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.

• Authors: Thomas Knösel, Sarah Heretsch, Annelore Altendorf-Hofmann, Petra Richter, Kathrin Katenkamp, Detlef Katenkamp, Alexander Berndt, Iver Petersen
• Journal: European journal of cancer (Oxford, England : 1990) (Eur J Cancer) Vol. 46 Issue 6 Pg. 1170-6 (Apr 2010) ISSN: 1879-0852 [Electronic] England
• PMID: 20189377 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Crown Copyright (c) 2010. Published by Elsevier Ltd. All rights reserved.

Chemical References

• Biomarkers, Tumor
• Co-Repressor Proteins
• Repressor Proteins
• TLE1 protein, human

Topics

• Adolescent
• Adult
• Aged
• Aged, 80 and over
• Biomarkers, Tumor (genetics, metabolism)
• Child
• Chromosomes, Human, 16-18 (genetics)
• Chromosomes, Human, X (genetics)
• Co-Repressor Proteins
• Female
• Gene Expression Regulation, Neoplastic
• Humans
• Male
• Middle Aged
• Repressor Proteins (genetics, metabolism)
• Sarcoma (genetics, metabolism)
• Sarcoma, Synovial (genetics, metabolism)
• Soft Tissue Neoplasms (genetics, metabolism)
• Translocation, Genetic (genetics)
• Young Adult