title: Accurate detection of the tumor clone in peripheral T-cell lymphoma biopsies by flow cytometric analysis of TCR-Vβ repertoire.
abstract: Multiparametric flow cytometry has proven to be a powerful method for detection and immunophenotypic characterization of clonal subsets, particularly in lymphoproliferative disorders of the B-cell lineage. Although in theory promising, this approach has not been comparably fulfilled in mature T-cell malignancies. Specifically, the T-cell receptor-Vβ repertoire analysis in blood can provide strong evidence of clonality, particularly when a single expanded Vß family is detected. The purpose of this study was to determine the relevance of this approach when applied to biopsies, at the site of tumor involvement. To this end, 30 peripheral T-cell lymphoma and 94 control biopsies were prospectively studied. Vβ expansions were commonly detected within CD4+ or CD8+ T cells (97% of peripheral T-cell lymphoma and 54% of non-peripheral T-cell lymphoma cases); thus, not differentiating malignant from reactive processes. Interestingly, we demonstrated that using a standardized evaluation, the detection of a high Vβ expansion was closely associated with diagnosis of peripheral T-cell lymphoma, with remarkable specificity (98%) and sensitivity (90%). This approach also identified eight cases of peripheral T-cell lymphoma that were not detectable by other forms of immunophenotyping. Moreover, focusing Vβ expression analysis to T-cell subsets with aberrant immunophenotypes, we demonstrated that the T-cell clone might be heterogeneous with regard to surface CD7 or CD10 expression (4/11 cases), providing indication on 'phenotypic plasticity'. Finally, among the wide variety of Vβ families, the occurrence of a Vβ17 expansion in five cases was striking. To our knowledge, this is the first report demonstrating the power of T-cell receptor-Vβ repertoire analysis by flow cytometry in biopsies as a basis for peripheral T-cell lymphoma diagnosis and precise T-cell clone identification and characterization.
authors.affiliation: Université Joseph Fourier Grenoble 1, France.
authors.forename: Dimitri
authors.initials: D
authors.lastname: Salameire
authors.forename: Françoise
authors.initials: F
authors.lastname: Solly
authors.forename: Blandine
authors.initials: B
authors.lastname: Fabre
authors.forename: Christine
authors.initials: C
authors.lastname: Lefebvre
authors.forename: Martine
authors.initials: M
authors.lastname: Chauvet
authors.forename: Rémy
authors.initials: R
authors.lastname: Gressin
authors.forename: Bernadette
authors.initials: B
authors.lastname: Corront
authors.forename: Agnès
authors.initials: A
authors.lastname: Ciapa
authors.forename: Martine
authors.initials: M
authors.lastname: Pernollet
authors.forename: Joël
authors.initials: J
authors.lastname: Plumas
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Macintyre
authors.forename: Mary B
authors.initials: MB
authors.lastname: Callanan
authors.forename: Dominique
authors.initials: D
authors.lastname: Leroux
authors.forename: Marie-Christine
authors.initials: MC
authors.lastname: Jacob
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism; D001706:Biopsy; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism / Q000473:pathology*; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism / Q000473:pathology*; D002999:Clone Cells; D005260:Female; D005434:Flow Cytometry / Q000379:methods*; D006801:Humans; D016130:Immunophenotyping; D008221:Lymphoid Tissue / Q000378:metabolism / Q000473:pathology; D016411:Lymphoma, T-Cell, Peripheral / Q000175:diagnosis* / Q000235:genetics / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000378:metabolism*
chemical_list: D014408:Biomarkers, Tumor; D016693:Receptors, Antigen, T-Cell, alpha-beta