title: DNA topoisomerase IIα and mitosin expression predict meningioma recurrence better than histopathological grade and MIB-1 after initial surgery.
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.
authors.affiliation: Departments of Laboratory Medicine, Children's and Women's Health, Norwegian University of Science and Technology (NTNU), Trondheim, Norway.
authors.forename: Theo L
authors.initials: TL
authors.lastname: Winther
authors.affiliation: Departments of Laboratory Medicine, Children's and Women's Health, Norwegian University of Science and Technology (NTNU), Trondheim, Norway.|Pathology and Medical genetics, St. Olavs Hospital, Trondheim, Norway.
authors.forename: Sverre H
authors.initials: SH
authors.lastname: Torp
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000951:Antigens, Neoplasm / Q000378:metabolism*; D014408:Biomarkers, Tumor / Q000378:metabolism*; D002868:Chromosomal Proteins, Non-Histone / Q000378:metabolism*; D004250:DNA Topoisomerases, Type II / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000378:metabolism*; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D019394:Ki-67 Antigen / Q000378:metabolism*; D008297:Male; D008577:Meningeal Neoplasms / Q000378:metabolism / Q000473:pathology* / Q000601:surgery; D008579:Meningioma / Q000378:metabolism / Q000473:pathology* / Q000601:surgery; D008840:Microfilament Proteins / Q000378:metabolism*; D008875:Middle Aged; D012008:Recurrence
chemical_list: D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D002868:Chromosomal Proteins, Non-Histone; D004268:DNA-Binding Proteins; D019394:Ki-67 Antigen; D008840:Microfilament Proteins; C094772:centromere protein F; D004250:DNA Topoisomerases, Type II