Solitary Fibrous Tumors: Loss of Chimeric Protein Expression and Genomic Instability Mark Dedifferentiation
Modern Pathology (2015) 28, 1074–1083 1074 © 2015 USCAP, Inc All rights reserved 0893-3952/15 $32.00 Solitary fibrous tumors: loss of chimeric protein expression and genomic instability mark dedifferentiation Gian P Dagrada1, Rosalin D Spagnuolo1, Valentina Mauro1,6, Elena Tamborini2, Luca Cesana2, Alessandro Gronchi3, Silvia Stacchiotti4, Marco A Pierotti5,7, Tiziana Negri1,8 and Silvana Pilotti1,8 1Laboratory of Experimental Molecular Pathology, Department of Diagnostic Pathology and Laboratory, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy; 2Department of Diagnostic Pathology and Laboratory, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy; 3Department of Surgery, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy; 4Adult Mesenchymal Tumor Medical Oncology Unit, Cancer Medicine Department, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy and 5Scientific Directorate, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy Solitary fibrous tumors, which are characterized by their broad morphological spectrum and unpredictable behavior, are rare mesenchymal neoplasias that are currently divided into three main variants that have the NAB2-STAT6 gene fusion as their unifying molecular lesion: usual, malignant and dedifferentiated solitary fibrous tumors. The aims of this study were to validate molecular and immunohistochemical/biochemical approaches to diagnose the range of solitary fibrous tumors by focusing on the dedifferentiated variant, and to reveal the genetic events associated with dedifferentiation by integrating the findings of array comparative genomic hybridization. We studied 29 usual, malignant and dedifferentiated solitary fibrous tumors from 24 patients (including paired samples from five patients whose tumors progressed to the dedifferentiated form) by means of STAT6 immunohistochemistry and (when frozen material was available) reverse-transcriptase polymerase chain reaction and biochemistry.
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