Artikel
Relevance of pro- and anti-apoptotic markers in meningiomas WHO grade I–III, and risk of malignisation at recurrence
Pro- und antiapoptotische Marker bei Meningeomen WHO Grad I–III und ihre Relevanz bei Malignisierung und Rezidivierung
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Autoren
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W. Stenzel
- Institut für Neuropathologie, Charité - Universitätsmedizin Berlin, Campus Virchow Klinikum, Berlin
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G. Röhn
- Neurochirurgische Klinik, Universitätsklinik zu Köln, Köln
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M. Hermann
- Abteilung für Neuropathologie, Universitätsklinik zu Köln, Köln
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M. Löhr
- Neurochirurgische Klinik, Universitätsklinik zu Köln, Köln
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J. A. Hampl
- Neurochirurgische Klinik, Universitätsklinik zu Köln, Köln
| Veröffentlicht: | 30. Mai 2008 |
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Gliederung
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Objective: To study the contribution of factors from the extrinsic (FAS), and the intrinsic pathway (Bax family) of apoptosis in meningiomas WHO grade I - III, and their biology at recurrence.
Methods: The expression of CD95, BCLxs, BCLxl and BCL2 was studied by immunohistochemistry in 9 meningiomas WHO grade I which did not recur over a 15 years observation period, 9 meningiomas WHO grade I, and their grade I recurrence, as well as 9 meningiomas WHO grade I with grade II recurrences. Further we analyzed 9 meningeomas WHO grade II, and 7 meningiomas WHO grade III. Additionally, the transcription of CD95, BCLxs, BCLxl and BCL2 mRNA was assessed using RT-PCR in these specimens, which were classified according to the current WHO classification 2007.
Results: The expression of Fas (CD95) on the cell surface of meningiomas was low in Grade I meningiomas, significantly higher in grade II and highest in grade III meningiomas. Recurrent grade I meningiomas did not show significant differences in Fas expression as compared to non-recurrent grade I meningiomas. Pro-apoptotic BCLxs was expressed at low levels in grade I meningiomas, and significantly higher in grade II and in grade III meningiomas, while anti-apoptotic BCL2, and BCLxl showed the inverse immunohistochemical expression-profile. On the mRNA level, transcription of pro-apoptotic BCLxs did not differ between grade I, recurrent grade I and grade II as well as grade III meningiomas. Conversely anti-apoptotic BCL2, but not BCLxl, showed highest transcription levels in grade I meningiomas, while grade II and grade III meningiomas exhibited significantly lower levels.
Conclusions: Both factors of the extrinsic-, and the intrinsic pathway for apoptosis contribute significantly to the pattern and frequency of apoptotic cells in meningiomas. The level of Fas, and BCLxs expression positively correlates with the tumor grade but does not allow a prediction as to whether a grade I meningioma at recurrence will show a higher tumor grade. The level of BCL2 expression, both on the protein level and on the mRNA level negatively correlates with the tumor grade, and also at recurrence, these meningiomas show lower levels of BCL2. Low levels of BCL2 expression and/or transcription of a meningioma may allow the prediction of an elevated risk of recurrence and of further malignisation, and eventually may serve as a molecular marker in the future.
