Abstract 5667: Epidemiology of tissue factor expression in soft tissue sarcoma

Objective: Soft tissue sarcoma (STS) is a heterogeneous group of rare, malignant mesenchymal tumors, comprising over 70 subtypes. Doxorubicin-based chemotherapy, the standard treatment for the majority of advanced or metastatic STS, has limited efficacy, with low response rates and poor disease control. Identifying new molecular targets is crucial for developing more effective treatments and overcoming resistance, considering the high unmet medical need in this indication. Tissue factor (TF) is a transmembrane protein essential for hemostasis and thrombosis. High levels of TF have been observed in cancers, particularly adenocarcinomas, where it promotes tumor growth, invasion, metastasis and angiogenesis. TF expression in tumors and in tumor-associated endothelial cells is currently considered a putative therapeutic target. Consequently, a TF-targeted antibody-drug conjugate (tisotumab vedotin) has been approved by the Food and Drug Administration for the treatment of cervical cancer.As its expression in STS remains unexplored, we aimed to assess the expression of TF in tissue microarrays (TMA) constructed from archival tumor material from patients and patient-derived xenograft (PDX) models. Methods: Immunohistochemical staining was performed on TMA. Over 550 patient samples with 2-3 cores per tumor were analyzed, covering the 11 most common STS subtypes, such as leiomyosarcoma (LMS), liposarcoma (LPS), angiosarcoma (AS) and myxofibrosarcoma (MFS).In addition, TMA from 31 PDX models from our XenoSarc platform, covering 14 STS subtypes, were included with at least 2 cores per model, with multiple passages of the xenografts to account for potential intra-tumor variability of TF expression during passaging.TMA were evaluated using the scoring: 0 (no expression), 1 (<25% positive cells), 2 (25-50%), and 3 (>50%); scores of 2 or 3 were considered as high expression. Results: Analysis of a multi-sarcoma clinical TMA revealed a limited number of cases with high expression of the target in only a few samples from AS, LPS, LMS and MFS, subtypes that were selected for further analysis using subtype-specific TMAs from these entities. High expression was found in 22.5% of MFS (27 out of 120 donors), 8.0% of AS (6 out of 79 cases), 4.7% of LMS (6 out of 128 patients), 3.2% of LPS (2 out of 62 patients). Detailed correlations with relevant clinical data are currently ongoing and results will be disclosed at the meeting.In the PDX, high TF expression was observed in 9 out of 31 models in at least one passage. Three out of 4 MFS models showed TF high expression in at least one passage and two high-grade sarcoma models maintained high expression across multiple passages (≥3). Conclusion: TF expression in STS is generally limited, with MFS showing the highest number of positivity in clinical samples and xenograft models. Nevertheless, the observed frequency appears insufficient to support TF as suggestive therapeutic target across other subtypes of sarcomas. Citation Format: Francesca La Greca, Agnieszka Wozniak, Chao-Chi Wang, Daniël Gorgels, Flavia Paternostro, Luna De Sutter, Lore De Cock, Kimberly Verbeeck, Ulla Vanleeuw, Raf Sciot, Patrick Schöffski. Epidemiology of tissue factor expression in soft tissue sarcoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 5667.