Cookies on this website
We use cookies to ensure that we give you the best experience on our website. If you click 'Continue' we'll assume that you are happy to receive all cookies and you won't see this message again. Click 'Find out more' for information on how to change your cookie settings.
Skip to main content

The mesenchymal, clear cell, and dedifferentiated chondrosarcoma subtypes are extremely rare, together constituting 10% to 15% of all chondrosarcomas. Their poor prognosis and lack of efficacious treatment emphasizes the need to elucidate the pathways playing a pivotal role in these tumors. We constructed tissue microarrays containing 42 dedifferentiated, 23 clear cell, and 23 mesenchymal chondrosarcomas and performed immunohistochemistry to study the expression of growth plate-signaling molecules and molecules shown to be involved in conventional chondrosarcoma. We observed high expression of SOX-9 and FGFR-3, as well as aberrant cellular localization of heparan sulfate proteoglycans, in all subtypes. TGFβ signaling through p-SMAD2 and PAI-1 was highly active in all chondrosarcoma subtypes, which suggests that TGFβ inhibitors as a possible therapeutic strategy in rare chondrosarcoma subtypes. As in conventional chondrosarcoma, antiapoptotic proteins (Bcl-2, and/or Bcl-xl) were highly expressed in all subtypes. Inhibition with the BH-3 mimetic ABT-737 rendered dedifferentiated chondrosarcoma cell lines sensitive to doxorubicin or cisplatin. Our data indicate that antiapoptotic proteins may play an important role in chemoresistance, suggesting a promising role for targeting Bcl-2 family members in chondrosarcoma treatment, irrespective of the subtype.

Original publication




Journal article


The American journal of pathology

Publication Date





1347 - 1356


Department of Pathology, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands.


Humans, Chondrosarcoma, Mesenchymal, Sarcoma, Clear Cell, Transforming Growth Factor beta, Neoplasm Proteins, Proto-Oncogene Proteins c-bcl-2, Antineoplastic Agents, Immunohistochemistry, Paraffin Embedding, Tissue Fixation, Signal Transduction, Drug Resistance, Neoplasm, Adult, Aged, Aged, 80 and over, Middle Aged, Female, Male, Cell Dedifferentiation, Young Adult, Molecular Targeted Therapy