Published in Cancer Detection and Prevention 2000; 24(4):356-363.

Cytochrome P450 lsoenzyme mRNA Expression Pattern in Human Urinary Bladder Malignancies and Normal Urothelium

Andreas Brauers, MD,a Edith Mane gold, MD,b Reinhard Buettner, MD,b Jens M. Baron, MD,c Hans F Merk, MD,c and Gerhard Jakse, MDa

University aClinic of Urology, binstitute of Pathology, and cClinic of Dermatology, Medical Faculty of the Technical University, Aachen, Germany

Address all correspondence and reprint requests to: Andreas Brauers, MD, University Clinic of Urology, Medical Faculty of the Technical University Aachen, PauwelsstraBe 30, D-52057 Aachen, Germany.

ABSTRACT: This study was designed to analyze the cytochrome P450 isoenzyme mRNA expression pattem of transitional cell carcinomas of the bladder (N = 19) and normal urothelium (N = 10). In addition, biopsies from normal urothelium (N = 32) taken at the time of transurethral resection of bladder cancer in eight patients from surrounding histologically normal urothelium also were characterized conceming their specific cyrochrome P450 mRNA expression pattem. A total of 13 of 19 of the analyzed tumor specimens (68%) revealed expression of cytochrome P450 1 B 1. Cytochrome P450 4B 1 and lAl mRNA expression were detected in 79% (15 of 19) and 53% (10 of 19) of the tumor specimens, with no correlation between tumor stage and grade of the neoplasm. Biopsies from macroscopically and histologically normal urothelium from tumor-invaded bladders also showed expression of cytochrome P450 lB1 in 75% (24 of 32), 4B1 in 62.5% (20 of 32), and lAl in 50% (16 of 32). Furthermore, a 75% homology conceming cytochrome P450 lB1 and 4B1 mRNA expression was observed between the bladder tumor and the biopsies from this bladder. The polymerase chain reaction analysis of normal urothelium from normal bladders that do not harbor a neoplasm revealed CYP450 mRNA expression for CYP450 lAl in 6 of 10; lBl in 5 of 10; 4B1 in 6 of 10; 2D6 in 2 of 10; and 2E1 in 2 of 10. According to our data, CYP450 1Bl mRNA expression is not tumor-specific. The present findings are the first to compare CYP450 expression in bladder cancer with biopsies from the same tumor-bearing bladder, and they indicate that, from the enzymatic point of view, bladder cancer also is a panurothelial field disease present in even normal urothelium.

KEY WORDS: bladder cancer, CYP450 expression, carcinogenesis.