Mitotic Index is an Independent Predictor of Recurrence-Free Survival in Meningioma

Brain Pathol. 2015 May;25(3):266-75. doi: 10.1111/bpa.12174. Epub 2014 Oct 29.

Abstract

While World Health Organization (WHO) grading of meningioma stratifies patients according to recurrence risk overall, there is substantial within-grade heterogeneity with respect to recurrence-free survival (RFS). Most meningiomas are graded according to mitotic counts per unit area on hematoxylin and eosin sections, a method potentially confounded by tumor cellularity, as well as potential limitations of accurate mitotic figure detection on routine histology. To refine mitotic figure assessment, we evaluated 363 meningiomas with phospho-histone H3 (Ser10) and determined the mitotic index (number of mitoses per 1000 tumor cells). The median mitotic indices among WHO grade I (n = 268), grade II (n = 84) and grade III (n = 11) tumors were 1, 4 and 12. Classification and regression tree analysis to categorize cut-offs identified three subgroups defined by mitotic indices of 0-2, 3-4 and ≥5, which on univariate analysis were associated with RFS (P < 0.01). In multivariate analysis, mitotic index subgrouped in this manner was significantly associated with RFS (P < 0.01) after adjustment for Simpson grade, WHO grade and MIB-1 index. Mitotic index was then examined within individual WHO grade, showing that for grade I and grade II meningiomas, mitotic index can add additional information to RFS risk. The results suggest that the use of a robust mitotic marker in meningioma could refine risk stratification.

Keywords: meningioma; mitotic index; pHH3; recurrence-free survival.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Child
  • Disease-Free Survival
  • Female
  • Histones / metabolism
  • Humans
  • Ki-67 Antigen / metabolism
  • Magnetic Resonance Imaging
  • Male
  • Meningeal Neoplasms / diagnosis*
  • Meningeal Neoplasms / mortality
  • Meningioma / diagnosis*
  • Meningioma / mortality
  • Middle Aged
  • Mitotic Index / methods*
  • Neoplasm Recurrence, Local / diagnosis*
  • Phosphorylation
  • Predictive Value of Tests
  • Tomography Scanners, X-Ray Computed
  • Young Adult

Substances

  • Histones
  • Ki-67 Antigen