Telomerase activity and hTERT protein expression in meningiomas: an analysis in vivo versus in vitro.

BACKGROUND Telomere length maintenance is essential for tumorigenesis. Most human tumours stabilise their chromosome ends by telomerase, a specialised reverse transcriptase that adds telomeric repeats (TTAGGG) to these ends. The main components of this telomerase complex are a reverse transcriptase (hTERT) and an integral RNA component (hTR). Most typical meningiomas, however, do not have active telomerase, although some express the hTERT component. The aim of this study was to evaluate telomerase activity and its reverse transcriptase for 33 (30 typical and three atypical) meningiomas in vivo and in vitro. MATERIALS AND METHODS Telomerase activity was examined by the telomeric repeat amplification protocol (TRAP) assay. The protein, telomerase reverse transcriptase, was visualised by immunohistochemistry. RESULTS In vivo, telomerase activity was detectable in one out of 30 typical meningiomas and in two out of three atypical meningiomas. hTERT protein expression in vivo was positive in 14 out of 33 (42%) cases. The mean percentage of positive nuclei was 12.9% (SD=21.0). In vitro, 22 out of 33 (66%) meningiomas were positive for hTERT, with a mean percentage of positive nuclei of 31.8% (SD=37.1). Only four expressed telomerase activity in vitro, from which three had expressed telomerase activity in vivo. A significant association was found for telomerase activity (p<0.001) and hTERT expression (p<0.001) in vivo versus in vitro; a significant association was found for hTERT expression and telomerase activity in vivo (p<0.05) and in vitro (p<0.05). CONCLUSION The results of our study suggest that hTERT expression is an early event in carcinogenesis in contrast to telomerase activity. Fast-proliferating hTERT-positive tumour cells may overgrow in vitro by clonal selection.