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Relationship between P-glycoprotein expression and p53 status in high-grade osteosarcoma
M Serra1, D Maurici, K Scotlandi
1Laboratorio di Ricerca Oncologica, Istituti Ortopedici Rizzoli, 40136 Bologna, Italy.
International Journal of Oncology
|January 26, 1999
Summary
In osteosarcoma, p53 gene status did not correlate with P-glycoprotein expression. However, increased P-glycoprotein levels in tumor cells were linked to a poorer prognosis, highlighting its adverse prognostic value.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- The MDR1 gene's transcription can be influenced by mutations or loss of function in the p53 gene.
- P-glycoprotein, the MDR1 gene product, is implicated in multidrug resistance in various cancers.
Purpose of the Study:
- To investigate the correlation between p53 status and P-glycoprotein overexpression in osteosarcoma.
- To assess the prognostic significance of P-glycoprotein expression and p53 status in osteosarcoma.
Main Methods:
- Immunohistochemistry was used to analyze P-glycoprotein expression and p53 status in 64 primary and 11 metastatic high-grade osteosarcomas.
- Nuclear accumulation of MDM2 protein was assessed as a mechanism for p53 inactivation.
Main Results:
- No significant association was found between mutant p53, MDM2 nuclear accumulation, and P-glycoprotein expression or clinical outcomes.
- Increased P-glycoprotein expression in tumor cells was significantly associated with a poor prognosis in osteosarcoma patients.
Conclusions:
- p53 status and MDM2 accumulation do not appear to be directly correlated with P-glycoprotein expression or clinical course in osteosarcoma.
- Elevated P-glycoprotein expression serves as a significant adverse prognostic marker in osteosarcoma.