title: TLE1 as a diagnostic immunohistochemical marker for synovial sarcoma emerging from gene expression profiling studies.
abstract: Synovial sarcoma is a soft tissue malignancy defined by the SYT-SSX fusion oncogene. Demonstration of the t(X;18) by cytogenetics, fluorescence in situ hybridization or reverse-transcriptase polymerase chain reaction has become the gold standard for diagnosis, but practical considerations limit the availability of these methods. Gene expression profiling studies performed by several independent groups have consistently identified TLE1 as an excellent discriminator of synovial sarcoma from other sarcomas, including histologically similar tumors such as malignant peripheral nerve sheath tumor. TLE proteins (human homologues of Groucho) are transcriptional corepressors that inhibit Wnt signaling and other cell fate determination signals, and so have an established role in repressing differentiation. We examined the expression of TLE proteins in synovial sarcoma and in a broad range of mesenchymal tumors using tissue microarrays to assess the value of anti-TLE antibodies in the immunohistochemical confirmation of synovial sarcoma. We demonstrate that TLE expression is a consistent feature of synovial sarcoma using both a well-characterized monoclonal antibody recognizing the TLE family of proteins and a commercially available polyclonal antibody raised against TLE1. Both antibodies gave intense and/or diffuse nuclear staining in 91/94 molecularly confirmed synovial sarcomas. Moderate staining is occasionally seen in schwannoma and solitary fibrous tumor/hemangiopericytoma. In contrast, TLE staining is detected much less frequently and at lower levels, if at all, in 40 other mesenchymal tumors. Our findings establish TLE as a robust immunohistochemical marker for synovial sarcoma, and may have implications for understanding the biology of synovial sarcoma and for developing experimental therapies for this cancer.
authors.affiliation: Genetic Pathology Evaluation Centre, British Columbia Cancer Agency, 600 West 10th Avenue, Vancouver, British Columbia, Canada V5Z 4E6.
authors.forename: Jefferson
authors.initials: J
authors.lastname: Terry
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Saito
authors.forename: Subbaya
authors.initials: S
authors.lastname: Subramanian
authors.forename: Cindy
authors.initials: C
authors.lastname: Ruttan
authors.forename: Cristina R
authors.initials: CR
authors.lastname: Antonescu
authors.forename: John R
authors.initials: JR
authors.lastname: Goldblum
authors.forename: Erinn
authors.initials: E
authors.lastname: Downs-Kelly
authors.forename: Christopher L
authors.initials: CL
authors.lastname: Corless
authors.forename: Brian P
authors.initials: BP
authors.lastname: Rubin
authors.forename: Matt
authors.initials: M
authors.lastname: van de Rijn
authors.forename: Marc
authors.initials: M
authors.lastname: Ladanyi
authors.forename: Torsten O
authors.initials: TO
authors.lastname: Nielsen
mesh_terms: D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D056970:Co-Repressor Proteins; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D007091:Image Processing, Computer-Assisted; D007124:Immunoenzyme Techniques; D008297:Male; D008875:Middle Aged; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D015203:Reproducibility of Results; D013584:Sarcoma, Synovial / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D012983:Soft Tissue Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D046888:Tissue Array Analysis
chemical_list: D014408:Biomarkers, Tumor; D056970:Co-Repressor Proteins; D012097:Repressor Proteins; C499043:TLE1 protein, human