(P 182) NOVEL TISSUE MICROARRAY (TMA) PLATFORM AS A TOOL FOR COLLABORATIVE SOFT TISSUE SARCOMA (STS) RESEARCH

Objective: Soft tissue sarcoma (STS) is a heterogeneous family of rare mesenchymal tumors, characterized by extensive histopathological and molecular diversity. Tissue microarray (TMA) is a tool that allows performing research in such orphan diseases in an efficient, cost-effective way. TMAs are paraffin blocks consisting of multiple small representative tissue cores from biological samples and can contain material from multiple donors, diverse sites of disease, or multiple different diseases.

Methods: Since 2015, we have constructed TMAs using archival tumor material from selected STS types (Lee et al. Sarcoma 2021:6675260). Specimen are annotated in terms of histopathological diagnosis, treatment of patients and clinical follow-up of the tissue donors and linked to a comprehensive clinical database. Each TMA block contains duplicate or triplicate 1.0-1.5 mm tissue cores from representative tumor areas selected by sarcoma pathologists. The construction of TMAs was performed according to next-generation tissue microarray (ngTMA®) protocols, using digital pathology.

Results: We have established disease-specific TMAs from 10 STS subtypes: alveolar soft part (n=59), clear cell (n=54), leiomyo- (n=55), lipo- (n=42), alveolar rhabdomyo- (n=24), angio- (n=64) and synovial sarcoma (n=92), solitary fibrous (n=87), inflammatory myofibroblastic (n=33) and gastrointestinal stromal tumor (72 cases). We also constructed a “multi-sarcoma” TMA covering a representative number of important subtypes for target screening purposes, namely angio-, dedifferentiated, pleomorphic and myxoid lipo-, leiomyo-, myxofibro-, rhabdomyo-, synovial, undifferentiated pleomorphic sarcoma and malignant peripheral nerve sheath tumor, with 7-11 individual cases per subtype combined on one TMA. In addition to TMAs constructed from clinical material, we have created TMAs from our extensive platform of patient-derived STS xenografts (Cornillie et al. Mol Cancer Ther 2019;18(6):1168-78; Wozniak et al. CTOS 2022), allowing us to screen models for specific targets in preparation of in vivo experiments. We are further expanding the list of TMAs with additional sarcoma entities, considering the heterogeneity of this tumor family.

Conclusion: Our extensive STS TMA platform is suitable for rapid and cost-effective morphological, immunohistochemical, and molecular characterization of tumors, as well as for the identification of potential novel diagnostic markers and drug targets and it is readily available for collaborative projects with academic and corporate research partners.