Urine telomerase activity for the detection of bladder cancer in females
Sunday, 5 August 2007 - Although bladder cancer incidence is higher worldwide in men than in women, women have a shorter median survival than men. This higher mortality rate could be due to the higher percentage of advanced tumours at first diagnosis, a greater frequency of unfavourable histologies and possibly to a thinner bladder wall, especially in elderly women, resulting in extravesical spread of tumour cells. Early diagnosis allows for timely and often decisive measures to be taken to deal with the cancer. The current gold standard for the diagnosis of bladder cancer consists of urine cytology and cystoscopy. The drawbacks of urine cytology is unsatisfactory sensitivity, especially for low grade, early stage tumors and for cystoscopy, it is an expensive and invasive procedure requiring at least local anesthesia. Telomerase activity for bladder cancer detection is one of the markers proposed to improve diagnostic sensitivity in urine. Telomerase is the enzyme that governs chromosomal length and, although it is switched off in almost all somatic cells, it is present in virtually all tumours. Previous studies have shown that telomerase activity in bladder washings and voided urine represents an important noninvasive tool for bladder cancer diagnosis. In a case-control study conducted on 212 women, including 144 healthy individuals and 68 patients, at first diagnosis of bladder cancer, Bravaccini et al. (2007) confirmed previously obtained diagnostic results and improved the accuracy of this diagnostic assay.
Telomerase activity was evaluated by quantitative telomeric repeat amplification protocol (TRAP) assay and expressed as arbitrary enzymatic units. At the best overall cut-off of 50 arbitrary enzymatic units sensitivity was 87% and specificity was 66%. A breakdown analysis as a function of age showed a higher assay accuracy in women younger than 75 years (sensitivity 91% and specificity 69%) compared to older women (sensitivity 64% and specificity 59%).
The authors concluded that other reasons in addition to age may account for the lower specificity in women with respect to men. In particular, a high number of telomerase positive nonurothelial cells in urine from females could be responsible for false-positive telomeric repeat amplification protocol results. Urine telomerase activity detected by telomeric repeat amplification protocol appears to be a good diagnostic tool in females although it is more accurate in younger than in older women.
Bravaccini, S., Sanchini, M. A., Granato, A. M., Gunelli, R., Nanni, O., Amadori, D., Calistri, D., & Silvestrini, R. (2007). Urine telomerase activity for the detection of bladder cancer in females. J Urol, 178(1), 57-61.