Buchumensky V, Klein A, Zemer R, Kessler O J, Zimlichman S, Nissenkorn I
Department of Urology, Meir General Hospital, Kfar Saba, Israel.
J Urol. 1998 Dec;160(6 Pt 1):1971-4.
Cytokeratins are constituents of the intermediate filaments of epithelial cells in which they are expressed in various combinations depending on epithelial type and degree of differentiation. Of the 20 known cytokeratins, cytokeratin 19 is expressed in normal urothelium cells, whereas the recently identified cytokeratin 20 (CK-20) is expressed in urothelial carcinoma but not normal urothelium cells. We examine whether CK-20 expression can be used as a bladder tumor marker for transitional cell carcinoma in cells isolated from urine.
The reverse transcriptase polymerase chain reaction method was used to determine expression of CK-20 in cells separated from urine of patients with bladder carcinoma. Cells were obtained from urine of 192 patients stratified into 3 groups of 21 healthy young volunteers without a history of transitional cell carcinoma, 27 with a negative bladder biopsy for transitional cell carcinoma and 144 with bladder transitional cell carcinoma. The parameters were tumor stage and grade, tumor size, number of tumors, urinary cytology and CK-20.
CK-20 amplification band (370 base pairs) was obtained with messenger ribonucleic acid extracted from transitional cell carcinoma cells of bladder tumor. CK-20 in the urine samples of the control group was negative (no false-positive results, specificity 100%). Among the 27 patients with pTo disease CK-20 was negative in 20 (specificity 74.1%). In the 7 patients with positive CK-20 histology showed chronic inflammation in 2, atypical hyperplasia in 3 and metaplasia in 1. In 1 patient who had a known history of transitional cell carcinoma the urothelium was normal. Among 144 patients with bladder transitional cell carcinoma CK-20 was positive in 131. Sensitivity of the method was much higher than urinary cytology (91 versus 56.3%, p <0.0001). We demonstrated no correlation between CK-20 and tumor grade.
Our results indicate that CK-20 is a potential marker for bladder cancer. The noninvasive detection method assesses urothelial cells from the voided urine specimen using reverse transcriptase-polymerase chain reaction. The CK-20 marker was significantly more sensitive than urinary cytology.
细胞角蛋白是上皮细胞中间丝的组成成分，根据上皮类型和分化程度以不同组合形式表达。在已知的20种细胞角蛋白中，细胞角蛋白19在正常尿路上皮细胞中表达，而最近鉴定出的细胞角蛋白20（CK-20）在尿路上皮癌中表达，但不在正常尿路上皮细胞中表达。我们研究CK-20表达是否可作为从尿液中分离的细胞中移行细胞癌的膀胱肿瘤标志物。
采用逆转录聚合酶链反应法测定膀胱癌患者尿液中分离细胞的CK-20表达。细胞取自192例患者的尿液，这些患者分为3组：21名无移行细胞癌病史的健康年轻志愿者、27例膀胱活检移行细胞癌阴性患者以及144例膀胱移行细胞癌患者。参数包括肿瘤分期和分级、肿瘤大小、肿瘤数量、尿液细胞学检查及CK-20。
从膀胱肿瘤移行细胞癌细胞中提取的信使核糖核酸获得了CK-20扩增条带（370个碱基对）。对照组尿液样本中的CK-20为阴性（无假阳性结果，特异性为100%）。在27例pTo期疾病患者中，20例CK-20为阴性（特异性为74.1%）。在CK-20阳性的7例患者中，组织学检查显示2例为慢性炎症，3例为非典型增生，1例为化生。在1例有移行细胞癌已知病史的患者中，尿路上皮正常。在144例膀胱移行细胞癌患者中，131例CK-20为阳性。该方法的敏感性远高于尿液细胞学检查（91%对56.3%，p<0.0001）。我们未发现CK-20与肿瘤分级之间存在相关性。
我们的结果表明CK-20是膀胱癌的一个潜在标志物。这种非侵入性检测方法使用逆转录-聚合酶链反应评估排尿尿液标本中的尿路上皮细胞。CK-20标志物比尿液细胞学检查明显更敏感。
