Strong association of SYT-SSX fusion type and morphologic epithelial differentiation in synovial sarcoma

Synovial sarcoma is characterized by a specific recurrent translocation t(X ;18), resulting in either the SYT-SSX1 or SYT-SSX2 gene fusion. Because thi s is the primary genetic alteration in these tumors, we sought to identify the impact of molecular heterogeneity of the t(X;18) on cell proliferation, apoptosis, and epithelial differentiation in synovial sarcoma. Seventy-thr ee patients with synovial sarcoma (18 biphasic, 55 monophasic) were selecte d on the basis of availability of tumor material for molecular and immunohi stochemical analysis. Tumors were classified as biphasic on the basis of mo rphologic glandular differentiation. SYT-SSX fusion transcripts were examin ed by reverse transcriptase polymerase chain reaction using tumor RNA extra cted from frozen or paraffin-embedded tissue. Cell proliferation was assess ed immunohistochemically by the Ki-67 labeling index. Apoptosis was analyze d immunohistochemically with BAX and BCL2 antibodies and by the TUNEL metho d. Immunohistochemical evidence of epithelial differentiation was assessed using antibodies to cytokeratins and epithelial membrane antigen. Approxima tely two thirds of the tumors had an SYT-SSX1 and one third had an SYT-SSX2 fusion transcript. There was a strong association between SYT-SSX fusion t ype and histologic subtype. All biphasic synovial sarcomas had the SYT-SSX1 fusion, whereas all tumors with SYT-SSX2 were of monophasic morphology. Th ere was, however, no association between SYT-SSX fusion type and expression of cytokeratins and epithelial membrane antigen among monophasic tumors. T umors with SYT-SSX2 had a significantly higher mean and median Ki-67 labeli ng index than those with SYT-SSX1, but a comparison of Ki-67 according to f usion type, histologic type, and sample source suggested that the main dete rminants of proliferation rate were the latter two factors. Specifically, m onophasic tumors and metastatic tumors showed significantly higher Ki-67 sc ores. Apoptosis (by TUNEL) was rarely observed, consistent with prominent e xpression of the anti-apoptotic protein BCL2 in almost all cases. TUNEL, BC L2, and BAX results did not correlate with SYT-SSX fusion type. These data confirm the strong association of SYT-SSX fusion transcript type with morph ologic but not immunophenotypic epithelial differentiation in synovial sarc oma.