Mucin 7 and cytokeratin 20 as new diagnostic urinary markers for bladder tumor.
OBJECTIVE
We determine the sensitivity and specificity of cytokeratin 20 (CK-20) and mucin 7 (MUC7) gene expression in voided urine samples taken from patients with bladder tumor and from control groups to investigate putative, noninvasive urinary markers for bladder tumor detection and monitoring.


METHODS
Voided urine samples were collected from 50 patients with histologically proven bladder neoplasms (pTaN0M0G1-3 in 19 and pTisN0M0G3-pT4pN1M1G3 in 31), 20 patients with urolithiasis, 20 patients with urinary tract infection, 20 patients with other urological neoplasms and 20 healthy volunteers. Total RNA was extracted from exfoliated cells collected from 200 ml. voided urine. All RNA samples were investigated by a specific CK-20 and MUC7 nested reverse transcriptase polymerase chain reaction.


RESULTS
The overall sensitivity of CK-20 gene expression in voided urine samples for the detection of bladder neoplasms was 78%. In contrast, voided urine samples from control patients and healthy volunteers showed a high rate of false-positive CK-20 detection resulting in a low specificity of 36%. The overall sensitivity of the MUC7 test for all bladder tumor cases was 66%. The sensitivity for papillary urothelial neoplasms (pTaN0M0G1-3) was 42% whereas analysis of the carcinoma in situ and invasive bladder cancer group (pTisN0M0G3-pT4pN1M1G3) yielded a sensitivity of 81%. The overall specificity of the MUC7 nested reverse transcriptase polymerase chain reaction method in the control groups was 80%.


CONCLUSIONS
A high positive CK-20 detection rate was found not only in voided urine samples from patients with bladder tumor, but also in urine specimens from control groups. Therefore, CK-20 is not a reliable urinary tumor marker for bladder neoplasms. In contrast to CK-20, analysis of MUC7 demonstrated a high sensitivity and high specificity for carcinoma in situ and invasive bladder cancer, thus fulfilling the criteria of a urinary tumor marker.
Retz
M
M
Department of Urology and Pediatric Urology, Saarland University, 66421 Homburg/Saar, Germany.
Lehmann
J
J
Amann
E
E
Wullich
B
B
Röder
C
C
Stöckle
M
M
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000652:urine*; D005260:Female; D015870:Gene Expression; D006801:Humans; D007381:Intermediate Filament Proteins / Q000235:genetics / Q000378:metabolism / Q000652:urine*; D053554:Keratin-20; D008297:Male; D008875:Middle Aged; D009077:Mucins / Q000235:genetics / Q000378:metabolism / Q000652:urine*; D011237:Predictive Value of Tests; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012471:Salivary Proteins and Peptides / Q000235:genetics / Q000378:metabolism / Q000652:urine*; D012680:Sensitivity and Specificity; D014407:Tumor Cells, Cultured; D001749:Urinary Bladder Neoplasms / Q000175:diagnosis* / Q000378:metabolism; D014545:Urinary Calculi / Q000652:urine; D014552:Urinary Tract Infections / Q000652:urine
D014408:Biomarkers, Tumor; D007381:Intermediate Filament Proteins; C507499:KRT20 protein, human; D053554:Keratin-20; C083238:MUC7 protein, human; D009077:Mucins; D012471:Salivary Proteins and Peptides