Eleonora Duregon1, Adele Cassenti1, Alessandra Pittaro1, Laura Ventura1, Rebecca Senetta1, Roberta Rudà1, Paola Cassoni1. 1. Department of Medical Sciences, University of Torino, Turin, Italy (A.C., A.P., R.S., P.C.); Department of Oncology, University of Torino at San Luigi Hospital, Orbassano, Italy (E.D.); Department of Statistical Sciences, University of Padua, Padova, Italy (L.V.); Department of Neuro-Oncology, University and City of Health and Science Hospital of Turin, Turin, Italy (R.R.).
Abstract
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 (R(m) = 0.83) and a good intraclass correlation (0.78), higher than H&E mitotic indices (R(m) = 0.77, intraclass correlation = 0.71). After further stratification of meningiomas according to World Health Organization grade, PHH3 performed better in terms of interobserver concordance (Kendall's W = 0.761) compared with H&E (Kendall's W = 0.697). Referring to the same meningioma groups identified by World Health Organization grade as the gold standard, the volume under the receiver operator characteristic surface was 0.91, indicating a very good diagnostic ability of PHH3 scores in discriminating the 3 meningioma groups. The 2 optimal PHH3-specific cutoff values were 6.61 and 22.02. CONCLUSION: PHH3 staining is a useful diagnostic complementary tool to standard H&E mitotic count, optimizing intra- and interobserver reproducibility. PHH3-specific mitotic thresholds should be adopted to avoid overgrading of meningioma when ancillary methods are employed.
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 (R(m) = 0.83) and a good intraclass correlation (0.78), higher than H&E mitotic indices (R(m) = 0.77, intraclass correlation = 0.71). After further stratification of meningiomas according to World Health Organization grade, PHH3 performed better in terms of interobserver concordance (Kendall's W = 0.761) compared with H&E (Kendall's W = 0.697). Referring to the same meningioma groups identified by World Health Organization grade as the gold standard, the volume under the receiver operator characteristic surface was 0.91, indicating a very good diagnostic ability of PHH3 scores in discriminating the 3 meningioma groups. The 2 optimal PHH3-specific cutoff values were 6.61 and 22.02. CONCLUSION:PHH3 staining is a useful diagnostic complementary tool to standard H&E mitotic count, optimizing intra- and interobserver reproducibility. PHH3-specific mitotic thresholds should be adopted to avoid overgrading of meningioma when ancillary methods are employed.
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