TLE1 is a robust diagnostic biomarker for synovial sarcomas and correlates with t(X;18): analysis of 319 cases.
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 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.
Knösel
Thomas
T
Institute of Pathology, Friedrich-Schiller University, Ziegelmühlenweg 1, 07743 Jena, Germany. thomas.knoesel@med.uni-jena.de
Heretsch
Sarah
S
Altendorf-Hofmann
Annelore
A
Richter
Petra
P
Katenkamp
Kathrin
K
Katenkamp
Detlef
D
Berndt
Alexander
A
Petersen
Iver
I
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D002648:Child; D002902:Chromosomes, Human, 16-18 / Q000235:genetics; D041321:Chromosomes, Human, X / Q000235:genetics; D056970:Co-Repressor Proteins; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D008875:Middle Aged; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D012509:Sarcoma / Q000235:genetics / Q000378:metabolism; D013584:Sarcoma, Synovial / Q000235:genetics / Q000378:metabolism*; D012983:Soft Tissue Neoplasms / Q000235:genetics / Q000378:metabolism*; D014178:Translocation, Genetic / Q000235:genetics*; D055815:Young Adult
D014408:Biomarkers, Tumor; D056970:Co-Repressor Proteins; D012097:Repressor Proteins; C499043:TLE1 protein, human