Experts from Several UPMC Departments Publish Dedifferentiated Chondrosarcoma Study in the Journal of Bone Oncology

November 22, 2021

Experts from the UPMC Departments of Pathology, Medicine, Orthopaedic Surgery, and Bioinformatics published a study in the Journal of Bone Oncology detailing differential expression of angiogenesis markers HSP70, HSP90, VEGF, and pERK1/2 in both components of dedifferentiated chondrosarcomas.

According to the study, dedifferentiated chondrosarcomas (DDCS) are highly malignant bimorphic mesenchymal tumors with poor outcome and limited treatment options. Genes and proteins involved in angiogenesis play an important role in the development of invasion and metastasis. 

Immunohistochemical stains targeting HSP70, pERK1/2 and VEGFA were applied to a TMA containing 29 DDCS cases representing both tumor components. Higher expression of HSP70 and pERK1/2 was noted in the dedifferentiated component. RNA sequencing performed in 8 paired cases of DDCS comparing well differentiated and dedifferentiated components, showed higher expression of several HSP70 family members and HSP90 in the dedifferentiated component.

Furthermore, high mobility group AT-hook 2 (HMAG2) and SET nuclear proto-oncogene demonstrated higher expression in the dedifferentiated component. Thus, the well differentiated and dedifferentiated components of DDCS are different, histologically and transcriptomically. The dedifferentiated component of DDCS shows higher expression of markers that are associated with malignant behavior. Some of these may represent future treatment targets.

Highlights from the study include:

  • Angiogenesis-related genes are important in the aggressive behavior of dedifferentiated chondrosarcoma.
  • RNA sequencing shows different gene expression in the two components of dedifferentiated chondrosarcoma.
  • Differences in heat shock protein expression in dedifferentiated chondrosarcoma suggest relevant treatment targets.

View the full study.

The Research Team

Kurt R. Weiss, MD
Department of Orthopaedic Surgery, UPMC

Rebecca J. Watters, PhD
Department of Orthopaedic Surgery, UPMC

Karen Schoedel, MD
Department of Pathology, UPMC

Virginia Miller, DO
Department of Pathology, UPMC

Anette Duensing, MD
Department of Pathology, UPMC

Ivy John, MD
Department of Pathology, UPMC

David Osei-Hwedieh, PhD
Department of Medicine, UPMC

Uma Chandran, PhD
Department of Bioinformatics, UPMC

Alexander Chang, PhD
Department of Bioinformatics, UPMC

Vishal Soman, PhD
Department of Bioinformatics, UPMC