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Prospective Evaluation of TLE1 as a Diagnostic Immunohistochemical Marker in Synovial Sarcoma

Jagdis, Amanda MD*; Rubin, Brian P. MD, PhD; Tubbs, Raymond R. MD; Pacheco, Marina MD*; Nielsen, Torsten O. MD, PhD, FRCPC*

The American Journal of Surgical Pathology: December 2009 - Volume 33 - Issue 12 - p 1743-1751
doi: 10.1097/PAS.0b013e3181b7ed36
Original Articles

Synovial sarcoma is a high-grade soft tissue sarcoma that can be challenging to diagnose on the basis of histology alone. It is defined by a characteristic translocation t(X;18) that produces the fusion oncogene SYT-SSX. The current diagnostic gold standard for synovial sarcoma is the demonstration of the translocation by fluorescence in situ hybridization, reverse transcriptase polymerase chain reaction, or cytogenetics, in an appropriate histologic context. TLE1 encodes a transcriptional corepressor that is overexpressed in synovial sarcomas. Gene and tissue microarray studies have identified TLE1 as an excellent bio-marker for distinguishing the synovial sarcoma from other soft tissue malignancies. We prospectively evaluated incoming soft tissue tumor cases where the histology and clinical setting made synovial sarcoma a real consideration in the differential diagnosis. TLE1, Bcl2, epithelial membrane antigen, and cytokeratin expression were assessed using commercially available antibodies. TLE1 gave intense, diffuse nuclear staining in 35 of 35 molecularly confirmed synovial sarcoma cases, and was rare to absent in the 73 other soft tissue tumors examined (positive staining was found only in 1 of 43 malignant peripheral nerve sheath tumors, the 1 tested fibrosarcoma, and 1 pleomorphic sarcoma). TLE1 was more sensitive and specific for synovial sarcoma than other currently available immunohistochemical markers including Bcl2, epithelial membrane antigen and cytokeratins, and had a positive predictive value of 92% and a negative predictive value of 100% in this clinical setting. Our findings confirm, in a prospective diagnostic context, that TLE1 is more sensitive and specific for synovial sarcoma than any other currently available immunohistochemical stains, and in some cases may preclude the need for molecular testing.

*Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, Canada

Departments of Anatomic Pathology, Molecular Genetics, and Taussig Cancer Center, Cleveland Clinic and Lerner College of Medicine of Case Western Reserve University, Cleveland, Ohio

Sources of support: Canadian Cancer Society, Michael Smith Foundation for Health Research, and Canadian Institutes for Health Research Training Program in Molecular Oncology.

Correspondence: Torsten O. Nielsen, MD, PhD, FRCPC, Anatomical Pathology JP1401 Vancouver Hospital, 855 West 12th Avenue Vancouver BC Canada V5Z 1M9 (e-mail:

© 2009 Lippincott Williams & Wilkins, Inc.