Evaluation of Immunophenotypic and Molecular Biomarkers for Sézary Syndrome Using Standard Operating Procedures
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Evaluation of Immunophenotypic and Molecular Biomarkers for Sézary Syndrome Using Standard Operating Procedures : A Multicenter Study of 59 Patients. / Boonk, Stephanie E; Zoutman, Willem H; Marie-Cardine, Anne; van der Fits, Leslie; Out-Luiting, Jacoba J; Mitchell, Tracey J; Tosi, Isabella; Morris, Stephen L; Moriarty, Blaithin; Booken, Nina; Felcht, Moritz; Quaglino, Pietro; Ponti, Renata; Barberio, Emanuela; Ram-Wolff, Caroline; Jäntti, Kirsi; Ranki, Annamari; Bernengo, Maria Grazia; Klemke, Claus-Detlev; Bensussan, Armand; Michel, Laurence; Whittaker, Sean; Bagot, Martine; Tensen, Cornelis P; Willemze, Rein; Vermeer, Maarten H.
in: J INVEST DERMATOL, Jahrgang 136, Nr. 7, 07.2016, S. 1364-1372.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - Evaluation of Immunophenotypic and Molecular Biomarkers for Sézary Syndrome Using Standard Operating Procedures
T2 - A Multicenter Study of 59 Patients
AU - Boonk, Stephanie E
AU - Zoutman, Willem H
AU - Marie-Cardine, Anne
AU - van der Fits, Leslie
AU - Out-Luiting, Jacoba J
AU - Mitchell, Tracey J
AU - Tosi, Isabella
AU - Morris, Stephen L
AU - Moriarty, Blaithin
AU - Booken, Nina
AU - Felcht, Moritz
AU - Quaglino, Pietro
AU - Ponti, Renata
AU - Barberio, Emanuela
AU - Ram-Wolff, Caroline
AU - Jäntti, Kirsi
AU - Ranki, Annamari
AU - Bernengo, Maria Grazia
AU - Klemke, Claus-Detlev
AU - Bensussan, Armand
AU - Michel, Laurence
AU - Whittaker, Sean
AU - Bagot, Martine
AU - Tensen, Cornelis P
AU - Willemze, Rein
AU - Vermeer, Maarten H
N1 - Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.
PY - 2016/7
Y1 - 2016/7
N2 - Differentiation between Sézary syndrome and erythrodermic inflammatory dermatoses can be challenging, and a number of studies have attempted to identify characteristic immunophenotypic changes and molecular biomarkers in Sézary cells that could be useful as additional diagnostic criteria. In this European multicenter study, the sensitivity and specificity of these immunophenotypic and recently proposed but unconfirmed molecular biomarkers in Sézary syndrome were investigated. Peripheral blood CD4(+) T cells from 59 patients with Sézary syndrome and 19 patients with erythrodermic inflammatory dermatoses were analyzed for cell surface proteins by flow cytometry and for copy number alterations and differential gene expression using custom-made quantitative PCR plates. Experiments were performed in duplicate in two independent centers using standard operating procedures with almost identical results. Sézary cells showed MYC gain (40%) and MNT loss (66%); up-regulation of DNM3 (75%), TWIST1 (69%), EPHA4 (66%), and PLS3 (66%); and down-regulation of STAT4 (91%). Loss of CD26 (≥80% CD4(+) T cells) and/or CD7 (≥40% CD4(+) T cells) and combination of altered expression of STAT4, TWIST1, and DNM3 or PLS3 could distinguish, respectively, 83% and 98% of patients with Sézary syndrome from patients with erythrodermic inflammatory dermatoses with 100% specificity. These additional diagnostic panels will be useful adjuncts in the differential diagnosis of Sézary syndrome versus erythrodermic inflammatory dermatoses.
AB - Differentiation between Sézary syndrome and erythrodermic inflammatory dermatoses can be challenging, and a number of studies have attempted to identify characteristic immunophenotypic changes and molecular biomarkers in Sézary cells that could be useful as additional diagnostic criteria. In this European multicenter study, the sensitivity and specificity of these immunophenotypic and recently proposed but unconfirmed molecular biomarkers in Sézary syndrome were investigated. Peripheral blood CD4(+) T cells from 59 patients with Sézary syndrome and 19 patients with erythrodermic inflammatory dermatoses were analyzed for cell surface proteins by flow cytometry and for copy number alterations and differential gene expression using custom-made quantitative PCR plates. Experiments were performed in duplicate in two independent centers using standard operating procedures with almost identical results. Sézary cells showed MYC gain (40%) and MNT loss (66%); up-regulation of DNM3 (75%), TWIST1 (69%), EPHA4 (66%), and PLS3 (66%); and down-regulation of STAT4 (91%). Loss of CD26 (≥80% CD4(+) T cells) and/or CD7 (≥40% CD4(+) T cells) and combination of altered expression of STAT4, TWIST1, and DNM3 or PLS3 could distinguish, respectively, 83% and 98% of patients with Sézary syndrome from patients with erythrodermic inflammatory dermatoses with 100% specificity. These additional diagnostic panels will be useful adjuncts in the differential diagnosis of Sézary syndrome versus erythrodermic inflammatory dermatoses.
KW - Adult
KW - Aged
KW - Aged, 80 and over
KW - Biomarkers/analysis
KW - CD4-Positive T-Lymphocytes/cytology
KW - Diagnosis, Differential
KW - Europe
KW - Female
KW - Flow Cytometry
KW - Gene Dosage
KW - Gene Expression Profiling
KW - Gene Expression Regulation
KW - Humans
KW - Immunophenotyping/standards
KW - Inflammation
KW - Male
KW - Middle Aged
KW - Polymerase Chain Reaction
KW - Reproducibility of Results
KW - Sensitivity and Specificity
KW - Sezary Syndrome/diagnosis
KW - Skin Diseases/diagnosis
U2 - 10.1016/j.jid.2016.01.038
DO - 10.1016/j.jid.2016.01.038
M3 - SCORING: Journal article
C2 - 26930587
VL - 136
SP - 1364
EP - 1372
JO - J INVEST DERMATOL
JF - J INVEST DERMATOL
SN - 0022-202X
IS - 7
ER -