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hTERT expression in sporadic renal cell carcinomas
V Paradis1, I Bièche, D Dargère
1Service d'Anatomie Pathologique, Hôpital de Bicêtre, Le Kremlin-Bicêtre, UPRES EA 1602, Faculté de Médecine, Paris-sud, France. vparadis@teaser.fr
The Journal of Pathology
|October 10, 2001
Summary
Telomerase activation, particularly human telomerase reverse transcriptase (hTERT) mRNA levels, is elevated in most renal cell carcinomas (RCC). Quantitative analysis revealed hTERT mRNA correlates with tumor stage in conventional RCC, suggesting telomerase
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Human telomerase, a reverse transcriptase, adds telomeric repeats to chromosome ends.
- Telomerase activation is crucial for cell immortalization and carcinogenesis, with hTERT as the rate-limiting component.
- Previous studies showed inconsistent prognostic relevance of telomerase in renal cell carcinomas (RCC).
Purpose of the Study:
- To re-evaluate the role of telomerase and its hTERT component in RCC biological behavior.
- To utilize novel quantitative techniques for assessing hTERT mRNA and telomerase activity.
- To investigate correlations between telomerase, proliferation index, and c-myc expression in RCC.
Main Methods:
- Quantitative evaluation of hTERT mRNA levels using real-time RT-PCR.
- Measurement of telomerase activity via ELISA TRAP assay.
- Analysis of proliferation index and c-myc mRNA levels in 41 RCC samples.
Main Results:
- Normalized hTERT mRNA expression was significantly higher in 73% of tumor samples compared to normal tissue.
- Telomerase activity was detected in 63% of RCC, with absent activity in normal adjacent tissues.
- hTERT mRNA and telomerase activity were lower in conventional RCC (CRCC) versus non-CRCC subtypes.
- In CRCC, hTERT mRNA expression correlated significantly with tumor stage (p=0.01).
- No correlation was found between c-myc mRNA levels and hTERT mRNA levels.
Conclusions:
- Telomerase is involved in the biological behavior of renal cell carcinomas.
- Quantitative hTERT mRNA measurement shows potential clinical interest for RCC.
- hTERT mRNA levels may serve as a biomarker, particularly in conventional RCC subtypes and staging.