TLE1 as a diagnostic immunohistochemical marker for synovial sarcoma emerging from gene expression profiling studies Journal Article


Authors: Terry, J.; Saito, T.; Subramanian, S.; Ruttan, C.; Antonescu, C. R.; Goldblum, J. R.; Downs-Kelly, E.; Corless, C. L.; Rubin, B. P.; van de Rijn, M.; Ladanyi, M.; Nielsen, T. O.
Article 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. Copyright © 2007 by Lippincott Williams & Wilkins.
Keywords: immunohistochemistry; adult; human tissue; protein expression; middle aged; unclassified drug; major clinical study; cancer diagnosis; reproducibility of results; gene; gene expression profiling; tumor markers, biological; protein; tumor marker; monoclonal antibody; immunoenzyme techniques; gene identification; tissue array analysis; tissue microarray; expression profiling; microarray; hemangiopericytoma; solitary fibrous tumor; synovial sarcoma; sarcoma, synovial; image processing, computer-assisted; repressor proteins; soft tissue neoplasms; protein antibody; neurilemoma; digital imaging; polyclonal antibody; tle; transducin; transducin like enhancer of split 1 protein; transducin like enhancer of split 1 gene
Journal Title: American Journal of Surgical Pathology
Volume: 31
Issue: 2
ISSN: 0147-5185
Publisher: Lippincott Williams & Wilkins  
Date Published: 2007-02-01
Start Page: 240
End Page: 246
Language: English
DOI: 10.1097/01.pas.0000213330.71745.39
PUBMED: 17255769
PROVIDER: scopus
DOI/URL:
Notes: --- - "Cited By (since 1996): 56" - "Export Date: 17 November 2011" - "CODEN: AJSPD" - "Source: Scopus"
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MSK Authors
  1. Tsuyoshi Saito
    22 Saito
  2. Cristina R Antonescu
    895 Antonescu
  3. Marc Ladanyi
    1326 Ladanyi