DNA topoisomerase IIα and mitosin expression predict meningioma recurrence better than histopathological grade and MIB-1 after initial surgery

PLoS One. 2017 Mar 16;12(3):e0172316. doi: 10.1371/journal.pone.0172316. eCollection 2017.

Abstract

Background: The 2016 WHO histopathological grade or conventional biomarker MIB-1 is insufficient for predicting meningioma recurrence after initial treatment and alternative strategies are required. In this study, we investigated whether DNA topoisomerase IIα and/or mitosin expression can predict tumor recurrence with greater accuracy than conventional methods.

Methods: The expression of MIB-1, topoisomerase IIα, and mitosin were determined as proliferation indices in tissue microarrays using immunohistochemistry. The accuracy of prognostication was assessed with receiver operating characteristic (ROC) analyses and standard survival analyses.

Results: Expression of topoisomerase IIα and mitosin was significantly higher in recurrent meningioma than in non-recurrent meningioma (P ≤ 0.031), but no difference in MIB-1 expression was observed (P = 0.854). ROC analysis found topoisomerase IIα and mitosin expression to be the most reliable predictors of recurrence compared to WHO histopathological grade and MIB-1 expression. This result was supported by the multivariate survival analysis, in which mitosin expression was a significant predictor of recurrence-free survival (P < 0.001) and no association was found with histopathological grade or MIB-1 expression (P ≥ 0.158).

Conclusions: The results suggest that topoisomerase IIα and mitosin improve prognostication of patients resected for meningioma. Tumors with higher topoisomerase IIα and/or mitosin expression have a higher risk of recurrence after initial treatment, and these patients may benefit from adjuvant treatment and closer radiological follow-up.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antigens, Neoplasm / metabolism*
  • Biomarkers, Tumor / metabolism*
  • Chromosomal Proteins, Non-Histone / metabolism*
  • DNA Topoisomerases, Type II / metabolism*
  • DNA-Binding Proteins / metabolism*
  • Disease-Free Survival
  • Female
  • Humans
  • Ki-67 Antigen / metabolism*
  • Male
  • Meningeal Neoplasms / metabolism
  • Meningeal Neoplasms / pathology*
  • Meningeal Neoplasms / surgery
  • Meningioma / metabolism
  • Meningioma / pathology*
  • Meningioma / surgery
  • Microfilament Proteins / metabolism*
  • Middle Aged
  • Recurrence

Substances

  • Antigens, Neoplasm
  • Biomarkers, Tumor
  • Chromosomal Proteins, Non-Histone
  • DNA-Binding Proteins
  • Ki-67 Antigen
  • Microfilament Proteins
  • centromere protein F
  • DNA Topoisomerases, Type II

Grants and funding

This study was funded by the Norwegian University of Science and Technology (website: http://www.ntnu.no/), and 50 000 kr was received by TLW. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.