p53 and MDM2 alterations in osteosarcomas: Correlation with clinicopathologic features and proliferative rate Journal Article


Authors: Lonardo, F.; Ueda, T.; Huvos, A. G.; Healey, J.; Ladanyi, M.
Article Title: p53 and MDM2 alterations in osteosarcomas: Correlation with clinicopathologic features and proliferative rate
Abstract: 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.
Keywords: immunohistochemistry; osteosarcoma; adult; human tissue; bone neoplasms; unclassified drug; gene mutation; human cell; major clinical study; proto-oncogene proteins; pathogenesis; protein blood level; cell division; gene amplification; neoplasm proteins; protein p53; nuclear proteins; tumor growth; protein determination; protein mdm2; proto-oncogene proteins c-mdm2; genes, p53; paget bone disease; blotting, southern; humans; human; male; female; priority journal; article
Journal Title: Cancer
Volume: 79
Issue: 8
ISSN: 0008-543X
Publisher: Wiley Blackwell  
Date Published: 1997-04-15
Start Page: 1541
End Page: 1547
Language: English
DOI: 10.1002/(sici)1097-0142(19970415)79:8<1541::aid-cncr15>3.0.co;2-y
PUBMED: 9118036
PROVIDER: scopus
DOI/URL:
Notes: Article -- Export Date: 17 March 2017 -- Source: Scopus
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MSK Authors
  1. Marc Ladanyi
    1326 Ladanyi
  2. John H Healey
    547 Healey
  3. Andrew G Huvos
    289 Huvos
  4. Fulvio B Lonardo
    23 Lonardo
  5. Takafumi Ueda
    12 Ueda