IJCEP Copyright © 2007-All rights reserved.
Int J Clin Exp Pathol 2013;6(11):2272-2279

Review Article
The SYT-SSX fusion protein and histological epithelial differentiation in synovial
sarcoma: relationship with extracellular matrix remodeling

Tsuyoshi Saito

Department of Human Pathology, Juntendo University, School of Medicine, Hongo 2-1-1, Bunkyo-ku, Tokyo 113-8421, Japan

Received August 14, 2013; Accepted August 31, 2013; Epub October 15, 2013; Published November 1, 2013

Abstract: Synovial sarcoma (SS) tumor cells, which have the chromosomal translocation t(X;18)(p11.2;q11.2), have an inherently greater
propensity for epithelial differentiation than other mesenchymal tumors, especially spindle cell sarcomas. This is caused by de-repression of
the transcription of E-cadherin by SYT-SSX1 and SYT-SSX2, which dissociate Snail or Slug, respectively, from the E-cadherin promoter.
However, a subset of SS with SYT-SSX1 loses E-cadherin expression despite adequate de-repression because of mutations in E-cadherin,
resulting in monophasic histology. The ratio of the expression levels of SYT-SSX1 and Snail is also associated with E-cadherin expression: the
lower the SYT-SSX1/Snail ratio, the lower the level of E-cadherin expression, and vice versa, thus affecting tumor histology. In addition, Wnt
signal activation caused by mutation of β-catenin, APC, or Axin 1 and 2 is associated with monophasic histology. Remodeling of the
extracellular matrix is also important. Only cells that survive all of these steps can finally exhibit biphasic histology. On the other hand, the SYT-
SSX2 fusion has a weaker de-repression effect on the E-cadherin promoter than does SYT-SSX1, so it is difficult for SYT-SSX2-expressing
tumors to achieve sufficient capacity for epithelial differentiation to form glandular structures. This review provides an interesting model for this
epithelial differentiation that shows a possible mechanism for the aberrant mesenchymal to epithelial transition of SS and suggests that it
might better be considered an epithelial to mesenchymal transition. (IJCEP1308039).

Keywords: Synovial sarcoma, chromosomal translocation t(X;18)(p11.2;q11.2), epithelial differentiation, E-cadherin, SYT-SSX1, SYT-SSX2

Address correspondence to: Dr. Tsuyoshi Saito, Department of Human Pathology, Juntendo University, School of Medicine, Hongo 2-1-1,
Bunkyo-ku, Tokyo 113-8421, Japan. E-mail: tysaitou@juntendo.ac.jp