Detection of circulating uroplakin-positive cells in patients with transitional cell carcinoma of the bladder
Detection of circulating uroplakin-positive cells in patients with transitional cell carcinoma of the bladder
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DOI：
10.1097/00005392-199909010-00093
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发表时间：
1999-09-01
影响因子：
6.6
通讯作者：
Wu, XR
中科院分区：
文献类型：
--
作者：
Li, SM;Zhang, ZT;Wu, XR
目的：虽然膀胱移行细胞癌（TCC）转移频繁，具有破坏性的后果，没有标志物可用于监测这一过程。尿斑蛋白是一组正常尿路上皮的特异性标志物，并且在大多数TCC中持续表达。在循环中检测到尿斑蛋白阳性细胞将是TCC患者中肿瘤细胞血行播散的强烈指示。提取60例TCC患者外周血总RNA（50例非转移性和10例转移性）和10例健康对照，逆转录并使用人尿斑蛋白II基因的寡核苷酸引物进行聚合酶链反应扩增（RT-PCR）。将表达尿斑蛋白的人膀胱癌细胞系（RT4）用作阳性对照以建立RT-PCR测定的灵敏度。我们发现，编码尿斑蛋白II（UPII）（一种15-kDa的尿路上皮特异性标记物）的mRNA的PCR扩增构成了用于检测100%的移行细胞癌组织的高度灵敏和特异的测定，并且该测定法可以在5-ml中检测单个膀胱癌细胞。血液样本UPII mRNA在2例未化疗的转移性膀胱癌患者和1/8例化疗患者的血液样品中检测到，而在50例非转移性膀胱癌患者或正常对照中未检测到。结论：Uroplakin II是一种高度特异性的人TCC标志物，外周血中Uroplakin II的检测与膀胱癌细胞的转移扩散有关。尿斑蛋白II的特异性和敏感性检测为检测膀胱癌转移、分期和监测化疗反应提供了有用的辅助手段。
Purpose: 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.Materials and Methods: 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.Results: 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.Conclusions: 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.