Detection of human telomerase reverse transcriptase mRNA in urine of patients with bladder cancer: evaluation of an emerging tumor marker.
OBJECTIVE
To assess the value of the telomerase enzyme as a bladder cancer detection marker, we investigated the expression of the catalytic subunit of the complex (human telomerase reverse transcriptase [hTERT]) in the urine of patients with malignant or benign urinary lesions, as well as of healthy individuals, and compared the results with urine cytology.


METHODS
Spontaneously voided samples were obtained from two groups of subjects: group 1, 146 previously untreated patients with a histologic diagnosis of transitional cell carcinoma or other urothelial neoplasm; and group 2, 128 control individuals, either healthy or with a nonmalignant bladder disease. Total RNA extracts from sedimented urothelial cells were analyzed by a reverse transcriptase-polymerase chain reaction assay for the presence of a 146-bp hTERT transcript. Urine samples were also examined by standard cytology.


RESULTS
Expression of hTERT was detected in 134 (92%) of 146 patients with bladder cancer, and only 64 (44%) yielded a positive result by cytology (P <0.001). The sensitivity advantage of the former technique became particularly evident in the detection of low-grade transitional cell carcinoma (93% versus 28%, P <0.001). Accordingly, the negative predictive value of the molecular assay was markedly greater than the one calculated for cytologic screening (91% versus 60%). On the other hand, both methods were at least 96% specific, with their positive predictive indexes exceeding 94%.


CONCLUSIONS
Our findings suggest that the assessment of hTERT expression in urine sediments represents a reliable tool for the detection of primary urothelial neoplasms, equally specific, yet far more sensitive, than conventional cytology.
Melissourgos
N
N
Department of Urology, G. Gennimatas General Hospital, Athens, Greece.
Kastrinakis
N G
NG
Davilas
I
I
Foukas
P
P
Farmakis
A
A
Lykourinas
M
M
D000230:Adenocarcinoma / Q000201:enzymology / Q000556:secondary / Q000652:urine; D014408:Biomarkers, Tumor / Q000652:urine*; D002294:Carcinoma, Squamous Cell / Q000201:enzymology / Q000652:urine; D004268:DNA-Binding Proteins; D005260:Female; D006801:Humans; D008297:Male; D011237:Predictive Value of Tests; D012333:RNA, Messenger / Q000652:urine*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012680:Sensitivity and Specificity; D019098:Telomerase / Q000235:genetics / Q000652:urine*; D014407:Tumor Cells, Cultured; D001749:Urinary Bladder Neoplasms / Q000201:enzymology* / Q000473:pathology / Q000652:urine*; D014556:Urine / Q000166:cytology
D014408:Biomarkers, Tumor; D004268:DNA-Binding Proteins; D012333:RNA, Messenger; D019098:Telomerase