Specificity of TLE1 Expression in Unclassified High-grade Sarcomas for the Diagnosis of Synovial Sarcoma

Abstract

Expression of the transducin-like enhancer of split 1 (TLE1) by immunohistochemistry (IHC) has been widely used as a biomarker for the diagnosis of synovial sarcoma. Although TLE1 expression can be identified in more than 90% of synovial sarcomas, positive staining has been reported in up to one third of nonsynovial sarcomas, including peripheral nerve sheath tumors and neoplasms of fibrous and adipose tissues. The low specificity of this test in soft tissue tumors raises concern on its clinical application as a diagnostic biomarker. As synovial sarcoma is frequent among the differential diagnosis of unclassified high-grade sarcomas, and considering that the specificity of TLE1 antibody in this tumor group remains unclear, we evaluated TLE1 expression by IHC in 42 unclassified high-grade sarcomas. SS18 (SYT) gene break-apart analyses by fluorescence in situ hybridization were simultaneously performed as a gold standard biomarker for synovial sarcoma. Five cases that were positive for the SS18 break-apart by fluorescence in situ hybridization were also positive for TLE1 by IHC, whereas the remaining 37 cases negative for SS18 break-apart were all negative for TLE1. The results showed no evidence of nonspecific TLE1 expression in the nonsynovial high-grade sarcomas. We concluded that TLE1 is a highly specific biomarker for synovial sarcoma in the setting of differential diagnosis of unclassified high-grade sarcomas.

Reappraisal of TLE‐1 immunohistochemical staining and molecular detection of SS18‐SSX fusion transcripts for synovial sarcoma

“…It was also found that no significant difference existed in TLE‐1 staining among the different subtypes of synovial sarcoma ( P ‐value >0.05). In other words, our study supports the use of TLE‐1 staining for the diagnosis of poorly differentiated synovial sarcoma …”

Synovial Sarcoma: Recent Discoveries as a Roadmap to New Avenues for Therapy

“…The identification of the corepressor TLE1 as an SS18-SSX interacting protein is also significant because expression profiling experiments have identified TLE1 among the most consistently highly expressed genes in primary synovial sarcoma specimens (29, 35). Incidentally, nuclear expression of TLE1 is readily detectable by immunohistochemistry on formalin-fixed paraffin-embedded tissues, and its diagnostic value for synovial sarcoma has been confirmed (36, 37), leading to its adoption into clinical use.…”

Clinicopathologic and Prognostic Significance of Transducin-Like Enhancer of Split 1 Protein Expression in Invasive Breast Cancer

“…TLE1 is involved in the Wnt/β-catenin signaling pathway, which is important in synovial sarcomas, and in the nuclear factor κB (NF-κB) pathway that regulates inflammation [891011]. TLE1 is a highly sensitive immunohistochemical marker for the diagnosis of synovial sarcoma; however, TLE1 expression is not specific for synovial sarcoma, as it is expressed in other tumor types [1213]. Knockdown of TLE1 in fibroblasts and synovial cells enhances the cytotoxic effect of chemotherapy, which suggests that TLE1 could be a promising therapeutic target for selectively treating synovial sarcoma without damaging healthy tissue [14].…”