title: Molecular profiling improves classification and prognostication of nodal peripheral T-cell lymphomas: results of a phase III diagnostic accuracy study.
abstract: OBJECTIVE
  The differential diagnosis among the commonest peripheral T-cell lymphomas (PTCLs; ie, PTCL not otherwise specified [NOS], angioimmunoblastic T-cell lymphoma [AITL], and anaplastic large-cell lymphoma [ALCL]) is difficult, with the morphologic and phenotypic features largely overlapping. We performed a phase III diagnostic accuracy study to test the ability of gene expression profiles (GEPs; index test) to identify PTCL subtype.
  
  
  METHODS
  We studied 244 PTCLs, including 158 PTCLs NOS, 63 AITLs, and 23 ALK-negative ALCLs. The GEP-based classification method was established on a support vector machine algorithm, and the reference standard was an expert pathologic diagnosis according to WHO classification.
  
  
  RESULTS
  First, we identified molecular signatures (molecular classifier [MC]) discriminating either AITL and ALK-negative ALCL from PTCL NOS in a training set. Of note, the MC was developed in formalin-fixed paraffin-embedded (FFPE) samples and validated in both FFPE and frozen tissues. Second, we found that the overall accuracy of the MC was remarkable: 98% to 77% for AITL and 98% to 93% for ALK-negative ALCL in test and validation sets of patient cases, respectively. Furthermore, we found that the MC significantly improved the prognostic stratification of patients with PTCL. Particularly, it enhanced the distinction of ALK-negative ALCL from PTCL NOS, especially from some CD30+ PTCL NOS with uncertain morphology. Finally, MC discriminated some T-follicular helper (Tfh) PTCL NOS from AITL, providing further evidence that a group of PTCLs NOS shares a Tfh derivation with but is distinct from AITL.
  
  
  CONCLUSIONS
  Our findings support the usage of an MC as additional tool in the diagnostic workup of nodal PTCL.
authors.affiliation: S. Orsola-Malpighi Hospital, University of Bologna, Bologna, Italy. pierpaolo.piccaluga@unibo.it
authors.forename: Pier Paolo
authors.initials: PP
authors.lastname: Piccaluga
authors.forename: Fabio
authors.initials: F
authors.lastname: Fuligni
authors.forename: Antonio
authors.initials: A
authors.lastname: De Leo
authors.forename: Clara
authors.initials: C
authors.lastname: Bertuzzi
authors.forename: Maura
authors.initials: M
authors.lastname: Rossi
authors.forename: Francesco
authors.initials: F
authors.lastname: Bacci
authors.forename: Elena
authors.initials: E
authors.lastname: Sabattini
authors.forename: Claudio
authors.initials: C
authors.lastname: Agostinelli
authors.forename: Anna
authors.initials: A
authors.lastname: Gazzola
authors.forename: Maria Antonella
authors.initials: MA
authors.lastname: Laginestra
authors.forename: Claudia
authors.initials: C
authors.lastname: Mannu
authors.forename: Maria Rosaria
authors.initials: MR
authors.lastname: Sapienza
authors.forename: Sylvia
authors.initials: S
authors.lastname: Hartmann
authors.forename: Martin L
authors.initials: ML
authors.lastname: Hansmann
authors.forename: Roberto
authors.initials: R
authors.lastname: Piva
authors.forename: Javeed
authors.initials: J
authors.lastname: Iqbal
authors.forename: John C
authors.initials: JC
authors.lastname: Chan
authors.forename: Denis
authors.initials: D
authors.lastname: Weisenburger
authors.forename: Julie M
authors.initials: JM
authors.lastname: Vose
authors.forename: Monica
authors.initials: M
authors.lastname: Bellei
authors.forename: Massimo
authors.initials: M
authors.lastname: Federico
authors.forename: Giorgio
authors.initials: G
authors.lastname: Inghirami
authors.forename: Pier Luigi
authors.initials: PL
authors.lastname: Zinzani
authors.forename: Stefano A
authors.initials: SA
authors.lastname: Pileri
mesh_terms: D003937:Diagnosis, Differential; D005260:Female; D005557:Formaldehyde; D006801:Humans; D016411:Lymphoma, T-Cell, Peripheral / Q000175:diagnosis* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D008297:Male; D016612:Paraffin Embedding; D011379:Prognosis; D016019:Survival Analysis; D016707:Tissue Fixation; D059467:Transcriptome
chemical_list: D005557:Formaldehyde