title: A new diagnostic algorithm for Burkitt and diffuse large B-cell lymphomas based on the expression of CSE1L and STAT3 and on MYC rearrangement predicts outcome.
abstract: BACKGROUND
  Aggressive mature B-cell non-Hodgkin's lymphomas (BCL) sharing features of Burkitt's lymphoma (BL) and diffuse large B-cell lymphoma (DLBCL) (intermediate BL/DLBCL) but deviating with respect to one or more characteristics are increasingly recognized. The limited knowledge about these biologically heterogeneous lymphomas hampers their assignment to a known entity, raising incertitude about optimal treatment approaches. We therefore searched for discriminative, prognostic, and predictive factors for their better characterization.
  
  
  METHODS
  We analyzed 242 cytogenetically defined aggressive mature BCL for differential protein expression. Marker selection was based on recent gene-expression profile studies. Predictive models for diagnosis were established and validated by a different set of lymphomas.
  
  
  RESULTS
  CSE1L- and inhibitor of DNA binding-3 (ID3)-overexpression was associated with the diagnosis of BL and signal transduction and transcription-3 (STAT3) with DLBCL (P<0.001 for all markers). All three markers were associated with patient outcome in DLBCL. A new algorithm discriminating BL from DLBCL emerged, including the expression of CSE1L, STAT3, and MYC translocation. This 'new classifier' enabled the identification of patients with intermediate BL/DLBCL who benefited from intensive chemotherapy regimens.
  
  
  CONCLUSIONS
  The proposed algorithm, which is based on markers with reliable staining properties for routine diagnostics, represents a novel valid tool in separating BL from DLBCL. Most interestingly, it allows segregating intermediate BL/DLBCL into groups with different treatment requirements.
authors.affiliation: Institute of Surgical Pathology, University Hospital Zurich, Zurich, Switzerland.
authors.forename: D
authors.initials: D
authors.lastname: Soldini
authors.forename: C
authors.initials: C
authors.lastname: Montagna
authors.forename: P
authors.initials: P
authors.lastname: Schüffler
authors.forename: V
authors.initials: V
authors.lastname: Martin
authors.forename: A
authors.initials: A
authors.lastname: Georgis
authors.forename: T
authors.initials: T
authors.lastname: Thiesler
authors.forename: A
authors.initials: A
authors.lastname: Curioni-Fontecedro
authors.forename: P
authors.initials: P
authors.lastname: Went
authors.forename: G
authors.initials: G
authors.lastname: Bosshard
authors.forename: S
authors.initials: S
authors.lastname: Dehler
authors.forename: L
authors.initials: L
authors.lastname: Mazzuchelli
authors.forename: M
authors.initials: M
authors.lastname: Tinguely
mesh_terms: D000465:Algorithms; D014408:Biomarkers, Tumor / Q000235:genetics*; D015153:Blotting, Western; D002051:Burkitt Lymphoma / Q000175:diagnosis* / Q000235:genetics; D029563:Cellular Apoptosis Susceptibility Protein / Q000235:genetics*; D005260:Female; D016259:Genes, myc; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D016403:Lymphoma, Large B-Cell, Diffuse / Q000175:diagnosis* / Q000235:genetics; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D050796:STAT3 Transcription Factor / Q000235:genetics*
chemical_list: D014408:Biomarkers, Tumor; D029563:Cellular Apoptosis Susceptibility Protein; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human