Expression of transitional cell-specific genes, uroplakin Ia and II, in bladder cancer: Detection of circulating cancer cells in the peripheral blood of metastatic patients

Background: Uroplakins (UP), urothelium-specific transmembrane proteins, are present only in urothelia and may be good candidates as tumor markers specific for transitional cell carcinomas (TCC). We investigated the expression of UP-Ia and UP-II genes in the tissues and peripheral blood of patients with TCC. Methods: We investigated UP-Ia and UP-II gene expression in tissues from 12 patients with TCC by reverse transcription-polymerase chain reaction (RT-PCR). HT1197, a TCC cell line, was used as an indicated cell line to assess a detection system for the UP-II gene-expressing cancer cells by nested RT-PCR. We also investigated UP-II gene expression in the peripheral blood of 12 other patients with TCC by nested RT-PCR. Results: Prior to the investigation of UP-Ia and UP-II gene expression, a partial nucleotide sequence of human UP-II gene cDNA was determined to prepare the primers for RT-PCR. Uroplakin genes were expressed in both cancerous and non-cancerous urothelia taken from all patients examined by RT-PCR, The detection sensitivity of our assay showed that one cancer cell could be detected in 5 mL peripheral blood. UP-II gene-expression was detected in the peripheral blood from all three patients with metastatic TCC but not from the nine patients with nonmetastatic TCC nor the three healthy volunteers. Conclusions: Uroplakins may be employed as tumor markers for transitional cell cancer, because they are highly conserved and well expressed not only in non-cancerous cells but also in cancer cells. Furthermore, detection of UP-II gene expression in blood by nested RT-PCR may provide helpful information in the diagnosis and management of TCC.