Lode Maes

The hTERT‐protein and Ki‐67 labelling index in recurrent and non‐recurrent meningiomas

Abstract.  Meningiomas are considered as benign neoplasms affecting the coverings of the central nervous system and compromise approximately 20% of all intracranial tumours. However, a number of these tumours recur even after total resection. The aim of this study is to evaluate the prognostic significance for recurrence of the human telomerase catalytic subunit (hTERT) in the cells of meningiomas. The expression of hTERT‐protein can be evaluated by immunohistochemical staining using a monoclonal antibody against hTERT (clone 44F42, NCL‐L‐hTERT). The interdependence between tumour recurrence and cell proliferation in this study is analysed by Ki‐67 immunoreactivity (clone MIB‐1). Archival material from 29 non‐recurrent and 32 recurrent tumours has been evaluated, including specimens from World Health Organization (WHO) stages I (n = 73), II (n = 2) and III (n = 12). Although the tumours were categorized as benign meningiomas following the WHO classification, recurrence in 22 of 50 cases did not correlate with the tumour stage. For hTERT staining, the following results were found for nucleolar and total nuclear staining, respectively: non‐recurrent meningiomas, 2.9% (± 7.7) and 3.0% (± 8.0); recurrent meningiomas at first resection, 16.8% (± 19.7) and 31.6% (± 30.2). Concerning the Ki‐67 labelling index (LI): for the group of non‐recurrent meningiomas, results were 2.1% (± 1.7) and for the recurrent group at first resection, 1.7% (± 2.0). A significant difference was seen for the hTERT staining (P < 0.001) between the non‐recurrent and recurrent meningiomas, whereas no statistical significance was found for Ki‐67. In conclusion hTERT‐positive meningiomas had a high incidence for recurrence. Ki‐67 was a good marker of cell proliferation status of the tumours, but did not correlate with recurrence; thus, hTERT alone seemed to be a potential predictor for recurrence.

Progression of astrocytomas and meningiomas: an evaluation in vitro.

Abstract.  Objectives/Background: In biological terms, progression means that malignancy increases as genetic mutations accumulate leading to increased proliferation and invasion capacity. By verifying the proliferation capacity, human telomerase reverse transcriptase (hTERT) expression and in vitro invasion, in a group of highly malignant glioblastomas, benign meningiomas and astrocytomas, at the initial stage of progression, we have analysed putative progression in vitro for proliferation and telomerase expression. Materials and Methods: The relative proliferation status (visualized with Ki‐67 antibodies) and presence of hTERT protein was analysed in 27 intracranial tumours (6 astrocytomas, 8 glioblastomas and 13 meningiomas) by immunohistochemistry on paraffin‐embedded biopsy tissue, as well as on primary tumour‐derived cell cultures. A confrontation model was used to analyse invasiveness in vitro. Results: The mean proliferation indices were 22.3 (SD = 18.1) for glioblastomas and 2.1 (SD = 1.9) for low‐grade (LG) astrocytomas. The group of benign meningiomas had a labelling index of 2.2 (SD = 2.7). Mean percentages of staining for hTERT varied between 36.5 (SD = 28.4) for glioblastomas and 10.2 (SD = 8.6) for LG astrocytomas. The group of benign meningiomas had a labelling index of 12.4 (SD = 19.2) for hTERT. A significant difference was seen for Ki‐67 (P < 0.05) and hTERT (P < 0.001) in vivo versus in vitro. No difference was seen between the group of invasive and non‐invasive tumour‐derived cell cultures for the histopathological markers Ki‐67 and hTERT (P > 0.05) in vitro. Conclusions: The elevated expression of hTERT and Ki‐67 in vitro provides a potential prognostic tool for early detection of the progression of brain tumours. As tumour cells require telomerase for continued proliferation, the expression of hTERT may mark immortality, leading to indefinite life span. On the other hand, hTERT expression and cell proliferation are not linked directly to invasion in vitro.