Identifikation molekularer Progressionsmarker des Harnblasenkarzinoms anhand der Mikrosatellitenanalyse
Für diese Arbeit wurde eine genetische Charakterisierung des Urothelkarzinoms der Harnblase durchgeführt. Als Methode kam die Mikrosatellitenanalyse zum Einsatz. Von den asservierten Tumorproben waren 58 zur weiteren Untersuchung brauchbar. Zudem gelang der Nachweis von freier DNA im Serum mit tumo...
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Table of Contents: The clinical behaviour of urothelial bladder cancer is very heterogenic. To further elucidate circumstances leading to differences in clinical and biological behaviour we performed a genetic characterization of 58 bladder cancer samples applying fluorescent microsatellite analysis investigating the chromosomal regions 5q, 8p, 9p, 9q, 13q, 14q, 17p, 17q and 20q with a total of 17 polymorphic microsatellite markers. A further aim of the underlying study was to identify free tumour-DNA in blood serum. The following chromosomal regions were significantly associated with advanced tumour stages and poor nuclear differentiation (p<0,05): 5p, 5q, 8p, 13q, 14 and 17p. Applying microsatellite analysis a serological tumour diagnosis was possible in 79.3 %. Serological tumour diagnosis was significantly associated with to high grade tumors. After 5 years 50 of 58 patients were available for follow-up. Of interest, none of the chromosomal regions associated with poor tumour characteristics at initial investigation showed an association with clinical outcome on follow-up evaluation. Clinical prognosis was only significantly associated with tumor stage. In this study molecular allelotyping applying microsatellite analysis with 17 markers failed to identify progression markers after a 5 year follow-up period. The failure of this study to identify markers with prognostic potential may be explained by the small cohort of bladder cancer patients investigated. Therefore, larger prospective studies investigating additional chromosomal regions are warranted to prove the true value of chromosomal allelotyping for better estimating the prognosis of the heterogenic bladder cancer disease.