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Potentially actionable targets in synovial sarcoma: A tissue microarray study.
De Cock, Lore; Paternostro, Flavia; Vanleeuw, Ulla; Wyns, Karo; Laenen, Annouschka; Lee, Che-Jui; Sciot, Raf; Wozniak, Agnieszka; Schöffski, Patrick.
Affiliation
  • De Cock L; Laboratory of Experimental Oncology, KU Leuven, Leuven Cancer Institute, Leuven, Belgium; Department of General Medical Oncology, University Hospitals Leuven, Leuven Cancer Institute, Leuven, Belgium. Electronic address: lore.decock@uzleuven.be.
  • Paternostro F; Laboratory of Experimental Oncology, KU Leuven, Leuven Cancer Institute, Leuven, Belgium.
  • Vanleeuw U; Laboratory of Experimental Oncology, KU Leuven, Leuven Cancer Institute, Leuven, Belgium.
  • Wyns K; Laboratory of Experimental Oncology, KU Leuven, Leuven Cancer Institute, Leuven, Belgium.
  • Laenen A; Department of Biostatistics, KU Leuven, Leuven Cancer Institute, Leuven, Belgium.
  • Lee CJ; Laboratory of Experimental Oncology, KU Leuven, Leuven Cancer Institute, Leuven, Belgium.
  • Sciot R; Department of Pathology, KU Leuven and University Hospitals Leuven, Leuven Cancer Institute, Leuven, Belgium.
  • Wozniak A; Laboratory of Experimental Oncology, KU Leuven, Leuven Cancer Institute, Leuven, Belgium.
  • Schöffski P; Laboratory of Experimental Oncology, KU Leuven, Leuven Cancer Institute, Leuven, Belgium; Department of General Medical Oncology, University Hospitals Leuven, Leuven Cancer Institute, Leuven, Belgium.
Transl Oncol ; 48: 102057, 2024 Oct.
Article in En | MEDLINE | ID: mdl-39029378
ABSTRACT

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.
Key words

Full text: 1 Collection: 01-internacional Database: MEDLINE Language: En Journal: Transl Oncol Year: 2024 Document type: Article Country of publication: United States

Full text: 1 Collection: 01-internacional Database: MEDLINE Language: En Journal: Transl Oncol Year: 2024 Document type: Article Country of publication: United States