Skip to main content
Log in

Tumor grade-related NDRG2 gene expression in primary and recurrent intracranial meningiomas

  • Clinical Study – Patient Study
  • Published:
Journal of Neuro-Oncology Aims and scope Submit manuscript


Approximately 30% of all primary CNS tumors are meningiomas. Depending on histological type, meningiomas can recur as follows: benign—with five-year recurrence of 5%, atypical—recurrence approximately 40%, and anaplastic with recurrence of 50–80%. In an attempt to understand the molecular mechanism of meningioma recurrence we investigated the N-Myc downstream-regulated gene 2 (NDRG2), which has recently been described as important in suppressing cellular carcinogenesis in different types of cancer. The objective of the study was to investigate NDRG2 gene expression at the mRNA level in primary and recurrent meningiomas as a potential marker of tumor aggressiveness, malignancy, and recurrence. Primary and recurrent meningiomas of WHO grades I, II, and III from 35 patients operated on between 2005 and 2008 year at the Department of Neurosurgery of Kaunas Medical University Hospital (Lithuania) were studied. Using the qRT-PCR method we measured NDRG2 gene expression at the mRNA level in primary (n = 24) and recurrent (n = 11) meningiomas. Statistically significant differences in NDRG2 gene expression level were observed between primary and recurrent meningioma groups (P < 0.05) and between benign (WHO grade I) and atypical (WHO grade II) meningiomas (P < 0.05). No statistically significant differences were observed (P > 0.05) among histological subtypes of benign (WHO grade I) meningiomas: fibrous, meningothelial, and transitional. In accordance with our results, reduction of NDRG2 gene expression at the mRNA level could help to explain malignant progression and predisposition to recurrence in meningiomas.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Subscribe and save

Springer+ Basic
EUR 32.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or Ebook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1

Similar content being viewed by others


  1. Perry A, Louis D, Scheithauer B, Budka H, von Deimling A (2007) Meningial tumors. In: Louis DN, Ohgaki H, Wiestler OD, Cavenee WK (eds) WHO classification of tumours of the central nervous system. IARC Press, Lyon, pp 164–172

    Google Scholar 

  2. Riemenschneider MJ, Perry A, Reifenberger G (2006) Histological classification and molecular genetics of meningiomas. The Lancet Neurol 5:1045–1054

    Article  CAS  Google Scholar 

  3. Simon MMD, Bostrom JPM, Hartmann CMD (2007) Molecular genetics of meningiomas: from basic research to potential clinical applications. Neurosurgery 60:787–798

    Article  PubMed  Google Scholar 

  4. Adegbite AB, Khan MI, Paine KWE, Tan LK (1983) The recurrence of intracranial meningiomas after surgical treatment. J Neurosurg 58:51–56

    Article  CAS  PubMed  Google Scholar 

  5. Perry A, Stafford SL, Scheithauer BW, Suman VJ, Lohse CM (1997) Meningioma grading: an analysis of histologic parameters. Am J Surg Pathol 21:1455–1465

    Article  CAS  PubMed  Google Scholar 

  6. Espinosa AB, Tabernero MD, Maillo A, Sayagues JM, Ciudad J, Merino M, Alguero MC, Lubombo AM, Sousa P et al (2006) The cytogenetic relationship between primary and recurrent meningiomas points to the need for new treatment strategies in cases at high risk of relapse. Clin Cancer Res 12:772–780

    Article  PubMed  Google Scholar 

  7. Maillo A, Orfao A, Espinosa AB, Sayagues JM, Merino M, Sousa P, Lara M, Tabernero MD (2007) Early recurrences in histologically benign/grade I meningiomas are associated with large tumors and coexistence of monosomy 14 and del(1p36) in the ancestral tumor cell clone. Neuro oncol 9:438–446

    Article  PubMed  Google Scholar 

  8. Mihaila D, Jankowski M, Gutierrez JA, Rosenblum ML, Newsham IF, Bogler O, Rempel SA (2003) Meningiomas: loss of heterozygosity on chromosome 10 and marker-specific correlations with grade, recurrence, and survival. Clin Cancer Res 9:4443–4451

    CAS  PubMed  Google Scholar 

  9. Kim YJ, Ketter R, Henn W, Zang K, Steudel WI, Feiden W (2006) Histopathologic indicators of recurrence in meningiomas: correlation with clinical and genetic parameters. Virchows Arch 449:529–538

    Article  CAS  PubMed  Google Scholar 

  10. Leone PE, Bello MJ, de Campos JM, Vaquero J, Sarasa JL, Pestana A, Rey JA (1999) NF2 gene mutations and allelic status of 1p, 14q and 22q in sporadic meningiomas. Oncogene 18:2231–2239

    Article  CAS  PubMed  Google Scholar 

  11. Pfisterer WK, Hendricks WP, Scheck AC, Nieman RA, Birkner TH, Krampla WW, Preul MC (2007) Fluorescent in situ hybridization and ex vivo 1H magnetic resonance spectroscopic examinations of meningioma tumor tissue: is it possible to identify a clinically-aggressive subset of benign meningiomas? Neurosurgery 61:1048–1061

    Google Scholar 

  12. Simon M, von Deimling A, Larson JJ, Wellenreuther R, Kaskel P, Waha A, Warnick RE, Tew JM J, Menon AG (1995) Allelic losses on chromosomes 14, 10, and 1 in atypical and malignant meningiomas: a genetic model of meningioma progression. Cancer Res 55:4696–4701

    CAS  PubMed  Google Scholar 

  13. Weber RG, Bostrom J, Wolter M, Baudis M, Collins VP, Reifenberger G, Lichter P (1997) Analysis of genomic alterations in benign, atypical, and anaplastic meningiomas: toward a genetic model of meningioma progression. Proc Natl Acad Sci USA 94:14719–14724

    Article  CAS  PubMed  Google Scholar 

  14. Lusis EA, Watson MA, Chicoine MR, Lyman M, Roerig P, Reifenberger G, Gutmann DH, Perry A (2005) Integrative genomic analysis identifies NDRG2 as a candidate tumor suppressor gene frequently inactivated in clinically aggressive meningioma. Cancer Res 65:7121–7126

    Article  CAS  PubMed  Google Scholar 

  15. Yao L, Zhang J, Liu X (2008) NDRG2: a Myc-repressed gene involved in cancer and cell stress. Acta Biochem Biophys Sin (Shanghai) 40:625–635

    Article  CAS  Google Scholar 

  16. Liu N, Wang L, Li X, Yang Q, Liu X, Zhang J, Zhang J, Wu Y, Ji S et al (2008) N-Myc downstream-regulated gene 2 is involved in p53-mediated apoptosis. Nucleic Acids Res 36:5335–5349

    Article  CAS  PubMed  Google Scholar 

  17. Lorentzen A, Vogel LK, Lewinsky RH, Saebo M, Skjelbred CF, Godiksen S, Hoff G, Tveit KM, Lothe IM et al (2007) Expression of NDRG2 is down-regulated in high-risk adenomas and colorectal carcinoma. BMC Cancer 7:192

    Article  PubMed  Google Scholar 

  18. Tepel M, Roerig P, Wolter M, Gutmann DH, Perry A, Reifenberger G, Riemenschneider MJ (2008) Frequent promoter hypermethylation and transcriptional downregulation of the NDRG2 gene at 14q11.2 in primary glioblastoma. Int J Cancer 123:2080–2086

    Article  CAS  PubMed  Google Scholar 

  19. Ildan F, Erman T, Göcer A, Tuna M, Bagdatoglu H, Cetinalp E, Burgut R (2007) Predicting the probability of meningioma recurrence in the preoperative and early postoperative period: a multivariate analysis in the midterm follow-up. Skull Base 17:157–172

    Article  PubMed  Google Scholar 

  20. Yamasaki F, Yoshioka H, Hama S, Sugiyama K, Arita K, Kurisu K (2000) Recurrence of meningiomas. Cancer 89:1102–1110

    Article  CAS  PubMed  Google Scholar 

  21. Ayerbe J, Lobato RD, de la Cruz J, Alday R, Rivas JJ, Gómez PA, Cabrera A (1999) Risk factors predicting recurrence in patients operated on for intracranial meningioma. A multivariate analysis. Acta Neurochir (Wien) 141:921–932

    Article  CAS  Google Scholar 

  22. Maillo A, Orfao A, Sayagues JM, Diaz P, Gomez-Moreta JA, Caballero M, Santamarta D, Santos-Briz A, Morales F, Tabernero MD (2003) New classification scheme for the prognostic stratification of meningioma on the basis of chromosome 14 abnormalities, patient age, and tumor histopathology. J Clin Oncol 21:3285–3295

    Article  PubMed  Google Scholar 

  23. Morokoff AP, Zauberman J, Black PM (2008) Surgery for convexity meningiomas. Neurosurgery 63:427–434

    Article  PubMed  Google Scholar 

  24. Carvalho L, Smirnov I, Baia G, Modrusan Z, Smith J, Jun P, Costello J, McDermott M, VandenBerg S, Lal A (2007) Molecular signatures define two main classes of meningiomas. Mol Cancer 6:64

    Article  PubMed  Google Scholar 

  25. Ozaki S, Nishizaki T, Ito H, Sasaki K (2004) Comparative genomic hybridization analysis of genetic alterations associated with malignant progression of meningioma. J Neurooncol 41:167–174

    Article  Google Scholar 

  26. Wrobel G, Roerig P, Kokocinski F, Neben K, Hahn M, Reifenberger G, Lichter P (2005) Microarray-based gene expression profiling of benign, atypical and anaplastic meningiomas identifies novel genes associated with meningioma progression. Int J Cancer 114:249–256

    Article  CAS  PubMed  Google Scholar 

  27. Lee DC, Kang YK, Kim WH, Jang YJ, Kim DJ, Park IY, Sohn BH, Sohn HA, Lee HG et al (2008) Functional and clinical evidence for NDRG2 as a candidate suppressor of liver cancer metastasis. Cancer Res 68:4210–4220

    Article  CAS  PubMed  Google Scholar 

  28. Schiffer D, Ghimenti C, Fiano V (2005) Absence of histological signs of tumor progression in recurrences of completely resected meningiomas. J Neurooncol 73:125–130

    Article  PubMed  Google Scholar 

Download references


We thank medical student Ruta Vilkaityte for her excellent technical assistance in RNA extraction. This work was supported by grant F-07013/07 by Lithuanian State Science and Studies Foundation.

Conflict of interest statement


Author information

Authors and Affiliations


Corresponding author

Correspondence to Daina Skiriute.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Skiriute, D., Tamasauskas, S., Asmoniene, V. et al. Tumor grade-related NDRG2 gene expression in primary and recurrent intracranial meningiomas. J Neurooncol 102, 89–94 (2011).

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: