Detection of human telomerase reverse transcriptase mRNA in urine of patients with bladder cancer: evaluation of an emerging tumor marker

Abstract

Objectives: 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.