The correlation between morphology and the expression of TGF-β signaling pathway proteins and epithelial-mesenchymal transition-related proteins in synovial sarcomas

Int J Clin Exp Pathol. 2013 Nov 15;6(12):2787-99. eCollection 2013.

Abstract

Synovial sarcoma (SS) is a malignant tumor of soft tissue and is noted for late local recurrence and metastasis. Aberrant epithelial-mesenchymal transition (EMT) has been implicated in the pathogenesis of diverse human malignancies. Immunohistochemical techniques were used to assess EMT-related proteins (E-cadherin, N-cadherin, β-catenin, Snail, and Slug) and the TGF-β1 pathway (TGF-β1 and Smad2/3) proteins expression in different histological subtypes and epithelial mesenchymal compositions of SS. The expression of cell-surface (E-cadherin) and cytoskeletal proteins (β-catenin) were higher significantly in biphasic SSs (BSSs) (70.4%, 51.9%) than MFSSs (both for 10%). Among monophasic fibrous SSs (MFSSs) samples, E-cadherin protein expression was negatively correlated with expression Snail, Slug, TGF-β1, and Smad2/3. The expression levels of Snail and Smad2/3 were correlated with the pTNM stage (I-II vs. III-IV; P=0.047, P=0.021) and TGF-β1 exhibited a tendency toward a positive correlation with pTNM stage (I-II vs. III-IV; P=0.052), but did not correlate with the histological grade (p>0.05). Interestingly, our data showed that expression of E-cadherin protein correlated with greater survival in SS patients. Overexpression of Snail, and TGF-β1 is associated with suppressed expression of E-cadherin in MFSSs, which supports the hypothesis that the MFSS subtype may have developed via neoplastic EMT.

Keywords: Synovial sarcomas; TGF-β1 signaling pathway; epithelial-mesenchymal transition; immunohistochemistry.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Antigens, CD / analysis
  • Biomarkers, Tumor / analysis*
  • Cadherins / analysis
  • Child
  • Epithelial-Mesenchymal Transition*
  • Female
  • Humans
  • Immunohistochemistry
  • Kaplan-Meier Estimate
  • Male
  • Middle Aged
  • Neoplasm Grading
  • Neoplasm Staging
  • Sarcoma, Synovial / chemistry*
  • Sarcoma, Synovial / mortality
  • Sarcoma, Synovial / pathology
  • Signal Transduction
  • Smad2 Protein / analysis
  • Smad3 Protein / analysis
  • Snail Family Transcription Factors
  • Soft Tissue Neoplasms / chemistry*
  • Soft Tissue Neoplasms / mortality
  • Soft Tissue Neoplasms / pathology
  • Transcription Factors / analysis
  • Transforming Growth Factor beta1 / analysis*
  • Young Adult
  • beta Catenin / analysis

Substances

  • Antigens, CD
  • Biomarkers, Tumor
  • CDH1 protein, human
  • CDH2 protein, human
  • CTNNB1 protein, human
  • Cadherins
  • SMAD2 protein, human
  • SMAD3 protein, human
  • SNAI1 protein, human
  • Smad2 Protein
  • Smad3 Protein
  • Snail Family Transcription Factors
  • TGFB1 protein, human
  • Transcription Factors
  • Transforming Growth Factor beta1
  • beta Catenin