title: Validation of nuclear STAT6 immunostaining as a diagnostic marker of meningeal solitary fibrous tumor (SFT)/hemangiopericytoma.
abstract: BACKGROUND
  NAB2-STAT6 gene fusion is a molecular characteristic of solitary fibrous tumors (SFT) and hemangiopericytoma, underscoring their definition as one diagnostic entity. NAB2-STAT6 fusion is associated with nuclear relocation of STAT6 protein that can be detected by immunohistochemistry. We evaluated the diagnostic value of STAT6 expression in meningeal tumors.
  
  
  METHODS
  77 meningeal tumors (17/77 (22.0%) SFT/hemangiopericytoma, 11/77 meningothelial meningioma, 10/77 atypical meningioma 8/77 chordoid meningioma, 9/77 fibroblastic meningioma, 10/77 transitional meningioma, 3/77 rhabdoid meningioma and 9/77 anaplastic meningioma) were included. STAT6 immunohistochemistry was performed on FFPE specimens using a fully automated slide-staining system and anti-STAT6 antibody SC-20:sc621. Two independent observers analyzed all specimens blinded to histological diagnoses, and a third observer was consulted in case of discordancy.
  
  
  RESULTS
  STAT6 immunohistochemistry yielded an exclusively nuclear immunostaining signal. 16/17 (94%) SFT/hemangiopericytoma specimens presented with clear-cut, wide-spread, and moderate to strong staining in tumor cell nuclei and were rated as STAT6-positive. In only 1 SFT case with weak and focal nuclear STAT6 immunostaining signal, STAT6 expression was rated discordant (observer 1: STAT6-negative, observers 2 and 3: STAT6-positive). All non-SFT/hemangiopericytoma cases were unanimously rated as STAT6-negative. In 76/77 (98.7%) cases the evaluation of STAT6 immunostaining results was in agreement among observers.
  
  
  CONCLUSIONS
  STAT6 immunohistochemistry is a robust method to verify diagnosis of SFT/hemangiopericytoma and should therefore be included in the diagnostic work-up of meningeal tumors. In singular cases, weak and focal STAT6 expression may lead to false-negative evaluation and may prompt further molecular work-up. .
authors.forename: Anna S
authors.initials: AS
authors.lastname: Berghoff
authors.forename: Philip
authors.initials: P
authors.lastname: Kresl
authors.forename: Michal
authors.initials: M
authors.lastname: Bienkowski
authors.forename: Christian
authors.initials: C
authors.lastname: Koelsche
authors.forename: Ursula
authors.initials: U
authors.lastname: Rajky
authors.forename: Johannes A
authors.initials: JA
authors.lastname: Hainfellner
authors.forename: Matthias
authors.initials: M
authors.lastname: Preusser
mesh_terms: D014408:Biomarkers, Tumor / Q000032:analysis*; D006801:Humans; D007150:Immunohistochemistry; D008577:Meningeal Neoplasms / Q000175:diagnosis*; D008579:Meningioma / Q000175:diagnosis*; D050800:STAT6 Transcription Factor / Q000032:analysis / Q000096:biosynthesis*; D054364:Solitary Fibrous Tumors / Q000175:diagnosis*
chemical_list: D014408:Biomarkers, Tumor; D050800:STAT6 Transcription Factor; C494101:STAT6 protein, human