title: Gene expression analysis provides a potential rationale for revising the histological grading of follicular lymphomas.
abstract: BACKGROUND
  Follicular lymphomas are currently subdivided into grades I, II, IIIa and IIIb. This distinction is, however, questioned.
  
  
  METHODS
  We studied the gene expression profile of 43 follicular lymphomas, 50 B-cell non-Hodgkin's lymphomas of different histotype, and 20 samples of normal B-lymphocytes in order to assess: (i) the relationship of follicular lymphoma with normal B cells and other B-cell non-Hodgkin's lymphomas; (ii) whether follicular lymphoma is a unique disease; and (iii) whether follicular lymphoma grade IIIb is closer to follicular lymphoma or diffuse large B-cell lymphoma of the germinal center B-cell type.
  
  
  RESULTS
  First, we found that the molecular profile of follicular lymphoma is intimately related to that of normal germinal center B cells, irrespectively of the histological grade. Secondly, we observed that follicular lymphoma has a relatively homogeneous gene expression profile that is distinct from that of other B-cell non-Hodgkin's lymphoma and does not include discrete molecular subgroups. However, by further clustering samples according to signatures differentially expressed among follicular lymphomas or in follicular lymphomas versus diffuse large B-cell lymphoma, we showed that grade I-IIIa tumors tend to cluster together, while grade IIIb follicular lymphoma constitutes a distinct subgroup, whose molecular signature is closer to that of the remaining follicular lymphomas than to that of diffuse large B-cell lymphoma of the germinal center B-cell type.
  
  
  CONCLUSIONS
  These data support the hypothesis that grade IIIb follicular lymphoma does indeed belong to the group of follicular lymphomas rather than diffuse large B-cell lymphomas, and also suggests a possible revision of the histological grading of follicular lymphomas, with their simple distinction into follicular lymphoma (grade I-IIIa) and follicular lymphoma/large cell (grade IIIb).
authors.affiliation: Molecular Pathology Laboratory, Unit of Hematopathology, Department of Hematology and Oncology, L. and A. Seràgnoli, S. Orsola Malpighi Hospital, University of Bologna, Via Massarenti, 9, 40138 Bologna, Italy. pierpaolo.piccaluga@unibo.it
authors.forename: Pier Paolo
authors.initials: PP
authors.lastname: Piccaluga
authors.forename: Andrea
authors.initials: A
authors.lastname: Califano
authors.forename: Ulf
authors.initials: U
authors.lastname: Klein
authors.forename: Claudio
authors.initials: C
authors.lastname: Agostinelli
authors.forename: Beatriz
authors.initials: B
authors.lastname: Bellosillo
authors.forename: Eva
authors.initials: E
authors.lastname: Gimeno
authors.forename: Sergi
authors.initials: S
authors.lastname: Serrano
authors.forename: Francisco
authors.initials: F
authors.lastname: Solè
authors.forename: Yonghui
authors.initials: Y
authors.lastname: Zang
authors.forename: Brunangelo
authors.initials: B
authors.lastname: Falini
authors.forename: Pier Luigi
authors.initials: PL
authors.lastname: Zinzani
authors.forename: Stefano A
authors.initials: SA
authors.lastname: Pileri
mesh_terms: D000328:Adult; D000368:Aged; D016000:Cluster Analysis; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D015894:Genome, Human; D006801:Humans; D016393:Lymphoma, B-Cell / Q000175:diagnosis / Q000235:genetics*; D008224:Lymphoma, Follicular / Q000145:classification / Q000175:diagnosis* / Q000235:genetics*; D008228:Lymphoma, Non-Hodgkin / Q000175:diagnosis / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D020411:Oligonucleotide Array Sequence Analysis