Presence of matrix metalloproteinase–2 and tissue inhibitor matrix metalloproteinase–2 gene polymorphisms and immunohistochemical expressions in intracranial meningiomas

Laboratory investigation

View More View Less
  • 1 Departments of Neurosurgery,
  • 2 Medical Genetics, and
  • 3 Pathology, Başkent University, School of Medicine, Ankara, Turkey
Restricted access

Purchase Now

USD  $45.00

JNS + Pediatrics - 1 year subscription bundle (Individuals Only)

USD  $505.00

JNS + Pediatrics + Spine - 1 year subscription bundle (Individuals Only)

USD  $600.00
Print or Print + Online

Object

Meningiomas are benign extraaxial tumors with a slow progression. Some of them, in spite of being benign in nature, may show an aggressive progression pattern. To investigate the behavioral characteristics of meningiomas, researchers have studied matrix metalloproteinases (MMPs), their tissue inhibitors (TIMPs), interstitial collagens, proteins, vascular endothelial growth factors (VEGF), and tumor necrosis factors.

Methods

In this study, the authors investigated MMP2 and TIMP2 gene polymorphisms in formalin-fixed paraffin-embedded tissue samples obtained from meningioma patients who had previously undergone surgery at the authors' institution. In addition, brain invasion, Ki-67 index, and MMP-2 and TIMP-2 expressions were investigated using immunohistochemical methods. MMP2 (735C>T, 1575G>A, 1306C>T) and TIMP2 (418G>C, 303C>T) gene polymorphisms were investigated from paraffin-embedded tissue sections using the polymerase chain reaction–restriction fragment length polymorphism method.

Results

There were statistically significant differences between genotype (p = 0.001) and allele frequencies (p = 0.001 and OR 7.4 [95% CI 1.5–36.2]) in patient and control groups for MMP2 1306C>T polymorphism. The authors did not find a statistically significant difference for other polymorphisms. GA genotype was found to be more frequent when brain invasion was suspected for MMP2 1575G>A polymorphism (p = 0.006). There was not a statistically significant difference for other MMP2 or TIMP2 gene polymorphisms.

Conclusions

The authors' results support the importance of MMPs and their tissue inhibitors in meningioma pathogenesis. In future studies, these gene polymorphisms, especially MMP2 1306C>T and 1575G>A, should be investigated for meningioma or brain invasion susceptibility in larger study groups.

Abbreviations used in this paper:MMP = matrix metalloproteinase; PCR = polymerase chain reaction; TIMP = tissue inhibitor of MMP.

JNS + Pediatrics - 1 year subscription bundle (Individuals Only)

USD  $505.00

JNS + Pediatrics + Spine - 1 year subscription bundle (Individuals Only)

USD  $600.00

Contributor Notes

Address correspondence to: İlker Coven, M.D., Başkent University Faculty of Medicine, Department of Neurosurgery, Hoca Cihan Mah. Saray Cad. No: 1 Selçuklu, Konya 04280, Turkey. email: covenilker@yahoo.com.

Please include this information when citing this paper: published online September 26, 2014; DOI: 10.3171/2014.8.JNS13515.

  • 1

    Büschges R, , Boström J, , Wolter M, , Blaschke B, , Weber RG, & Lichter P, : 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 92:551554, 2001

    • Search Google Scholar
    • Export Citation
  • 2

    Cornelius LA, , Nehring LC, , Harding E, , Bolanowski M, , Welgus HG, & Kobayashi DK, : Matrix metalloproteinases generate angiostatin: effects on neovascularization. J Immunol 161:68456852, 1998

    • Search Google Scholar
    • Export Citation
  • 3

    DeClerck YA, , Perez N, , Shimada H, , Boone TC, , Langley KE, & Taylor SM: Inhibition of invasion and metastasis in cells transfected with an inhibitor of metalloproteinases. Cancer Res 52:701708, 1992

    • Search Google Scholar
    • Export Citation
  • 4

    Egeblad M, & Werb Z: New functions for the matrix metalloproteinases in cancer progression. Nat Rev Cancer 2:161174, 2002

  • 5

    Kachra Z, , Beaulieu E, , Delbecchi L, , Mousseau N, , Berthelet F, & Moumdjian R, : Expression of matrix metalloproteinases and their inhibitors in human brain tumors. Clin Exp Metastasis 17:555566, 1999

    • Search Google Scholar
    • Export Citation
  • 6

    Kohn EC, & Liotta LA: Molecular insights into cancer invasion: strategies for prevention and intervention. Cancer Res 55:18561862, 1995

    • Search Google Scholar
    • Export Citation
  • 7

    Kugler A: Matrix metalloproteinases and their inhibitors. Anticancer Res 19:2C 15891592, 1999

  • 8

    Kumar R, , Malik N, , Tungaria A, & Kawal P: Matrix metalloproteinase-2 gene polymorphism is not associated with increased glioblastoma multiforme susceptibility: an Indian institutional experience. Neurol India 59:236240, 2011

    • Search Google Scholar
    • Export Citation
  • 9

    Maes L, , Lippens E, , Kalala JPO, & de Ridder L: The hTERT-protein and Ki-67 labelling index in recurrent and non-recurrent meningiomas. Cell Prolif 38:312, 2005

    • Search Google Scholar
    • Export Citation
  • 10

    Miyake H, , Hara I, , Gohji K, , Yamanaka K, , Hara S, & Arakawa S, : Relative expression of matrix metalloproteinase-2 and tissue inhibitor of metalloproteinase-2 in mouse renal cell carcinoma cells regulates their metastatic potential. Clin Cancer Res 5:28242829, 1999

    • Search Google Scholar
    • Export Citation
  • 11

    Moses MA: The regulation of neovascularization of matrix metalloproteinases and their inhibitors. Stem Cells 15:180189, 1997

  • 12

    Nakagawa T, , Kubota T, , Kabuto M, , Sato K, , Kawano H, & Hayakawa T, : Production of matrix metalloproteinases and tissue inhibitor of metalloproteinases-1 by human brain tumors. J Neurosurg 81:6977, 1994

    • Search Google Scholar
    • Export Citation
  • 13

    Nakasu S, , Hirano A, , Shimura T, & Llena JF: Incidental meningiomas in autopsy study. Surg Neurol 27:319322, 1987

  • 14

    Nordqvist AC, , Smurawa H, & Mathiesen T: Expression of matrix metalloproteinases 2 and 9 in meningiomas associated with different degrees of brain invasiveness and edema. J Neurosurg 95:839844, 2001

    • Search Google Scholar
    • Export Citation
  • 15

    Okada M, , Miyake K, , Matsumoto Y, , Kawai N, , Kunishio K, & Nagao S: Matrix metalloproteinase-2 and matrix metalloproteinase-9 expressions correlate with the recurrence of intracranial meningiomas. J Neurooncol 66:2937, 2004

    • Search Google Scholar
    • Export Citation
  • 16

    Ozen O, , Demirhan B, & Altinörs N: Correlation between histological grade and MIB-1 and p53 immunoreactivity in meningiomas. Clin Neuropathol 24:219224, 2005

    • Search Google Scholar
    • Export Citation
  • 17

    Ozer O, , Sahin FI, , Aydemir F, , Ozen O, , Yilmaz Z, & Altinörs N: Her-2/neu gene amplification in paraffin-embedded tissue sections of meningioma patients. Turk Neurosurg 19:135138, 2009

    • Search Google Scholar
    • Export Citation
  • 18

    Peng B, , Cao L, , Ma X, , Wang W, , Wang D, & Yu L: Meta-analysis of association between matrix metalloproteinases 2, 7 and 9 promoter polymorphisms and cancer risk. Mutagenesis 25:371379, 2010

    • Search Google Scholar
    • Export Citation
  • 19

    Riemenschneider MJ, , Perry A, & Reifenberger G: Histological classification and molecular genetics of meningiomas. Lancet Neurol 5:10451054, 2006. (Erratum in Lancet Neurol 6: 105, 2007)

    • Search Google Scholar
    • Export Citation
  • 20

    Rooprai HK, , Van Meter T, , Rucklidge GJ, , Hudson L, , Everall IP, & Pilkington GJ: Comparative analysis of matrix metalloproteinases by immunocytochemistry, immunohistochemistry and zymography in human primary brain tumors. Int J Oncol 13:11531157, 1998

    • Search Google Scholar
    • Export Citation
  • 21

    Rooprai HK, , van Meter TE, , Robinson SD, , King A, , Rucklidge GJ, & Pilkington GJ: Expression of MMP-2 and -9 in short-term cultures of meningioma: influence of histological subtype. Int J Mol Med 12:977981, 2003

    • Search Google Scholar
    • Export Citation
  • 22

    Siddique K, , Yanamandra N, , Gujrati M, , Dinh D, , Rao JS, & Olivero W: Expression of matrix metalloproteinases, their inhibitors, and urokinase plasminogen activator in human meningiomas. Int J Oncol 22:289294, 2003

    • Search Google Scholar
    • Export Citation
  • 23

    Stetler-Stevenson WG: The tumor microenvironment: regulation by MMP-independent effects of tissue inhibitor of metalloproteinases-2. Cancer Metastasis Rev 27:5766, 2008

    • Search Google Scholar
    • Export Citation
  • 24

    Stetler-Stevenson WG, , Liotta LA, & Kleiner DE Jr: Extracellular matrix 6: role of matrix metalloproteinases in tumor invasion and metastasis. FASEB J 7:14341441, 1993

    • Search Google Scholar
    • Export Citation
  • 25

    Uzüm N, & Ataoğlu GA: Histopathological parameters with Ki-67 and bcl-2 in the prognosis of meningiomas according to WHO 2000 classification. Tumori 94:389397, 2008

    • Search Google Scholar
    • Export Citation
  • 26

    Zang KD: Meningioma: a cytogenetic model of a complex benign human tumor, including data on 394 karyotyped cases. Cytogenet Cell Genet 93:207220, 2001

    • Search Google Scholar
    • Export Citation

Metrics

All Time Past Year Past 30 Days
Abstract Views 244 86 3
Full Text Views 191 4 2
PDF Downloads 165 3 1
EPUB Downloads 0 0 0