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Recurrence and Progression in Meningiomas

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Tumors of the Central Nervous System, Volume 7

Part of the book series: Tumors of the Central Nervous System ((TCNS,volume 7))

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Abstract

Meningiomas are mostly benign tumors that originate from the coverings of brain and spinal cord. Only a minority of cases shows progression to an anaplastic tumor (WHO grade II and III). Multiple and familial cases are rare and mostly associated with (hereditary) neurofibromatosis 2 (NF2). Meningiomas show an unexpectedly high recurrence rate. Also, completely removed low-grade tumors can recur. On cytogenetical level, meningiomas are the best-studied tumors in humans. The majority of high-grade, but only a minority of low-grade meningiomas show loss of merlin, a cytoskeleton-cytoplasm-linker protein. Merlin is the product of the NF2 gene located on chromosome 22. A second tumor suppressor gene on chromosome 22 on 22q12.3 is the gene for the tissue inhibitor of metalloproteinase 3 (TIMP3), which appears to be involved in meningioma progression and a high-grade meningioma phenotype. In contrast to other solid tumors, progression of meningiomas is correlated with increasing hypodiploidy, showing characteristic clonal evolutions that mostly include chromosomes 14, 18, and 19 and, more rarely, 6 and 10. Structural aberrations are rare, except for the loss of the short arm of one chromosome 1, which appears to be the decisive step for anaplastic growth. A bio-statistical approach, is proposed, using an oncogenetic tree model that estimates the most likely cytogenetic pathways of meningioma patients in terms of accumulation of chromosome changes in tumor cells. The genetic progression score (GPS) estimates the genetic status of a tumor as progression in the corresponding tumor cells along this model. High GPS values are highly correlated with early recurrence of meningiomas (p<10−4). This correlation holds true even when patients are stratified by WHO grade. Tumor location also has an impact on genetic progression. Clinical relevance of the GPS is demonstrated with respect to origin, WHO grade, and recurrence of the tumor. As a quantitative measure, the GPS allows a more precise assessment of the prognosis of meningiomas than categorical cytogenetic markers based on single chromosomal aberrations. Comparative histochemical and molecular cytogenetic studies point to the alkaline phosphatase gene (ALPL, liver-bone-kidney type) located on 1p36.1-p34 as a candidate tumor suppressor gene.

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Authors and Affiliations

  1. Department of Neurosurgery, Saarland University, D-66421, Homburg/Saar, Germany

    Ralf Ketter, Klaus D. Zang & Steffi Urbschat

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  1. Ralf Ketter
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  2. Klaus D. Zang
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  3. Steffi Urbschat
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Correspondence to Ralf Ketter .

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  1. , Kean University, Room 213, Library building, Morris Avenue 1000, Union, 07083, New Jersey, USA

    M.A. Hayat

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Ketter, R., Zang, K.D., Urbschat, S. (2012). Recurrence and Progression in Meningiomas. In: Hayat, M. (eds) Tumors of the Central Nervous System, Volume 7. Tumors of the Central Nervous System, vol 7. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-2894-3_21

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  • DOI: https://doi.org/10.1007/978-94-007-2894-3_21

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