Comparative diagnostic value of urine cytology, UBC-ELISA, and fluorescence in situ hybridization for detection of transitional cell carcinoma of urinary bladder in routine clinical practice.
OBJECTIVE
Fluorescence in situ hybridization (FISH) has been reported to have much better sensitivity for the detection of bladder transitional cell carcinoma (TCC) than urine cytology. We comparatively tested cytology, FISH, and the cytokeratin-detection test of urinary bladder cancer (UBC) in routine clinical practice.


METHODS
In a prospective study, FISH, the urinary bladder cancer test (UBC-enzyme-linked immunosorbent assay [ELISA]), and cytology were used in 166 patients. Of the 166 patients, 62 had primary TCC (group 1), 71 had undergone transurethral resection of primary TCC before routine secondary transurethral resection (group 2), and 33 control had not undergone TCC (group 3). All patients with false-positive test results were followed up for a mean follow-up time of 22 months.


RESULTS
The overall sensitivity of FISH, UBC-ELISA, and cytology was 53.2% (95% confidence interval 40% to 66%), 40.3% (95% confidence interval 28% to 53%), and 71.0% (95% confidence interval 59% to 83%), respectively (P <0.05). For grade 3 TCC, both FISH and cytology reached a sensitivity of 93.3%. In the 104 patients without TCC, the specificity of FISH, UBC-ELISA, and cytology was 74.0%, 75.0%, and 83.7%, respectively. During follow-up, 33.3% of patients with a false-positive FISH result developed recurrence, as did 23.1% with false-positive UBC results and 29.4% with false-positive cytology findings (P >0.05). Receiver operating characteristic analysis showed an area under the curve for FISH, UBC, and cytology of 0.636, 0.577, and 0.773, respectively. Only cytology and FISH were significantly predictive of a TCC finding on histologic examination (P <0.001 and P = 0.003, respectively).


CONCLUSIONS
In routine clinical practice, conventional cytology in experienced hands can be superior to FISH. False-positive results with all three test systems used warrant a high suspicion of subclinical precursor lesions of TCC recurrence.
May
Matthias
M
Department of Urology, Institute of Pathology, Rostock University, Rostock, Germany. M.May@ctk.de
Hakenberg
Oliver W
OW
Gunia
Sven
S
Pohling
Peter
P
Helke
Christian
C
Lübbe
Lieselotte
L
Nowack
Rudolf
R
Siegsmund
Michael
M
Hoschke
Bernd
B
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D019540:Area Under Curve; D014408:Biomarkers, Tumor / Q000032:analysis*; D002295:Carcinoma, Transitional Cell / Q000737:chemistry / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology / Q000601:surgery; D004797:Enzyme-Linked Immunosorbent Assay; D005189:False Positive Reactions; D005260:Female; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D053538:Keratin-18 / Q000032:analysis*; D053533:Keratin-8 / Q000032:analysis*; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000175:diagnosis / Q000235:genetics / Q000473:pathology; D011237:Predictive Value of Tests; D011446:Prospective Studies; D012372:ROC Curve; D012680:Sensitivity and Specificity; D001749:Urinary Bladder Neoplasms / Q000737:chemistry / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology / Q000601:surgery; D014556:Urine / Q000166:cytology
D014408:Biomarkers, Tumor; D053538:Keratin-18; D053533:Keratin-8