Comparison of human telomerase reverse transcriptase messenger RNA and telomerase activity as urine markers for diagnosis of bladder carcinoma.
BACKGROUND
Human telomerase reverse transcriptase (hTERT) has been identified as the catalytic subunit of telomerase ribonucleoprotein complex known to be required for cellular immortality and oncogenesis. Although human telomerase activity (hTA) is considered as a general marker for malignancy based on its presence in most malignant tumors including bladder cancer, its detection in urine is affected by many factors. The objective of this study was to compare the clinical utility of detecting urine hTERT messenger RNA (mRNA) by multiplex hTERT/GAPDH RT-PCR and urine hTA by telomerase repeat amplification protocol (TRAP) in the diagnosis of bladder cancer.


RESULTS
Cystoscopy urine samples or bladder washes prospectively collected from 35 patients with confirmed (35) or clinically suspected (5) transitional cell carcinoma (TCC) of the bladder were examined by TRAP, hTERT/GAPDH RT-PCR, and urine cytology. The control group comprised 21 healthy volunteers and 3 patients without TCC. The hTERT/GAPDH RT-PCR test showed significantly higher diagnostic sensitivity than TRAP assay (94.3% vs 48.6%, P <.001) and urine cytology (95.2% vs 61.9%, P =.008) for confirmed TCCs. In particular, for superficial TCCs low grade (I-II), the hTERT/GAPDH RT-PCR test outperformed TRAP (90% vs 25%, P <.001) and urine cytology (91.7% vs 58.3%, P =.46). The overall specificity of the hTERT/GAPDH RT-PCR, TRAP and urine cytology was 92% (22/24), 100% (24/24), and 100% (3/3), respectively. A positive hTERT mRNA expression was also detected in urologic specimens from 3 patients with previous history of TCC, 3 to 6 months before cystoscopic evidence of cancer.


CONCLUSIONS
In this pilot study, the hTERT mRNA expression in urine sediments is a more sensitive marker for diagnosis of TCC of the bladder than hTA and cytology. However, there is a higher false-positive rate.
Bialkowska-Hobrzanska
H
H
Molecular Biology Diagnostic Laboratory, Lawson Research Institute, St. Joseph's Health Centre, University of Western Ontario, 268 Grosvenor Street, London, Ontario, N6A 4V2, Canada.
Bowles
L
L
Bukala
B
B
Joseph
M G
MG
Fletcher
R
R
Razvi
H
H
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000652:urine*; D002295:Carcinoma, Transitional Cell / Q000175:diagnosis* / Q000201:enzymology* / Q000652:urine; D020134:Catalytic Domain / Q000235:genetics; D004268:DNA-Binding Proteins; D004789:Enzyme Activation / Q000235:genetics; D005260:Female; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases / Q000378:metabolism; D006801:Humans; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D011446:Prospective Studies; D012313:RNA; D012333:RNA, Messenger / Q000652:urine; D012334:RNA, Neoplasm / Q000652:urine; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019098:Telomerase / Q000652:urine*; D001749:Urinary Bladder Neoplasms / Q000175:diagnosis* / Q000201:enzymology* / Q000652:urine; D014556:Urine / Q000166:cytology
D014408:Biomarkers, Tumor; D004268:DNA-Binding Proteins; D012333:RNA, Messenger; D012334:RNA, Neoplasm; C422952:telomerase RNA; D012313:RNA; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases; D019098:Telomerase