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KMID : 1001020030010010086
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Journal of Urologic Oncology
2003 Volume.1 No. 1 p.86 ~ p.94
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Usefulness of Telomerase Activity Using Real-Time PCR for Detection of Bladder Cancer
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Ryu Soo-Bang
Noh Joon-Hwa
Kang Taek-Won
Oh Bong-Ryoul
Park Yang-Il
Choi Chan
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Abstract
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Purpose: Activation of telomerase is one of the key steps in carcinogenesis, and one of its components, telomerase reverse transcriptase (TERT), is considered as the rate-limiting factor. The aim of the study was to assess the role of TERT component in the biological behavior and possibility for detection of bladder tumor.
Materials and Methods: To examine the rTERT activity during bladder carcinogenesis, 40 female Spraque- Dawley rats (200-250 g) were given drinking water containing 0.05% N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN) and tap water (20 controls), and after 10, 20, 25, and 30 weeks, bladders were harvested. Normal and BBN-treated rat bladders were analyzed for mRNA expression of rTERT by real-time RT-PCR. Levels of hTERT mRNA were analyzed in tissues and voided urine samples of 34 bladder tumor patients and 39 patients with benign urologic disease.
Results: rTERT activity significantly increased in the stage after hyperplasia at 10 weeks, then elevated with carcinogenesis at 20 weeks. From the stage after invasive cancer at 25 weeks, rTERT activity was decreased. hTERT activity was detected in 88.2% (30 of 34) of bladder tumor, while normal tissue was 25.6% (10 of 39) negative. hTERT mRNA expression was significantly higher in the tumor sample than in the normal tissue (p＜0.05), regardless of tumor stage or grade. The patients with transitional cell carcinoma had significantly greater urinary hTERT levels than controls (p＜0.05). When we used the cutoff value from ROC analysis to distinguish malignant from nonmalignant status, the sensitivity and specificity of hTERT were 70.6% and 76.9%, respectively, whereas the sensitivity and specificity of urine cytology were 44.1% and 100%, respectively.
Conclusions: These results indicate that enhanced expression of rTERT activity occurs early bladder carcinogenesis and support the involvement of rTERT in the development of bladder cancer. The hTERT mRNA analysis by real-time PCR has a higher sensitivity than cytology, especially in low stage and low grade tumor. The combination of two tumor markers, cytology and hTERT assay seems to be more effective tool for bladder cancer detection.
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KEYWORD
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Bladder cancer, Rat bladder, N-butyl-N-(4-hydroxybutyl)nitrosamine, Telomerase reverse transcriptase
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