TLE1 as a Diagnostic Immunohistochemical Marker for... : The American Journal of Surgical Pathology (original) (raw)

Original Articles

TLE1 as a Diagnostic Immunohistochemical Marker for Synovial Sarcoma Emerging From Gene Expression Profiling Studies

Terry, Jefferson MD*; Saito, Tsuyoshi MD, PhD†; Subramanian, Subbaya PhD‡; Ruttan, Cindy MSc*; Antonescu, Cristina R. MD†; Goldblum, John R. MD§; Downs-Kelly, Erinn MD§; Corless, Christopher L. MD, PhD∥; Rubin, Brian P. MD, PhD¶; van de Rijn, Matt MD, PhD‡; Ladanyi, Marc MD†; Nielsen, Torsten O. MD, PhD*

*Genetic Pathology Evaluation Centre, British Columbia Cancer Agency, 600 West 10th Avenue, Vancouver, British Columbia, Canada V5Z 4E6

†Department of Pathology, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10021

‡Department of Pathology, Stanford University Medical Center, 300 Pasteur Drive, Stanford, CA 94305

§Department of Anatomic Pathology, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH 44195

∥Department of Pathology and OHSU Cancer Institute, Oregon Health and Science University, Portland, OR 97239-3098

¶Department of Anatomical Pathology, University of Washington Medical Center, Seattle, WA 98195

Supported by grants from the Terry Fox Foundation (to Torsten O. Nielsen), the National Institute of Health (to Marc Ladanyi), and the US Department of Defense (DoD DAMD17-03-1-0297, to Matt van de Rijn). Torsten O. Nielsen is a scholar of the Michael Smith Foundation for Health Research. Jefferson Terry is a recipient of a Canadian Institutes of Health Research Doctoral Fellowship. T.S. is a recipient of a postdoctoral fellowship from The Uehara Memorial Foundation (Japan). The Genetic Pathology Evaluation Centre is supported by an unrestricted education grant from Sanofi-Aventis.

Reprints: Torsten O. Nielsen, MD, PhD, Anatomical Pathology, Vancouver Coastal Health Research Institute, Room JP1502, 855 West 12th Avenue, Vancouver, British Columbia, Canada, V5Z 1M9 (e-mail: [email protected]).

Reprints also to: Marc Ladanyi, MD, Department of Pathology, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10021 (e-mail: [email protected]).

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.