SS18-SSX and SSX c-terminus antibodies for identification of specific fusion oncoprotein in mesenchymal neoplasms

Chromosomal rearrangement can be identified by direct methods or by using immunohistochemistry for a component of the fusion oncoprotein as a surrogate marker. Our aim was to gain insights into the staining profile using novel SS18-SSX and SSX c-terminus antibodies in SS18 fusion tumours and to investigate their potential use in soft tissue tumours harbouring SSX fusion partner outside the spectrum of synovial sarcoma. A retrospective analysis of 310 soft tissue sarcomas [via tissue microarray (TMA)] diagnosed at our Institution between 1999 and 2019 was performed. As controls, whole tissue sections from 14 genetically confirmed synovial sarcomas and one EWSR1::SSX2 rearranged sarcoma diagnosed between 2020 and 2023 were included. Two different antibodies for SSX locus were used: SSX c-terminus and SS18-SSX. Twenty-one of 310 (6.8%) and 25 of 310 (8.1%) sarcomas on the TMA showed nuclear staining with SS18-SSX and SSX, respectively. From the 24 synovial sarcomas, 17 (70.8%) stained positive for both antibodies, and in five of these cases, nuclear staining for SSX was weak. In four (16.7%) cases, only SS18-SSX was positive, and in three (12.5%) cases, only SSX staining was found. Furthermore, SSX nuclear expression was only found in four of 62 (6.5%) myxofibrosarcomas. In the control cohort, 11 of 14 synovial sarcomas (78.6%) showed positive staining for both antibodies. The remaining three cases were negative for SS18-SSX, but demonstrated at least focally strong positivity for SSX. The EWSR1::SSX2 rearranged sarcoma showed strong nuclear positivity for SSX. SS18-SSX and SSX c-terminus antibodies are reliable diagnostic markers that can be used as a surrogate marker for identification of a specific fusion. The SS18-SSX antibody is more specific and shows strong nuclear staining in synovial sarcomas, whereas SSX can present with weak staining and is less specific. However, the latter can be used in soft tissue tumours harbouring SSX fusion partner outside the spectrum of synovial sarcoma.