Structural alteration of p53 protein in patients with muscle invasive bladder transitional cell carcinoma

Recent data imply that 3-dimensional (D) p53 protein modeling provides more specific information on its function in patients with pancreatic adenocarc inoma. In addition to immunohistochemical and single strand conformational polymorphism analysis, we performed 3-D p53 protein modeling and correlated our results with the disease-free survival of patients with muscle invasiv e transitional cell carcinoma of the bladder who underwent surgery. Materials and Methods: We identified 43 patients and analyzed p53 status in each by immunohistochemical testing, single strand conformational polymorp hism and DNA sequencing with 3-D protein modeling. Median followup was 38 m onths (range 4 to 92). The results of each analysis were compared and corre lated with cancer specific survival. Statistical analysis was performed usi ng the log rank test on Kaplan-Meier survival curves. Results: The population included 30 men and 13 women 35 to 84 years old (me dian age 65). Nuclear over expression of p53 protein was observed in 26 of the 43 cases (60%). Lymph node involvement did not correlate with p53 over expression. Significantly more patients with lymph node metastasis died of cancer. Median survival in the 26 patients with p53 over expression was 28 months versus 57 in those with negative staining (p = 0.25). Mutation analy sis by single strand conformational polymorphism revealed no abnormality in 24 patients (56%) with a median survival of 28 months, whereas we noted ab normal mutational analysis in 19 (44%) with a median survival of 38 months (p = 0.33). Of 19 single strand conformational polymorphism positive cases DNA sequencing showed mutation near the DNA binding site in 10 (53%), mutat ion away from the site in 6 (32%) and no mutation in 3 (17%). No survival d ifference was detected in cases with mutation away and near the DNA binding site, respectively (p = 0.69). Conclusions: In this group of patients treated with radical cystectomy for muscle invasive bladder transitional cell carcinoma, analysis of p53 protei n and the p53 gene by immunohistochemical testing, single strand conformati onal polymorphism and mutational analysis did not correlate with cancer spe cific survival.