title: Evaluation of Immunophenotypic and Molecular Biomarkers for Sézary Syndrome Using Standard Operating Procedures: A Multicenter Study of 59 Patients.
abstract: 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.
authors.affiliation: Department of Dermatology, Leiden University Medical Center, Leiden, The Netherlands. Electronic address: s.e.boonk@lumc.nl.
authors.forename: Stephanie E
authors.initials: SE
authors.lastname: Boonk
authors.affiliation: Department of Dermatology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Willem H
authors.initials: WH
authors.lastname: Zoutman
authors.affiliation: INSERM U976, Hospital Saint-Louis, Paris, France; Paris Diderot University, Hospital Saint-Louis, Paris, France.
authors.forename: Anne
authors.initials: A
authors.lastname: Marie-Cardine
authors.affiliation: Department of Dermatology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Leslie
authors.initials: L
authors.lastname: van der Fits
authors.affiliation: Department of Dermatology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Jacoba J
authors.initials: JJ
authors.lastname: Out-Luiting
authors.affiliation: St. John's Institute of Dermatology, Division of Genetics and Molecular Medicine, Faculty of Life Sciences & Medicine, King's College London, London, UK.
authors.forename: Tracey J
authors.initials: TJ
authors.lastname: Mitchell
authors.affiliation: St. John's Institute of Dermatology, Division of Genetics and Molecular Medicine, Faculty of Life Sciences & Medicine, King's College London, London, UK.
authors.forename: Isabella
authors.initials: I
authors.lastname: Tosi
authors.affiliation: Clinical Oncology, Guy's and St. Thomas' NHS Foundation Trust, London, UK.
authors.forename: Stephen L
authors.initials: SL
authors.lastname: Morris
authors.affiliation: St. John's Institute of Dermatology, Division of Genetics and Molecular Medicine, Faculty of Life Sciences & Medicine, King's College London, London, UK.
authors.forename: Blaithin
authors.initials: B
authors.lastname: Moriarty
authors.affiliation: Department of Dermatology, Venereology and Allergy, University Medical Center Mannheim, Ruprecht-Karls-University of Heidelberg, Mannheim, Germany.
authors.forename: Nina
authors.initials: N
authors.lastname: Booken
authors.affiliation: Department of Dermatology, Venereology and Allergy, University Medical Center Mannheim, Ruprecht-Karls-University of Heidelberg, Mannheim, Germany.
authors.forename: Moritz
authors.initials: M
authors.lastname: Felcht
authors.affiliation: Department of Medical Sciences, Dermatologic Clinic, Turin University, Turin, Italy.
authors.forename: Pietro
authors.initials: P
authors.lastname: Quaglino
authors.affiliation: Department of Medical Sciences, Dermatologic Clinic, Turin University, Turin, Italy.
authors.forename: Renata
authors.initials: R
authors.lastname: Ponti
authors.affiliation: Department of Medical Sciences, Dermatologic Clinic, Turin University, Turin, Italy.
authors.forename: Emanuela
authors.initials: E
authors.lastname: Barberio
authors.affiliation: INSERM U976, Hospital Saint-Louis, Paris, France; Paris Diderot University, Hospital Saint-Louis, Paris, France; Department of Dermatology, Hospital Saint-Louis, Paris, France.
authors.forename: Caroline
authors.initials: C
authors.lastname: Ram-Wolff
authors.affiliation: Department of Dermatology and Allergology, University of Helsinki and Skin and Allergy Hospital, Helsinki University Central Hospital, Helsinki, Finland.
authors.forename: Kirsi
authors.initials: K
authors.lastname: Jäntti
authors.affiliation: Department of Dermatology and Allergology, University of Helsinki and Skin and Allergy Hospital, Helsinki University Central Hospital, Helsinki, Finland.
authors.forename: Annamari
authors.initials: A
authors.lastname: Ranki
authors.affiliation: Department of Medical Sciences, Dermatologic Clinic, Turin University, Turin, Italy.
authors.forename: Maria Grazia
authors.initials: MG
authors.lastname: Bernengo
authors.affiliation: Department of Dermatology, Venereology and Allergy, University Medical Center Mannheim, Ruprecht-Karls-University of Heidelberg, Mannheim, Germany.
authors.forename: Claus-Detlev
authors.initials: CD
authors.lastname: Klemke
authors.affiliation: INSERM U976, Hospital Saint-Louis, Paris, France; Paris Diderot University, Hospital Saint-Louis, Paris, France.
authors.forename: Armand
authors.initials: A
authors.lastname: Bensussan
authors.affiliation: INSERM U976, Hospital Saint-Louis, Paris, France; Paris Diderot University, Hospital Saint-Louis, Paris, France.
authors.forename: Laurence
authors.initials: L
authors.lastname: Michel
authors.affiliation: St. John's Institute of Dermatology, Division of Genetics and Molecular Medicine, Faculty of Life Sciences & Medicine, King's College London, London, UK.
authors.forename: Sean
authors.initials: S
authors.lastname: Whittaker
authors.affiliation: INSERM U976, Hospital Saint-Louis, Paris, France; Paris Diderot University, Hospital Saint-Louis, Paris, France; Department of Dermatology, Hospital Saint-Louis, Paris, France.
authors.forename: Martine
authors.initials: M
authors.lastname: Bagot
authors.affiliation: Department of Dermatology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Cornelis P
authors.initials: CP
authors.lastname: Tensen
authors.affiliation: Department of Dermatology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Rein
authors.initials: R
authors.lastname: Willemze
authors.affiliation: Department of Dermatology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Maarten H
authors.initials: MH
authors.lastname: Vermeer
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000032:analysis*; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology; D003937:Diagnosis, Differential; D005060:Europe; D005260:Female; D005434:Flow Cytometry; D018628:Gene Dosage; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006801:Humans; D016130:Immunophenotyping / Q000592:standards*; D007249:Inflammation; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D012751:Sezary Syndrome / Q000175:diagnosis* / Q000276:immunology; D012871:Skin Diseases / Q000175:diagnosis / Q000276:immunology
chemical_list: D015415:Biomarkers