Expression of telomerase mRNA component (hTR) in transitional cell carcinoma of the upper urinary tract

BACKGROUND. Telomerase is a ribonucleoprotein enzyme that synthesizes telomeric repeats onto chromosomal ends using a segment of its RNA component as a template. Its activity has become an established indicator of the diagnosis, biologic behavior, and prognosis of several tumors. However, to the authors' knowledge, no previous study has investigated the diagnostic and prognostic importance of the expression of telomerase RNA component (hTR) in transitional cell carcinoma of the upper urinary tract (TCC-UUT). METHODS. The authors investigated hTR expression using in situ hybridization in 130 cases of TCC-UUT, and also its relation to proliferating cell nuclear antigen (PCNA) immunoreactivity, immunoreactivity for p53 oncoprotein, clinicopathologic parameters, and clinical outcome. RESULTS. Positive hTR expression was recognized in 98.4% of the samples and was apparent within the cytoplasm of tumor cells. In normal urothelium, its expression was restricted to the basal cell layers, whereas in the dysplastic lesions of TCC-UUT it was detected with the same intensity and distribution as in the tumor itself. No correlation was found between hTR expression and clinicopathologic findings, PCNA index, or the expression of p53 oncoprotein, although hTR score did tend to increase with disease stage. In univariate and multivariate analyses of disease free and overall survival rates, high hTR expression was associated with significant decreases in both rates. CONCLUSIONS. The expression of hTR appears to be a useful indicator of prognosis for patients with TCC-UUT. In addition, evidence of up-regulation of hTR may also be useful in the diagnosis of this disease. Cancer 1999;86:2109-16. (C) 1999 American Cancer Society.