Prediction of survival in FL based on molec features of tumor-infiltrating immune cells

Comment in:: N Engl J Med. 2004 Nov 18;351(21):2152-3.; N Engl J Med. 2005 Apr 7;352(14):1496-7; author reply 1496-7.; N Engl J Med. 2005 Apr 7;352(14):1496-7; author reply 1496-7.; N Engl J Med. 2005 Feb 17;352(7):724-5; author reply 724-5.; N Engl J Med. 2005 Feb 17;352(7):724-5; author reply 724-5.; N Engl J Med. 2005 Feb 17;352(7):724-5; author reply 724-5.

Prediction of survival in follicular lymphoma based on molecular features of tumor-infiltrating immune cells.
Dave SS, Wright G, Tan B, Rosenwald A, Gascoyne RD, Chan WC, Fisher RI, Braziel RM, Rimsza LM, Grogan TM, Miller TP, LeBlanc M, Greiner TC, Weisenburger DD, Lynch JC, Vose J, Armitage JO, Smeland EB, Kvaloy S, Holte H, Delabie J, Connors JM, Lansdorp PM, Ouyang Q, Lister TA, Davies AJ, Norton AJ, Muller-Hermelink HK, Ott G, Campo E, Montserrat E, Wilson WH, Jaffe ES, Simon R, Yang L, Powell J, Zhao H, Goldschmidt N, Chiorazzi M, Staudt LM.

National Cancer Institute, NIH, Bethesda, Md 20892, USA.

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. Copyright 2004 Massachusetts Medical Society.

PMID: 15548776 [PubMed - indexed for MEDLINE]