Association of SYT-SSX Fusion Types with Proliferative Activity and Prognosis in Synovial Sarcoma
Department of Pathology, Nagoya City University Medical School, Nagoya, Japan. Modern Pathology
(Impact Factor: 6.19).
06/2000; 13(5):482-8. DOI: 10.1038/modpathol.3880083
The t(X;18)(p11.2;q11.2) translocation commonly found in synovial sarcoma (SS) results in the fusion of the SYT gene on chromosome 18 to either of two closely related genes, SSX1 and SSX2, on chromosome X. It has been suggested that patients who have SS bearing SYT-SSX1 fusion have worse prognosis than those bearing SYT-SSX2 fusion. However, little is known about the biologic basis or the relationship with the histopathologic risk factors in regard to the different fusion types. We analyzed 19 cases of SS with no metastasis at diagnosis. These tumors were classified by reverse transcription-polymerase chain reaction to SYT-SSX1 and SYT-SSX2 types. The expression of Ki-67, p27, p53, and bcl-2 and various clinicopathologic parameters including mitotic rate were compared between the two fusion types. The SYT-SSX1 type fusion was associated with high Ki-67 expression (P = .011) and high mitotic rate (P = .070). No significant differences were found between the two types as to the expression of p27, p53, and bcl-2 and other clinicopathologic parameters. The survival analysis showed that SYT-SSX1-type fusion, high Ki-67 expression, and high mitotic rate correlated with shorter metastasis-free survival. These data suggested that SYT-SSX fusion type is associated with tumor cell proliferative activity and prognosis of patients who have SS.
Available from: Maria Debiec-Rychter
- "Both by functional and expression profiling studies, it has been shown that these proteins may have distinct molecular activities even though their sequences are highly homologous and they induce tumors with similar pathological features. Inagaki et al.  compared the impact of SS18-SSX1 and SS18-SSX2 fusion types on the expression level of several tumor cell proliferation-associated genes and other tumor-related pathological parameters in SS primary tumor specimens. As compared to the SS18-SSX2 fusion protein, the SS18-SSX1 fusion protein is related to higher mitotic rate and higher proliferation index as measured by Ki-67 staining. "
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ABSTRACT: Synovial sarcoma (SS), an aggressive type of soft tissue tumor, occurs mostly in adolescents and young adults. The origin and molecular mechanism of the development of SS remain only partially known. Over 90% of SS cases are characterized by the t(X;18)(p11.2;q11.2) translocation, which results mainly in the formation of
SS18-SSX1 or SS18-SSX2 fusion genes. In recent years, several reports describing direct and indirect interactions of SS18-SSX1/SSX2 oncoproteins have been published. These reports suggest that the fusion proteins particularly affect the cell growth, cell proliferation, TP53 pathway, and chromatin remodeling mechanisms, contributing to SS oncogenesis. Additional research efforts are required to fully explore the protein-protein interactions of SS18-SSX oncoproteins and the pathways that are regulated by these partnerships for the development of effective targeted therapy.
Available from: ncbi.nlm.nih.gov
- "The molecular analysis of SYT gene alteration played an important role in the diagnosis of synovial sarcoma. The gene fusion type of SYT-SSX1, as identified in this case, has been reported with worse prognosis than that with SYT-SSX2 . "
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ABSTRACT: Poorly differentiated synovial sarcomas are diagnostically challenging soft tissue tumors. They can be indistinguishable from other "small blue cell tumors" based on morphology and even immunohistochemical studies. Here we report a rare case of poorly differentiated metastatic synovial sarcoma to lung without known primary, diagnosed with molecular genetic analysis. The tumor was negative for EMA and cytokeratin, previously reported as the most sensitive immunostaining markers for synovial sarcomas. SYT-SSX gene fusion, characteristic for synovial sarcoma, was identified in this case by FISH and RT-PCR assays.
- "A number of studies have suggested that i) patients with SYT-SSX-containing synovial sarcoma have worse overall and five-year metastasis-free survival and ii) SYT-SSX1 has a higher proliferative activity. Ladayni et al. also demonstrated that tumors with the SYT-SSX2 transcript were confined to monophasic tumors and had better prognosis than tumors with the SYT-SSX1 transcript. "
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ABSTRACT: Malignant small round cell tumors are characterised by small, round, relatively undifferentiated cells. They generally include Ewing's sarcoma, peripheral neuroectodermal tumor, rhabdomyosarcoma, synovial sarcoma, non-Hodgkin's lymphoma, retinoblastoma, neuroblastoma, hepatoblastoma, and nephroblastoma or Wilms' tumor. Other differential diagnoses of small round cell tumors include small cell osteogenic sarcoma, undifferentiated hepatoblastoma, granulocytic sarcoma, and intraabdominal desmoplastic small round cell tumor. Differential diagnosis of small round cell tumors is particularly difficult due to their undifferentiated or primitive character. Tumors that show good differentiation are generally easy to diagnose, but when a tumor is poorly differentiated, identification of the diagnostic, morphological features is difficult and therefore, no definitive diagnosis may be possible. As seen in several study reports, fine needle aspiration cytology (FNAC) has become an important modality of diagnosis for these tumors. The technique yields adequate numbers of dissociated, viable cells, making it ideally suitable for ancillary techniques. Typically, a multimodal approach is employed and the principal ancillary techniques that have been found to be useful in classification are immunohistochemistry and immunophenotyping by flow cytometry, reverse transcriptase polymerase chain reaction (RT-PCR), fluorescence in situ hybridization (FISH), and electron microscopy. However, the recent characterization of chromosomal breakpoints and the corresponding genes involved in malignant small round cell tumors means that it is possible to use molecular genetic approaches for detection.
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