Prognostic significance of the mitotic index using the mitosis marker anti-phosphohistone H3 in meningiomas

Mitotic activity is one of the most reliable prognostic factors in meningiomas. The identification of mitoticfigures (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 andfacilitated 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 werefound as the most appropriate prognostic cutoff valuesfor 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 muItivariate Cox hazards modeling (P =.0007 and P =.0004, respectively).