Quantitative telomerase activity in human brain tumors

Object. Shortening of telomeres may contribute to the control of the proliferative capacity of normal cells, and telomerase, a ribonucleoprotein DNA polymerase that elongates telomeric DNA, has been suggested to facilitate tumorigenesis and tumor immortality. Telomerase expression has in fact been detected in various kinds of tumors. Since there is an insufficiency of data on telomerase activity in brain tumors, the present study examined the role of telomerase activity in brain tumors. Methods. A total of 66 brain tumor samples, including 27 meningiomas, 31 diffusely infiltrating astrocytomas and 8 metastatic brain tumors, were investigated. Telomerase expression was examined by the polymerase chain reaction (PCR) based telomeric repeat amplification protocol (TRAP) assay and the telomerase activity level was quantitated by an improved PCR enzyme-linked immunosorbent assay (ELISA). The telomerase activity was also compared with the histopathological diagnosis, MIB-1 proliferative cell index (PCI), and p53 immunoreactivity. Results. Telomerase expression was detected in 11% of meningiomas, 9% of grade II, 58% of grade III, 75% of grade IV astrocytomas, and 100% of metastatic brain tumors. In addition, metastatic brain tumors exhibited high levels of telomerase activity (7.73 ′ 3.46 pmole/ml) and grade IV astrocytomas exhibited higher telomerase activity levels than did grade III astrocytomas (grade III, 0.52 ′ 0.54; grade IV, 2.58 ′ 3.31 pmole/ml). Moreover, the telomerase activity level demonstrated a significant positive correlation with the histopathological grade and the PCI in diffusely infiltrating astrocytomas ( p < 0.05 and p < 0.01, respectively). Conclusion. The above results suggest that telomerase expression and activity levels provide an important indicator of the malignancy and growth potential of brain tumors.