Detection of circulating uroplakin-positive cells in patients with transitional cell carcinoma of the bladder

Purpose: Although transitional cell carcinoma of the bladder (TCC) metastas izes frequently with devastating consequences, no marker has been available to monitor this process. Uroplakins are a group of specific markers for no rmal urothelium and are continuously expressed by the majority of TCCs. Det ection of uroplakin-positive cells in the circulation would be a strong ind ication of hematogenous dissemination of tumor cells in patients with TCC. Materials and Methods: Total RNAs were extracted from peripheral blood of 6 0 patients with TCC (50 non-metastatic and 10 metastatic) and 10 healthy co ntrols, reverse-transcribed and subjected to polymerase chain reaction ampl ification (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 uroplaki n II (UPII), a 15-kDa urothelium-specific marker, constitutes a highly sens itive 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 pa tients 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 metas tatic spread of bladder cancer cells. The specific and sensitive detection of uroplakin II provides a useful adjunct for detecting bladder cancer meta stasis, staging, and monitoring chemotherapeutic response.