Better see to better agree: Phosphohistone H3 (PHH3) increases inter-observer agreement in mitotic count for meningioma grading and imposes new specific thresholds

Background: Mitotic count on hematoxylin and eosin (H&E)-stained slides is a crucial diagnostic criterion in meningioma grading. However, mitosis assessment on H&E slides can be impaired by technical factors and by pathologist's experience. Phosphohistone H3 (PHH3) serine-10 is a mitosis-specific antibody that has proven to facilitate mitotic count in various tumors. Methods: A series of 70 meningiomas (15 grade I, 40 grade II, 15 grade III) was used to validate PHH3 intra- and interobserver reproducibility and to identify PHH3-specific mitotic thresholds. Four pathologists with different experience in neuropathology counted mitoses on both H&E- and PHH3-stained slides. Results: H&E and PHH3 mitotic rates were highly correlated (Pearson's r = 0.92, P <. 0001). PHH3 mitotic counts had both a good mean interobserver correlation (Rm = 0.83) and a good intraclass correlation (0.78), higher than H&E mitotic indices (Rm = 0.77, intraclass correlation = 0.71). After further stratification of ...