Quantification of hTERT mRNA and Telomerase Activity in Bladder Washings of Patients with Recurrent Urothelial Cell Carcinomas

摘要

In patients with superficial urothelial cell carcinomas (UCCs), 80% of tumors recur after transurethral resection. A minority (10–20%) of these recurrent tumors will progress to high-grade and muscle-invasive disease (1). Prediction of progression would enable the urologist to determine individual therapy to reduce mortality.For the detection of recurrent disease, endoscopic evaluation (cystoscopy) is considered the gold standard (1). Cystoscopy is supplemented with urine or bladder wash cytology that can detect cells from carcinoma in situ (CIS) or small high-grade tumors, both of which greatly increase progression risk and frequently are missed with cystoscopy (1)(2). Unfortunately, cytology is susceptible to observer variability, and a more standardized method for exfoliated tumor cell analysis is needed (3).Telomerase is a promising tumor marker that can be detected in 95% of all UCCs, but not in healthy urothelia (4). However, the relationship between telomerase activity and prognostic indicators, such as stage and grade, is not clear (4)(5)(6). As a more quantitative alternative, we developed a method to assess the expression of the hTERT gene, which codes for the catalytic subunit of telomerase (7). An endogenous control ( 18S rRNA expression) was included in this assay to normalize for conditions affecting the accurate quantification of hTERT mRNA. Application of the novel method to bladder tissue samples showed that all UCCs, but no healthy urothelia, expressed hTERT (8). Moreover, a significant correlation was found with clinicopathological indices (8). When we applied cutoff values for normalized hTERT , the assay could discriminate between low, medium, and high-grade UCCs (8). This suggested that the presence of hTERT mRNA is not only a diagnostic marker, but when quantified accurately, may also be used as a prognostic marker. In this study, we investigated whether aggressive exfoliated tumor cells can be identified by quantification …