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Background  Urinary bladder carcinoma stage T1 is an unpredictable disease that in some cases has a good prognosis with only local or no recurrence, but in others can appear as a more aggressive tumor with progression to more advanced stages. The aim here was to investigate stage T1 tumors regarding  MDM2  promoter SNP309 polymorphism, mutations in the  p53  gene, and expression of p53 and p16 measured by immunohistochemistry, and subsequently relate these changes to tumor recurrence and progression. We examined a cohort of patients with primary stage T1 urothelial carcinoma of the bladder and their tumors.    Methods  After re-evaluation of the original slides and exclusions, the study population comprised 141 patients, all with primary stage T1 urothelial carcinoma of the bladder. The hospital records were screened for clinical parameters and information concerning presence of histologically proven recurrence and progression. The paraffin-embedded tumor material was evaluated by immunohistochemistry. Any mutations found in the  p53  gene were studied by single-strand conformation analysis and Sanger sequencing. The  MDM2  SNP309 polymorphism was investigated by pyrosequencing. Multivariate analyses concerning association with prognosis were performed, and Kaplan-Meier analysis was conducted for a combination of changes and time to progression.    Results  Of the 141 patients, 82 had at least one  MDM2  SNP309 G allele, and 53 had a mutation in the  p53  gene, but neither of those anomalies was associated with a worse prognosis. A mutation in the  p53  gene was associated with immunohistochemically visualized p53 protein expression at a cut-off value of 50%. In the group with  p53  mutation Kaplan-Meier analysis showed higher rate of progression and shorter time to progression in patients with immunohistochemically abnormal p16 expression compared to them with normal p16 expression (p = 0.038).    Conclusions   MDM2  SNP309 promoter polymorphism and mutations in  p53  were not associated with worse prognosis in this cohort of patients with primary stage T1 urinary bladder carcinoma. However, patients with abnormal p16 expression and a mutated  p53  gene had a higher rate of and a shorter time to progression, and  p53  gene mutation was associated with an abnormal immunohistochemistry for p53 at a cut-off of 50%.

MDM2 SNP309 promoter polymorphism and p53 mutations in urinary bladder carcinoma stage T1