Overexpression of TLE1 Is a Robust Biomarker for Synovial Sarcomas and Correlates with t(X;18): Analysis of 373 Cases
Th Knosel, S Heretsch, A Altendorf-Hofmann, P Richter, K Katenkamp, D Katenkamp, A Berndt, I Petersen. Friedrich-Schiller University, Jena, Germany
Background: Genomewide expression profiling has identified a number of genes expressed at higher levels in synovial sarcoma than in other sarcomas. Our objectives in this study were: 1) to test wether the differentially expressed gene, TLE1, is also distinct on the protein level 2) to evaluate this biomarker in a series of well characterized synovial sarcomas 3) to correlate the overexpression of TLE1 with t(X;18) and other established biomarkers.
Design: 373 spindle cell sarcomas from the german consultation and reference center of soft tissue tumors initially suspected for synovial sarcoma were revisited. Of these 202 specimens were analyzed immunohistochemically using the antibody TLE1. The staining was scored semiquantitatively as -, negative; +, weak; ++, moderate; and +++, strong positive. Furthermore, of these 118 specimens were analyzed using FISH and/or PCR to detect t(X;18) SYT-SSX translocation. We correlated the TLE1 overexpression with the translocation status and the other established biomarkers (EMA, PanCK, CD34, bcl2).
Results: TLE1 overexpression was observed in 96.5% of the synovial sarcomas (score +)and discriminates them from other soft tissue spindle cell tumors (p<0.001). Multivariate analysis showed that positive TLE1 and negative CD34 staining were statistically independent diagnostic markers. Furthermore molecular analysis showed that t(X;18) were clearly correlated with overexpression of the gene TLE1 (p<0.001).
Conclusions: Overexpression of TLE1 is significantly correlated with t(X;18) and may serve in synovial sarcomas as a new powerful diagnostic biomarker and potential therapeutic target.
Category: Bone & Soft Tissue
Monday, March 9, 2009 11:00 AM
Platform Session: Section E, Monday Morning