TELOMERASE ACTIVITY IN BLADDER-CARCINOMA AND ITS IMPLICATION FOR NONINVASIVE DIAGNOSIS BY DETECTION OF EXFOLIATED CANCER-CELLS IN URINE

BACKGROUND. Telomerase is an enzyme that can reconstitute the ends (te lomeres) of chromosomes after cell division and thus circumvent the cu mulative damage that occurs in normal adult somatic cells during succe ssive mitotic cycles. Recently, it has been proposed that this enzyme should, therefore, be detectable in immortal malignant cells but not i n their normal counterparts, which stop dividing and senesce. Accordin gly, telomerase activity has been reported in many types of malignant tumors, including those of the gastrointestinal tract, breast, and lun g but little information was available regarding its status in bladder carcinoma or in exfoliated cancer cells. METHODS. In the current stud y, telomerase activity was examined by a polymerase chain reaction-bas ed assay designated TRAP (telomeric repeat amplification protocol) in tissue samples from 56 bladder carcinomas, 17 nonneoplastic bladder le sions, and 2 dysplastic lesions of the urinary tract. The feasibility of identifying cancer patients by the detection of telomerase activity in exfoliated cancer cells in the urine was also investigated. Such a ctivity was assayed in centrifuged urine cell pellets from 26 bladder carcinoma patients and from 83 patients with no evidence of malignant disease. RESULTS. Evidence of telomerase tvas detected in solid tissue specimens from 48 of the 56 bladder carcinomas (86%) regardless of tu mor stage or differentiation, whereas it was not found in any normal b ladder tissue specimen. However, it was present in the dysplastic blad der lesions as well as in nearly all Stage I well differentiated carci nomas, suggesting that its activation occurs for the early stages of c arcinogenesis and could perhaps be a useful marker for the detection o f early primary or recurrent bladder tumors. Telomerase activity was d etected with various signal intensities in urine specimens from 16 of the 26 patients with bladder carcinoma (62% sensitivity), whereas only 3 of 83 nonmalignant urine samples showed any activity (96.4% specifi city); this was very weak. CONCLUSIONS. These results suggest that tel omerase could be a good diagnostic marker for the early noninvasive id entification of patients with bladder carcinoma by facilitating the de tection of exfoliated immortal cancer cells in their urine. (C) 1997 A merican Cancer Society.