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

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

Adriana Olar  1 , Khalida M Wani, Erik P Sulman, Alireza Mansouri, Gelareh Zadeh, Charmaine D Wilson, Franco DeMonte, Gregory N Fuller, Kenneth D Aldape
Affiliations

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

Adriana Olar et al. Brain Pathol. 2015 May.

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.

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Figures

Figure 1
Figure 1
Histone H3 phosphorylated (pHH3), 400×: The differences in cellularity can be striking among different tumors or among intratumoral regions introducing subjectivity to interpretation. The pHH3 index (mitotic figures per 1000 cells) can be used as an objective tool for assessing mitotic activity. This value will also be independent of the size of the microscope field used.
Figure 2
Figure 2
Recurrence‐free survival (RFS) among all World Health Organization (WHO) grade meningiomas.
Figure 3
Figure 3
Mitotic index vs. MIB‐1 index. There is a modest linear correlation with MIB‐1 index (Pearson's r = 0.639, MIC‐ρ2 = −0.092, Spearman's rank correlation ρ = 0.558, P‐value < 0.01).
Figure 4
Figure 4
Classification and regression tree (CART) analysis identified histone H3 phosphorylated (pHH3) cut‐offs of potential significance in meningioma recurrence.
Figure 5
Figure 5
Recurrence‐free survival (RFS) among all World Health Organization (WHO) grade meningiomas stratified by mitotic index subgroups.
Figure 6
Figure 6
Recurrence‐free survival (RFS) among World Health Organization (WHO) grade I meningiomas (A) and WHO grade II meningiomas (B) stratified by mitotic index subgroups.
Figure 7
Figure 7
Recurrence‐free survival (RFS) among meningiomas with gross total resection (Simpson grades 1–3) (A) and meningiomas with subtotal resection (Simpson grade 4) (B) stratified by mitotic index subgroups.
Figure 8
Figure 8
Recurrence‐free survival (RFS) among skull base meningiomas (A) and non‐skull base meningiomas (B) stratified by mitotic index subgroups.
See this image and copyright information in PMC

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