Microarray analysis identifies distinct gene expression profiles associated with histological subtype in human osteosarcoma.

Osteosarcoma is the most common primary malignant bone tumour. Currently osteosarcoma classification is based on histological appearance. It was the aim of this study to use a more systematic approach to osteosarcoma classification based on gene expression analysis and to identify subtype specific differentially expressed genes. We analysed the global gene expression profiles of ten osteosarcoma samples using Affymetrix U133A arrays (five osteoblastic and five non-osteoblastic osteosarcoma patients). Differential gene expression analysis yielded 75 genes up-regulated and 97 genes down-regulated in osteoblastic versus non-osteoblastic osteosarcoma samples, respectively. These included genes involved in cell growth, chemotherapy resistance, angiogenesis, steroid- and neuropeptide hormone receptor activity, acute-phase response and serotonin receptor activity and members of the Wnt/ß-catenin pathway and many others. Furthermore, we validated the highly differential expression of six genes including angiopoietin 1, IGFBP3, ferredoxin 1, BMP, decorin, and fibulin 1 in osteoblastic osteosarcoma relative to non-osteoblastic osteosarcoma. Our results show the utility of gene expression analysis to study osteosarcoma subtypes, and we identified several genes that may play a role as potential therapeutic targets in the future.

Advances in bone tumour treatment in 30 years with respect to survival and limb salvage. A single institution experience.

We analysed 721 patients with primary malignant bone tumours treated in a single institution with regard to diagnosis, treatment and prognosis. From 1965 to 1974, 154 patients were treated, of whom 17% had no surgery, 36% underwent resection and 46% underwent amputation. Margins of resection were intralesional in 21%, 72% of patients received chemotherapy and overall survival rate was 24%. From 1975 to 1984, 174 patients were treated, of whom 12% had no surgery, 54% underwent limb salvage procedures and 34% underwent amputation or resection-replantation. Margins of resection were intralesional in 16% 67% of patients received chemotherapy and overall survival rate was 46%. From 1985 to 1994, 393 patients were treated, of whom 7% had no surgery, 77% underwent limb salvage procedures - mainly with endoprostheses - and 15% underwent amputation or resection-replantation. Margins of resection were intralesional in 12%, 68% of patients received chemotherapy and overall survival rate was 62%. Advancements in the treatment of primary malignant bone tumours justify limb salvage procedures in combination with highly effective polychemotherapy in specialised centres and has resulted in an overall survival rate of more than 60%.