Mitotic and Proliferative Indices in WHO Grade III Meningioma

SIMPLE SUMMARY: Malignant meningiomas are rare primary intracranial tumors associated with considerable morbidity and mortality. The diagnosis is based on the number of mitotic figures (mitotic index, MI). Consequently, the quantification of mitotic figures is prone to inter- and intraobserver variability. The mitotic marker, phosphohistone-H3 (PHH3), has been shown to be a more robust mitotic marker. Despite the prognostic value of MI across all meningioma grades, little is known of the prognostic value of the MI within malignant meningioma. Therefore, this study investigates the MI in a series of malignant meningiomas to analyze the association to progression-free survival and mitotic and proliferative indices. Furthermore, we investigated the precision (repeatability) of mitotic counts and the agreement between MI and PHH3 MI. ABSTRACT: Meningiomas with inherently high mitotic indices and poor prognosis, such as WHO grade III meningiomas, have not been investigated separately to establish interchangeability between conventional mitotic index counted on H&E stained slides (MI) and mitotic index counted on phosphohistone-H3 stained slides (PHH3 MI). This study investigates the agreement of MI and PHH3 MI and to analyze the association of progression-free survival (PFS) and MI, PHH3 MI, and the proliferative index (PI, Ki-67) in WHO grade III meningioma. Tumor specimens from 24 consecutive patients were analyzed for expression of Ki-67, PHH3 MI, and MI. Quantification was performed independently by two observers who made replicate counts in hot spots and overall tumor staining. Repeatability in replicate counts from MI and PHH3 MI was low in both observers. Consequently, we could not report the agreement. MI, PHH3 MI and hot spot counts of Ki-67 were associated with PFS (MI hot spot HR = 1.61, 95% CI 1.12–2.31, p = 0.010; PHH3 MI hot spot HR = 1.59, 95% CI 1.15–2.21, p = 0.006; Ki-67 hot spot HR = 1.06, 95% CI 1.02–1.11. p = 0.004). We found markedly low repeatability of manually counted MI and PHH3 MI in WHO grade III meningioma, and we could not conclude that the two methods agreed. Subsequently, quantification with better repeatability should be sought. All three biomarkers were associated with PFS.