Li S M, Zhang Z T, Chan S, McLenan O, Dixon C, Taneja S, Lepor H, Sun T T, Wu X R
Department of Urology, Kaplan Comprehensive Cancer Center, New York University Medical School, and the Veteran Affairs Medical Center in Manhattan, New York 10016, USA.
J Urol. 1999 Sep;162(3 Pt 1):931-5. doi: 10.1097/00005392-199909010-00093.
Although transitional cell carcinoma of the bladder (TCC) metastasizes frequently with devastating consequences, no marker has been available to monitor this process. Uroplakins are a group of specific markers for normal urothelium and are continuously expressed by the majority of TCCs. Detection of uroplakin-positive cells in the circulation would be a strong indication of hematogenous dissemination of tumor cells in patients with TCC.
Total RNAs were extracted from peripheral blood of 60 patients with TCC (50 non-metastatic and 10 metastatic) and 10 healthy controls, reverse-transcribed and subjected to polymerase chain reaction amplification (RT-PCR) using oligonucleotide primers of human uroplakin II gene. A uroplakin-expressing human bladder cancer cell line (RT4) was used as a positive control to establish the sensitivity of the RT-PCR assay.
We showed that the PCR-amplification of the mRNA encoding uroplakin II (UPII), a 15-kDa urothelium-specific marker, constitutes a highly sensitive and specific assay for detecting 100% of transitional cell carcinoma tissue, and that this assay can detect a single bladder cancer cell in a 5-ml. blood sample. UPII mRNA was detected in the blood samples of 2 patients with metastatic bladder cancer without chemotherapy and 1 out of 8 such patients with chemotherapy, but not in those of 50 non-metastatic patients or normal controls.
Uroplakin II is a highly specific marker for human TCC and the detection of uroplakin II in the peripheral blood is associated with metastatic spread of bladder cancer cells. The specific and sensitive detection of uroplakin II provides a useful adjunct for detecting bladder cancer metastasis, staging, and monitoring chemotherapeutic response.
尽管膀胱移行细胞癌（TCC）常发生转移并带来严重后果，但尚无标志物可用于监测这一过程。尿血小板溶素是正常尿路上皮的一组特异性标志物，大多数TCC持续表达。循环中检测到尿血小板溶素阳性细胞将强烈提示TCC患者肿瘤细胞发生血行播散。
从60例TCC患者（50例非转移性和10例转移性）及10例健康对照者的外周血中提取总RNA，逆转录后使用人尿血小板溶素II基因的寡核苷酸引物进行聚合酶链反应扩增（RT-PCR）。使用表达尿血小板溶素的人膀胱癌细胞系（RT4）作为阳性对照以确定RT-PCR检测的敏感性。
我们发现，编码15 kDa尿路上皮特异性标志物尿血小板溶素II（UPII）的mRNA的PCR扩增构成了一种高度敏感和特异的检测方法，可检测100%的移行细胞癌组织，并且该检测方法可在5 ml血样中检测到单个膀胱癌细胞。在2例未接受化疗的转移性膀胱癌患者的血样中检测到UPII mRNA，8例接受化疗的此类患者中有1例检测到，但50例非转移性患者或正常对照者的血样中未检测到。
尿血小板溶素II是人类TCC的高度特异性标志物，外周血中尿血小板溶素II的检测与膀胱癌细胞的转移扩散相关。尿血小板溶素II的特异性和敏感性检测为检测膀胱癌转移、分期及监测化疗反应提供了有用的辅助手段。
