Mononucleotide markers of microsatellite instability in carcinomas of the urinary bladder.

ABSTRACT

AIMS: To determine the presence of microsatellite instability (MSI) and to assess the expression of the human mismatch repair (MMR) gene products hMLH1 and hMSH2 in primary transitional cell carcinomas (TCCs) of the urinary bladder in relation to clinico-pathological parameters. METHODS: Seventy-two cases of primary TCC were screened for the presence of alterations in MSI markers by molecular techniques and evaluated immunohistochemically for the expression of hMLH1 and hMSH2 proteins. Clinical data were available in 70 cases. The percentage of MSI rose to 16.6%. RESULTS: Reduced (<20%) hMLH1 expression was closely related to the presence of MSI (p=0.0004). Neither MMR proteins nor MSI was associated with grade, stage, papillary status. Clinical outcome analysed as a function of MSI did not show significant differences in terms of both disease-free and overall survival. Reduced hMLH1 expression was a significant predictor of shorter disease-free survival in univariate and multivariate analysis. CONCLUSIONS: The presence of MSI is not related to classical clinico-pathological parameters in TCCs, nor does it appear to be of prognostic significance. hMLH1 was an important indicator for recurrence.