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


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.
Li
S M
SM
Department of Urology, Kaplan Comprehensive Cancer Center, New York University Medical School, and the Veteran Affairs Medical Center in Manhattan, New York 10016, USA.
Zhang
Z T
ZT
Chan
S
S
McLenan
O
O
Dixon
C
C
Taneja
S
S
Lepor
H
H
Sun
T T
TT
Wu
X R
XR
D014408:Biomarkers, Tumor / Q000032:analysis*; D002295:Carcinoma, Transitional Cell / Q000097:blood* / Q000188:drug therapy / Q000556:secondary*; D018450:Disease Progression; D006801:Humans; D008565:Membrane Proteins / Q000032:analysis*; D009360:Neoplastic Cells, Circulating / Q000737:chemistry*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012680:Sensitivity and Specificity; D001749:Urinary Bladder Neoplasms / Q000097:blood* / Q000188:drug therapy / Q000473:pathology; D060170:Uroplakin II
D014408:Biomarkers, Tumor; D008565:Membrane Proteins; C554658:UPK2 protein, human; D060170:Uroplakin II