Seminars in Neurosurgery 2003; 14(3): 187-192
DOI: 10.1055/s-2004-817735
Copyright © 2002 by Thieme Medical Publishers, Inc., 333 Seventh Avenue, New York, NY 10001, USA. Tel.: +1(212) 584-4662

Pathophysiology of Malignant Meningiomas

Marcus L. Ware1 , Alfredo Quinones-Hinojosa2 , Michael W. McDermott 1,2,3
  • 1Department of Neurological Surgery, University of California, San Francisco, San Francisco, California
  • 2Department of Radiation Oncology, University of California, San Francisco, San Francisco, California
  • 3The Brain Tumor Research Center, University of California, San Francisco, San Francisco, California
Further Information

Publication History

Publication Date:
02 June 2004 (online)

ABSTRACT

Although most meningiomas are benign and are treated with surgery alone, a few are malignant and can be difficult to treat. These more aggressive tumors were first characterized by their histology. With advances in molecular biology, we have learned a great deal about the development of these tumors. Cytogenetic studies have shown that benign meningiomas have mutations in chromosome 22. Further studies show that the NF2 gene, located on chromosome 22, is involved in meningioma formation. More aggressive tumors have been shown to have several mutations in other chromosomes, including chromosome 1p, 14q, and 18q. Here, we review these findings and the candidate genes involved in meningioma tumorigenesis.

REFERENCES

  • 1 Rachlin J, Rosenblum M. Etiology and biology of meningiomas. In: Al-Mefty O, ed. Meningiomas New York: Raven 1991: 22-37
  • 2 Simpson D. The recurrence of intracranial meningiomas after surgical treatment.  J Neurol Neurosurg Psychiatry . 1957;  20 22-39
  • 3 Mirimanoff R O, Dosoretz D E, Linggood R M, Ojemann R G, Martuza R L. Meningioma: analysis of recurrence and progression following neurosurgical resection.  J Neurosurg . 1985;  62 18-24
  • 4 Palma L, Celli P, Franco C, Cervoni L, Cantore G. Long-term prognosis for atypical and malignant meningiomas: a study of 71 surgical cases.  J Neurosurg . 1997;  86 793-800
  • 5 Jaaskelainen J, Haltia M, Servo A. Atypical and anaplastic meningiomas: radiology, surgery, radiotherapy, and outcome.  Surg Neurol . 1986;  25 233-242
  • 6 Cushing H, Eisenhardt L. Meningiomas: Their Classification, Regional Behavior, Life History, and Surgical End Results.  Springfield, IL: Thomas; 1938
  • 7 Wilson C B. Meningiomas: genetics, malignancy, and the role of radiation in induction and treatment. The Richard C. Schneider Lecture.  J Neurosurg . 1994;  81 666-675
  • 8 Kleihues P, Louis D N, Scheithauer B W. et al . The WHO classification of tumors of the nervous system.  J Neuropathol Exp Neurol . 2002;  61 215-229
  • 9 Perry A, Scheithauer B W, Stafford S L, Lohse C M, Wollan P C. “Malignancy” in meningiomas: a clinicopathologic study of 116 patients, with grading implications.  Cancer . 1999;  85 2046-2056
  • 10 Perry A, Stafford S L, Scheithauer B W, Suman V J, Lohse C M. Meningioma grading: an analysis of histologic parameters.  Am J Surg Pathol . 1997;  21 1455-1465
  • 11 Zang K D, Singer H. Chromosomal constitution of meningiomas.  Nature . 1967;  216 84-85
  • 12 Mark J, Levan G, Mitelman F. Identification by fluorescence of the G chromosome lost in human meningomas.  Hereditas . 1972;  71 163-168
  • 13 Zankl H, Zang K D. Cytological and cytogenetical studies on brain tumors. 4. Identification of the missing G chromosome in human meningiomas as no. 22 by fluorescence technique.  Humangenetik . 1972;  14 167-169
  • 14 Dumanski J P, Carlbom E, Collins V P, Nordenskjold M. Deletion mapping of a locus on human chromosome 22 involved in the oncogenesis of meningioma.  Proc Natl Acad Sci U S A . 1987;  84 9275-9279
  • 15 Doco-Fenzy M, Cornillet P, Scherpereel B. et al . Cytogenetic changes in 67 cranial and spinal meningiomas: relation to histopathological and clinical pattern.  Anticancer Res . 1993;  13 845-850
  • 16 Ruttledge M H, Sarrazin J, Rangaratnam S. et al . Evidence for the complete inactivation of the NF2 gene in the majority of sporadic meningiomas.  Nat Genet . 1994;  6 180-184
  • 17 Zang K D. Meningioma: a cytogenetic model of a complex benign human tumor, including data on 394 karyotyped cases.  Cytogenet Cell Genet . 2001;  93 207-220
  • 18 Katsuyama J, Papenhausen P R, Herz F, Gazivoda P, Hirano A, Koss L G. Chromosome abnormalities in meningiomas.  Cancer Genet Cytogenet . 1986;  22 63-68
  • 19 Maltby E L, Ironside J W, Battersby R D. Cytogenetic studies in 50 meningiomas.  Cancer Genet Cytogenet . 1988;  31 199-210
  • 20 Rey J A, Bello M J, de Campos M J. et al . Abnormalities of chromosome 22 in human brain tumors determined by combined cytogenetic and molecular genetic approaches.  Cancer Genet Cytogenet . 1993;  66 1-10
  • 21 Rey J A, Bello M J, de Campos M J, Kusak E, Moreno S. Chromosomal involvement secondary to -22 in human meningiomas.  Cancer Genet Cytogenet . 1988;  33 275-290
  • 22 Casalone R, Simi P, Granata P. et al . Correlation between cytogenetic and histopathological findings in 65 human meningiomas.  Cancer Genet Cytogenet . 1990;  45 237-243
  • 23 Vagner-Capodano A M, Grisoli F, Gambarelli D, Sedan R, Pellet W, De Victor B. Correlation between cytogenetic and histopathological findings in 75 human meningiomas.  Neurosurgery . 1993;  32 892-900
  • 24 Biegel J A, Parmiter A H, Sutton L N, Rorke L B, Emanuel B S. Abnormalities of chromosome 22 in pediatric meningiomas.  Genes Chromosomes Cancer . 1994;  9 81-87
  • 25 Lekanne Deprez H R, Riegman P H, van Drunen E. et al . Cytogenetic, molecular genetic and pathological analyses in 126 meningiomas.  J Neuropathol Exp Neurol . 1995;  54 224-235
  • 26 Perry A, Jenkins R B, Dahl R J, Moertel C A, Scheithauer B W. Cytogenetic analysis of aggressive meningiomas: possible diagnostic and prognostic implications.  Cancer . 1996;  77 2567-2573
  • 27 Bello M J, de Campos M J, Kusak M E. et al . Allelic loss at 1p is associated with tumor progression of meningiomas.  Genes Chromosomes Cancer . 1994;  9 296-298
  • 28 Henn W, Cremerius U, Heide G. et al . Monosomy 1p is correlated with enhanced in vivo glucose metabolism in meningiomas.  Cancer Genet Cytogenet . 1995;  79 144-148
  • 29 Niedermayer I, Feiden W, Henn W, Steilen-Gimbel H, Steudel W I, Zang K D. Loss of alkaline phosphatase activity in meningiomas: a rapid histochemical technique indicating progression-associated deletion of a putative tumor suppressor gene on the distal part of the short arm of chromosome 1.  J Neuropathol Exp Neurol . 1997;  56 879-886
  • 30 Bostrom J, Muhlbauer A, Reifenberger G. Deletion mapping of the short arm of chromosome 1 identifies a common region of deletion distal to D1S496 in human meningiomas.  Acta Neuropathol (Berl) . 1997;  94 479-485
  • 31 Lamszus K, Kluwe L, Matschke J, Meissner H, Laas R, Westphal M. Allelic losses at 1p, 9q, 10q, 14q, and 22q in the progression of aggressive meningiomas and undifferentiated meningeal sarcomas.  Cancer Genet Cytogenet . 1999;  110 103-110
  • 32 Leone P E, Bello M J, de Campos M J. et al . NF2 gene mutations and allelic status of 1p, 14q and 22q in sporadic meningiomas.  Oncogene . 1999;  18 2231-2239
  • 33 Ketter R, Henn W, Niedermayer I. et al . Predictive value of progression-associated chromosomal aberrations for the prognosis of meningiomas: a retrospective study of 198 cases.  J Neurosurg . 2001;  95 601-607
  • 34 Dumanski J P, Rouleau G A, Nordenskjold M, Collins V P. Molecular genetic analysis of chromosome 22 in 81 cases of meningioma.  Cancer Res . 1990;  50 5863-5867
  • 35 Lekanne Deprez H R, Bianchi A B, Groen N A. et al . Frequent NF2 gene transcript mutations in sporadic meningiomas and vestibular schwannomas.  Am J Hum Genet . 1994;  54 1022-1029
  • 36 De Vitis R L, Tedde A, Vitelli F. et al . Screening for mutations in the neurofibromatosis type 2 (NF2) gene in sporadic meningiomas.  Hum Genet . 1996;  97 632-637
  • 37 Peyrard M, Fransson I, Xie Y G. et al . Characterization of a new member of the human beta-adaptin gene family from chromosome 22q12, a candidate meningioma gene.  Hum Mol Genet . 1994;  3 1393-1399
  • 38 Lekanne Deprez H R, Groen N A, van Biezen A N. et al . A t(4;22) in a meningioma points to the localization of a putative tumor-suppressor gene.  Am J Hum Genet . 1991;  48 783-790
  • 39 Peyrard M, Seroussi E, Sandberg-Nordqvist A C. et al . The human LARGE gene from 22q12.3-q13.1 is a new, distinct member of the glycosyltransferase gene family.  Proc Natl Acad Sci U S A . 1999;  96 598-603
  • 40 Muller P, Henn W, Niedermayer I. et al . Deletion of chromosome 1p and loss of expression of alkaline phosphatase indicate progression of meningiomas.  Clin Cancer Res . 1999;  5 3569-3577
  • 41 Zang K D. Cytological and cytogenetical studies on human meningioma.  Cancer Genet Cytogenet . 1982;  6 249-274
  • 42 Cai D X, Banerjee R, Scheithauer B W, Lohse C M, Kleinschmidt-Demasters B K, Perry A. Chromosome 1p and 14q FISH analysis in clinicopathologic subsets of meningioma: diagnostic and prognostic implications.  J Neuropathol Exp Neurol . 2001;  60 628-636
  • 43 Scoles D R, Huynh D P, Morcos P A. et al . Neurofibromatosis 2 tumour suppressor schwannomin interacts with betaII-spectrin.  Nat Genet . 1998;  18 354-359
  • 44 Weber R G, Bostrom J, Wolter M. et al . Analysis of genomic alterations in benign, atypical, and anaplastic meningiomas: toward a genetic model of meningioma progression.  Proc Natl Acad Sci U S A . 1997;  94 14719-14724
  • 45 Shoshan Y, Chernova O, Juen S S. et al . Radiation-induced meningioma: a distinct molecular genetic pattern?.  J Neuropathol Exp Neurol . 2000;  59 614-620
  • 46 Arslantas A, Artan S, Oner U. et al . Comparative genomic hybridization analysis of genomic alterations in benign, atypical and anaplastic meningiomas.  Acta Neurol Belg . 2002;  102 53-62
  • 47 Buschges R, Bostrom J, Wolter M. et al . Analysis of human meningiomas for aberrations of the MADH2, MADH4, APM-1 and DCC tumor suppressor genes on the long arm of chromosome 18.  Int J Cancer . 2001;  92 551-554
  • 48 Tran Y K, Bogler O, Gorse K M, Wieland I, Green M R, Newsham I F. A novel member of the NF2/ERM/4.1 superfamily with growth suppressing properties in lung cancer.  Cancer Res . 1999;  59 35-43
  • 49 Gutmann D H, Donahoe J, Perry A. et al . Loss of DAL-1, a protein 4.1-related tumor suppressor, is an important early event in the pathogenesis of meningiomas.  Hum Mol Genet . 2000;  9 1495-1500
  • 50 Perry A, Cai D X, Scheithauer B W. et al . Merlin, DAL-1, and progesterone receptor expression in clinicopathologic subsets of meningioma: a correlative immunohistochemical study of 175 cases.  J Neuropathol Exp Neurol . 2000;  59 872-879
  • 51 Rempel S A, Schwechheimer K, Davis R L, Cavenee W K, Rosenblum M L. Loss of heterozygosity for loci on chromosome 10 is associated with morphologically malignant meningioma progression.  Cancer Res . 1993;  53 2386-2392
  • 52 Simon M, von Deimling A, Larson J J. et al . Allelic losses on chromosomes 14, 10, and 1 in atypical and malignant meningiomas: a genetic model of meningioma progression.  Cancer Res . 1995;  55 4696-4701
  • 53 Liggett Jr H W, Sidransky D. Role of the p16 tumor suppressor gene in cancer.  J Clin Oncol . 1998;  16 1197-1206
  • 54 Rouleau G A, Wertelecki W, Haines J L. et al . Genetic linkage of bilateral acoustic neurofibromatosis to a DNA marker on chromosome 22.  Nature . 1987;  329 246-248
  • 55 Rouleau G A, Merel P, Lutchman M. et al . Alteration in a new gene encoding a putative membrane-organizing protein causes neuro-fibromatosis type 2.  Nature . 1993;  363 515-521
  • 56 Akagi K, Kurahashi H, Arita N. et al . Deletion mapping of the long arm of chromosome 22 in human meningiomas.  Int J Cancer . 1995;  60 178-182
  • 57 Merel P, Hoang-Xuan K, Sanson M. et al . Predominant occurrence of somatic mutations of the NF2 gene in meningiomas and schwannomas.  Genes Chromosomes Cancer . 1995;  13 211-216
  • 58 Ng H K, Lau K M, Tse J Y. et al . Combined molecular genetic studies of chromosome 22q and the neurofibromatosis type 2 gene in central nervous system tumors.  Neurosurgery . 1995;  37 764-773
  • 59 Harada T, Irving R M, Xuereb J H. et al . Molecular genetic investigation of the neurofibromatosis type 2 tumor suppressor gene in sporadic meningioma.  J Neurosurg . 1996;  84 847-851
  • 60 Gutmann D H, Giordano M J, Fishback A S, Guha A. Loss of merlin expression in sporadic meningiomas, ependymomas and schwannomas.  Neurology . 1997;  49 267-270
  • 61 Huynh D P, Mautner V, Baser M E, Stavrou D, Pulst S M. Immunohistochemical detection of schwannomin and neurofibromin in vestibular schwannomas, ependymomas and meningiomas.  J Neuropathol Exp Neurol . 1997;  56 382-390
  • 62 Hitotsumatsu T, Iwaki T, Kitamoto T. et al . Expression of neurofibromatosis 2 protein in human brain tumors: an immunohistochemical study.  Acta Neuropathol (Berl) . 1997;  93 225-232
  • 63 Ueki K, Wen-Bin C, Narita Y, Asai A, Kirino T. Tight association of loss of merlin expression with loss of heterozygosity at chromosome 22q in sporadic meningiomas.  Cancer Res . 1999;  59 5995-5998
  • 64 McClatchey A I, Saotome I, Ramesh V, Gusella J F, Jacks T. The Nf2 tumor suppressor gene product is essential for extraembryonic development immediately prior to gastrulation.  Genes Dev . 1997;  11 1253-1265
  • 65 Pelton P D, Sherman L S, Rizvi T A. et al . Ruffling membrane, stress fiber, cell spreading and proliferation abnormalities in human Schwannoma cells.  Oncogene . 1998;  17 2195-2209
  • 66 Bashour A M, Meng J J, Ip W, MacCollin M, Ratner N. The neurofibromatosis type 2 gene product, merlin, reverses the F-actin cytoskeletal defects in primary human schwannoma cells.  Mol Cell Biol . 2002;  22 1150-1157
  • 67 Lallemand D, Curto M, Saotome I, Giovannini M, McClatchey A I. NF2 deficiency promotes tumorigenesis and metastasis by destabilizing adherens junctions.  Genes Dev . 2003;  17 1090-1100
  • 68 Lim J Y, Kim H, Kim Y H. et al . Merlin suppresses the SRE-dependent transcription by inhibiting the activation of Ras-ERK pathway.  Biochem Biophys Res Commun . 2003;  302 238-245
  • 69 Kamei Y, Watanabe M, Nakayama T, Kanamaru K, Waga S, Shiraishi T. Prognostic significance of p53 and p21WAF1/ CIP1 immunoreactivity and tumor micronecrosis for recurrence of meningiomas.  J Neurooncol . 2000;  46 205-213
  • 70 Sanson M, Cornu P. Biology of meningiomas.  Acta Neurochir (Wien) . 2000;  142 493-505