title: MDM2 and CDK4 expression in periosteal osteosarcoma.
abstract: Periosteal osteosarcoma is defined by the World Health Organization as an intermediate-grade, malignant, cartilaginous, and bone-forming neoplasm arising on the surface of bone. Unlike other subtypes of osteosarcoma, no data have been published about mouse double minute 2 (MDM2) and cyclin-dependent kinase 4 (CDK4) expression. For this reason, we evaluated the molecular and immunohistochemical features of MDM2 and CDK4 in 27 cases relative to 20 patients with a diagnosis of periosteal osteosarcoma, surgically treated at the Rizzoli Institute between 1981 and 2014. When possible, these results were compared with the MDM2 amplification status as determined by fluorescence in situ hybridization (FISH). All but 1 case (26/27, 96.3%) were negative for MDM2 protein using immunohistochemistry both in primary and in recurrent periosteal osteosarcoma, whereas gene amplification of MDM2 was not detected in any tumor analyzed (10 cases). The positive immunohistochemical case shows a weak/moderate focal nuclear expression of MDM2 antibody in the prevalent cartilaginous component and in the spindle cells of peripheral fibroblastic areas associated with osteoid production in a primary periosteal osteosarcoma. CDK4 immunohistochemical expression was negative in all 27 cases. This retrospective analysis has demonstrated that MDM2 and CDK4 are very rarely expressed in primary and recurrent periosteal osteosarcomas and therefore do not appear to be molecules central to the control of cancer development, growth, and progression in periosteal osteosarcoma. Therefore, when compared with low-grade central and parosteal osteosarcomas, MDM2 and CDK4 markers cannot be used diagnostically to differentiate this subtype of osteosarcoma.
authors: Pathology Department, Rizzoli Institute, Bologna, Italy 40136. Electronic address: alberto.righi@ior.it.
authors: Alberto
authors: A
authors: Righi
authors: Pathology Department, Rizzoli Institute, Bologna, Italy 40136.
authors: Marco
authors: M
authors: Gambarotti
authors: Pathology Department, Rizzoli Institute, Bologna, Italy 40136.
authors: Stefania
authors: S
authors: Benini
authors: Pathology Department, Rizzoli Institute, Bologna, Italy 40136; Department of Biomedical and Neuromotor Sciences, University of Bologna, Bologna, Italy 40126.
authors: Gabriella
authors: G
authors: Gamberi
authors: Pathology Department, Rizzoli Institute, Bologna, Italy 40136.
authors: Stefania
authors: S
authors: Cocchi
authors: Pathology Department, Rizzoli Institute, Bologna, Italy 40136.
authors: Piero
authors: P
authors: Picci
authors: Pathology Department, Rizzoli Institute, Bologna, Italy 40136; Department of Pathology, Villa Erbosa Hospital, Bologna, Italy 40129.
authors: Franco
authors: F
authors: Bertoni
mesh_terms: D000293:Adolescent; D000328:Adult; D014408:Biomarkers, Tumor / Q000378:metabolism*; D001859:Bone Neoplasms / Q000378:metabolism* / Q000473:pathology; D002648:Child; D051358:Cyclin-Dependent Kinase 4 / Q000378:metabolism*; D005260:Female; D005784:Gene Amplification / Q000502:physiology; D006801:Humans; D008297:Male; D009364:Neoplasm Recurrence, Local / Q000235:genetics; D012516:Osteosarcoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D010521:Periosteum / Q000378:metabolism*; D051736:Proto-Oncogene Proteins c-mdm2 / Q000378:metabolism*; D012189:Retrospective Studies; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2; C495900:CDK4 protein, human; D051358:Cyclin-Dependent Kinase 4
keywords: Bone; CDK4; Immunohistochemistry; MDM2; Perisoteal osteosarcoma