Expanding the Use of an SS18-SSX Antibody for Molecular Assays in Synovial Sarcoma.
Journal
Applied immunohistochemistry & molecular morphology : AIMM
ISSN: 1533-4058
Titre abrégé: Appl Immunohistochem Mol Morphol
Pays: United States
ID NLM: 100888796
Informations de publication
Date de publication:
01 09 2022
01 09 2022
Historique:
received:
04
05
2022
accepted:
13
06
2022
pubmed:
27
7
2022
medline:
11
9
2022
entrez:
26
7
2022
Statut:
ppublish
Résumé
Synovial sarcoma is an aggressive malignancy that generally affects adolescents and young adults and is characterized by high rates of recurrence and metastasis, with a 10-year survival rate of about 50%. The fusion oncoprotein SS18-SSX, the product of a pathognomonic chromosomal translocation t(X;18), is the oncogenic driver of this sarcoma, disrupting differentiation through widespread epigenetic dysregulation. Experimental research into SS18-SSX biology has been limited by the lack of an antibody that specifically detects the endogenous fusion oncoprotein as opposed to its native SS18 or SSX components. Recently, a rabbit monoclonal antibody was developed and made commercially available, which specifically detects the fusion junction site epitope of SS18-SSX as found in at least 95% of synovial sarcomas. Here, we characterize a suite of molecular biology assays using this new antibody, both confirming existing and reporting on novel applications. We demonstrate its high sensitivity and specificity for synovial sarcoma diagnosis on patient samples through positive immunohistochemical staining on synovial sarcoma, tissue microarray, and full face sections. In addition, we demonstrate detection of the human SS18-SSX protein when expressed in a genetically engineered mouse model of synovial sarcoma. We also demonstrate nuclear staining of SS18-SSX in synovial sarcoma cells using immunofluorescence, and visualize the interaction between SS18-SSX and the BAF complex member BRG1 through a proximity ligation assay. Lastly, we confirm the interaction between SS18-SSX and promoter regions of target genes through chromatin immunoprecipitation. This antibody represents a breakthrough in sarcoma research and has value in multiple applications to expand the knowledge of synovial sarcoma biology.
Identifiants
pubmed: 35880992
doi: 10.1097/PAI.0000000000001049
pii: 00129039-202209000-00001
pmc: PMC9444294
doi:
Substances chimiques
Antibodies, Monoclonal
0
Oncogene Proteins, Fusion
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
531-539Subventions
Organisme : NCI NIH HHS
ID : U54 CA231652
Pays : United States
Informations de copyright
Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc.
Déclaration de conflit d'intérêts
The authors declare no conflict of interest.
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