title: The role of phosphorylated signal transducer and activator of transcription 3 (pSTAT3) in peripheral nerve sheath tumours.
abstract: OBJECTIVE
  STAT3 is a pro-oncogenic transcription factor that requires phosphorylation for transcriptional activation. The aim of this study was to evaluate the role of phosphorylated STAT3 (pSTAT3) expression in neurofibromas, schwannomas, and malignant peripheral nerve sheath tumours (MPNSTs).
  
  
  RESULTS
  Twenty-six neurofibromas, 62 schwannomas and 39 MPNSTs from a formalin-fixed paraffin-embedded tissue microarray were examined. Immunohistochemical analysis was performed with an anti-pSTAT3 (Tyr705) antibody. Nuclear expression was reviewed for both intensity and percentage of tumoral labelling. Distributions of disease-specific overall survival (DSOS) and event-free survival (EFS) were estimated with the Kaplan-Meier method, and compared between two pSTAT3 groups by use of the log-rank test. MPNSTs had higher median tumoral labelling than neurofibromas (P = 0.0012) or schwannomas (P = 0.0008). Moderate to strong pSTAT3 expression (defined as at least moderate labelling in ≥50% of cells) was found more frequently in MPNSTs than in neurofibromas (P = 0.026). Among MPNSTs, pSTAT3 expression differed between primary, recurrent and metastatic disease (P = 0.063 with increased expression in recurrent and metastatic cases). pSTAT3 expression (at least moderate labelling in ≥10% of cells) in primary MPNSTs was associated with worse DSOS (P = 0.048) and trended towards being associated with worse EFS (P = 0.063). Paired specimens revealed no increase in pSTAT3 expression in the recurrences or metastases relative to the primary tumour, suggesting that pSTAT3 expression may be an early indicator of aggressive disease at disease onset.
  
  
  CONCLUSIONS
  pSTAT3 is expressed in a higher proportion of MPNSTs than neurofibromas and schwannomas. Moderate to strong pSTAT3 expression in ≥10% of cells was found to be a negative prognostic factor for DSOS among primary MPNSTs, suggesting a role of pSTAT3 in the progression of these tumours.
authors.affiliation: Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Gauri
authors.initials: G
authors.lastname: Panse
authors.affiliation: Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Cheuk H
authors.initials: CH
authors.lastname: Leung
authors.affiliation: Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Davis R
authors.initials: DR
authors.lastname: Ingram
authors.affiliation: Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Khalida
authors.initials: K
authors.lastname: Wani
authors.affiliation: Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Keila E
authors.initials: KE
authors.lastname: Torres
authors.affiliation: Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Heather
authors.initials: H
authors.lastname: Lin
authors.affiliation: Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.|Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Alexander J
authors.initials: AJ
authors.lastname: Lazar
authors.affiliation: Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.|Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Wei-Lien
authors.initials: WL
authors.lastname: Wang
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis*; D002648:Child; D018450:Disease Progression; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D018317:Nerve Sheath Neoplasms / Q000378:metabolism* / Q000473:pathology*; D009442:Neurilemmoma / Q000378:metabolism / Q000473:pathology; D009455:Neurofibroma / Q000378:metabolism / Q000473:pathology; D010766:Phosphorylation; D011379:Prognosis; D050796:STAT3 Transcription Factor / Q000378:metabolism*; D046888:Tissue Array Analysis
chemical_list: D014408:Biomarkers, Tumor; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human
keywords: 
  MPNST
  ; nerve sheath tumours; pSTAT3; prognosis