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

Abstract

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.

• Authors: Manish Mani Subramaniam, Samuel Navarro, Antonio Llombart-Bosch
• Journal: Archives of pathology & laboratory medicine (Arch Pathol Lab Med) Vol. 135 Issue 8 Pg. 1001-9 (Aug 2011) ISSN: 1543-2165 [Electronic] United States
• PMID: 21809991 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Biomarkers, Tumor
• Cadherins
• FXYD5 protein, human
• Ion Channels
• Membrane Glycoproteins
• Microfilament Proteins
• Neoplasm Proteins
• SNAI1 protein, human
• Snail Family Transcription Factors
• Transcription Factors

Topics

• Biomarkers, Tumor (metabolism)
• Cadherins (metabolism)
• Epithelial-Mesenchymal Transition
• Humans
• Immunohistochemistry (methods)
• Ion Channels
• Membrane Glycoproteins (metabolism)
• Microfilament Proteins
• Neoplasm Proteins (metabolism)
• Sarcoma, Synovial (diagnosis, metabolism)
• Snail Family Transcription Factors
• Tissue Array Analysis
• Transcription Factors (metabolism)