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

BACKGROUND. Telomerase is a ribonucleoprotein enzyme that synthesizes telom eric repeats onto chromosomal ends using a segment of its RNA component as a template. Its activity has become an established indicator of the diagnos is, biologic behavior, and prognosis of several tumors. However, to the aut hors' knowledge, no previous study has investigated the diagnostic and prog nostic importance of the expression of telomerase RNA component (hTR) in tr ansitional cell carcinoma of the upper urinary tract (TCC-UUT). METHODS. The authors investigated hTR expression using in situ hybridizatio n in 130 cases of TCC-UUT, and also its relation to proliferating cell nucl ear 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, it s expression was restricted to the basal cell layers, whereas in the dyspla stic lesions of TCC-UUT it was detected with the same intensity and distrib ution as in the tumor itself. No correlation was found between hTR expressi on and clinicopathologic findings, PCNA index, or the expression of p53 onc oprotein, although hTR score did tend to increase with disease stage. In un ivariate and multivariate analyses of disease free and overall survival rat es, high hTR expression was associated with significant decreases in both r ates. CONCLUSIONS. The expression of hTR appears to be a useful indicator of prog nosis 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;86:210 9-16. (C) 1999 American Cancer Society.