Article
Ki67 proliferation rate, macroscopic brain invasion and Simpson Score are predictors for tumor recurrence in WHO grade II meningiomas
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Authors
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Peter Baumgarten
- Neurologisches Institut (Edinger Institut), Goethe Universität, Frankfurt am Main, Germany; Klinik und Poliklinik für Neurochirurgie, Goethe Universität, Frankfurt am Main, Germany
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Simon Bernatz
- Neurologisches Institut (Edinger Institut), Goethe Universität, Frankfurt am Main, Germany
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Christian Senft
- Klinik und Poliklinik für Neurochirurgie, Goethe Universität, Frankfurt am Main, Germany
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Volker Seifert
- Klinik und Poliklinik für Neurochirurgie, Goethe Universität, Frankfurt am Main, Germany
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Michel Mittelbronn
- Neurologisches Institut (Edinger Institut), Goethe Universität, Frankfurt am Main, Germany
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Patrick N. Harter
- Neurologisches Institut (Edinger Institut), Goethe Universität, Frankfurt am Main, Germany
| Published: | June 8, 2016 |
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Outline
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Objective: According to the current WHO classification, meningiomas are classified as grade II if they display (I) signs of atypia, (II) chordoid or clear cell differentiation, (III) increased mitotic activity or (IV) histopathological brain invasion. Here we investigate the association of proliferative and mitotic activity as well as the VEGF receptor system with progression free survival (PFS) in a large cohort of grade II meningiomas. Additionally, we reevaluated micro- and macroscopic brain invasion as sole criteria for upgrading meningiomas in our cohort.
Method: We investigated 152 grade II meningiomas including 114 atypical meningiomas, 14 chordoid, 1 clear cell as well as 23 meningiomas, which solely showed brain invasion. We analyzed whole mount paraffin sections for Ki67 expression and mitotic activity. Additionally, we analyzed corresponding tissue micro arrays for VEGFR-1/2 expression in endothelial cells. We recorded PFS and neurosurgical parameters such as macroscopic brain invasion and Simpson score.
Results: Meningiomas that solely showed brain invasion as a criterion for WHO grade II did not recur in our cohort. Atypical meningiomas, which showed microscopic brain invasion were associated with reduced PFS. Macroscopic brain invasion observed by the neurosurgeon and higher Simpson scores were significantly associated with reduced PFS. Neither VEGFR-1 nor VEGFR-2 expression on endothelial cells were associated with PFS, while meningiomas with Ki67 expression (>5%) showed significantly shorter PFS.
Conclusions: Our data suggests that Ki67 index as well as macroscopic brain invasion and Simpson score are crucial for WHO grade II meningioma recurrence and should therefore be recorded and taken into account when evaluating the individual risk for meningioma recurrence. In contrast the potential third line therapy targets VEGFR-1 and VEGFR-2 do not predict recurrence. Microscopic brain invasiveness alone is no sign for reduced PFS and should therefore be reevaluated for future editions of the WHO classification of CNS tumors.
