p53 and MDM2 alterations in osteosarcomas: correlation with clinicopathologic features and proliferative rate.
BACKGROUND
Alterations of the p53 gene and of MDM2, a gene coding for a p53 binding protein, have been implicated in the pathogenesis of osteosarcoma (OS).


METHODS
To determine the frequency of alterations of the p53/MDM2 pathway in OS and their possible correlation with clinicopathologic features, MDM2 copy number and p53 protein levels were determined in a series of 83 samples of OS by quantitative Southern blot analysis and immunohistochemistry, respectively.


RESULTS
Positivity for p53 was found in 26.5% and MDM2 amplification in 6.6% of the samples analyzed in a mutually exclusive fashion with one exception. Overall, alterations of the p53/MDM2 pathway occurred in 34% of cases; p53 accumulation was not associated with a higher proliferative rate. The mean age of patients with p53 positive OS (40 years) was older than that of the p53 negative group (28 years) (P < 0.04). Furthermore, three of the four cases of OS arising in Paget's disease showed p53 accumulation.


CONCLUSIONS
Alterations of the p53/MDM2 pathway are frequent in OS and usually represent mutually exclusive tumorigenic events. p53 does not appear to be a major determinant of proliferative rate in OS.
Lonardo
F
F
Department of Pathology, Memorial Sloan-Kettering Cancer Center, New York, New York 10021, USA.
Ueda
T
T
Huvos
A G
AG
Healey
J
J
Ladanyi
M
M
D000328:Adult; D015139:Blotting, Southern; D001859:Bone Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D002455:Cell Division / Q000235:genetics; D005784:Gene Amplification; D016158:Genes, p53 / Q000235:genetics*; D006801:Humans; D007150:Immunohistochemistry; D009363:Neoplasm Proteins / Q000235:genetics* / Q000378:metabolism; D009687:Nuclear Proteins; D012516:Osteosarcoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D011518:Proto-Oncogene Proteins / Q000235:genetics* / Q000378:metabolism; D051736:Proto-Oncogene Proteins c-mdm2
D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins; C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2