title: Mitotic Index is an Independent Predictor of Recurrence-Free Survival in Meningioma.
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.
authors.affiliation: Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
authors.forename: Adriana
authors.initials: A
authors.lastname: Olar
authors.forename: Khalida M
authors.initials: KM
authors.lastname: Wani
authors.forename: Erik P
authors.initials: EP
authors.lastname: Sulman
authors.forename: Alireza
authors.initials: A
authors.lastname: Mansouri
authors.forename: Gelareh
authors.initials: G
authors.lastname: Zadeh
authors.forename: Charmaine D
authors.initials: CD
authors.lastname: Wilson
authors.forename: Franco
authors.initials: F
authors.lastname: DeMonte
authors.forename: Gregory N
authors.initials: GN
authors.lastname: Fuller
authors.forename: Kenneth D
authors.initials: KD
authors.lastname: Aldape
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002648:Child; D018572:Disease-Free Survival; D005260:Female; D006657:Histones / Q000378:metabolism; D006801:Humans; D019394:Ki-67 Antigen / Q000378:metabolism; D008279:Magnetic Resonance Imaging; D008297:Male; D008577:Meningeal Neoplasms / Q000175:diagnosis* / Q000401:mortality; D008579:Meningioma / Q000175:diagnosis* / Q000401:mortality; D008875:Middle Aged; D008940:Mitotic Index / Q000379:methods*; D009364:Neoplasm Recurrence, Local / Q000175:diagnosis*; D010766:Phosphorylation; D011237:Predictive Value of Tests; D015898:Tomography Scanners, X-Ray Computed; D055815:Young Adult
chemical_list: D006657:Histones; D019394:Ki-67 Antigen
keywords: meningioma; mitotic index; pHH3; recurrence-free survival