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P53 mutation predicts intravesical adriamycin instillation failure in superficial transitional cell carcinoma of
Koji Shiraishi1, Satoshi Eguchi, Jun Mohri
1Department of Urology, Saiseikai Shimonoseki General Hospital, 3-4-1 Kifunecho, Shimonoseki, Yamaguchi 751-8502, Japan. k-siraisi@simo.saiseikai.or.jp
Background:
We studied whether p53 status has any predictive value on the outcome of intravesical adriamycin (ADR) instillation for superficial transitional cell carcinoma (TCC) of the bladder.
Materials And Methods:
Paraffin-embedded specimens were obtained from 70 consecutive patients by transurethral resection (TUR). All patients received intravesical instillation with either Epirubicin (n = 45) or Pirarubicin (n = 25). P53 mutation and overexpression were examined for single-strand conformation polymorphism (SSCP) and immunohistochemistry (IHC), respectively.
Results:
In 18.2% of tumors, mutation was observed, including exon 5, 6 or 7. P53 overexpression was observed in 22.9% of tumors. High concordance between SSCP and IHC was shown (p = 0.0001), while there was a certain number of discrepant cases. The recurrence-free rate was significantly different between the group with and without p53 mutation, but not stage, grade or p53 IHC.
Conclusion:
P53 mutation predicts the failure of intravesical ADR instillation. Aggressive therapeutic approaches following initial TUR should be considered for patients with p53 mutation.
Insights
p53 gene mutations, not overexpression, predict treatment failure in superficial bladder cancer receiving intravesical adriamycin (ADR) chemotherapy. Patients with p53 mutations may require more aggressive therapies after transurethral resection.
Area of Science:
- Oncology
- Molecular Biology
- Urologic Oncology
Background:
- Superficial transitional cell carcinoma (TCC) of the bladder is often treated with intravesical chemotherapy.
- The predictive value of p53 tumor suppressor gene status for treatment outcomes remains unclear.
Purpose of the Study:
- To investigate the association between p53 gene alterations (mutation and overexpression) and the efficacy of intravesical adriamycin (ADR) or its analogs in superficial bladder TCC.
- To determine if p53 status can predict treatment response and recurrence-free survival.
Main Methods:
- Analysis of paraffin-embedded tumor specimens from 70 patients with superficial TCC treated with intravesical Epirubicin or Pirarubicin.
- Detection of p53 mutations using single-strand conformation polymorphism (SSCP) and p53 overexpression via immunohistochemistry (IHC).
Main Results:
- p53 mutations were identified in 18.2% of tumors, and p53 overexpression in 22.9%.
- A significant correlation was observed between SSCP and IHC results (p = 0.0001).
- Patients with p53 mutations showed a significantly lower recurrence-free rate compared to those without, whereas p53 IHC, tumor stage, and grade did not predict outcomes.
Conclusions:
- p53 gene mutation is a significant predictor of treatment failure for intravesical ADR instillation in superficial bladder cancer.
- Consideration of more aggressive treatment strategies is recommended for patients with p53 mutations following transurethral resection.
