Clinical significance oftelomerase activity in bladder wash specimens

Telomeres are the specialized structures at the end of all eukaryotic chromosomes that are thought to give important functions in protecting genomic DNAfrom degradation and deleterious recombination events. The enzyme telomerase maintains a constant telomere length observed in immortalized cells, allowing unlimited celi proliferation. Almost all cancer cells including transitional cell carcinoma express telomerase activity. We detected telomerase activity in bladder wash specimen and also in bladder cancer and normal tissues, and compared them with final pathologic diagnosis. Bladder wash specimens of 23 patients with bladder transitional cell carcinoma (TCC) were obtained before transurethral resection of bladder (TURB) and normal and cancer tissues during TURB. Telomerase activity was analyzed in each of three specimens using telomeric repeat amplification protocol (TRAP) assay which is based on polymerase chain reaction (PCR) technique. Cytolopathologtc diagnosis was performed using Papanicolaou's stain with cytocentrifuged cytology preparation. We observed telomerase activity in 95.7% (22/23) of both cancer tissues and bladder wash cytology; only one case, which was in an early stage, did not express telomerase activity. Telomerase activity was not detected in all normal tissues except one, which was obtained from a patient with carcinoma in situ. 69.6% (16/23) of wash specimens was positive in cytopathologic diagnosis. The accuracy of wash cytology in pathologic grade 2 or 3 was relatively high (83.3%, 15/18). However, in five cases of grade 1 TCC only 20% (1/5) of cytologie diagnosis was positive whereas the telomerase activity of wash specimen was detected in 80%(4/5). Cytopathologic diagnosis Telomerase Activity Pathology (No. of Pts.) Normal Equivocal Malignant Positive Negative grade 1 (5) 2 2 1 4 1 grade 2 (11 ) 3 8 11 grade 3 (7) 7 7 Our data demonstrates that not only the majority of human bladder cancers but also bladder wash specimens obtained from patients with TCG expressed telomerase activity. It indicates that telomerase activity maybe a reliable marker in detecting bladder cancer especially in cases of low grade bladder cancer which wash cytology might miss.