Differential expression of angiogenesis markers HSP70, HSP90, VEGF and pERK1/2 in both components of dedifferentiated chondrosarcomas

Karen Schoedel; Virginia Miller; David Osei-Hwedieh; Rebecca Watters; Anette Duensing; Ivy John; Uma Chandran; Alexander Chang; Vishal Soman; Kurt Weiss

doi:10.1016/j.jbo.2021.100370

Differential expression of angiogenesis markers HSP70, HSP90, VEGF and pERK1/2 in both components of dedifferentiated chondrosarcomas

J Bone Oncol. 2021 May 18:29:100370. doi: 10.1016/j.jbo.2021.100370. eCollection 2021 Aug.

Authors

Affiliations

¹ Departments of Pathology, University of Pittsburgh Medical Center, United States.
² The School of Medicine, University of Pittsburgh Medical Center, United States.
³ Orthopedic Surgery, University of Pittsburgh Medical Center, United States.
⁴ Bioinformatics, University of Pittsburgh Medical Center, United States.

Abstract

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.

Keywords: Angiogenesis; CS, chondrosarcoma; Chondrosarcoma; DD, dedifferentiated component of dedifferentiated chondrosarcoma (no matrix); DDCS, dedifferentiated chondrosarcoma; HSP70; HSP90; IPEX, immunohistochemistry; VEGF; WD, well differentiated chondroid matrix containing component of dedifferentiated chondrosarcoma; pERK1/2.