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Mitotic Index is an Independent Predictor of Recurrence-Free Survival in Meningioma
Adriana Olar1, Khalida M Wani, Erik P Sulman
1Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
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.
Insights
A new mitotic marker refines meningioma risk stratification, improving recurrence-free survival (RFS) prediction beyond current World Health Organization (WHO) grading. This robust method enhances accuracy for WHO grade I and II tumors.
Area of Science:
- Neuropathology
- Oncology
- Cancer Biology
Background:
- World Health Organization (WHO) grading of meningioma stratifies recurrence risk but shows significant within-grade heterogeneity in recurrence-free survival (RFS).
- Current grading relies on mitotic counts from H&E sections, which can be confounded by tumor cellularity and limitations in mitotic figure detection.
- There is a need for more precise methods to assess meningioma aggressiveness and predict patient outcomes.
Purpose of the Study:
- To evaluate the utility of phospho-histone H3 (Ser10) as a robust mitotic marker for meningioma risk stratification.
- To determine if mitotic index, assessed by phospho-histone H3, improves recurrence-free survival (RFS) prediction compared to existing methods.
- To refine risk stratification within World Health Organization (WHO) grades, particularly for grades I and II meningiomas.
Main Methods:
- Assessed 363 meningiomas using phospho-histone H3 (Ser10) staining to determine the mitotic index (mitoses per 1000 tumor cells).
- Utilized classification and regression tree analysis to define mitotic index subgroups (0-2, 3-4, ≥5).
- Performed univariate and multivariate analyses, adjusting for Simpson grade, WHO grade, and MIB-1 index, to assess association with RFS.
Main Results:
- Median mitotic indices were 1 for WHO grade I, 4 for grade II, and 12 for grade III meningiomas.
- Mitotic index subgroups (0-2, 3-4, ≥5) were significantly associated with RFS in both univariate and multivariate analyses (P < 0.01).
- Mitotic index provided additional prognostic information for RFS within WHO grade I and II meningiomas.
Conclusions:
- Phospho-histone H3 (Ser10) is a robust marker that refines meningioma risk stratification.
- Mitotic index, determined by this marker, significantly improves the prediction of recurrence-free survival.
- This approach offers enhanced prognostic accuracy, especially for lower-grade meningiomas, addressing limitations of current grading systems.
