Response to a taxol based chemotherapy regimen in advanced transitional cell carcinoma is independent of p53 expression

Most studies have observed that p53 positivity (mutation) is a poor prognostic factor in patients with muscle invasive transitional cell carcinoma (TCC). Since current in vitro studies indicate that taxol induced apoptasis occurs independent of p53 mutations, it would appear that taxol based chemotherapies would be a logical choice in advanced TCC, which have a high percentage of p53 mutations. Our study evaluated a cohort of patients with advanced TCC, with the hypothesis that response to a taxol based chemotherapy regimen would be independent of p53 status. Twenty-seven patients with advanced TCC were treated on an IRB approved protocol with taxol, carboplatin, and methotrexate. Resfonse was determined by standard NCI criteria. Four of the patients were treated with an adjuncuve protocol, of the remaining twenty-three patients, nine responded whereas fourteen patients demonstrated no response to therapy. Immunohistochemistry (IHC) was performed with a DO1/DO7 antibody cocktail. Nineteen of twenty-three patients were IHC(+) for p53. Of the nine responders seven were p53 IHC(+). Of the fourteen non-responders, twelve were p53 IHC(+). Therefore, we conclude that, 1) advanced TCC has a high rate of p53 IHC(+), presumed to be p53 mutations, and 2) response to taxol bused chemotherapy regimens is independent of p53, confirming previous in vitro observations. This is one of the first clinical examinations of p53 with taxol based chemotherapies.