Immunohistochemical study of correlation between histologic subtype and expression of epithelial-mesenchymal transition-related proteins in synovial sarcomas.

Context: 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.

Design: 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.