Abstract
According to current World Health Organization (WHO) criteria, counting mitotic figures (MF), which is equal to the mitotic index (MI), on paraffin sections stained with hematoxylin and eosin (HE) is one of the recognized classification methods for meningiomas. However, it is not always easy to find the area of highest mitotic activity, and there are different perspectives among pathologists with regard to differentiating MF from non-MF, i.e., which are apoptotic figures and which are crushed or distorted cells. Moreover, there is an issue of overgrading in meningiomas with preoperative feeder embolization. Recently, anti-phosphohistone-H3 (PHH3) antibody has been reported as a mitosis-specific marker for meningioma grading. In this study, we attempted PHH3 immunostaining for our meningioma cases and verified not only the sensitivity of PHH3 immunostaining but also that of its usefulness in grading meningiomas. Forty-five initial histologically confirmed meningiomas (37 benign, 7 atypical, and 1 anaplastic) were reviewed according to current WHO criteria based on counting MF on HE-stained slides. PHH3-immunostained MF were counted in the same way, and the MIB-1 labeling index (LI) was calculated for each sample. PHH3-labeled MF were easily identified and permitted rapid recognition of the areas of highest mitotic activity. As a result, significant increase of PHH3 mitotic index (PHH3-MI) in comparison with HE mitotic index (HE-MI) and strong correlations with HE-MI to PHH3-MI as well as PHH3-MI to MIB-1 LI were demonstrated. Furthermore, no significant differences of PHH3-MI between cases with and without feeder embolization were demonstrated. As such, PHH3 may be a sensitive and useful marker for meningioma grading as based on the MF.
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Kliehues P, Cavenee WK (2000) Pathology and genetics of tumors of the nervous system. International Agency for Research on Cancer (IARC), Lyon, pp 175–195
Perry A, Chicoine MR, Filiput E, et al (2001) Clinicopathologic assessment and grading of embolized meningiomas. A correlative study of 64 patients. Cancer (Phila) 92:701–711
Ng HK, Poon WS, Goh K, et al (1996) Histopathology of postembolized meningiomas. Am J Surg Pathol 20:1224–1230
Hendzel MJ, Wei Y, Mancini MA (1997) Mitosis specific phosphorylation of histone H3 initiates primarily within pericentromeric heterochromatin during G2 and spreads in an ordered fashion coincident with mitotic chromosome condensation. Chromosoma (Berl) 106:348–360
Shibata K, Inagaki M, Ajiro K (1990) Mitosis-specific histone H3 phosphorylation in vitro in nucleosome structure. Eur J Biochem 192:87–93
Shibata K, Ajiro K (1993) Cell cycle-dependent suppressive effect of histone H1 on mitosis specific H3 phosphorylation. Eur J Biochem 268:18431–18434
Ribalta T, McCutcheon IE, Aldape KD, et al (2004) The mitosis-specific antibody anti-phosphohistone-H3 (PHH3) facilitates rapid reliable grading of meningiomas according to WHO 2000 criteria. Am J Surg Pathol 28:1532–1536
Kim YJ, Ketter R, Steudel WI, et al (2007) Prognostic significance of the mitotic index using the mitosis marker anti-phosphohistone H3 in meningiomas. Am J Clin Pathol 128:118–125
Baehner R, Weidner N (2000) Enhanced mitotic figure counting in breast carcinomas using a mitosis-specific antibody: anti-phosphohistone-H3 (PHH3). Mod Pathol 13:17A
Colman H, Giannini C, Huang L, et al (2006) Assessment and prognostic significance of mitotic index using the mitosis marker phospho-histone H3 in low and intermediate-grade infiltrating astrocytomas. Am J Surg Pathol 30:657–664
Perry A, Scheithauer BW, Stafford SL, et al (1999) “Malignancy” in meningiomas. A clinicopathologic study of 116 patients, with grading implications. Cancer (Phila) 85:2046–2056
Perry A, Gutmann DH, Reifenberger G (2004) Molecular pathogenesis of meningiomas. J Neurooncol 70:183–202
Goto H, Tomono Y, Ajiro K (1999) Identification of novel phosphorylation site on histone H3 coupled with mitotic chromosome condensation. J Biol Chem 274:25543–25549
Hirata A, Inada K, Tsukamoto T (2004) Characterization of a monoclonal antibody, HTA28, recognizing a histone H3 phosphorylation site as a useful marker of M-phase cells. J Histochem Cytochem 52:1503–1509
Gurley LR, D’Anna JA, Barhan SS, et al (1978) Histone phosphorylation and chromatin structure during mitosis in Chinese hamster cells. Eur J Biochem 84:1–15
Juan G, Traganos F, James WM, et al (1998) Histone H3 phosphorylation and expression of cyclones A and B1 measured in individual cells during their progression through G2 and mitosis. Cytometry 32:71–77
Hendzel MJ, Nishioka WK, Raymond Y, et al (1998) Chromatin condensation is not associated with apoptosis. J Biol Chem 273:24470–24478
Kondziolka D, Bernstein M, Resch L, et al (1987) Significance of hemorrhage into brain tumors. Clinicopathological study. J Neurosurg 67:852–857
Perry A, Stafford SL, Scheithauer BW, et al (1998) The prognostic significance of MIB-1, p53, and DNA flow cytometry in completely resected primary meningiomas. Cancer (Phila) 82:2262–2269
Takahashi JA, Ueda T, Hashimoto N, et al (2000) The combination of mitotic and Ki-67 indices as a useful method for predicting short-term recurrence of meningiomas. Surg Neurol 61:149–156
Simpson D (1957) The recurrence of intracranial meningiomas after surgical treatment. J Neurol Neurosurg Psychiatry 20: 22–39
Jaaskelainen J (1986) Seemingly complete removal of histologically benign intracranial meningioma: late recurrence rate and factors predicting recurrence in 657 patients. A multivariate analysis. Surg Neurol 26:461–469
Kuroiwa T, Tanaka H, Ohta T, et al (1996) Preoperative embolization of highly vascular brain tumors: clinical and histopathological findings. Noshuyo Byori 13:27–36
Kai Y, Hamada J, Morioka M, et al (2002) Appropriate interval between embolization and surgery in patients with meningioma. Am J Neuroradiol 23:139–142
Nasr MR, El-Zammar O (2008) Comparison of PHH3, Ki-67, and surviving immunoreactivity in benign and malignant melanocytic lesions. Am J Dermatopathol 30:117–122
Tapia C, Kutzner H, Mentzel T, et al (2006) Two mitosis-specific antibodies, MPM-2 and phospho-histone H3 (Ser28), allow rapid and precise determination of mitotic activity. Am J Surg Pathol 30:83–89
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Fukushima, S., Terasaki, M., Sakata, K. et al. Sensitivity and usefulness of anti-phosphohistone-H3 antibody immunostaining for counting mitotic figures in meningioma cases. Brain Tumor Pathol 26, 51–57 (2009). https://doi.org/10.1007/s10014-009-0249-9
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DOI: https://doi.org/10.1007/s10014-009-0249-9