Page 1 Bone Metastases Kenneth Rankin Orthopaedic Postgraduate Teaching 22nd November 2010 Page 2 Bone Metastases Kenneth Rankin Orthopaedic Postgraduate Teaching 22nd November 2010 Overview • Molecular mechanisms • Origin & distribution • Clinical features • Medical management • Surgical management • Cases Page 3 Bone Metastases Kenneth Rankin Orthopaedic Postgraduate Teaching 22nd November 2010 Overview • Molecular mechanisms • Origin & distribution • Clinical features • Medical management • Surgical management • Cases Molecular mechanisms of metastasis • Analysis of 735 autopsy records of breast cancer patients • Identified a non-random pattern of metastases • The Lancet 1889 : ‘seed and soil hypothesis’ Dr Stephen Paget Surgeon & pathologist 1855-1926 Page 4 Bone Metastases Kenneth Rankin Orthopaedic Postgraduate Teaching 22nd November 2010 Overview • Molecular mechanisms • Origin & distribution • Clinical features • Medical management • Surgical management • Cases Molecular mechanisms of metastasis • Analysis of 735 autopsy records of breast cancer patients • Identified a non-random pattern of metastases • The Lancet 1889 : ‘seed and soil hypothesis’ Dr Stephen Paget Surgeon & pathologist 1855-1926 Integrin Extracellular matrix Cadherin Dysregulation of these allows cancer cells to breakaway from the ECM and other cells Page 5 Bone Metastases Kenneth Rankin Orthopaedic Postgraduate Teaching 22nd November 2010 Overview • Molecular mechanisms • Origin & distribution • Clinical features • Medical management • Surgical management • Cases Molecular mechanisms of metastasis • Analysis of 735 autopsy records of breast cancer patients • Identified a non-random pattern of metastases • The Lancet 1889 : ‘seed and soil hypothesis’ Dr Stephen Paget Surgeon & pathologist 1855-1926 Integrin Extracellular matrix Cadherin Dysregulation of these allows cancer cells to breakaway from the ECM and other cells Loss of adhesion ?E-Cadherin expression VEGF Resident blood vessel Primary site Zone of severe hypoxia HIF Intravasation (Interaction with Endothelial cells) HIF= Hypoxia inducible factor VEGF= Vascular endothelial growth factorRead More