Transcriptional factors for epithelial-mesenchymal transition are associated with mesenchymal differentiation in gliosarcoma

Brain Pathol. 2012 Sep;22(5):670-6. doi: 10.1111/j.1750-3639.2012.00571.x. Epub 2012 Mar 5.

Abstract

Gliosarcoma is a rare variant of glioblastoma characterized by a biphasic pattern of glial and mesenchymal differentiation. It is unclear whether mesenchymal differentiation in gliosarcomas is because of extensive genomic instability and/or to a mechanism similar to epithelial-mesenchymal transition (EMT). In the present study, we assessed 40 gliosarcomas for immunoreactivity of Slug, Twist, matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9), which are involved in EMT in epithelial tumors. Nuclear Slug expression was observed in >50% of neoplastic cells in mesenchymal tumor areas of 33 (83%) gliosarcomas, but not in glial areas (P < 0.0001). Nuclear Twist expression was observed in >50% of neoplastic cells in mesenchymal tumor areas of 35 (88%) gliosarcomas, but glial tumor areas were largely negative except in four cases (P < 0.0001). Expression of MMP-2 and MMP-9 was also significantly more extensive in mesenchymal than in glial tumor areas. None of 20 ordinary glioblastomas showed Slug or Twist expression in >10% neoplastic cells. Thus, expression of Slug, Twist, MMP-2 and MMP-9 was characteristic of mesenchymal tumor areas of gliosarcomas, suggesting that mechanisms involved in the EMT in epithelial neoplasms may play roles in mesenchymal differentiation in gliosarcomas.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Brain Neoplasms / complications
  • Brain Neoplasms / pathology*
  • Cell Differentiation / physiology*
  • Epithelial-Mesenchymal Transition / physiology*
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Glial Fibrillary Acidic Protein / metabolism
  • Gliosarcoma / complications
  • Gliosarcoma / pathology*
  • Gliosis / etiology
  • Humans
  • Male
  • Matrix Metalloproteinase 2 / metabolism
  • Matrix Metalloproteinase 9 / metabolism
  • Middle Aged
  • Snail Family Transcription Factors
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*
  • Twist-Related Protein 1 / metabolism

Substances

  • Glial Fibrillary Acidic Protein
  • SNAI1 protein, human
  • Snail Family Transcription Factors
  • Transcription Factors
  • Twist-Related Protein 1
  • Matrix Metalloproteinase 2
  • Matrix Metalloproteinase 9