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 non-metastatic 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.