Brauers A, Manegold E, Buettner R, Baron J M, Merk H F, Jakse G
University Clinic of Urology, Medical Faculty of the Technical University, Aachen, Germany.
Cancer Detect Prev. 2000;24(4):356-63.
This study was designed to analyze the cytochrome P450 isoenzyme mRNA expression pattern 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 concerning their specific cytochrome P450 mRNA expression pattern. A total of 13 of 19 of the analyzed tumor specimens (68%) revealed expression of cytochrome P450 1B1. Cytochrome P450 4B1 and 1A1 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 1B1 in 75% (24 of 32), 4B1 in 62.5% (20 of 32), and 1A1 in 50% (16 of 32). Furthermore, a 75% homology concerning cytochrome P450 1B1 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 1A1 in 6 of 10; 1B1 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 1B1 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.
本研究旨在分析膀胱移行细胞癌（N = 19）和正常尿路上皮（N = 10）中细胞色素P450同工酶mRNA的表达模式。此外，还对8例患者在经尿道膀胱肿瘤切除时取自周围组织学正常尿路上皮的32份正常尿路上皮活检标本的细胞色素P450 mRNA特异性表达模式进行了特征分析。在19份分析的肿瘤标本中，共有13份（68%）显示细胞色素P450 1B1表达。在79%（19份中的15份）和53%（19份中的10份）的肿瘤标本中检测到细胞色素P450 4B1和1A1 mRNA表达，肿瘤分期与肿瘤分级之间无相关性。来自肿瘤侵犯膀胱的宏观和组织学正常尿路上皮的活检标本也显示，75%（32份中的24份）表达细胞色素P450 1B1，62.5%（32份中的20份）表达4B1，50%（32份中的16份）表达1A1。此外，在膀胱肿瘤与该膀胱的活检标本之间观察到细胞色素P450 1B1和4B1 mRNA表达有75%的同源性。对无肿瘤的正常膀胱的正常尿路上皮进行聚合酶链反应分析显示，10份中有6份CYP450 1A1表达CYP450 mRNA；10份中有5份1B1表达；10份中有6份4B1表达；10份中有2份2D6表达；10份中有2份2E1表达。根据我们的数据，CYP450 1B1 mRNA表达并非肿瘤特异性。本研究结果首次将膀胱癌中的CYP450表达与来自同一患癌膀胱的活检标本进行比较，结果表明，从酶学角度来看，膀胱癌也是一种泛尿路上皮区域性疾病，甚至存在于正常尿路上皮中。
