Journal article
A Novel SS18-SSX Fusion-specific Antibody for the Diagnosis of Synovial Sarcoma
The American journal of surgical pathology, Vol.44(7), pp.922-933
07/2020
DOI: 10.1097/PAS.0000000000001447
PMCID: PMC7289668
PMID: 32141887
Abstract
Synovial sarcoma (SS), an aggressive soft tissue sarcoma with a predilection for the extremities of young adults, harbors the pathognomonic t(X;18)(p11;q11) translocation, resulting in SS18-SSX rearrangements. SS includes monophasic, biphasic, and poorly differentiated variants, which show considerable histologic overlap with a range of other tumor types, making the diagnosis challenging on limited biopsies. Immunohistochemistry (IHC) is routinely used in the differential diagnosis; however, presently available markers lack specificity. Thus, cytogenetic or molecular genetic techniques are often employed to confirm the diagnosis. Here, we report the development and characterization of 2 novel antibodies: an SS18-SSX fusion-specific antibody (E9X9V, designed to the breakpoint) as well as an SSX-specific antibody (E5A2C, designed to the SSX C-terminus). We validated the selectivity and specificity of the antibodies using immunoblotting, immunoprecipitation, and chromatin immunoprecipitation followed by next-generation sequencing in SS cell lines and demonstrated that both antibodies capture SS18-SSX on chromatin at established target sites (eg, TLE1 and BCL2) genome-wide. Using IHC in whole sections from 400 tumors including 100 genetically confirmed cases of SS and 300 histologic mimics, the SS18-SSX fusion-specific antibody revealed strong diffuse nuclear staining in 95 of 100 (95%) SS cases, whereas none of the 300 control tumors showed any staining. The SSX antibody showed strong diffuse nuclear staining in all 100 (100%) SS cases; 13 (4%) of the 300 other tumors were also positive, 5 of which displayed >50% nuclear staining. In summary, a novel SS18-SSX fusion-specific antibody is highly sensitive (95%) and specific (100%) for SS, and an antibody to the SSX C-terminus is also highly sensitive (100%), but slightly less specific (96%). IHC using the SS18-SSX antibody could replace molecular genetic or cytogenetic testing in most cases, and these reagents together will also provide the research community with valuable tools for further biochemical and genomic interrogation of the SS18-SSX fusion protein.
Details
- Title: Subtitle
- A Novel SS18-SSX Fusion-specific Antibody for the Diagnosis of Synovial Sarcoma
- Creators
- Esther Baranov - Brigham and Women's HospitalMatthew J McBride - Harvard UniversityAndrew M Bellizzi - University of Iowa Hospitals and ClinicsAzra H Ligon - Brigham and Women's HospitalChristopher D M Fletcher - Brigham and Women's HospitalCigall Kadoch - Harvard UniversityJason L Hornick - Brigham and Women's Hospital
- Resource Type
- Journal article
- Publication Details
- The American journal of surgical pathology, Vol.44(7), pp.922-933
- DOI
- 10.1097/PAS.0000000000001447
- PMID
- 32141887
- PMCID
- PMC7289668
- NLM abbreviation
- Am J Surg Pathol
- ISSN
- 0147-5185
- eISSN
- 1532-0979
- Grant note
- R01 CA237241 / NCI NIH HHS DP2 CA195762 / NCI NIH HHS P30 CA086862 / NCI NIH HHS
- Language
- English
- Date published
- 07/2020
- Academic Unit
- Pathology
- Record Identifier
- 9984185279002771
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