SEMIQUANTITATIVE ANALYSIS OF TELOMERASE ACTIVITY IN EXFOLIATED HUMAN UROTHELIAL CELLS AND BLADDER TRANSITIONAL-CELL CARCINOMA

Objective To determine the utility of detecting telomerase activity in transitional cell bladder cancer, using the telomeric repeat amplific ation protocol (TRAP) assay, and thus provide a test for the detection and monitoring of bladder cancer, especially low-grade tumours. Patie nts, subjects and methods Telomerase activity was assayed in bladder c ancer tissues and the exfoliated urothelial cells from 29 patients wit h bladder cancer, 10 with benign disease, and in 10 healthy subjects u sing the TRAP assay. The levels were assessed semiquantitatively by ca lculating the ratio to an internal telomerase assay standard. Results Telomerase activity was very low in the exfoliated urothelial cells fr om all healthy subjects and patients with benign disease, with a mean (SD) ratio of 0.25 (0.03) and 0.33 (0.04), respectively. A threshold r atio of 0.4 was calculated as the mean + 2 SD of the telomerase activi ty level of the exfoliated urothelial cells from patients with benign disease. Using this threshold, telomerase activity was negative in exf oliated urothelial cells from all benign cases (100% specificity) and positive in all 26 bladder cancer tissue samples assayed. In tumour ti ssue, telomerase activity was not associated with tumour grade, size o r stage. Telomerase activity in exfoliated urothelial cells from patie nts with bladder cancer was positive in 25 of 29 samples (86% sensitiv ity). The sensitivity of telomerase activity in exfoliated cells was s even of nine in G1, 10 of 12 in G2 and all eight G3 tumours; the corre sponding sensitivity for voided urine cytology in G1, G2 and G3 tumour s was two of nine, six of 12 and six of eight, respectively. Conclusio n These results indicate that telomerase activation occurs as an early step in carcinogenesis and the semi-quantitative analysis of telomera se activity in exfoliated urothelial cells could be a minimally invasi ve and useful method for detecting bladder cancer, even in low-grade t umours.