Characterization of Rare Chondrosarcoma Subtypes
D Meijer, K Szuhai, BE van den Akker, D de Jong, T Krenacs, NA Athanasou, AM Flanagan, P Picci, S Daugaard, B Liegl-Atzwanger, PC Hogendoorn, JV Bovee. On Behalf of the EuroBoNet Consortium, http://www.eurobonet.eu/, Leiden, Netherlands
Background: Besides conventional chondrosarcoma several rare chondrosarcoma subtypes are defined, together constituting 10-15% of all chondrosarcomas. Clear cell chondrosarcoma (CCS) (2%) is a low-grade malignant tumor which rarely metastasizes, but commonly recurs after curettage. About 15% of the patients die as a result of the disease. Mesenchymal chondrosarcoma (MCS) (2%) is a highly malignant lesion occurring in the bone and soft tissue of relatively young patients. The tumor consists of differentiated cartilage mixed with undifferentiated small round cells and usually follows an aggressive course with a high rate of distant metastases and a 5-year overall survival of 55%. Dedifferentiated chondrosarcoma (DDCS) (10%) is a tumor containing a high-grade non-cartilaginous (DD; dedifferentiated) sarcoma and a usually low-grade malignant (WD; well-differentiated) cartilage-forming tumor, with a sharply defined junction between the two components. It bears a poor prognosis and no targets for therapy have been reported so far. The lack of efficacious treatment of these rare tumors emphasizes the need to learn more about their characteristics and to unravel potential targets for therapy.
Design: We constructed tissue microarrays (TMAs) containing 2mm cores of 45 DDCS (WD and DD), 24 CCS, and 25 MCS, in triplicate. The TMAs are immunohistochemically stained for estrogen-signaling molecules, growth plate-signaling molecules, and other molecules which might be potential targets for therapy. In addition, from the paraffin-embedded tissue genomic information was gathered using Agilent 44K oligo arrays.
Results: For Cox-2, 30% of the WD components of DDCS were positive. Almost all DD, CCS, and MCS were negative. In MCS 88% of the small cells and 32% of the cartilage were positive for Bcl2. In CCS, WD, and DD 48%, 4%, and 12% were positive, respectively. We demonstrated the presence of ESR1 and aromatase protein in the majority of tumors in all subtypes. ArrayCGH showed that the two components of DDCS share similar aberrations, with additional aberrations in the DD, e.g. a homozygous deletion of p16.
Conclusions: As most of the tumors are negative for Cox-2, celecoxib treatment is not recommended. However, application of Bcl2 inhibitors might chemosensitize MCS, and the presence of ESR1 and aromatase support a possible effect of anti-estrogen treatment in all subtypes.
Category: Bone & Soft Tissue
Tuesday, March 23, 2010 9:30 AM
Poster Session III # 24, Tuesday Morning