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hTERT expression in sporadic renal cell carcinomas
Author(s) -
Paradis Valérie,
Bièche Ivan,
Dargère Delphine,
Bonvoust Franck,
Ferlicot Sophie,
Olivi Martine,
Ben Lagha Nadia,
Blanchet Pascal,
Benoît Gérard,
Vidaud Michel,
Bedossa Pierre
Publication year - 2001
Publication title -
the journal of pathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.964
H-Index - 184
eISSN - 1096-9896
pISSN - 0022-3417
DOI - 10.1002/path.917
Subject(s) - telomerase reverse transcriptase , telomerase , carcinogenesis , cancer research , messenger rna , cell , biology , cell growth , renal cell carcinoma , telomere , microbiology and biotechnology , chemistry , cancer , medicine , pathology , gene , genetics
Human telomerase is a specialized reverse transcriptase that catalyses telomeric repeat addition at the ends of chromosomes. Activation of this enzyme is one of the key steps in cell immortalization and carcinogenesis, and one of its components, hTERT, is considered as the rate‐limiting factor. While telomerase activity was found to be prognostically relevant in various cancers, 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 quantitative evaluation of hTERT mRNA level by a real‐time RT‐PCR procedure and the mesuring of telomerase activity by an ELISA TRAP assay. Since experimental evidence supports a relationship between cell proliferation or c‐myc expression and telomerase, the proliferation index and c‐myc mRNA levels were also studied. Forty‐one RCC (29 conventional renal cell carcinomas (CRCC), 10 papillary RCC and two urothelial carcinomas) were studied. In 73% of cases, normalized hTERT mRNA expression was significantly higher in the tumour sample than in the normal tissue. Telomerase activity was detected in 63% of RCC, while corresponding normal tissue was always negative. Analysis of correlations showed firstly that both telomerase activity and hTERT mRNA level were 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, respectively); secondly, that in the group of CRCC, hTERT mRNA expression level 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 © 2001 John Wiley & Sons, Ltd.