Purpose: The nested reverse transcription polymerase chain reaction (RT-PCR) method was used to determine expression of uroplakin II (UP II) or cytokeratin 20 (CK-20) in cells separated from the peripheral blood of patients with urothelial cancer. We examine whether UP II or CK-20 expression can be used as a urothelial cancer marker for urothelial cancer in cells isolated from peripheral blood.
Materials and methods: Peripheral blood was taken from 20 healthy volunteers without a history of urothelial cancer, from 10 patients with a negative bladder biopsy for urothelial cancer and from 108 patients with urothelial cancer. Results of a nested RT-PCR assay were compared with pathological stage and recurrence.
Results: None of the peripheral blood samples from the control subjects revealed a positive polymerase chain reaction result. Among 108 patients with transitional cell carcinoma of the bladder nested RT-PCR for UP II was positive in 25 (23%) versus 31 (29%) for CK-20 (p >0.05). Nested RT-PCR for UP II was positive in 5 (8%) patients with superficial stage disease (pTa and pT1) versus 8 (11%) positive for CK-20. Nested RT-PCR for UP II was positive in 15 (58%) patients with a stage of pT2 or advanced stages versus 17 (65%) positive for CK-20. Nested RT-PCR for UP II was positive in 13 (20%) and 10 (56%) patients with grades 2 and 3, respectively, versus 17 (27%) and 12 (67%) nested RT-PCR positive for CK-20. A significant difference in the Kaplan-Meier recurrence-free actuarial curve was noted among patients with superficial stage who were positive and negative on nested RT-PCR for UP II and CK-20 in peripheral blood, respectively, but not in the invasive stage. On multivariate analysis nested RT-PCR for UP II and CK-20 in peripheral blood were independent prognostic factors in patients with superficial stage disease but not with invasive stage disease. Lung and/or liver metastasis developed in 5 (80%) of 6 patients whose results after chemotherapy (consisting of cisplatin, doxorubicin hydrochloride, vinblastine sulfate and methotrexate) for nested RT-PCR for UP II and CK-20 remained positive.
Conclusions: These results seem to indicate that UP II and CK-20 mRNA in the blood may be useful tumor markers for predicting patient survival and the extent of urothelial cancer.