TGF‐βRII, BAX, IGFIIR, caspase‐5, hMSH3 and hMSH6 alterations are not associated with microsatellite instability or p53 mutations in invasive urothelial carcinoma of the urinary bladder

Abstract

Aim: The aim of this study was to determine the potential synchronous contribution of alterations in TGF‐βRII, BAX, IGFIIR, caspase‐5, hMSH3 and hMSH6 genes to the development and clinical outcome of bladder cancer, in relation to p53 mutations, microsatellite status and hMLH1/hMSH2 expression.

Methods: Molecular biology techniques as well as immunohistochemistry were applied in 69 samples from patients with urothelial carcinoma.

Results: Microsatellite alterations were observed in TGF‐βRII(A)₁₀ (16%) and BAX(G)₈ (3%), irrespective of the presence of p53 mutations, but not in IGFIIR(G)₈, caspase‐5(A)_10, hMSH3(A)₈ and hMSH6(C)₈. A statistically significant correlation could be found only between hMLH1 expression and the presence of microsatellite instability (Fisher's exact test, p = 0,013). Survival analysis indicated that apart from grade and T‐category, hMLH1 expression was the only parameter significantly affecting overall survival (p = 0.021 in univariate and p = 0.015 in multivariate analysis) and recurrence‐free survival (p = 0.0463 in univariate and p = 0.022 in multivariate analysis).

Conclusions: We conclude that alterations of the examined target genes of MSI are rare in urinary bladder carcinoma and they are not associated with microsatellite instability or the presence of p53 mutations.

• BAX
• hMSH3
• hMSH6
• IGFIIR
• TGF‐βRII
• urothelial carcinoma
• MSI