Molecular profiling improves classification and prognostication of nodal peripheral T-cell lymphomas: results of a phase III diagnostic accuracy study.

Pier Paolo Piccaluga, Fabio Fuligni, Antonio De Leo, Clara Bertuzzi, Maura Rossi, Francesco Bacci, Elena Sabattini, Claudio Agostinelli, Anna Gazzola, Maria Antonella Laginestra, Claudia Mannu, Maria Rosaria Sapienza, Sylvia Hartmann, Martin L. Hansmann, Roberto Piva, Javeed Iqbal, John C. Chan, Denis Weisenburger, Julie M. Vose, Monica BelleiMassimo Federico, Giorgio Inghirami, Pier Luigi Zinzani, Stefano A. Pileri

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Abstract

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. 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. 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. Our findings support the usage of an MC as additional tool in the diagnostic workup of nodal PTCL.

Original languageEnglish
Pages (from-to)3019-3025
Number of pages7
JournalJournal of Clinical Oncology
Volume31
Issue number24
DOIs
Publication statusPublished - Aug 20 2013

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Peripheral T-Cell Lymphoma
T-Cell Lymphoma
Anaplastic Large-Cell Lymphoma
Paraffin
Formaldehyde
Transcriptome
Differential Diagnosis

ASJC Scopus subject areas

  • Medicine(all)

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Molecular profiling improves classification and prognostication of nodal peripheral T-cell lymphomas : results of a phase III diagnostic accuracy study. / Piccaluga, Pier Paolo; Fuligni, Fabio; De Leo, Antonio; Bertuzzi, Clara; Rossi, Maura; Bacci, Francesco; Sabattini, Elena; Agostinelli, Claudio; Gazzola, Anna; Laginestra, Maria Antonella; Mannu, Claudia; Sapienza, Maria Rosaria; Hartmann, Sylvia; Hansmann, Martin L.; Piva, Roberto; Iqbal, Javeed; Chan, John C.; Weisenburger, Denis; Vose, Julie M.; Bellei, Monica; Federico, Massimo; Inghirami, Giorgio; Zinzani, Pier Luigi; Pileri, Stefano A.

In: Journal of Clinical Oncology, Vol. 31, No. 24, 20.08.2013, p. 3019-3025.

Research output: Contribution to journalArticle

Piccaluga, PP, Fuligni, F, De Leo, A, Bertuzzi, C, Rossi, M, Bacci, F, Sabattini, E, Agostinelli, C, Gazzola, A, Laginestra, MA, Mannu, C, Sapienza, MR, Hartmann, S, Hansmann, ML, Piva, R, Iqbal, J, Chan, JC, Weisenburger, D, Vose, JM, Bellei, M, Federico, M, Inghirami, G, Zinzani, PL & Pileri, SA 2013, 'Molecular profiling improves classification and prognostication of nodal peripheral T-cell lymphomas: results of a phase III diagnostic accuracy study.', Journal of Clinical Oncology, vol. 31, no. 24, pp. 3019-3025. https://doi.org/10.1200/JCO.2012.42.5611
Piccaluga, Pier Paolo ; Fuligni, Fabio ; De Leo, Antonio ; Bertuzzi, Clara ; Rossi, Maura ; Bacci, Francesco ; Sabattini, Elena ; Agostinelli, Claudio ; Gazzola, Anna ; Laginestra, Maria Antonella ; Mannu, Claudia ; Sapienza, Maria Rosaria ; Hartmann, Sylvia ; Hansmann, Martin L. ; Piva, Roberto ; Iqbal, Javeed ; Chan, John C. ; Weisenburger, Denis ; Vose, Julie M. ; Bellei, Monica ; Federico, Massimo ; Inghirami, Giorgio ; Zinzani, Pier Luigi ; Pileri, Stefano A. / Molecular profiling improves classification and prognostication of nodal peripheral T-cell lymphomas : results of a phase III diagnostic accuracy study. In: Journal of Clinical Oncology. 2013 ; Vol. 31, No. 24. pp. 3019-3025.
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AU - Piccaluga, Pier Paolo

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AU - Bertuzzi, Clara

AU - Rossi, Maura

AU - Bacci, Francesco

AU - Sabattini, Elena

AU - Agostinelli, Claudio

AU - Gazzola, Anna

AU - Laginestra, Maria Antonella

AU - Mannu, Claudia

AU - Sapienza, Maria Rosaria

AU - Hartmann, Sylvia

AU - Hansmann, Martin L.

AU - Piva, Roberto

AU - Iqbal, Javeed

AU - Chan, John C.

AU - Weisenburger, Denis

AU - Vose, Julie M.

AU - Bellei, Monica

AU - Federico, Massimo

AU - Inghirami, Giorgio

AU - Zinzani, Pier Luigi

AU - Pileri, Stefano A.

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N2 - 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. 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. 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. Our findings support the usage of an MC as additional tool in the diagnostic workup of nodal PTCL.

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