Telomerase activity and expression of the telomerase catalytic subunit, hTERT, in meningioma progression

Object. In recent reports, 6 to 19% of meningiomas have been classified as atypical or anaplastic/malignant. Some atypical and anaplastic meningiomas appear to arise from benign tumors by progression. Telomerase activation ha s recently been associated with malignant progression of human tumors. The authors have investigated a series of benign, atypical, and anaplastic/mali gnant meningiomas for telomerase activity and expression of the telomerase catalytic subunit human telomerase reverse transcriptase (hTERT). Methods. A quantitative telomeric repeat amplification protocol was used to detect telomerase enzyme activity in seven (21%) of 34 benign, but in nine (75%) of 12 atypical and in seven (100%) of seven anaplastic/malignant men ingiomas. Very high levels of telomerase activity were observed only in hig hly aggressive tumors. Messenger (m)RNA expression of the catalytic subunit hTERT was found in 11 (33%) of 33 benign, 12 (92%) of 13 atypical, and all seven anaplastic/malignant tumors. All telomerase-positive lesions were al so positive for hTERT mRNA, whereas no telomerase activity was detected in six (21%) of 29 hTERT-positive tumors. This indicates that upregulation of hTERT is the rate-limiting step for telomerase activation in the majority o f meningiomas. Expression of telomerase and hTERT was seen in all four tumo rs with gross brain invasion. All recurrent tumors or meningiomas recurring during follow up expressed hTERT. Conclusions. The results are consistent with a role for telomerase activati on during the development of malignancy in meningiomas. Hence, expression o f telomerase activity and hTERT might prove to be potentially useful marker s for the evaluation of these tumors.