Amplification and protein expression of chromosome 12q13-15 genes in osteosarcomas of the jaws

Lopes, M.A.; Nikitakis, N.G.; Ord, R.A.; Sauk, J.

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Volume 37, Issue 7 , Pages 566-571, October 2001

Amplification and protein expression of chromosome 12q13-15 genes in osteosarcomas of the jaws

M.A. Lopes
- Department of Oral Diagnosis, Faculty of Odontology of Piracicaba, UNICAMP, São Paulo, Brazil
- Corresponding author. Present address: Department of Oral and Maxillofacial Pathology, Dental School, University of Maryland, 666 West Baltimore Street, Baltimore, MD 21201 USA. Tel.: +1-410-706-7936; fax: +1-410-706-0193
N.G. Nikitakis
- Department of Pathology, University of Maryland at Baltimore, Baltimore, Maryland, USA
R.A. Ord
- Dental School and UMAB Greenebaum Cancer Center, University of Maryland at Baltimore, Baltimore, Maryland, USA
J. Sauk Jr.
- Department of Pathology, University of Maryland at Baltimore, Baltimore, Maryland, USA
- Dental School and UMAB Greenebaum Cancer Center, University of Maryland at Baltimore, Baltimore, Maryland, USA

Received 21 August 2000; received in revised form 10 October 2000; accepted 10 October 2000.

Abstract

Overexpression and amplification of several genes (MDM2, CDK4 and SAS) located on chromosome 12q13-15 have been noted to occur in various human sarcomas. As a result, two major growth regulation pathways may be inhibited. MDM2 may down regulate the p53-mediated growth control and CDK4 may affect pRB-mediated events. To determine the frequency of alterations in these genes and their correlation with clinicopathologic features, we analyzed the MDM2 and CDK4 protein levels by immunohistochemistry and assessed MDM2, CDK4 and SAS amplification by real-time PCR in nine osteosarcomas of the jaws. Positive staining for CDK4 and MDM2 was observed in eight cases (88.8%) and five cases (55.5%), respectively. Intense CDK4 staining was noted in four cases (two high grade, one intermediate grade and one low grade). Intense MDM2 staining was observed in the same four previous cases, as well as, one additional high-grade tumor. Individual DNA amplification for CDK4, MDM2 and SAS was observed in six cases for each gene. Co-amplification was observed in five cases that showed CDK4 and MDM2 concomitant amplification and four cases that displayed amplification for all of the genes. In addition, among the five cases that presented CDK4 and MDM2 amplification, strong overexpression of CDK4 and MDM2 was observed in three and in four cases, respectively (three high grade and one intermediate grade). These results suggest that 12q13-15 genes are involved in neoplastic disease and concurrent amplification and overexpression of these genes might help to define high-grade tumors.