Epithelioid Sarcoma: Opportunities for Biology-Driven Targeted Therapy.
Bottom Line: In this review, we will summarize clinically relevant biomarkers (e.g., SMARCB1, CA125, dysadherin, and others) with respect to targeted therapeutic opportunities.We will also examine the role of EGFR, mTOR, and polykinase inhibitors (e.g., sunitinib) in the management of local and disseminated disease.Toward building a consortium of pharmaceutical, academic, and non-profit collaborators, we will discuss the state of resources for investigating ES with respect to cell line resources, tissue banks, and registries so that a roadmap can be developed toward effective biology-driven therapies.
Affiliation: Royal Marsden Hospital , London , UK.
Epithelioid sarcoma (ES) is a soft tissue sarcoma of children and young adults for which the preferred treatment for localized disease is wide surgical resection. Medical management is to a great extent undefined, and therefore for patients with regional and distal metastases, the development of targeted therapies is greatly desired. In this review, we will summarize clinically relevant biomarkers (e.g., SMARCB1, CA125, dysadherin, and others) with respect to targeted therapeutic opportunities. We will also examine the role of EGFR, mTOR, and polykinase inhibitors (e.g., sunitinib) in the management of local and disseminated disease. Toward building a consortium of pharmaceutical, academic, and non-profit collaborators, we will discuss the state of resources for investigating ES with respect to cell line resources, tissue banks, and registries so that a roadmap can be developed toward effective biology-driven therapies.
No MeSH data available.
Related in: MedlinePlus
Mentions: Epithelioid sarcoma (ES), first described by Enzinger over half a century ago (1), is a rare neoplasm accounting for <1% of adult soft tissue sarcomas and between 4 and 8% of pediatric non-rhabdomyosarcomatous sarcomas (2, 3). ES is presumed to be a mesenchymal malignancy, but ES characteristically exhibits both mesenchymal and epithelial markers. The cell of origin and molecular drivers are still a matter of debate. ES is divided into two recognizable clinicopathological entities, classic ES (also called distal-type ES), and proximal-type ES (Figures 1A–E). These two subtypes are thought be a continuum of disease rather than distinct entities (4). Distal-type ES is histologically identifiable by tumor nodules with central necrosis surrounded by large polygonal cells and spindle cells merging in the periphery (5) (Figures 1A,B). Described variants include angiomatoid variant, fibroma-like variant, and myxoid variant. Proximal-type ES is characterized by a multinodular pattern and sheet-like growth of large polygonal cells, often accompanied by a focal or predominant rhabdoid morphology (6) (Figures 1C,D). A specific marker has not yet been identified in ES. On immunohistochemistry (IHC), virtually all cases are positive for cytokeratin (CK) and epithelial membrane antigen (EMA) and most cases co-express vimentin. The marker CD34 is expressed in 60–70% of cases. IHC studies are typically negative for S-100, neurofilament protein, carcinoembryonic antigen, factor VIII-related antigen and CD-31, and INI-1 (SMARCB1) whose expression is lost in tumor nuclei (7). Establishing a diagnosis of ES can be difficult as tumors can present with a wide range of appearances and immunophenotypes. The differential diagnosis include fibrous histiocytoma, nodular fasciitis, other reactive proliferations, fibromatosis, giant cell tumor of tendon sheath, sclerosing epithelioid fibrosarcoma, and even some carcinomas and melanomas (7). IHC is helpful in differentiating these entities. Epithelioid vascular tumors can resemble ES and efforts must be made to exclude a diagnosis of epithelioid hemangioendothelioma. In epithelioid hemangioendothelioma, the unique translocation t(1;3)(p36;q25), resulting in the fusion of WWTR1 with CAMTA1I establishes a firm diagnosis (8).
No MeSH data available.