Frequent TRPS1 expression in synovial sarcoma is associated with SS18-SSX fusion oncoprotein activity

Hum Pathol. 2022 Sep 24;S0046-8177(22)00239-8. doi: 10.1016/j.humpath.2022.09.006. Online ahead of print.

Abstract

Synovial sarcoma is an aggressive translocation-associated soft tissue tumor driven by an SS18-SSX fusion oncoprotein. TRPS1 is a recently identified marker for breast carcinoma, but less is known about its expression in other tumor types. We encountered a case of synovial sarcoma showing strong and diffuse expression of TRPS1. To better characterize this observation, we examined the immunohistochemical expression of TRPS1 in 165 cases of synovial sarcoma, including 70 primary, 21 recurrent, and 74 metastatic tumors, using tissue microarrays. TRPS1 expression was observed in 86% of cases. Among the positive cases, TRPS1 labeled >50% of tumor cells in 57% of cases, and staining intensity was strong or moderate in 68%. Metastatic tumors more frequently demonstrated strong and diffuse TRPS1 expression compared to primary tumors. To understand the mechanism of TRPS1 expression, we interrogated publicly available gene expression and ChIP-seq datasets and found that TRPS1 transcript levels are increased in synovial sarcoma compared to other soft tissue sarcomas. Data from ChIP-seq experiments showed enrichment of SS18-SSX protein at the TRPS1 locus and co-localization with RNA pol II. The TRPS1 locus is also enriched in several histone modifications associated with active transcription. In functional knockdown data, repression of SS18::SSX in synovial sarcoma cell lines is associated with reduced TRPS1 transcript levels, further supporting a model whereby TRPS1 expression is mediated, at least in part, by the SS18-SSX fusion oncoprotein. Knowledge of TRPS1 expression in synovial sarcoma may help avoid potential diagnostic pitfalls in the immunohistochemical workup of tumors.

Keywords: Gene fusion; Immunohistochemistry; SS18-SSX; Synovial sarcoma; TRPS1.