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.
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Co-amplification of MDM2 and CDK4 has been reported in several types of cancers including sarcoma, glioblastoma, bladder cancer and gastric cancer.
“Moreover, the co-amplification of MDM2 and CDK4 has been reported in several type of cancers including sarcoma, glioblastoma, bladder cancer, gastric cancer, etc.40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50”
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- Authors
- Righi, A., Gambarotti, M., Benini, S., Gamberi, G., Cocchi, S., Picci, P., & Bertoni, F.
- Affiliations
- Istituto Ortopedico Rizzoli (IT)
- Corresponding author
- Righi, Alberto
- Venue
- Human Pathology
- Publisher
- Elsevier BV
- Published
- 2015-04
- Volume
- 46
- Issue
- 4
- Pages
- 549-553
- ISSN
- 0046-8177 (ISSN-L)
- OpenAlex
- W2061394941
- Cited by
- 42
- References
- 27
- Citations by year
- 2025: 3 · 2024: 2 · 2023: 2 · 2022: 4 · 2021: 5 · 2020: 10 · 2019: 6 · 2018: 2 · 2017: 5 · 2016: 1 · 2015: 1 · 2014: 1
- FWCI
- 2.14
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Human Pathology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Sarcoma Diagnosis and Treatment
- Health Sciences › Medicine › Rheumatology › Bone Tumor Diagnosis and Treatments
- Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
- Keywords
- periosteal osteosarcoma, MDM2, CDK4, MDM2 amplification, recurrent osteosarcoma, immunohistochemical expression, diagnostic biomarkers, parosteal osteosarcoma
- MeSH terms
- Adolescent, Adult, Bone Neoplasms, Child, Female, Gene Amplification, Humans, Male, Neoplasm Recurrence, Local, Periosteum, Retrospective Studies, Osteosarcoma, Biomarkers, Tumor, Cyclin-Dependent Kinase 4, Proto-Oncogene Proteins c-mdm2, Young Adult
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