The clinicopathological analysis of receptor tyrosine kinases in meningiomas: the expression of VEGFR-2 in meningioma was associated with a higher WHO grade and shorter progression-free survival

Brain Tumor Pathol. 2019 Jan;36(1):7-13. doi: 10.1007/s10014-018-0332-1. Epub 2018 Dec 5.

Abstract

WHO grade II/III meningiomas recur frequently and there is currently no established molecular target therapy for meningioma. No previous studies have revealed the association between receptor tyrosine kinases (RTKs) and the recurrence of meningiomas. This study aims to elucidate the association between RTKs and the clinicopathological characteristics and recurrence of meningioma. We investigated the immunohistochemical expression of RTKs (VEGFR-1/2/3, PDGFR-alpha/beta and c-Kit) in 81 meningiomas (WHO grade I, n = 64, WHO grade II/III, n = 17) in 74 patients. Immunohistochemistry revealed that 29 WHO grade I (45%), 10 WHO grade II (77%), and 4 WHO grade III (100%) tumors were VEGFR-2-positive, and that the VEGFR-2 expression was significantly correlated with the WHO grade. In univariate analyses to investigate the clinicopathological factors associated with recurrence, Simpson grade IV/V resection, a larger tumor size, a high VEGFR-2 expression level, WHO grade II/III, a high Ki-67 expression level, and the non-expression of PgR were identified as significant factors. Furthermore, patients with VEGFR-2-positive meningiomas showed significantly shorter progression-free survival. In the multivariate analysis, WHO grade II/III and the location were significantly associated with recurrence. In conclusion, our study suggests that VEGFR-2 inhibitors might be one of the best candidates for molecular therapy against recurrent meningiomas.

Keywords: Meningioma; Receptor tyrosine kinase; Recurrence/regrowth; VEGFR-2; WHO grade.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Disease Progression
  • Disease-Free Survival
  • Female
  • Gene Expression*
  • Genetic Association Studies*
  • Humans
  • Immunohistochemistry
  • Male
  • Meningeal Neoplasms / genetics*
  • Meningeal Neoplasms / pathology*
  • Meningioma / genetics*
  • Meningioma / pathology*
  • Middle Aged
  • Neoplasm Recurrence, Local
  • Neoplasm Staging
  • Time Factors
  • Vascular Endothelial Growth Factor Receptor-2 / genetics*
  • Vascular Endothelial Growth Factor Receptor-2 / metabolism*
  • World Health Organization

Substances

  • Vascular Endothelial Growth Factor Receptor-2