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

T Knösel, S Heretsch, A Altendorf-Hofmann… - European Journal of …, 2010 - Elsevier
T Knösel, S Heretsch, A Altendorf-Hofmann, P Richter, K Katenkamp, D Katenkamp…
European Journal of Cancer, 2010Elsevier
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 …
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.
Elsevier
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