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Relation between expression pattern of wild-type p53 and multidrug resistance proteins in human nephroblastomas
Ingrid Hodorová1, Silvia Rybárová, Janka Vecanová
1Department of Anatomy, P.J. Šafárik University, Faculty of Medicine, Šrobárova 2, SK-04180 Košice, Slovak Republic.
Abstract:
One of the best characterized resistance mechanisms of human cancer is multidrug resistance (MDR) mediated by P-glycoprotein (Pgp/MDR1) and multidrug-resistant related protein (MRP1). In addition to Pgp/MDR1 and MRP1, p53 inactivation or mutation might play a relevant role in therapeutic failure. This study involved 25 children (17 girls and 8 boys) aged 7 months to 10 years treated for unilateral Wilms' tumor. 25 tissue samples of Wilms' tumor and 5 samples of normal human kidneys were obtained from the Department of Pathological Anatomy, Jessenius Faculty of Medicine in Martin, Slovak Republic. We used an indirect immunohistochemical method to determine expression of Pgp/MDR1, MRP1 and wild-type p53 in 25 tissue samples of nephroblastoma. The minority of nephroblastoma specimens showed positivity for both MDR proteins, as well as for wild-type p53. 24% of tissue samples revealed positive results for Pgp/MDR1, 48% for MRP1 and 8% for wild-type p53. Furthermore, our study showed a statistically significant difference between p53 and MRP1 protein expression (p<0.01), but not between p53 and Pgp/MDR1 (p>0.05). No correlation was found between the expression of both multidrug resistance proteins (Pgp/MDR1 and MRP1) and the expression of wild-type p53. Immunohistochemical detection of the expression of MDR proteins and wild-type p53 at the time of diagnosis might assist in choosing specific chemotherapeutics to improve prognosis and therapy.
Insights
Multidrug resistance (MDR) proteins P-glycoprotein (Pgp/MDR1) and multidrug-resistant related protein (MRP1) were evaluated in pediatric Wilms' tumors. While MRP1 expression was significantly different from wild-type p53, no correlation was found between MDR proteins and p53.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Multidrug resistance (MDR) is a significant challenge in cancer therapy, often mediated by P-glycoprotein (Pgp/MDR1) and multidrug-resistant related protein (MRP1).
- p53 tumor suppressor gene alterations may also contribute to therapeutic failure in various cancers, including Wilms' tumor.
Purpose of the Study:
- To investigate the expression of Pgp/MDR1, MRP1, and wild-type p53 in pediatric Wilms' tumor samples.
- To determine potential correlations between these proteins and their implications for treatment strategies.
Main Methods:
- Indirect immunohistochemistry was employed to detect Pgp/MDR1, MRP1, and wild-type p53 expression.
- 25 Wilms' tumor tissue samples from children were analyzed.
Main Results:
- Positive expression for Pgp/MDR1 was found in 24% of samples, MRP1 in 48%, and wild-type p53 in 8%.
- A statistically significant difference was observed between p53 and MRP1 expression (p<0.01), but not between p53 and Pgp/MDR1 (p>0.05).
- No correlation was identified between the expression of MDR proteins and wild-type p53.
Conclusions:
- The expression of MDR proteins and wild-type p53 varies in Wilms' tumors.
- Immunohistochemical analysis of these markers at diagnosis could potentially guide the selection of chemotherapeutics for improved patient outcomes.
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