. Grogan, M.D., Thomas P. Miller, M.D., Michael LeBlanc, Ph.D., Timothy C. Greiner, M.D., Dennis D. Weisenburger, M.D., James C. Lynch, Ph.D., Julie Vose, M.D., James O. Armitage, M.D., Erlend B. Smeland, M.D., Ph.D., Stein Kvaloy, M.D., Ph.D., Harald Holte, M.D., Ph.D., Jan Delabie, M.D., Ph.D., Joseph M. Connors, M.D., Peter M. Lansdorp, M.D., Ph.D., Qin Ouyang, Ph.D., T. Andrew Lister, M.D., Andrew J. Davies, M.D., Andrew J. Norton, M.D., H. Konrad Muller-Hermelink, M.D., German Ott, M.D., Elias Campo, M.D., Emilio Montserrat, M.D., Wyndham H. Wilson, M.D., Ph.D., Elaine S. Jaffe, M.D., Richard Simon, Ph.D., Liming Yang, Ph.D., John Powell, M.S., Hong Zhao, M.S., Neta Goldschmidt, M.D., Michael Chiorazzi, B.A., and Louis M. Staudt, M.D., Ph.D.
Background Patients with follicular lymphoma may survive forperiods of less than 1 year to more than 20 years after diagnosis.We used gene-expression profiles of tumor-biopsy specimens obtainedat diagnosis to develop a molecular predictor of the lengthof survival.
Methods Gene-expression profiling was performed on 191 biopsyspecimens obtained from patients with untreated follicular lymphoma.Supervised methods were used to discover expression patternsassociated with the length of survival in a training set of95 specimens. A molecular predictor of survival was constructedfrom these genes and validated in an independent test set of96 specimens.
Results Individual genes that predicted the length of survivalwere grouped into gene-expression signatures on the basis oftheir expression in the training set, and two such signatureswere used to construct a survival predictor. The two signaturesallowed patients with specimens in the test set to be dividedinto four quartiles with widely disparate median lengths ofsurvival (13.6, 11.1, 10.8, and 3.9 years), independently ofclinical prognostic variables. Flow cytometry showed that thesesignatures reflected gene expression by nonmalignant tumor-infiltratingimmune cells.
Conclusions The length of survival among patients with follicularlymphoma correlates with the molecular features of nonmalignantimmune cells present in the tumor at diagnosis.
Source Information
From National Cancer Institute (S.S.D., G.W., B.T., A.R., W.H.W., E.S.J., R.S., H.Z., N.G., M.C., L.M.S.); Center for Information Technology (L.Y., J.P.); and National Heart, Lung, and Blood Institute (S.S.D.) — all in Bethesda, Md.; British Columbia Cancer Center, Vancouver, Canada (R.D.G., J.M.C., P.M.L., Q.O.); University of Nebraska Medical Center, Omaha (W.C.C., T.C.G., D.D.W., J.C.L., J.V., J.O.A.); Southwest Oncology Group, San Antonio, Tex. (R.I.F., T.M.G., T.P.M., M.L.); University of Rochester School of Medicine, Rochester, N.Y. (R.I.F.); Oregon Health and Science University, Portland (R.M.B.); University of Arizona Cancer Center, Tucson (L.M.R., T.M.G., T.P.M.); Fred Hutchinson Cancer Research Center, Seattle (M.L.); Norwegian Radium Hospital, Oslo (E.B.S., S.K., H.H., J.D.); Cancer Research UK, St. Bartholomew's Hospital, London (T.A.L., A.J.D., A.J.N.); University of Würzburg, Würzburg, Germany (A.R., H.K.M.-H., G.O.); and University of Barcelona, Barcelona, Spain (E.C., E.M.).
Address reprint requests to Dr. Staudt at the National Cancer Institute, Bldg. 10, Rm. 4N114, NIH, Bethesda, MD 20892, or at lstaudt{at}mail.nih.gov.
Lymphoma-Infiltrating Immune Cells
Kobayashi K., Murashige N., Kishi Y. Jr., Naresh K. N., Gajewski T. F., Dave S. S., Staudt L. M.
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N Engl J Med 2005;
352:724-725, Feb 17, 2005.
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(2007). Asterias: integrated analysis of expression and aCGH data using an open-source, web-based, parallelized software suite. Nucleic Acids Res
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(2007). How I treat indolent lymphoma. Blood
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(2007). Nonmalignant T cells stimulate growth of T-cell lymphoma cells in the presence of bacterial toxins. Blood
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Mulligan, G., Mitsiades, C., Bryant, B., Zhan, F., Chng, W. J., Roels, S., Koenig, E., Fergus, A., Huang, Y., Richardson, P., Trepicchio, W. L., Broyl, A., Sonneveld, P., Shaughnessy, J. D. Jr, Leif Bergsagel, P., Schenkein, D., Esseltine, D.-L., Boral, A., Anderson, K. C.
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