Immune signature and molecular profiling of epithelioid hemangioendothelioma (EHE)

Background Epithelioid hemangioendothelioma (EHE) is an extremely rare sarcoma; as such, it can pose a clinical dilemma based solely on its rarity. In addition, the spectrum of disease varies greatly between an indolent disease and aggressive disease with widespread metastases. EHE tumors most commonly affect the soft tissues, liver, lungs and bones. The rarity of this tumor makes diagnosis and treatment extremely difficult, as many do not have the expertise to manage it appropriately. EHE typically appears in young adults, though the tumor may be diagnosed in younger or older adults. The systemic treatment is limited to targeted agents (sirolimus, pazopanib, sunitinib), chemotherapy (vincristine, paclitaxel) and interferon. These agents have shown minimal benefit and there is need to evaluate other therapeutic options. Over the last half century, it has become well established that cancers can elicit a host immune response that can target them with high specificity. Only within the last decade, with the advances in high output gene sequencing and bioinformatics approaches, are we now on the forefront of harnessing the host's immune system to treat cancer. Immunotherapy is the platform being used to access this immune response. Hypothesis EHE carries a genomic complexity that will have immune signature and a neoepitope that predicts response to immunotherapy. Objective(s) To characterize the immune signature and molecular profiling of EHEs. Patients and methods • Patients with EHE treated in Mount Sinai and Princess Margaret Hospital Network. • Cases of EHE identified from institutional database. • Use of archival tissue (biopsy or resected). • Formalin fixed paraffin embedded (FFPE) samples would be stained for CD3, CD4, CD8, CD20, CD68 • Immune scoring would be performed. • Tumor-infiltrating lymphocytes (TILs) would be assessed using a 4-tiered scale: 0 (no lymphocytes); 1 (1-10/HPF); 2 (11-50/HPF), 3 (51-100/HPF). • Tumor DNA would be extracted from FFPE samples and undergo whole exome sequencing (WES). • ctDNA would also be analyzed Conclusion This project would help to understand this rare tumor subset and create avenues for therapeutic options. This could be the harbinger of creating durable responses especially in the metastatic setting.