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Prognostic Significance of the Mitotic Index Using the Mitosis Marker Anti–Phosphohistone H3 in Meningiomas

Yoo-Jin Kim MD, Ralf Ketter MD, Wolf-Ingo Steudel MD, Wolfgang Feiden MD
DOI: http://dx.doi.org/10.1309/HXUNAG34B3CEFDU8 118-125 First published online: 1 July 2007


Mitotic activity is one of the most reliable prognostic factors in meningiomas. The identification of mitotic figures (MFs) and the areas of highest mitotic activity in H&E-stained slides is a tedious and subjective task. Therefore, we compared the results from immunostaining for the mitosis-specific antibody anti–phosphohistone H3 (PHH3 mitotic index [MI]) with standard MF counts (H&E MI) and the Ki-67 labeling index (LI). The relationship between these proliferation indices and prognosis was investigated in a retrospective series of 265 meningiomas. The PHH3 staining method yielded greater sensitivity in the detection of MFs and facilitated MF counting. Mitotic thresholds of H&E MI of 4 or more per 10 high-power fields (HPF) and PHH3 MI of 6 or more per 10 HPF were found as the most appropriate prognostic cutoff values for the prediction of recurrence-free survival. All 3 proliferation indices were univariately associated with recurrences and deaths. In contrast with the Ki-67 LI, H&E MI and PHH3 MI also remained as independent predictors in the multivariate Cox hazards modeling (P = .0007 and P = .0004, respectively).

Key Words:
  • Meningioma grading
  • Recurrence
  • Phosphohistone H3
  • PHH3
  • Mitosis
  • Ki-67