title: Solitary fibrous tumor - clinicopathologic, immunohistochemical and molecular analysis of 28 cases.
abstract: BACKGROUND
  Solitary fibrous tumor is a mesenchymal tumor of fibroblastic type, which can affect any region of the body. Recently, a recurrent gene fusion NAB2-STAT6 has been identified as molecular hallmark. The NAB2-STAT6 fusion leads to EGR1 activation and transcriptional deregulation of EGR1-dependent target genes and is a driving event in initiation of SFT. In this study, we report the clinicopathologic and RT-PCR findings and evaluated expression of STAT6 and EGR1 protein in a cohort of 28 SFTs.
  
  
  METHODS
  28 patients with a median age of 54 years were included with SFTs originating at different sites, most occurring in the lung and pleura (9, 32%), 5 in soft tissues of the lower extremities (18%) and 5 in the head and neck (18%). For detection of the NAB2-STAT6 fusion gene, RT-PCR was performed using RNA extracted from formalin-fixed and paraffin-embedded tissues. Immunohistochemistry was performed on all cases with antibodies against STAT6 and EGR1.
  
  
  RESULTS
  All patients were treated by surgery, 3 with adjuvant chemo- or radiotherapy. Follow-up data of 18 patients could be obtained of which 2 patients died of metastatic disease 13 months and 52 years after first diagnosis. Sixteen patients have no evidence of disease with a median follow up of 29.5 months (range 7 - 120 months). NAB2-STAT6 fusion transcripts were found in 19/28 cases (68%). The most common fusion was between NAB2 exon 4 and STAT6 exon 3 (11/19, 58%), mainly occurring in pleuropulmonary lesions. All cases showed strong nuclear expression of STAT6 (28/28, 100%) while EGR1 showed low-level variable nuclear expression in all samples, comparable with the EGR1 expression results of the control group.
  
  
  CONCLUSIONS
  The identification of the NAB2-STAT6 fusion in SFTs can provide important diagnostic information, especially in cases with aberrant morphology or when biopsy material is limited. STAT6 immunohistochemistry is another useful tool in diagnosing SFT. EGR1 immunohistochemistry indicates low-level protein expression in accordance with EGR1 activation due to distorted NAB2 activity.
  The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/13000_2014_224.
authors.affiliation: Department of Pathology, Radboud University Medical Center, P.O. Box 9101, 6500 HB, Nijmegen, The Netherlands. rob.vogels@radboudumc.nl.
authors.forename: Rob J C
authors.initials: RJ
authors.lastname: Vogels
authors.affiliation: Department of Medical Oncology, Radboud University Medical Center, Nijmegen, The Netherlands. Myrella.Vlenterie@radboudumc.nl.
authors.forename: Myrella
authors.initials: M
authors.lastname: Vlenterie
authors.affiliation: Department of Medical Oncology, Radboud University Medical Center, Nijmegen, The Netherlands. Yvonne.Versleijen-Jonkers@radboudumc.nl.
authors.forename: Yvonne M H
authors.initials: YM
authors.lastname: Versleijen-Jonkers
authors.affiliation: Department of Pathology, Rijnstate Hospital, Arnhem, The Netherlands. ERuijter@rijnstate.nl.
authors.forename: Emiel
authors.initials: E
authors.lastname: Ruijter
authors.affiliation: Department of Pathology, Radboud University Medical Center, P.O. Box 9101, 6500 HB, Nijmegen, The Netherlands. Elise.Bekers@radboudumc.nl.
authors.forename: Elise M
authors.initials: EM
authors.lastname: Bekers
authors.affiliation: Department of Pathology, Radboud University Medical Center, P.O. Box 9101, 6500 HB, Nijmegen, The Netherlands. Marian.Verdijk@radboudumc.nl.
authors.forename: Marian A J
authors.initials: MA
authors.lastname: Verdijk
authors.affiliation: Department of Pathology, Radboud University Medical Center, P.O. Box 9101, 6500 HB, Nijmegen, The Netherlands. Monique.Link@radboudumc.nl.
authors.forename: Monique M
authors.initials: MM
authors.lastname: Link
authors.affiliation: Department of Surgical Oncology, Radboud University Medical Center, Nijmegen, The Netherlands. Han.Bonenkamp@radboudumc.nl.
authors.forename: Johannes J
authors.initials: JJ
authors.lastname: Bonenkamp
authors.affiliation: Department of Medical Oncology, Radboud University Medical Center, Nijmegen, The Netherlands. Winette.vanderGraaf@radboudumc.nl.
authors.forename: Winette T A
authors.initials: WT
authors.lastname: van der Graaf
authors.affiliation: Department of Pathology, Radboud University Medical Center, P.O. Box 9101, 6500 HB, Nijmegen, The Netherlands. Piet.Slootweg@radboudumc.nl.
authors.forename: Pieter J
authors.initials: PJ
authors.lastname: Slootweg
authors.affiliation: Department of Pathology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands. a.j.h.suurmeijer@umcg.nl.
authors.forename: Albert J H
authors.initials: AJ
authors.lastname: Suurmeijer
authors.affiliation: Department of Pathology, Radboud University Medical Center, P.O. Box 9101, 6500 HB, Nijmegen, The Netherlands. Patricia.Groenen@radboudumc.nl.
authors.forename: Patricia J T A
authors.initials: PJ
authors.lastname: Groenen
authors.affiliation: Department of Pathology, Radboud University Medical Center, P.O. Box 9101, 6500 HB, Nijmegen, The Netherlands. Uta.Flucke@radboudumc.nl.
authors.forename: Uta
authors.initials: U
authors.lastname: Flucke
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis / Q000235:genetics; D051766:Early Growth Response Protein 1 / Q000032:analysis; D005260:Female; D050939:Gene Fusion; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D012097:Repressor Proteins / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D050800:STAT6 Transcription Factor / Q000032:analysis / Q000235:genetics; D054364:Solitary Fibrous Tumors / Q000737:chemistry / Q000175:diagnosis* / Q000235:genetics / Q000401:mortality / Q000473:pathology / Q000628:therapy; D013997:Time Factors; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; C497325:EGR1 protein, human; D051766:Early Growth Response Protein 1; C491000:NAB2 protein, human; D012097:Repressor Proteins; D050800:STAT6 Transcription Factor; C494101:STAT6 protein, human