title: Immunohistochemical study of correlation between histologic subtype and expression of epithelial-mesenchymal transition-related proteins in synovial sarcomas.
abstract: BACKGROUND
  Synovial sarcomas are mesenchymal tumors with epithelial nature and comprise biphasic and monophasic fibrous subtypes. However, factors determining epithelial or spindle cell differentiation are still unexplored. Aberrant epithelial-mesenchymal transition has been implicated in the pathogenesis of diverse human malignancies.
  
  
  OBJECTIVE
  To analyze the correlation between cellular phenotype and expression of proteins associated with different epithelial-mesenchymal transition-related pathways.
  
  
  METHODS
  Immunohistochemical analysis of E-cadherin, Snail, Slug, and dysadherin, components of the Wnt/wingless and PI3K/Akt pathways, was performed on 14 biphasic and 27 monophasic fibrous tumors.
  
  
  RESULTS
  In monophasic fibrous tumors, increased expression of Snail (17 of 27; 63%), Slug (18 of 27; 67%), and dysadherin (14 of 27; 52%) and activation of Wnt (nucleocytoplasmic β-catenin accumulation in 63%; n = 27; and positive expression of GSK3 and pGSK3 in 24 of 27 [89%] and 21 of 27 [78%], respectively) and PI3K/Akt (Akt: 22 of 27 [81%]; pAkt: 25 of 27 [93%]; and PI3K: 20 of 27 [74%]) signaling correlated significantly with inactivated E-cadherin expression (1 of 27; 4%) (all P < .05). In contrast, preserved E-cadherin expression (12 of 14; 86%) in the glandular component of the biphasic subtype was associated with significantly decreased Snail (3 of 14; 21%) (P = .02) and dysadherin (2 of 14; 14%) expression (P < .001).
  
  
  CONCLUSIONS
  Overexpression of Snail, Slug, and dysadherin and activation of Wnt and PI3K/Akt signaling was associated with inactivated E-cadherin in the spindle cells of monophasic fibrous synovial sarcomas, further supporting the hypothesis that this subtype may have developed through neoplastic epithelial-mesenchymal transition.
authors.affiliation: Department of Pathology, Medical School, University of Valencia, Spain.
authors.forename: Manish Mani
authors.initials: MM
authors.lastname: Subramaniam
authors.forename: Samuel
authors.initials: S
authors.lastname: Navarro
authors.forename: Antonio
authors.initials: A
authors.lastname: Llombart-Bosch
mesh_terms: D014408:Biomarkers, Tumor / Q000378:metabolism*; D015820:Cadherins / Q000378:metabolism; D058750:Epithelial-Mesenchymal Transition; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D007473:Ion Channels; D008562:Membrane Glycoproteins / Q000378:metabolism; D008840:Microfilament Proteins; D009363:Neoplasm Proteins / Q000378:metabolism; D013584:Sarcoma, Synovial / Q000175:diagnosis* / Q000378:metabolism; D000071250:Snail Family Transcription Factors; D046888:Tissue Array Analysis; D014157:Transcription Factors / Q000378:metabolism
chemical_list: D014408:Biomarkers, Tumor; D015820:Cadherins; C451410:FXYD5 protein, human; D007473:Ion Channels; D008562:Membrane Glycoproteins; D008840:Microfilament Proteins; D009363:Neoplasm Proteins; C000604407:SNAI1 protein, human; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors