title: The diagnostic utility of reduced immunohistochemical expression of SMARCB1 in synovial sarcomas: a validation study.
abstract: Synovial sarcoma is a malignant mesenchymal neoplasm of uncertain histogenesis, characterized by a specific SS18-SSX fusion. The diagnosis of synovial sarcoma can be challenging based on morphology and conventional immunohistochemistry alone, and identification of the fusion gene by molecular genetics may be necessary for diagnosis. Several recent studies have demonstrated the diagnostic utility of the reduced expression of SMARCB1 in synovial sarcomas as measured using immunohistochemistry. Therefore, we undertook a validation study using synovial sarcomas and other spindle or round cell tumors that could enter differential diagnosis of monophasic or poorly differentiated synovial sarcomas. Among 36 synovial sarcomas that were successfully evaluated, the expression of SMARCB1 was diffusely reduced in 33 cases (92%) at variable degrees. In contrast, the expression of SMARCB1 was not reduced in any of the 93 evaluable non-synovial sarcoma tumors (5 thymomas, 5 sarcomatoid mesotheliomas, 10 schwannomas, 9 mesenchymal chondrosarcomas, 20 solitary fibrous tumors, 19 Ewing sarcomas, and 25 malignant peripheral nerve sheath tumors). A few schwannomas and malignant peripheral nerve sheath tumors showed mosaic or complete loss of SMARCB1 expression. Reduced expression of SMARCB1 immunoreactivity was therefore found to be highly sensitive and specific for synovial sarcoma, and can be useful for rapidly and accurately confirming the diagnosis of synovial sarcoma. This reduction in SMARCB1 expression likely reflects the BAF47 ejection mechanism of the SS18-SSX fusion product and can therefore be viewed as an indirect visualization of this fusion product.
authors.affiliation: Department of Pathology and Clinical Laboratories, National Cancer Center Hospital, Tokyo, 104-0045 Japan.
authors.forename: Junko
authors.initials: J
authors.lastname: Ito
authors.affiliation: Division of Rare Cancer Research, National Cancer Center Research Institute, Tokyo, 104-0045 Japan; Department of Orthopedic Surgery, Keio University School of Medicine, Tokyo, 160-0016 Japan.
authors.forename: Naofumi
authors.initials: N
authors.lastname: Asano
authors.affiliation: Department of Musculoskeletal Oncology, National Cancer Center Hospital, Tokyo, 104-0045 Japan; Rare Cancer Center, National Cancer Center Hospital, Tokyo, 104-0045 Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Kawai
authors.affiliation: Department of Pathology and Clinical Laboratories, National Cancer Center Hospital, Tokyo, 104-0045 Japan; Rare Cancer Center, National Cancer Center Hospital, Tokyo, 104-0045 Japan. Electronic address: akyoshid@ncc.go.jp.
authors.forename: Akihiko
authors.initials: A
authors.lastname: Yoshida
mesh_terms: D014408:Biomarkers, Tumor / Q000032:analysis* / Q000235:genetics; D002148:Calmodulin-Binding Proteins / Q000235:genetics; D002454:Cell Differentiation; D002868:Chromosomal Proteins, Non-Histone / Q000032:analysis*; D004268:DNA-Binding Proteins / Q000032:analysis*; D003937:Diagnosis, Differential; D015536:Down-Regulation; D050939:Gene Fusion; D015321:Gene Rearrangement; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D009363:Neoplasm Proteins / Q000235:genetics; D016133:Polymerase Chain Reaction; D011237:Predictive Value of Tests; D011518:Proto-Oncogene Proteins / Q000235:genetics; D034802:RNA-Binding Protein EWS; D016601:RNA-Binding Proteins / Q000235:genetics; D012097:Repressor Proteins / Q000235:genetics; D015203:Reproducibility of Results; D000071796:SMARCB1 Protein; D013584:Sarcoma, Synovial / Q000737:chemistry* / Q000235:genetics / Q000473:pathology; D014157:Transcription Factors / Q000032:analysis*
chemical_list: D014408:Biomarkers, Tumor; D002148:Calmodulin-Binding Proteins; D002868:Chromosomal Proteins, Non-Histone; D004268:DNA-Binding Proteins; C500986:EWSR1 protein, human; D009363:Neoplasm Proteins; D011518:Proto-Oncogene Proteins; D034802:RNA-Binding Protein EWS; D016601:RNA-Binding Proteins; D012097:Repressor Proteins; D000071796:SMARCB1 Protein; C513266:SMARCB1 protein, human; C093961:SS18 protein, human; D014157:Transcription Factors; C093962:synovial sarcoma X breakpoint proteins
keywords: Diagnosis; Immunohistochemistry; SMARCB1; SS18-SSX; Synovial sarcoma