Immunohistochemical Profiles of Matrix Metalloproteinases and Vascular Endothelial Growth Factor Overexpression in the Antoni B Area of Vestibular Schwannomas

World Neurosurg. 2020 Dec:144:e72-e79. doi: 10.1016/j.wneu.2020.07.208. Epub 2020 Aug 3.

Abstract

Objective: To evaluate the clinical manifestations of cystic vestibular schwannomas (VSs), investigate the immunohistochemical profiles of matrix metalloproteinases (MMPs) and vascular endothelial growth factor (VEGF) expression in Antoni A and B areas, and speculate the pathogenesis of cystic formation and intratumoral hemorrhage.

Methods: Clinical features and outcomes of 24 cases of cystic VSs and 38 cases of solid VSs were retrospectively compared. Immunohistochemical studies were conducted to evaluate the characteristics of MMPs and VEGF in cystic and solid VSs.

Results: The tumor size was 38.92 ± 1.86 mm and 31.95 ± 1.74 mm in the cystic and solid VSs group, respectively (P = 0.011). Cystic VSs were rich in the Antoni B area. MMP-9 expression was low in the Antoni A and B areas. MMP-2 was moderately expressed. No significant difference in MMP-2 expression existed between the Antoni A and B areas (P > 0.05). VEGF and MMP-14 expression were moderate in the Antoni A area and intense in the Antoni B area, and the expression of both was significantly greater in the Antoni B area than in the Antoni A area (P < 0.001).

Conclusions: MMP-14 and VEGF expression were significantly greater in the Antoni B area than in the Antoni A area. Upregulated MMP-14 may degrade loose collagen in the Antoni B area and contribute to cystic formation. MMP-14 can enhance VEGF activity, which may induce extravasation of a plasma ultrafiltrate, cystic expansion, and intratumoral hemorrhage. Therefore, MMP-14 inhibition may be a therapeutic strategy for treating cystic VSs.

Keywords: Antoni A; Antoni B; Cystic formation; Cystic vestibular schwannoma; Matrix metalloproteinase; Vascular endothelial growth factor.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Female
  • Humans
  • Immunohistochemistry
  • Intracranial Hemorrhages / diagnostic imaging
  • Intracranial Hemorrhages / etiology
  • Intracranial Hemorrhages / pathology
  • Magnetic Resonance Imaging
  • Male
  • Matrix Metalloproteinase 14 / biosynthesis
  • Matrix Metalloproteinase 14 / genetics
  • Matrix Metalloproteinase 2 / biosynthesis
  • Matrix Metalloproteinase 2 / genetics
  • Matrix Metalloproteinase 9 / biosynthesis
  • Matrix Metalloproteinase 9 / genetics
  • Matrix Metalloproteinases / biosynthesis*
  • Middle Aged
  • Neuroma, Acoustic / complications
  • Neuroma, Acoustic / genetics
  • Neuroma, Acoustic / metabolism*
  • Neurosurgical Procedures
  • Retrospective Studies
  • Vascular Endothelial Growth Factor A / biosynthesis*
  • Vascular Endothelial Growth Factor A / genetics
  • Young Adult

Substances

  • VEGFA protein, human
  • Vascular Endothelial Growth Factor A
  • Matrix Metalloproteinases
  • MMP2 protein, human
  • Matrix Metalloproteinase 2
  • MMP9 protein, human
  • Matrix Metalloproteinase 9
  • MMP14 protein, human
  • Matrix Metalloproteinase 14