(P 285) TUMOUR-INFILTRATING MAST CELLS IN ANGIOSARCOMAS CORRELATE WITH CLINCIAL PHENOTYPES AND IMMUNO-ONCOLOGY PATHWAYS

Objective: Angiosarcomas are rare, aggressive soft tissue sarcomas with poor prognosis. In advanced disease, current treatment modalities including chemotherapy and targeted agents, are limited in efficacy and resistance typically ensues. Recent studies have uncovered angiosarcoma subtypes enriched in immune-related signalling and immune cells, including tumours with mast cell infiltration of unclear significance. Therefore, this study aims to investigate the association between mast cell density with clinical features and immuno-oncogenic pathways.

Methods: Immunohistochemical detection of mast cells using anti-tryptase antibody (TPSAB1) was performed on a cohort of 60 angiosarcoma samples. Quantification of mast cell density by H-scores was performed by two independent readers. In addition, NanoString IO360 gene expression data was generated from formalin-fixed paraffin-embedded (FFPE) samples. Correlation of H-scores with NanoString mast cell scores was performed using Spearman’s correlation. Survival analyses were conducted using Kaplan Meier curves.

Results: Mast cells were observed in all cases examined and the degree of infiltration ranged from 1% to 90%. H-scores showed a significant moderate correlation with NanoString mast cell scores (r = 0.53, p < 0.001). Both H-scores and NanoString mast cell scores were significantly associated with head and neck angiosarcomas, non-epithelioid morphology and lower tumour grades (all p < 0.05). A significant but weak correlation with NanoString regulatory T-cell scores was also observed (r = 0.27-0.32, p < 0.05). NanoString mast cell scores positively correlated with signalling pathways relating to antigen presentation, and negatively correlated with apoptosis, DNA damage repair and cell proliferation. Interestingly, for patients with metastatic angiosarcoma, high mast cell density displayed a trend towards reduced overall (HR 2.7; 95% CI 0.96 — 7.61; p =0.0597) and progression-free survival (HR 2.7; 95% CI 0.96 — 7.53; p =0.0586).

Conclusion: We demonstrated the presence of tumour-infiltrating mast cells in angiosarcomas and the involvement of mast cells in specific immuno-oncology pathways. Future research in these pathways may elucidate the roles of mast cells in angiosarcomas and uncover new therapeutic options.