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World Journal of Surgical Oncology Aug 2018Synovial sarcoma (SS) is a soft tissue sarcoma that rarely occurs in the spine, and a minimal number of cases have been reported in the literature. Spinal SS is...
BACKGROUND
Synovial sarcoma (SS) is a soft tissue sarcoma that rarely occurs in the spine, and a minimal number of cases have been reported in the literature. Spinal SS is challenging in diagnosis and treatment and has a poor prognosis. The aim of this study was to summarize and analyse the clinical features and outcomes of patients with spinal SS.
METHODS
A total of 16 cases of patients with spinal SS admitted to our institution were reviewed retrospectively. General information, radiological findings and treatment strategies were collected. These patients were followed up regarding their continuing treatment, local or distant recurrence and survival.
RESULTS
Spinal SS patients in this series ranged in age from 12 to 68 years (median, 33). Four en bloc resections and 12 piecemeal resections were performed. Improved Frankel (P = 0.002), visual analogue scale (P = 0.002) and Karnofsky Performance Status (P = 0.002) scores were seen postoperatively. The mean follow-up period was 35.9 ± 23.5 (median 31.5, range 4-87) months, with four local recurrences and three distant metastases detected. Eight patients (50.0%) died of disease by the last follow-up. The 1-, 3- and 5-year overall survival rates were 87.5%, 61.4% and 40.9%, respectively. Preoperative chemotherapy was used in three patients to facilitate surgical resection, and adjuvant chemotherapy and radiotherapy were used in six patients.
CONCLUSIONS
Spinal SS has a relatively high risk of local recurrence and distant metastasis. Surgical intervention can improve the neurological function and relieve pain in these patients. En bloc excision is an effective treatment strategy to improve survival and prevent local recurrence. Management of spinal SS should be under the instruction of a multidisciplinary team.
Topics: Adolescent; Adult; Aged; Child; Female; Humans; Male; Middle Aged; Retrospective Studies; Sarcoma, Synovial; Spinal Neoplasms; Treatment Outcome; Young Adult
PubMed: 30149806
DOI: 10.1186/s12957-018-1471-x -
Applied Radiation and Isotopes :... Mar 2021Synovial sarcoma is a rare tumor requiring new treatment methods. A 46-year-old woman with primary monophasic synovial sarcoma in the left thigh involving the sciatic...
Synovial sarcoma is a rare tumor requiring new treatment methods. A 46-year-old woman with primary monophasic synovial sarcoma in the left thigh involving the sciatic nerve, declining surgery because of potential dysfunction of the affected limbs, received two courses of BNCT. The tumor thus reduced was completely resected with no subsequent recurrence. The patient is now able to walk unassisted, and no local recurrence has been observed, demonstrating the applicability of BNCT as adjuvant therapy for synovial sarcoma. Further study and analysis with more experience accumulation are needed to confirm the real impact of BNCT efficacy for its application to synovial sarcoma.
Topics: Boron Neutron Capture Therapy; Combined Modality Therapy; Female; Humans; Middle Aged; Positron Emission Tomography Computed Tomography; Sarcoma, Synovial
PubMed: 33444907
DOI: 10.1016/j.apradiso.2020.109407 -
Molecular Cancer Research : MCR Jun 2023Synovial sarcoma, a rare malignant soft tissue tumor, is characterized by a specific chromosomal translocation t(X;18). The resulting chimeric SS18-SSX fusion protein...
UNLABELLED
Synovial sarcoma, a rare malignant soft tissue tumor, is characterized by a specific chromosomal translocation t(X;18). The resulting chimeric SS18-SSX fusion protein drives synovial sarcoma pathogenesis by integrating into the BAF complex and dysregulating gene transcription. Because previous functional analyses revealed a connection between SS18-SSX and the activity of the transcriptional coregulators YAP1/TAZ and β-catenin, respectively, this study examined a potential interdependence between these essential effector proteins in synovial sarcoma. In a large cohort of synovial sarcoma tissue specimens, IHC analyses revealed a substantial subset of synovial sarcoma with concurrent nuclear accumulation of YAP1/TAZ and β-catenin. In vitro, small-molecule inhibitor treatment, RNAi-mediated knockdown, and vector-based overexpression assays demonstrated that YAP1, TAZ, and β-catenin transcriptional activity is not only stimulated by the SS18-SSX fusion protein, but that they also mutually enhance each other's activation. These analyses showed the highest cooperative effect with overexpression of YAP1 in combination with β-catenin. Coimmunoprecipitation experiments detected nuclear interactions between YAP1, β-catenin, and the SS18-SSX fusion protein, the latter being an integral part of the BAF complex. Disruption of BAF complex assembly affected the coregulation of YAP1 and β-catenin, indicating that this chromatin remodeling complex plays a crucial role for interdependent YAP1 and β-catenin activation in synovial sarcoma cells.
IMPLICATIONS
This study provides deeper insights into synovial sarcoma tumor biology demonstrating a mutual dependence between YAP1/TAZ and β-catenin transcriptional activity and a complex interplay with the SS18-SSX fusion protein within the BAF complex.
Topics: Humans; beta Catenin; Sarcoma, Synovial; Oncogene Proteins, Fusion; Transcription Factors; Cell Nucleus
PubMed: 36920288
DOI: 10.1158/1541-7786.MCR-22-0588 -
Journal of Surgical Oncology Jun 2022While historically aggressive, some synovial sarcomas (SS) are clinically indolent. This study sought to determine whether SS grade predicts oncologic outcomes and...
BACKGROUND AND OBJECTIVES
While historically aggressive, some synovial sarcomas (SS) are clinically indolent. This study sought to determine whether SS grade predicts oncologic outcomes and whether Grade 1 disease might exist.
METHODS
Thirty-five cases from 2010 to 2019 were retrospectively reviewed. Clinicopathological data were analyzed and Kaplan-Meier assessed survival.
RESULTS
The median patient age was 37 years (interquartile range: 28-51.5). The local control rate was 74.3%, and recurrence-free survival (RFS) was worse in positive versus negative margin resections (p = 0.023). The incidence of metastasis was 21.9% (n = 7) at a median 31 ± 31.7 months, and metastasis-free survival was 50.0% in Grade 3 SS versus 86.5% in Grade 2 (p = 0.026). Among a theoretical Grade 1 group, the overall survival (OS) and RFS profiles were improved compared to Grade 2 and 3 SS, respectively (p = 0.014 and p = 0.030). The Grade 1 group had a 15.8% (n = 3) metastatic rate and 80% 10-year survival.
CONCLUSIONS
Tumor grade appears to predict outcomes in SS. A theoretical Grade 1 group showed improved OS and RFS versus Grades 2 and 3 SS, with metastatic rates and long-term survival resembling the historical literature for other low-grade soft tissue sarcomas. Our group continues to support the French Federation of Cancer Centers diagnostic strategy and NCCN treatment guidelines for SS.
Topics: Adult; Humans; Margins of Excision; Retrospective Studies; Sarcoma; Sarcoma, Synovial; Time Factors
PubMed: 35249228
DOI: 10.1002/jso.26838 -
The American Surgeon Jun 2023
Topics: Humans; Sarcoma, Synovial; Rectum; Pelvis
PubMed: 35147049
DOI: 10.1177/00031348221074221 -
Trends in Cancer Jun 2021Synovial sarcoma is a soft tissue malignancy driven by the SS18-SSX fusion oncoprotein. In Nature Medicine, Jerby-Arnon et al. present a single-cell dataset for synovial...
Synovial sarcoma is a soft tissue malignancy driven by the SS18-SSX fusion oncoprotein. In Nature Medicine, Jerby-Arnon et al. present a single-cell dataset for synovial sarcoma that reveals a novel 'core oncogenic program' driven by SS18-SSX, with implications for treatment strategies based on epigenetics, cell-cycle control, and immune augmentation.
Topics: Carcinogenesis; Epigenesis, Genetic; Humans; Oncogene Proteins, Fusion; Sarcoma, Synovial
PubMed: 33893065
DOI: 10.1016/j.trecan.2021.03.002 -
Nature Communications Sep 2022Autologous T cells transduced to express a high affinity T-cell receptor specific to NY-ESO-1 (letetresgene autoleucel, lete-cel) show promise in the treatment of...
Autologous T cells transduced to express a high affinity T-cell receptor specific to NY-ESO-1 (letetresgene autoleucel, lete-cel) show promise in the treatment of metastatic synovial sarcoma, with 50% overall response rate. The efficacy of lete-cel treatment in 45 synovial sarcoma patients (NCT01343043) has been previously reported, however, biomarkers predictive of response and resistance remain to be better defined. This post-hoc analysis identifies associations of response to lete-cel with lymphodepleting chemotherapy regimen (LDR), product attributes, cell expansion, cytokines, and tumor gene expression. Responders have higher IL-15 levels pre-infusion (p = 0.011) and receive a higher number of transduced effector memory (CD45RA- CCR7-) CD8 + cells per kg (p = 0.039). Post-infusion, responders have increased IFNγ, IL-6, and peak cell expansion (p < 0.01, p < 0.01, and p = 0.016, respectively). Analysis of tumor samples post-treatment illustrates lete-cel infiltration and a decrease in expression of macrophage genes, suggesting remodeling of the tumor microenvironment. Here we report potential predictive and pharmacodynamic markers of lete-cel response that may inform LDR, cell dose, and strategies to enhance anticancer efficacy.
Topics: Antigens, Neoplasm; Biomarkers; CD8-Positive T-Lymphocytes; Humans; Membrane Proteins; Receptors, Antigen, T-Cell; Sarcoma, Synovial; Tumor Microenvironment
PubMed: 36075914
DOI: 10.1038/s41467-022-32491-x -
Journal of Oncology Pharmacy Practice :... Apr 2022Sarcomas probably develop after malignant transformation of embryonic mesenchymal cells and have broad spectrum histopathologically since they can develop from striated...
Sarcomas probably develop after malignant transformation of embryonic mesenchymal cells and have broad spectrum histopathologically since they can develop from striated skeletal muscle and smooth muscle, fat and fibrous tissue, bone, cartilage and other mesenchymal tissues. The most common histological subtypes of soft tissue sarcoma in adults are: liposarcoma, leiomyosarcoma, poorly differentiated pleomorphic sarcoma, and gastrointestinal stromal tumor. Molecular and genetic studies of soft tissue sarcomas, which are considered as heterogeneous groups in terms of their molecular and clinical characteristics, are still an important area of interest The heterogeneity of the molecular and genetic alterations of these malignancies, which are mostly treated with surgery and chemotherapy, also offers hope to the researchers in terms of treatment targets. In this article, molecular biologic features of the soft tissue sarcomas including liposarcoma, rhabdomyosarcoma, leiomyosarcoma, synovial sarcoma, and angiosarcoma are discussed in the light of recent developments in molecular biology, targeted therapies and immunotherapy.
Topics: Adult; Hemangiosarcoma; Humans; Leiomyosarcoma; Liposarcoma; Rhabdomyosarcoma; Sarcoma; Sarcoma, Synovial; Soft Tissue Neoplasms
PubMed: 35043739
DOI: 10.1177/10781552211073139 -
Cancer Discovery Feb 2015Oncogenesis in synovial sarcoma is driven by the chromosomal translocation t(X,18; p11,q11), which generates an in-frame fusion of the SWI/SNF subunit SS18 to the... (Review)
Review
UNLABELLED
Oncogenesis in synovial sarcoma is driven by the chromosomal translocation t(X,18; p11,q11), which generates an in-frame fusion of the SWI/SNF subunit SS18 to the C-terminal repression domains of SSX1 or SSX2. Proteomic studies have identified an integral role of SS18-SSX in the SWI/SNF complex, and provide new evidence for mistargeting of polycomb repression in synovial sarcoma. Two recent in vivo studies are highlighted, providing additional support for the importance of WNT signaling in synovial sarcoma: One used a conditional mouse model in which knockout of β-catenin prevents tumor formation, and the other used a small-molecule inhibitor of β-catenin in xenograft models.
SIGNIFICANCE
Synovial sarcoma appears to arise from still poorly characterized immature mesenchymal progenitor cells through the action of its primary oncogenic driver, the SS18-SSX fusion gene, which encodes a multifaceted disruptor of epigenetic control. The effects of SS18-SSX on polycomb-mediated gene repression and SWI/SNF chromatin remodeling have recently come into focus and may offer new insights into the basic function of these processes. A central role for deregulation of WNT-β-catenin signaling in synovial sarcoma has also been strengthened by recent in vivo studies. These new insights into the the biology of synovial sarcoma are guiding novel preclinical and clinical studies in this aggressive cancer.
Topics: Animals; Humans; Neoplasm Proteins; Sarcoma, Synovial; Translocation, Genetic
PubMed: 25614489
DOI: 10.1158/2159-8290.CD-14-1246 -
Synovial Sarcoma of the Nerve-Clinical and Pathological Features: Case Series and Systematic Review.Neurosurgery Dec 2019Synovial sarcoma of the nerve is a rare entity with several cases and case series reported in the literature. Despite an improved understanding of the biology, the...
BACKGROUND
Synovial sarcoma of the nerve is a rare entity with several cases and case series reported in the literature. Despite an improved understanding of the biology, the clinical course is difficult to predict.
OBJECTIVE
To compile a series of patients with synovial sarcoma of the peripheral nerve (SSPN) and assess clinical and pathological factors and their contribution to survival and recurrence.
METHODS
Cases from 2 institutions collected in patients undergoing surgical intervention for SSPN. Systematic review including PubMed and Scopus databases were searched for related articles published from 1970 to December 2018. Eligibility criteria: (1) case reports or case series reporting on SSPN, (2) clinical course and/or pathological features of the tumor reported, and (3) articles published in English.
RESULTS
From patients treated at our institutions (13) the average follow-up period was 3.2 yr. Tumor recurrence was seen in 4 cases and death in 3. Systematic review of the literature yielded 44 additional cases with an average follow-up period of 3.6 yr. From pooled data, there were 10 recurrences and 7 deaths (20% and 14%, respectively). Adjuvant treatment used in 62.5% of cases. Immunohistochemical markers used in diagnosis varied widely; the most common are the following: Epithelial membrane antigen (EMA), cytokeratin, vimentin, cluster of differentiation (CD34), and transducin-like enhancer of split 1 (TLE1). Statistical analysis illustrated tumor size and use of chemotherapy to be negative predictors of survival. No other factors, clinically or from pathologist review, were correlated with recurrence or survival.
CONCLUSION
By combining cases from our institution with historical data and performing statistical analysis we show correlation between tumor size and death.
Topics: Biomarkers, Tumor; Humans; Peripheral Nervous System Neoplasms; Sarcoma, Synovial
PubMed: 31435657
DOI: 10.1093/neuros/nyz321