Graduate Student Expo 2011
Ashley Defrancisco, PhD/Pathology Residency candidate
The influence of bone resoprtion osteosarcoma Etiopathogenesis
Advisor: T. Fan
Appendicular osteosarcoma (OS) is the most common primary malignant bone tumor affecting dogs and human beings. The etiopathogenesis of OS remains incompletely characterized; however in people, gene mutations in p53 and Rb (retinoblastoma), responsible for cell replication and cell proliferation respectively actively participate in OS development. Similarly in dogs, p53 mutations, as well as P-TEN (phosphate and tensin homolog) and C-MET (transforming gene) mutations increase the risk for OS. Despite the identification of specific genes involved in OS pathogenesis, other factors such as skeletal metabolism which may participate in OS development remains poorly characterized.
Observationally, OS demonstrates strong site predilection for regions of high mechanical stress and weight bearing in both dogs and humans. Additionally, OS predominantly involves the metaphysis of long bones, which is a region of trabecular bone with increased homeostatic turnover rate compared to adjacent compact bone. Male, large/giant breed dogs and tall, adolescent males are most commonly affected, again suggesting the participation of skeletal remodeling and formation in OS predisposition. Importantly, people with Paget’s disease, who experience repeated cycles of abnormal bone turnover, are at increased risk for OS development. Given the signalment, affected anatomic location, and predisposing skeletal metabolic factors, the dynamics of bone resorption and formation appear to participate in the etiopathogenesis of OS.