There are more than 50 different types of sarcoma. Members of the Sarcoma Center are conducting research on many of them. Below are selected research initiatives.

Epithelioid Hemangioendothelioma (EHE)

Epithelioid hemangioendothelioma (EHE) is a rare, low-grade cancer that can arise from the blood vessels in different parts of the body. In people with low-grade tumors that are isolated to a single site in the body, surgery can provide a cure. But in other patients, the disease can act more aggressively. The rarity of the disease and the lack of laboratory models has slowed the discovery of new therapeutics.

EHE tumors express either the more common WWTR1-CAMTA1 or the less frequent YAP1-TFE3 oncogenic fusion. Both of these gene translocations have been cloned at MSK.

Over the past decade, the lab of Cristina Antonescu has assembled a large collection of EHE tumor samples, including frozen and archival tissue from both primary and metastatic sites in the body. The samples are of a variety of grades and have annotated clinical data, including the patients’ response to various clinical trials. This collection represents an invaluable resource for further genomic analyses, including genetic and epigenetic mining to provide novel target vulnerabilities and therapeutic strategies for people with advanced disease.

Scientific Leads

Ongoing Projects

• Design genetically engineered CRISPR-Cas9 cell culture models of WWTR1-CAMTA1 and YAP1-TFE3 fusions to investigate pathogenesis and drug screening
• Genomic and epigenetic profiling of various clinical and molecular EHE subsets to identify potential new vulnerabilities and therapeutic targets

Publications

• Rosenbaum E, Jadeja B, Xu B, Zhang L, Agaram NP, Travis W, Singer S, Tap WD, Antonescu CR. Prognostic stratification of clinical and molecular epithelioid hemangioendothelioma subsets.  Mod Pathol. 2020 Apr;33(4):591-602.
• Suurmeijer AJH, Dickson BC, Swanson D, Sung YS, Zhang L, Antonescu CR. Variant WWTR1 gene fusions in epithelioid hemangioendothelioma-A genetic subset associated with cardiac involvement. Genes Chromosomes Cancer. 2020 Jul;59(7):389-395.
• Antonescu CR, Dickson BC, Sung YS, Zhang L, Suurmeijer AJH, Stenzinger A, Mechtersheimer G, Fletcher CDM.  Recurrent YAP1 and MAML2 Gene Rearrangements in Retiform and Composite Hemangioendothelioma. Am J Surg Pathol. 2020; 44(12):1677-1684.
• Stacchiotti S, Miah AB, Frezza AM, Messiou C, Morosi C, Caraceni A, Antonescu CR, et al.  Epithelioid hemangioendothelioma, an ultra-rare cancer: a consensus paper from the community of experts. ESMO Open. 2021 Jun;6(3):100170.

Angiosarcoma

Angiosarcoma (AS) is a rare subtype of sarcoma subtype that has a range of clinicopathologic and genetic features. These tumors can be primary (most often found in the breast or head and neck) or secondary (most frequently caused by external-beam radiation therapy for breast cancer).

Almost half of the people initially treated with surgery for AS will ultimately develop metastatic disease, and between 20 and 40% of patients have disease that has already spread at the time of diagnosis. The clinical course and response to treatment varies for these tumors depending on where they start. Some studies have suggested that cutaneous AS tumors that arises on the face and scalp have longer survival and higher response rates.

Research at MSK has identified activating KDR (VEGFR2) mutations in 10% of AS tumors, including primary tumors found in the breast and those that are associated with radiation exposure.

MSK investigators have also identified common MYC amplifications and less frequent FLT4 amplifications in most AS tumors that are associated with radiation and lymphedema. These mutations have also been found in 10% of primary AS tumors.

Scientific Leads

Ongoing Projects

• Genomic and Transcriptomic Correlates of Response to Immune Checkpoint Blockade-based Therapy in Angiosarcoma
  Investigators: Evan Rosenbaum, William Tap, Shaleigh Smith, Cristina Antonescu, Sandra D’Angelo
   
• MSK-IMPACT–Targeted Sequencing Delineates Diverse Genomic Subsets and Potential Therapeutic Targets in Angiosarcoma Patients
  Investigators: Evan Rosenbaum, William Tap, Shaleigh Smith, Cristina Antonescu, Sandra D’Angelo
   
• Development of Murine Models for Radiation-Induced Human Angiosarcoma
  Investigators: Yu Chen, Ping Chi, Scott Lowe, Cristina Antonescu

Publications

• Huang SC, Zhang L, Sung YS, Chen CL, Kao YC, Agaram NP, Singer S, Tap WD, D’Angelo S, Antonescu CR.  Recurrent CIC gene abnormalities in angiosarcomas: A molecular study of 120 cases with concurrent investigation of PLCG1, KDR, MYC, and FLT4 gene alterations. Am J Surg Pathol. 2016; 40:645-55.
• Kelly CM, Antonescu CR, Bowler T, Munhoz R, Chi P, Dickson MA, Gounder MM, Keohan ML, Movva S, Dholakia R, Ahmad H, Biniakewitz M, Condy M, Phelan H, Callahan M, Wong P, Singer S, Ariyan C, Bartlett EK, Crago A, Yoon S, Hwang S, Erinjeri JP, Qin LX, Tap WD, D’Angelo SP. Objective Response Rate Among Patients With Locally Advanced or Metastatic Sarcoma Treated With Talimogene Laherparepvec in Combination With Pembrolizumab: A Phase 2 Clinical Trial. JAMA Oncol. 2020; 6:402-408.
• Kuba MG, Xu B, D’Angelo SP, Rosenbaum E, Plitas G, Ross DS, Brogi E, Antonescu CR.  The impact of MYC amplification on clinicopathologic features and prognosis of radiation-associated angiosarcomas of the breast. Histopathology. 2021 Nov;79(5):836-846