Detection of circulating cancer cells expressing uroplakins and epidermal growth factor receptor in bladder cancer patients.
Our purpose was to determine the clinical relevance of the detection of circulating tumor cells (CTCs) expressing urothelial and epithelial markers in bladder cancer patients. Sixty-two patients who presented to Memorial Sloan-Kettering Cancer Center between July 2000 and September 2001 were studied. Peripheral blood was tested by nested RT-PCR assay for uroplakins (UPs) Ia, Ib, II and III as well as for epidermal growth factor receptor (EGFR). We determined the sensitivity and specificity of each individual marker and the combinations of UPIa/UPII and UPIb/UPIII. The latter strategy was based on our data, which showed that UPIa and UPIb form heterodimers with UPII and UPIII, respectively. Forty patients had clinically advanced bladder cancer and 22 had no evidence of disease at the time of assay. Eight of the 22 patients recurred during the follow-up period. All 8 patients were positive at presentation for UPIa/UPII. The combination of UPIa/UPII provided the best sensitivity (75%) of detecting CTCs, with a specificity of 50%. The combination of UPIb/UPIII was the most specific (79%) but had modest sensitivity (31%). Detection of EGFR-positive cells alone and in combination with UPs was inferior to that for UPIa/UPII. Combinations of urothelial markers are superior to single urothelial or epithelial markers in detecting CTCs in bladder cancer patients. Further efforts are under way to confirm the potential predictive value of these markers in a prospectively designed study of a larger cohort of patients.
Osman
Iman
I
Kaplan Comprehensive Cancer Center, New York, NY, USA. iman.osman@med.nyu.edu
Kang
Melissa
M
Lee
Andy
A
Deng
Fang-Ming
FM
Polsky
David
D
Mikhail
Maryann
M
Chang
Caroline
C
David
Dexter A
DA
Mitra
Nandita
N
Wu
Xue-Ru
XR
Sun
Tung-Tien
TT
Bajorin
Dean F
DF
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D066246:ErbB Receptors / Q000032:analysis*; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D008297:Male; D008562:Membrane Glycoproteins / Q000032:analysis*; D008565:Membrane Proteins / Q000032:analysis*; D008875:Middle Aged; D009360:Neoplastic Cells, Circulating; D011237:Predictive Value of Tests; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012680:Sensitivity and Specificity; D001749:Urinary Bladder Neoplasms / Q000473:pathology*; D060170:Uroplakin II; D060171:Uroplakin III; D060167:Uroplakin Ia; D060169:Uroplakin Ib
D008562:Membrane Glycoproteins; D008565:Membrane Proteins; C086451:UPK1A protein, human; C086452:UPK1B protein, human; C554658:UPK2 protein, human; D060170:Uroplakin II; D060171:Uroplakin III; D060167:Uroplakin Ia; D060169:Uroplakin Ib; D066246:ErbB Receptors