title: Gene-expression and immunohistochemical study of specific T-cell subsets and accessory cell types in the transformation and prognosis of follicular lymphoma.
abstract: OBJECTIVE
  Despite the generally favorable clinical course in follicular lymphoma (FL), a minority of patients have a poor prognosis-with death within 3 years of diagnosis-most often due to transformation to aggressive disease.
  
  
  METHODS
  In this study, we analyzed the potential of predicting early transformation on the basis of gene expression and immunologic parameters in FL biopsy samples taken at diagnosis.
  
  
  RESULTS
  At the gene-expression level, FL is a highly uniform disease at the time of diagnosis, precluding the detection of sufficiently validated prognostic gene-expression profiles suitable for a clinical setting. Combinations of differentially expressed genes indicate that immunologic mechanisms play a differential role in the risk of early transformation. Using immunohistochemistry for specific cell populations, the spatial distribution to neoplastic follicles and the activation of CD4-positive T-helper cells (P = .002) and specifically T-helper 1 (P = .004) were shown to be highly discriminatory to predict early transformation. A role for functional modulation of follicular dendritic cells could also be supported (P = .04). Other cell populations, including CD68-positive macrophages and regulatory T cells, were not differentially present.
  
  
  CONCLUSIONS
  These results support the identification of FL as an immunologically functional disease in which an interaction of the tumor cells and the functional composition of the microenvironment determines the clinical behavior.
authors.affiliation: Department of Pathology, The Netherlands Cancer Institute, Amsterdam, The Netherlands.
authors.forename: Annuska M
authors.initials: AM
authors.lastname: Glas
authors.forename: Laurent
authors.initials: L
authors.lastname: Knoops
authors.forename: Leonie
authors.initials: L
authors.lastname: Delahaye
authors.forename: Marie José
authors.initials: MJ
authors.lastname: Kersten
authors.forename: Robby E
authors.initials: RE
authors.lastname: Kibbelaar
authors.forename: Lodewyk A
authors.initials: LA
authors.lastname: Wessels
authors.forename: Ryan
authors.initials: R
authors.lastname: van Laar
authors.forename: J Han J M
authors.initials: JH
authors.lastname: van Krieken
authors.forename: Joke W
authors.initials: JW
authors.lastname: Baars
authors.forename: John
authors.initials: J
authors.lastname: Raemaekers
authors.forename: Philip M
authors.initials: PM
authors.lastname: Kluin
authors.forename: Laura J
authors.initials: LJ
authors.lastname: van't Veer
authors.forename: Daphne
authors.initials: D
authors.lastname: de Jong
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015496:CD4-Positive T-Lymphocytes; D002471:Cell Transformation, Neoplastic; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D007150:Immunohistochemistry; D008224:Lymphoma, Follicular / Q000235:genetics* / Q000276:immunology* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D011379:Prognosis; D012189:Retrospective Studies; D016176:T-Lymphocyte Subsets; D006377:T-Lymphocytes, Helper-Inducer