title: CD30-positive peripheral T-cell lymphomas share molecular and phenotypic features.
abstract: Peripheral T-cell lymphoma, not otherwise specified is a heterogeneous group of aggressive neoplasms with indistinct borders. By gene expression profiling we previously reported unsupervised clusters of peripheral T-cell lymphomas, not otherwise specified correlating with CD30 expression. In this work we extended the analysis of peripheral T-cell lymphoma molecular profiles to prototypical CD30(+) peripheral T-cell lymphomas (anaplastic large cell lymphomas), and validated mRNA expression profiles at the protein level. Existing transcriptomic datasets from peripheral T-cell lymphomas, not otherwise specified and anaplastic large cell lymphomas were reanalyzed. Twenty-one markers were selected for immunohistochemical validation on 80 peripheral T-cell lymphoma samples (not otherwise specified, CD30(+) and CD30(-); anaplastic large cell lymphomas, ALK(+) and ALK(-)), and differences between subgroups were assessed. Clinical follow-up was recorded. Compared to CD30(-) tumors, CD30(+) peripheral T-cell lymphomas, not otherwise specified were significantly enriched in ALK(-) anaplastic large cell lymphoma-related genes. By immunohistochemistry, CD30(+) peripheral T-cell lymphomas, not otherwise specified differed significantly from CD30(-) samples [down-regulated expression of T-cell receptor-associated proximal tyrosine kinases (Lck, Fyn, Itk) and of proteins involved in T-cell differentiation/activation (CD69, ICOS, CD52, NFATc2); upregulation of JunB and MUM1], while overlapping with anaplastic large cell lymphomas. CD30(-) peripheral T-cell lymphomas, not otherwise specified tended to have an inferior clinical outcome compared to the CD30(+) subgroups. In conclusion, we show molecular and phenotypic features common to CD30(+) peripheral T-cell lymphomas, and significant differences between CD30(-) and CD30(+) peripheral T-cell lymphomas, not otherwise specified, suggesting that CD30 expression might delineate two biologically distinct subgroups.
authors.affiliation: University Institute of Pathology, Centre Hospitalier Universitaire Vaudois (CHUV), Lausanne, Switzerland. bettina.bisig@chuv.ch
authors.forename: Bettina
authors.initials: B
authors.lastname: Bisig
authors.forename: Aurélien
authors.initials: A
authors.lastname: de Reyniès
authors.forename: Christophe
authors.initials: C
authors.lastname: Bonnet
authors.forename: Pierre
authors.initials: P
authors.lastname: Sujobert
authors.forename: David S
authors.initials: DS
authors.lastname: Rickman
authors.forename: Teresa
authors.initials: T
authors.lastname: Marafioti
authors.forename: Georges
authors.initials: G
authors.lastname: Delsol
authors.forename: Laurence
authors.initials: L
authors.lastname: Lamant
authors.forename: Philippe
authors.initials: P
authors.lastname: Gaulard
authors.forename: Laurence
authors.initials: L
authors.lastname: de Leval
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002648:Child; D002675:Child, Preschool; D005260:Female; D005500:Follow-Up Studies; D020869:Gene Expression Profiling / Q000379:methods; D006801:Humans; D017730:Ki-1 Antigen / Q000096:biosynthesis* / Q000235:genetics*; D016411:Lymphoma, T-Cell, Peripheral / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D055815:Young Adult
chemical_list: D017730:Ki-1 Antigen