hTERT expression in sporadic renal cell carcinomas

Human telomerase is a specialized reverse transcriptase that catalyses telo meric repeat addition at the ends of chromosomes. Activation of this enzyme is one of the key steps in cell immortalization and carcinogenesis, and on e of its components, hTERT, is considered as the rate-limiting factor. Whil e telomerase activity was found to be prognostically relevant in various ca ncers, results obtained from renal cell carcinomas (RCC) failed to show any correlation with the usual prognostic factors. The aim of the study was to reassess the role of telomerase and its hTERT component in the biological behaviour of RCC using new quantitative techniques, such as the quantitativ e evaluation of hTERT mRNA level by a real-time RT-PCR procedure and the me suring of telomerase activity by an ELISA TRAP assay. Since experimental ev idence supports a relationship between cell proliferation or c-myc expressi on and telomerase, the proliferation index and c-myc mRNA levels were also studied. Forty-one RCC (29 conventional renal cell carcinomas (CRCC), 10 pa pillary RCC and two urothelial carcinomas) were studied. In 73% of cases, n ormalized hTERT mRNA expression was significantly higher in the tumour samp le than in the normal tissue. Telomerase activity was detected in 63% of RC C, while corresponding normal tissue was always negative. Analysis of corre lations showed firstly that both telomerase activity and hTERT mRNA level w ere lower in the group of CRCC versus non-CRCC (TRAP: 0.3 +/- 0.1 versus 0. 6 +/- 0.2, p < 0.05; hTERT/PO mRNA: 5 +/- 3 versus 37 +/- 8, p < 0.001, res pectively); secondly, that in the group of CRCC, hTERT mRNA expression leve l was correlated with the stage of the tumour (p = 0.01); and thirdly, that no correlation was observed between c-myc mRNA level and hTERT mRNA level. In conclusion, these results support the involvement of telomerase in RCC and the potential interest of hTERT mRNA quantification. Copyright (C) 2001 John Wiley & Sons, Ltd.