MDM2 and CDK4 expression in periosteal osteosarcoma

Abstract

Periosteal osteosarcoma is defined by World Health Organization as an intermediate-grade, malignant cartilage and bone forming neoplasm arising on the surface of bone. At difference to the other subtypes of osteosarcoma, in literature no data has been published about MDM2 and CDK4 expression. For this, we evaluate the immunohistochemistry expression of MDM2 and CDK4 to detect overexpression caused by gene amplification in 18 cases of periosteal osteosarcoma, surgically treated in Rizzoli Institute between 1981 and 2013. All but one case (17/18, 94.4%) were negative for MDM2 and CDK4 using immunohistochemistry. The positive case shows a strong nuclear expression of both antibodies in the prevalent cartilaginous component and in the spindle cells of peripheral fibroblastic areas associated with osteoid-producing. In conclusion, at difference to low grade central osteosarcoma and parosteal osteosarcomas, MDM2 and CDK4 are very rarely expressed in periosteal osteosarcoma and therefore do not appear to be a molecule central to the control of cancer development, growth and progression in periosteal osteosarcoma. These two markers can be used diagnostically to differentiate these subtypes of osteosarcoma and underline a different genetic pathway for the pathogenesis of this rare subtype of osteosarcoma. Periosteal osteosarcoma is defined by World Health Organization as an intermediate-grade, malignant cartilage and bone forming neoplasm arising on the surface of bone. At difference to the other subtypes of osteosarcoma, in literature no data has been published about MDM2 and CDK4 expression. For this, we evaluate the immunohistochemistry expression of MDM2 and CDK4 to detect overexpression caused by gene amplification in 18 cases of periosteal osteosarcoma, surgically treated in Rizzoli Institute between 1981 and 2013. All but one case (17/18, 94.4%) were negative for MDM2 and CDK4 using immunohistochemistry. The positive case shows a strong nuclear expression of both antibodies in the prevalent cartilaginous component and in the spindle cells of peripheral fibroblastic areas associated with osteoid-producing. In conclusion, at difference to low grade central osteosarcoma and parosteal osteosarcomas, MDM2 and CDK4 are very rarely expressed in periosteal osteosarcoma and therefore do not appear to be a molecule central to the control of cancer development, growth and progression in periosteal osteosarcoma. These two markers can be used diagnostically to differentiate these subtypes of osteosarcoma and underline a different genetic pathway for the pathogenesis of this rare subtype of osteosarcoma.