TLE1 is a robust diagnostic biomarker for synovial sarcomas and correlates with t(X;18): Analysis of 319 cases

Abstract

Introduction 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 whether the differentially expressed gene, Transducin-Like Enhancer of split (TLE1) belonging to the groucho/TLE family, is also distinct on the protein level; (2) to evaluate this biomarker in a series of well-characterised synovial sarcomas on standard, full-sized tissue sections and (3) to correlate the expression of TLE1 with t(X;18) and other established biomarkers. Methods Three-hundred and eighty four spindle cell sarcomas from the German consultation and reference centre of soft tissue tumours initially suspected for synovial sarcoma were revisited. Three-hundred and nineteen of these specimens were analysed immunohistochemically using a monoclonal antibody TLE1 and standard, full-sized tissue sections. The nuclear staining was scored semiquantitatively as −, negative; +, weak; ++, moderate and +++, strong positive. Furthermore, 118 specimens among these were further analysed using FISH and/or PCR to detect t(X;18). We correlated the TLE1 expression with the t(X;18) translocation and other established biomarkers (EMA, PanCK, CK7, CD34 and BCL2). Results TLE1 expression was observed in 96% of the synovial sarcomas (score ⩾ +, 249/259) and discriminates them from other soft tissue tumours ( p < 0.001). Multivariate analysis showed that positive TLE1 staining was a statistically independent diagnostic marker. Furthermore molecular analysis showed that t(X;18) was clearly correlated with TLE1 protein expression ( p < 0.001). Conclusions Expression of TLE1 is significantly correlated with t(X;18) and may serve as a new robust diagnostic biomarker in synovial sarcomas and potential therapeutic target.