Elevated telomerase activity, c-MYC-, and hTERT mRNA expression: association with tumour progression in malignant lipomatous tumours
Article first published online: 11 FEB 2003
Copyright © 2003 John Wiley & Sons, Ltd.
The Journal of Pathology
Volume 199, Issue 4, pages 517–525, April 2003
How to Cite
Schneider-Stock, R., Boltze, C., Jäger, V., Epplen, J., Landt, O., Peters, B., Rys, J. and Roessner, A. (2003), Elevated telomerase activity, c-MYC-, and hTERT mRNA expression: association with tumour progression in malignant lipomatous tumours. J. Pathol., 199: 517–525. doi: 10.1002/path.1315
- Issue published online: 6 MAR 2003
- Article first published online: 11 FEB 2003
- Manuscript Accepted: 24 OCT 2002
- Manuscript Revised: 21 JUN 2002
- Manuscript Received: 31 JAN 2002
- telomerase activity;
- c-MYC expression;
- hTERT expression;
The role of telomerase activity in tumour progression of liposarcomas is not well understood. Therefore, we investigated 72 liposarcomas of different histological subtypes for an association between telomeric lengths and telomerase activity, and assessed the association between the catalytic subunit human telomerase reverse transcriptase (hTERT) and its activator c-MYC. Telomeric repeat fragment lengths were determined using radioactive DNA–fingerprint analysis with the telomere-specific probe (TTAGGG)3, whereas telomerase activity was ascertained using the non-radioactive TRAP-assay. To evaluate the expression of hTERT and c-MYC, we applied real-time RT-PCR using a LightCycler. Eight tumours were investigated by microdissection. The MIB1-proliferation index and hTERT and c-MYC protein expression were determined immunohistochemically. Genetic alterations showed a high degree of tumour specificity. Highly malignant myxoid/round cell liposarcomas showed the longest telomeres, the strongest telomerase activity, and the highest hTERT and c-MYC expression levels compared with the pure myxoid variants (p < 0.001), which are of low malignancy. Pleomorphic liposarcoma was characterized by zero or low hTERT and c-MYC expression and telomerase activity, but long telomeres, underlining their different pathogenetic pathway. Elevated gene expression was accompanied by protein immunopositivity. MIB1-proliferation index did not correlate with other molecular markers. We conclude that hTERT and c-MYC expression are associated with telomerase activity in liposarcomas. Elevated hTERT and c-MYC expression as well as high telomerase activity play a role in the tumour progression of this sarcoma type. Nevertheless, each histological subtype of liposarcomas is defined by a specific molecular pattern. Telomerase activation is the most common pathway in liposarcomas maintaining telomeric length. Copyright © 2003 John Wiley & Sons, Ltd.