Expression of human Telomerase Reverse Transcriptase (hTERT) mRNA in tumor cells from urine, as tumor marker for monitoring both relapse and urothelial microdissemination in bladder carcinoma

N.Álvareza, F. Áriasb, E.Fernándezb, A.Escuderob, MD, G. Gómeza, A. Gómeza, MV. Toledoa, MD, A.Moyanoa, MD, and E. Casoa, MD, PhD.

aLaboratorio de Oncología Molecular Aplicada. Servicio de Oncología Médica, b Servicio de Urología, Hospital Ramón y Cajal. Madrid. Spain

AIM. Telomerase activity (TeA) detected in urine allows us to identify occult exfoliated tumor cells (1). The hTERT gene is considered to be a crucial factor for the formation of functional telomerase and, there is a close correlation between hTERT gene expression and TeA in tumor cell lines (2,3). Here, we attempt to study the predictive value of the expression of hTERT mRNA in urine samples from superficial bladder cancer patients and its correlation with TeA. METHODS. Urine samples collected from 50 patients before surgical treatment for superficial bladder carcinoma were analysed for hTERT mRNA expression by RT-PCR and Southern blot hybridization with biotin-labeled probe. Urine cytologic examination was performed and TeA was determined by Telomerase PCR-ELISA method (1). Total RNA was isolated from the cellular lysate of exfoliated urothelial cells. RESULTS. In 84% of patients, TeA was positive in urine with a high sensitivity (73%) and specificity (92%). As expected, a 265 bp DNA band for hTERT was detected in 87% of urine samples. In all controls the hTERT was negative. Expression of hTERT mRNA showed an inverse correlation with cell differentiation: 70% in G1, 77% in G2 and 89% in G3. The hTERT/TeA profile was: +/+ in 65.2%, -/+ in 17.4%, +/- in 8.7%, -/- in 8.7%. In comparison to cytology, both hTERT and TeA were superior regardless of G or pT stage of tumor. CONCLUSION. Amplification of hTERT mRNA with or without TeA is a biomarker for detection of occult carcinoma cells. It is also an important noninvasive tool for screening of relapse and/or tumoral microdissemination at the upper urothelial tract after surgical treatment in bladder cancer patients. REFERENCES: 1. Árias F. et al. Arch. Esp. de Urol.,53: 231-236,2000. 2. Meyerson M. et al. Cell,90:785-795, 1997. 3. Latil A. et al. Int. J. Cancer, 89:172-176.2000.

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Paper presented at the International Symposium on Predictive Oncology and Intervention Strategies; Paris, France; February 9 - 12, 2002; in the section on Predictive Markers.

This presentation was a winner in our poster contest and was recognized with the Symposium Presidents' Award for Scientific Excellence.