PMID- 25680902 OWN - NLM STAT- MEDLINE DCOM- 20150608 LR - 20161125 IS - 1532-8392 (Electronic) IS - 0046-8177 (Linking) VI - 46 IP - 4 DP - 2015 Apr TI - MDM2 and CDK4 expression in periosteal osteosarcoma. PG - 549-53 LID - S0046-8177(14)00515-2 [pii] LID - 10.1016/j.humpath.2014.12.006 [doi] AB - 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. CI - Copyright (c) 2015 Elsevier Inc. All rights reserved. FAU - Righi, Alberto AU - Righi A AD - Pathology Department, Rizzoli Institute, Bologna, Italy 40136. Electronic address: alberto.righi@ior.it. FAU - Gambarotti, Marco AU - Gambarotti M AD - Pathology Department, Rizzoli Institute, Bologna, Italy 40136. FAU - Benini, Stefania AU - Benini S AD - Pathology Department, Rizzoli Institute, Bologna, Italy 40136. FAU - Gamberi, Gabriella AU - Gamberi G AD - Pathology Department, Rizzoli Institute, Bologna, Italy 40136; Department of Biomedical and Neuromotor Sciences, University of Bologna, Bologna, Italy 40126. FAU - Cocchi, Stefania AU - Cocchi S AD - Pathology Department, Rizzoli Institute, Bologna, Italy 40136. FAU - Picci, Piero AU - Picci P AD - Pathology Department, Rizzoli Institute, Bologna, Italy 40136. FAU - Bertoni, Franco AU - Bertoni F AD - Pathology Department, Rizzoli Institute, Bologna, Italy 40136; Department of Pathology, Villa Erbosa Hospital, Bologna, Italy 40129. LA - eng PT - Journal Article DEP - 20141231 PL - United States TA - Hum Pathol JT - Human pathology JID - 9421547 RN - 0 (Biomarkers, Tumor) RN - EC 2.3.2.27 (MDM2 protein, human) RN - EC 2.3.2.27 (Proto-Oncogene Proteins c-mdm2) RN - EC 2.7.11.22 (CDK4 protein, human) RN - EC 2.7.11.22 (Cyclin-Dependent Kinase 4) SB - IM MH - Adolescent MH - Adult MH - Biomarkers, Tumor/*metabolism MH - Bone Neoplasms/*metabolism/pathology MH - Child MH - Cyclin-Dependent Kinase 4/*metabolism MH - Female MH - Gene Amplification/physiology MH - Humans MH - Male MH - Neoplasm Recurrence, Local/genetics MH - Osteosarcoma/genetics/*metabolism/pathology MH - Periosteum/*metabolism MH - Proto-Oncogene Proteins c-mdm2/*metabolism MH - Retrospective Studies MH - Young Adult OTO - NOTNLM OT - Bone OT - CDK4 OT - Immunohistochemistry OT - MDM2 OT - Perisoteal osteosarcoma EDAT- 2015/02/15 06:00 MHDA- 2015/06/09 06:00 CRDT- 2015/02/15 06:00 PHST- 2014/10/29 00:00 [received] PHST- 2014/12/16 00:00 [revised] PHST- 2014/12/17 00:00 [accepted] PHST- 2015/02/15 06:00 [entrez] PHST- 2015/02/15 06:00 [pubmed] PHST- 2015/06/09 06:00 [medline] AID - S0046-8177(14)00515-2 [pii] AID - 10.1016/j.humpath.2014.12.006 [doi] PST - ppublish SO - Hum Pathol. 2015 Apr;46(4):549-53. doi: 10.1016/j.humpath.2014.12.006. Epub 2014 Dec 31.