¹Uniklinik Köln, Urologie, Köln, Deutschland
²Stratifyer Molecular Pathology GmbH, Köln, Deutschland

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Introduction: A known target of the NFκB transcription factor complex is the promoter region of Cyclooxygenase 2 (Cox-2). Overexpression of Cox-2 is particularly associated with the development of cisplatin resistance. Mxi-2 forms a complex with the NFκB p65 subunit. It is now being investigated whether the overexpression of Cox-2 in cisplatin resistance is due to a base substitution in the NFκB binding region and whether Mxi-2 is involved in the overexpression of Cox-2.

Materials and methods: DNA was isolated from urothelial carcinoma cell lines (RT4, HTB-9, T24(-R), TCCSUP(-R)) and analyzed for the T/G base exchange at the Cox-2 promoter using TaqMan SNP analysis. DNA was also isolated from urine samples from patients with cisplatin-sensitive (n=11) and -resistant bladder cancer (n=12) and analyzed using SNP analysis. The Mxi-2 ELISA was performed according to established standard protocols.

Results: SNP analysis identified homozygous mutated type (G/G), heterozygous mutated type (T/G), or wild type (T/T) in the cell lines and urine samples used. The ELISA showed overexpression of Mxi-2 in patients with cisplatin-sensitive bladder cancer (OD Median 0.50 ± 0,029) vs cisplatin-resistant bladder cancer (OD Median 0.43 ± 0,078).

Conclusion: The collected results suggest that predictive statements regarding the effectiveness of cisplatin-containing therapy may be possible by determining the polymorphism in the NFκB binding site of the Cox-2 promoter in combination with patient Mxi-2 level. Patients with low Mxi-2 levels and a heterozygous or homozygous mutated type should undergo close imaging controls during neoadjuvant chemotherapy.