Phosphohistone-H3 Proliferation Index Is Superior to Mitotic Index and MIB-1 Expression as a Predictor of Recurrence in Human Meningiomas

Abstract

Objectives: This study investigated the prognostic value of the phosphohistone-H3 (PHH3) proliferation index (PI) in human meningiomas and compared the reliability with the conventional mitotic index and MIB-1 biomarker.

Methods: Proliferative activity was determined in 160 patients by standardized immunohistochemistry on tissue microarrays and related to recurrence.

Results: All three proliferation assessment methods were significantly associated with World Health Organization grade. The optimal cutoff values for recurrence prediction were 3% for the MIB-1 PI and 0.5% for the PHH3 PI. Increased PHH3 PI was significantly associated with recurrence-free survival in univariate Cox proportional hazards regression analysis (P = .011) and remained an independent predictor in multivariate analysis (P = .005). Mitotic index and MIB-1 PI did not reach statistical significance.

Conclusions: PHH3 immunostaining allowed for the easiest, fastest, and most objective assessment of proliferation and proved to be the most accurate and reliable method for predicting recurrence in patients resected for meningiomas.

Keywords: Ki-67; Meningioma; PHH3; Prognosis; Recurrence-free survival.