Synovial Sarcoma

Among MAGE-As, MAGE-A4 had the highest prevalence (65%), followed by MAGE-A10 (15%) and MAGE-A9 (13%)...Complementary immunohistochemical analyses were used to establish the positive correlation between RNA and protein expression for MAGE-A4 and NY-ESO-1. These data inform the strategy for optimal coverage of the SyS patient population with T-cell therapies, offering patients with SyS new options for single or combined second lines of treatment.

Such entities may benefit from alternative treatments or strategies to overcome SLFN11 deficiency-related drug resistance. Our approach and results should serve as a foundation for future biomarker-associated clinical trials.

Additionally, we confirmed that this cell line was useful for evaluating the efficacy of anticancer drugs. Our results suggest that NCC-SS6-C1 is a useful tool for basic and pre-clinical studies of SS.

The primary tumor cohort showed no association between NY-ESO-1 expression and OS (including stratification by HLA-A∗02 subtype and treatment line), when adjusting for important prognostic factors, possibly due to small sample sizes.

NGS results revealed NRAS and CDKN2A mutations and absence of fusions, resulting in a new review of the histologic material with a broader immunohistochemical panel, finding strong positivity to melanic antibodies. This case is an illustrative example of a malignant melanoma with small round cell morphology showing aberrant expression of CD99, BCL2, TLE1 and SS18-SSX antibodies exposing a potentially hazardous pitfall highlighting the importance of a wide differential diagnosis and the role of confirmational studies with molecular tests.

Oral administration effectively inhibited HS-SY-II xenograft tumor growth in mice. CW-3308 is a promising lead compound for further optimization and extensive evaluation for the treatment of synovial sarcoma, rhabdoid tumor, and other BRD9-dependent human diseases.

Moreover, these markers could represent therapeutic targets in advanced stages. However, further, larger series of SSs and molecular studies are necessary to corroborate our present findings.

Synovial histiocytic sarcomas and myxosarcomas can cause lysis in multiple bones surrounding the joint, but they have different prognoses and require histopathology and sometimes immunohistochemistry to diagnose them. Synovial sarcoma and synovial cell sarcoma are terms used in the human medical literature for a tumor that is not of synovial origin; these terms should not be used in veterinary medicine.

Furthermore, EXO1, NCAPG, POLQ and UHRF1 were identified as potential candidate metastasis-associated genes. This study provides further research insights and helps explore the mechanisms of SS metastasis.

In support of this notion, we find that blockade of FYN activity synergistically enhances HDACi action to reduce synovial sarcoma cell proliferation and migration. Our results support a role for FYN in attenuation of anti-cancer activity upon inhibition of SS18-SSX function and demonstrate the feasibility of targeting FYN to improve the effectiveness of HDACi treatment against synovial sarcoma.

A high fraction of young patients with soft tissue sarcoma harbor PVs. Among the genes affected, we substantiate a potential role of MYO5B and propose a potential role for MYO3A.

This study is a comprehensive study providing real-world data on the expression of several actionable proteins in a large proportion of SynSa samples. All evaluated markers were expressed in a clinically meaningful proportion of cases represented in our TMA, supporting the relevance of ongoing preclinical and clinical research with novel agents directed against these targets.

In summary, among the soft tissue tumors tested, ISL1 is a highly sensitive but moderately specific marker for DSRCT and may be useful to distinguish from round cell mimics including EWS and CIC::DUX4 sarcomas. The oncogenic role of ISL1 in these tumors warrants further investigation.

This is the first reported case of synovial sarcoma of the hypopharynx in the Philippines confirmed by SS18 FISH. Due to the size of the mass, chemoradiotherapy followed by surgery is the current plan of management for this patient.

Molecular analysis, through targeted RNA sequencing, was of invaluable help in reaching the correct diagnosis. Despite locally advanced disease at presentation, the patient showed an unexpectedly brilliant response to chemotherapy.

Among the 110 mimicking round cell malignancies, 12 tumors showed MUC5AC positivity, including occasional cases of synovial sarcoma and small cell carcinoma, whereas the remaining 98 samples were negative. Despite its lower specificity than that of ETV4 and sparse reactivity that requires careful interpretation, MUC5AC may serve as a useful marker for CIC/ATXN1-rearranged sarcoma because of its wider accessibility.

We demonstrated that TWIST1 downregulation restored romidepsin efficacy even in spheroid form, and concomitant SN38 treatment along with romidepsin reproduced the reaction. The current study demonstrated the benefits and concerns of using HDACi for SS treatment in 2D and 3D culture conditions and provided molecular evidence that concomitant treatment with SN38 can overcome drug resistance to HDACi by suppressing TWIST1 expression.

Sequencing revealed a homozygous V596E (transcript ENSCAFT00845055173.1) BRAF mutation, consistent with the known biology of TCC. In neither case was HS truly present in this patient, but immunocytochemistry provided information that helped to optimize the patient's chemotherapy recommendations.

P1, N=44, Suspended, M.D. Anderson Cancer Center | Recruiting --> Suspended

We also found that positive nuclear CXCR4 expression in the initial biopsies was associated with poor RFS (p = 0.022) in undifferentiated pleomorphic sarcomas. In conclusion, our study adds to the evidence that CXCR4 expression in tumor tissue is a promising prognostic factor for STSs.

TAK-981 synergized with cytotoxic chemotherapy through increased DNA damage, leading to tumor regression. Targeting the SUMOylation pathway in SS restores cBAF complexes and blocks the SS18::SSX-ncBAF transcriptome, identifying a therapeutic vulnerability in SS, positioning the in-clinic TAK-981 to treat SS.

The covariates were generally not associated with MAGE-A4 expression, except for patient age in ovarian cancer and histology in non-small cell lung cancer. This report shows the eligibility rate from biomarker screening for TCR T cell therapies and provides epidemiological data for future clinical development of MAGE-A4-targeted therapies.

P2, N=28, Not yet recruiting, University Hospital Heidelberg

Currently, there are several CDK9 inhibitors in preclinical and clinical investigations. This review aims to highlight the recent discovery and results on the transcriptional role and therapeutic potential of CDK9 in sarcoma.

These results might have broad implications for the clinical management and surveillance of sarcoma.

Evidence on this very rarest type of breast malignancy is still evolving. The interest in the case described here relies on its rarity, difficulties in achieving diagnosis and formulation of the proper management.

P1, N=44, Recruiting, M.D. Anderson Cancer Center | Suspended --> Recruiting

Our understanding of the potential cause of sarcomas with different subtypes is limited. Establishing a comprehensive global database for patients with sarcomas from all ethnic groups is essential to deepen our understanding of the potential risk factors and the pathophysiology of all sarcoma subtypes.

P1, N=27, Terminated, Fred Hutchinson Cancer Center | Active, not recruiting --> Terminated; The study was terminated early with 27 out of 28 planned subjects enrolled. This decision was multifactorial, including slow enrollment in the last remaining cohort and a lack of evidence of clinical benefit.

P2, N=267, Completed, Epizyme, Inc. | Active, not recruiting --> Completed | Trial completion date: Jun 2024 --> Feb 2024

Detection of EWSR1 rearrangement by FISH is of utmost significance in the diagnosis of bone and soft tissue tumors. Cases with atypical positive signals should be further scrutinized, correlating with their histomorphology and verifying by NGS if necessary.

P1, N=55, Terminated, Foghorn Therapeutics Inc. | N=104 --> 55 | Trial completion date: May 2025 --> Dec 2023 | Active, not recruiting --> Terminated | Trial primary completion date: Dec 2024 --> Dec 2023; Sponsor decision

P1, N=44, Recruiting, Seattle Children's Hospital | Trial completion date: Jun 2038 --> Jun 2040 | Trial primary completion date: Jun 2024 --> Jun 2025

PCSS is an exceedingly rare neoplasm, and should be distinguished from other various malignant epithelial and mesenchymal tumors. The clinical history, histopathological and immunohistochemical features, and molecular findings are all essential to the definitive diagnosis of PCSS.

P2, N=267, Active, not recruiting, Epizyme, Inc. | Trial primary completion date: Jun 2024 --> Feb 2024

Our results show that fusion testing can be a helpful diagnostic tool, especially in cases with unusual or uncommon morphology in superficial sites. Furthermore, it can allow for the identification of potential therapeutic targets in some instances.

Afami-cel treatment resulted in durable responses in heavily pre-treated patients with HLA-A*02 and MAGE-A4-expressing synovial sarcoma. This study shows that T-cell receptor therapy can be used to effectively target solid tumours and provides rationale to expand this approach to other solid malignancies.

P1, N=44, Suspended, M.D. Anderson Cancer Center | Not yet recruiting --> Suspended

However, histone acetylation may be one of the epigenetic mechanisms involved in PRAME regulation. Thus, the therapeutic combination of histone deacetylase inhibitors and PRAME immunotherapy merits further investigation.

Additionally, knockdown of SS18-SSX, which upregulates BCL2, reduced the sensitivity to ABBV-075. These findings suggest the potential utility of BET inhibitors targeting the SS18-SSX-regulated intrinsic apoptotic pathway as a promising therapeutic strategy for SS.

P1/2, N=100, Enrolling by invitation, Epizyme, Inc. | Trial completion date: Dec 2024 --> Nov 2025 | Trial primary completion date: Dec 2024 --> Nov 2025

We herein present the cytologic findings of monomorphic SETTLE and highlight the potential cytomorphologic and immunophenotypic pitfalls. We also highlight how tumors with high-risk features can be a therapeutic challenge.