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Original Article
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Volume 351:2159-2169 November 18, 2004 Number 21
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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.

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ABSTRACT

Background Patients with follicular lymphoma may survive for periods of less than 1 year to more than 20 years after diagnosis. We used gene-expression profiles of tumor-biopsy specimens obtained at diagnosis to develop a molecular predictor of the length of survival.

Methods Gene-expression profiling was performed on 191 biopsy specimens obtained from patients with untreated follicular lymphoma. Supervised methods were used to discover expression patterns associated with the length of survival in a training set of 95 specimens. A molecular predictor of survival was constructed from these genes and validated in an independent test set of 96 specimens.

Results Individual genes that predicted the length of survival were grouped into gene-expression signatures on the basis of their expression in the training set, and two such signatures were used to construct a survival predictor. The two signatures allowed patients with specimens in the test set to be divided into four quartiles with widely disparate median lengths of survival (13.6, 11.1, 10.8, and 3.9 years), independently of clinical prognostic variables. Flow cytometry showed that these signatures reflected gene expression by nonmalignant tumor-infiltrating immune cells.

Conclusions The length of survival among patients with follicular lymphoma correlates with the molecular features of nonmalignant immune 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.

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Related Letters:

Immune Signatures in Follicular Lymphoma
Tibshirani R., Hong W.-J., Warnke R., Chu G., Staudt L. M., Wright G., Dave S.
Extract | Full Text | PDF  
N Engl J Med 2005; 352:1496-1497, Apr 7, 2005. Correspondence

Lymphoma-Infiltrating Immune Cells
Kobayashi K., Murashige N., Kishi Y. Jr., Naresh K. N., Gajewski T. F., Dave S. S., Staudt L. M.
Extract | Full Text | PDF  
N Engl J Med 2005; 352:724-725, Feb 17, 2005. Correspondence

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