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

J Neurosurg. 2014 Dec;121(6):1478-82. doi: 10.3171/2014.8.JNS13515. Epub 2014 Sep 26.

Abstract

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.

Keywords: MMP = matrix metalloproteinase; MMP-2 polymorphism; PCR = polymerase chain reaction; TIMP = tissue inhibitor of MMP; TIMP-2 polymorphism; immunohistochemistry; meningioma; oncology.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Female
  • Gene Expression Regulation, Enzymologic
  • Gene Expression Regulation, Neoplastic
  • Gene Frequency
  • Genetic Predisposition to Disease / genetics
  • Genotype
  • Humans
  • Immunohistochemistry
  • Male
  • Matrix Metalloproteinase 2 / genetics*
  • Matrix Metalloproteinase 2 / metabolism
  • Meningeal Neoplasms / genetics*
  • Meningeal Neoplasms / metabolism
  • Meningioma / genetics*
  • Meningioma / metabolism
  • Polymorphism, Genetic
  • Tissue Inhibitor of Metalloproteinase-2 / genetics*
  • Tissue Inhibitor of Metalloproteinase-2 / metabolism

Substances

  • TIMP2 protein, human
  • Tissue Inhibitor of Metalloproteinase-2
  • MMP2 protein, human
  • Matrix Metalloproteinase 2