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Published on: January 9, 2019
Mitotic and Proliferative Indices in WHO Grade III Meningioma
Andrea Daniela Maier1,2, Christian Beltoft Brøchner2, Jiri Bartek1,3,4
1Department of Neurosurgery, Copenhagen University Hospital, Rigshospitalet, Inge Lehmanns Vej 6, 2100 Copenhagen, Denmark.
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.
Insights
This study found low repeatability for counting mitotic figures in WHO grade III meningiomas using standard (MI) and phosphohistone-H3 (PHH3 MI) methods. Despite poor agreement, both MI and PHH3 MI, along with Ki-67, correlated with progression-free survival.
Area of Science:
- Neuropathology
- Oncology
- Cell Biology
Background:
- WHO grade III meningiomas are aggressive tumors with poor prognosis.
- Accurate assessment of mitotic activity is crucial for grading and predicting outcomes.
- Interchangeability of conventional mitotic index (MI) and phosphohistone-H3 mitotic index (PHH3 MI) in high-grade meningiomas remains unestablished.
Purpose of the Study:
- To investigate the agreement between MI and PHH3 MI in WHO grade III meningiomas.
- To analyze the association of MI, PHH3 MI, and Ki-67 (proliferative index) with progression-free survival (PFS).
Main Methods:
- Tumor specimens from 24 WHO grade III meningioma patients were analyzed.
- Quantification of Ki-67, MI, and PHH3 MI was performed by two independent observers.
- Repeatability of counts was assessed in hot spots and overall tumor staining.
Main Results:
- Repeatability of MI and PHH3 MI counts was low for both observers, precluding agreement assessment.
- MI, PHH3 MI, and Ki-67 hot spot counts were significantly associated with PFS (p < 0.010 for MI and PHH3 MI; p = 0.004 for Ki-67).
- Markedly low repeatability of manual mitotic counts was observed in WHO grade III meningiomas.
Conclusions:
- Current manual counting methods for MI and PHH3 MI show poor repeatability in WHO grade III meningiomas.
- The study could not establish agreement between MI and PHH3 MI.
- Further research is needed to develop more reproducible quantification methods for these biomarkers, which are all associated with PFS.
