TY - JOUR
T1 - Evaluation of immunophenotypic and molecular biomarkers for Sézary syndrome using standard operating procedures: multicenter study of 59 cases
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.
PY - 2016/2/28
Y1 - 2016/2/28
N2 - Abstract Differentiation between Sézary syndrome (SS) and erythrodermic inflammatory dermatoses (EID) 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 criterion. In this European multicenter study the sensitivity and specificity of these immunophenotypic and recently proposed but unconfirmed molecular biomarkers in SS was investigated. Peripheral blood CD4+ T-cells from 59 SS and 19 EID patients were analyzed for cell surface proteins by flow cytometry, and for copy number alterations and differential gene expression using custom made qPCR 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%), upregulation of DNM3 (75%), TWIST1 (69%), EPHA4 (66%) and PLS3 (66%) and downregulation 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 SS patients from EID cases with 100% specificity. These additional diagnostic panels will be useful adjuncts in the differential diagnosis of SS versus EID.
AB - Abstract Differentiation between Sézary syndrome (SS) and erythrodermic inflammatory dermatoses (EID) 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 criterion. In this European multicenter study the sensitivity and specificity of these immunophenotypic and recently proposed but unconfirmed molecular biomarkers in SS was investigated. Peripheral blood CD4+ T-cells from 59 SS and 19 EID patients were analyzed for cell surface proteins by flow cytometry, and for copy number alterations and differential gene expression using custom made qPCR 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%), upregulation of DNM3 (75%), TWIST1 (69%), EPHA4 (66%) and PLS3 (66%) and downregulation 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 SS patients from EID cases with 100% specificity. These additional diagnostic panels will be useful adjuncts in the differential diagnosis of SS versus EID.
U2 - 10.1016/j.jid.2016.01.038
DO - 10.1016/j.jid.2016.01.038
M3 - Article
SN - 0022-202X
JO - Journal of Investigative Dermatology
JF - Journal of Investigative Dermatology
ER -