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Updated: Jun 20, 2025
A Next-generation Tissue Microarray ngTMA Protocol for Biomarker Studies
Published on: September 23, 2014
Potentially actionable targets in synovial sarcoma: A tissue microarray study
Lore De Cock1, Flavia Paternostro2, Ulla Vanleeuw2
1Laboratory of Experimental Oncology, KU Leuven, Leuven Cancer Institute, Leuven, Belgium; Department of General Medical Oncology, University Hospitals Leuven, Leuven Cancer Institute, Leuven, Belgium.
Background:
Synovial sarcoma (SynSa) is one of the most common translocation-related soft tissue sarcomas. Patients with metastatic SynSa have limited treatment options and a very poor prognosis. Several novel experimental therapies are currently being explored in clinical trials, including T cell-based therapies targeting cancer testis antigens such as New York esophageal squamous cell carcinoma 1 (NY-ESO-1) or melanoma-associated antigen A4 (MAGE-A4), and degraders targeting bromodomain-containing protein 9 (BRD9). Preclinical studies investigate inhibitors of Yes associated protein 1 (YAP1), transcriptional co-activator with PDZ-binding motif (TAZ) and inhibitors of chemokine receptor 4 (CXCR4).
Methods:
We explored the immunohistochemical expression of these targets using a tissue microarray (TMA) constructed from 91 clinical SynSa samples and correlated these findings with corresponding clinicopathological data.
Results:
Expression of MAGE-A4 and NY-ESO-1 was found in 69 % and 56 % of the samples, respectively. NY-ESO-1 was statistically higher expressed in samples from metastatic lesions as compared to samples from primary tumors. Nuclear expression of YAP1 and TAZ was observed in 92 % and 51 % of the samples, respectively. CXCR4 was expressed in the majority of the samples (82 %). BRD9 was highly expressed in all specimens. No prognostic role could be identified for any of the investigated proteins.
Conclusion:
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.
Insights
This study found that key proteins like MAGE-A4, NY-ESO-1, YAP1, TAZ, CXCR4, and BRD9 are expressed in synovial sarcoma (SynSa) tissues. This supports ongoing research into new treatments for this rare cancer.
Area of Science:
- Oncology
- Molecular Biology
- Pathology
Background:
- Synovial sarcoma (SynSa) is a common soft tissue sarcoma with limited treatment options for metastatic disease.
- Novel therapies targeting cancer testis antigens (NY-ESO-1, MAGE-A4), BRD9, YAP1, TAZ, and CXCR4 are under investigation.
Purpose of the Study:
- To investigate the expression of actionable therapeutic targets in Synovial Sarcoma.
- To correlate protein expression with clinicopathological data in a large cohort of SynSa samples.
Main Methods:
- Immunohistochemical analysis of a tissue microarray (TMA) from 91 SynSa samples.
- Correlation of protein expression (MAGE-A4, NY-ESO-1, YAP1, TAZ, CXCR4, BRD9) with clinicopathological features.
Main Results:
- High expression rates for MAGE-A4 (69%), NY-ESO-1 (56%), YAP1 (92%), TAZ (51%), CXCR4 (82%), and BRD9 (100%).
- NY-ESO-1 expression was higher in metastatic lesions compared to primary tumors.
- No significant prognostic role identified for any of the investigated proteins.
Conclusions:
- This study provides real-world data on actionable protein expression in SynSa.
- The widespread expression of these markers supports the clinical relevance of ongoing targeted therapy research for Synovial Sarcoma.
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