Subject(s)
Osteosarcoma/diagnosis , Osteosarcoma/therapy , Adolescent , Alkaline Phosphatase/blood , Antigens, CD/blood , Biopsy , Chemotherapy, Adjuvant , Child , Combined Modality Therapy , Europe/epidemiology , Female , Follow-Up Studies , Humans , Incidence , L-Lactate Dehydrogenase/blood , Male , Neoplasm Metastasis , Neoplasm Staging , Osteosarcoma/pathology , Periodic Acid-Schiff Reaction , Prognosis , Radiotherapy , Risk Assessment , Secondary Prevention , Treatment OutcomeABSTRACT
Bone- and cartilage-forming tumours (osteosarcomas and chondrosarcomas) are rare malignant neoplasms. These tumours are clinically aggressive and often need extensive local and/or systemic treatment. Whereas no other treatment but surgery is currently available for chondrosarcomas, osteosarcomas show an approximately 50-80% response rate to adjuvant chemotherapy. Surgical removal of these tumours is currently mostly performed with limb salvage, but amputation may be required in some cases. In addition, the tumours have a risk of local recurrences adversely affecting the prognosis compared to the primary tumour. In this report we will mainly focus on two of the most prevalent malignant bone tumours, conventional osteosarcoma and conventional chondrosarcoma, and use these to illustrate the problems with the diagnosis of bone sarcomas in general.
Subject(s)
Bone Neoplasms/pathology , Chondrosarcoma/pathology , Osteosarcoma/pathology , Bone Neoplasms/diagnosis , Bone Neoplasms/drug therapy , Bone Neoplasms/surgery , Cartilage Diseases , Chondrosarcoma/diagnosis , Chondrosarcoma/drug therapy , Chondrosarcoma/surgery , Humans , Osteosarcoma/diagnosis , Osteosarcoma/drug therapy , Osteosarcoma/surgeryABSTRACT
Hedgehog (HH) signalling is important for specific developmental processes, and aberrant, increased activity has been described in various tumours. Disturbed HH signalling has also been implicated in the hereditary syndrome, Multiple Osteochondromas. Indian Hedgehog (IHH), together with parathyroid hormone-like hormone (PTHLH), participates in the organization of growth plates in long bones. PTHLH signalling is absent in osteochondromas, benign tumours arising adjacent to the growth plate, but is reactivated when these tumours undergo malignant transformation towards secondary peripheral chondrosarcoma. We describe a gradual decrease in the expression of Patched (PTCH) and glioma-associated oncogene homologue 1 (GLI1) (both transcribed upon IHH activity), and GLI2 with increasing malignancy, suggesting that IHH signalling is inactive and PTHLH signalling is IHH independent in secondary peripheral chondrosarcomas. cDNA expression profiling and immunohistochemical studies suggest that transforming growth factor-beta (TGF-beta)-mediated proliferative signalling is active in high-grade chondrosarcomas since TGF-beta downstream targets were upregulated in these tumours. This is accompanied by downregulation of energy metabolism-related genes and upregulation of the proto-oncogene jun B. Thus, the tight regulation of growth plate organization by IHH signalling is still seen in osteochondroma, but gradually lost during malignant transformation to secondary peripheral chondrosarcoma and subsequent progression. TGF-beta signalling is stimulated during secondary peripheral chondrosarcoma progression and could potentially regulate the retained activity of PTHLH.
