====== Histone H3 ======

Histone H3 Lysine 27 ([[H3K27]]): [[Histone H3]] is a protein involved in packaging [[DNA]] in the cell nucleus. [[H3K27]] refers to a specific amino acid, lysine, at position 27 on the histone H3 protein. Modifications to H3K27 play a crucial role in the epigenetic regulation of gene expression.

[[Histone H3]] is a nuclear core [[histone]] protein of [[DNA]] [[chromatin]], with an important role in [[chromosome]] condensation and [[cell cycle]] [[progression]] during [[mitosis]] and [[meiosis]] after [[phosphorylation]] of serine-10 and serine-28 residues. Phosphorylation occurs during late [[G2]] to early prophase, while dephosphorylation occurs slowly from late anaphase to early telophase. Therefore in metaphase, histone H3 is always heavily phosphorylated and positive for PHH3, whereas interphase does not or minimally express PHH3 – a property that allows PHH3 to stain only mitotically active cells, therefore proliferation-specific.

PHH3 has been verified in multiple studies concerning various tumors (colorectal adenocarcinoma, ovarian serous adenocarcinoma, pulmonary neuroendocrine carcinoma, uterine smooth muscle tumors, astrocytomas, and meningiomas), for its sensitive and specific role as a marker of mitotic figures (MFs) and excellent correlation with outcome 

[[Histone H3 phosphorylation]] on serine-10 is specific to mitosis and phosphorylated histone H3 (PHH3) proliferation markers (as counts defined per area or as indices defined per cell numbers) are increasingly being used to evaluate proliferation in various tumors.
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Medical [[record]]s were [[retrospective]]ly reviewed for all [[intracranial meningioma]] cases which diagnosed and underwent [[surgery]] at Bezmialem Vakif University Hospital between 2012 and 2017. All [[World health organization grade 1 meningioma]] and [[World health organization grade 2 meningioma]] patients constituted the core sample for this study.

This series included 104 (69 female, 35 male) patients, with a median age of 57.3 years. The mean preoperative course was 23.0 ± 40.5 months. The most common [[symptom]] was [[headache]] (76%) and followed by [[seizure]] (24%), [[weakness]] (18%) and [[visual disturbance]]s (14%). Seventy one (68.2%) patients were diagnosed as WHO grade I [[meningioma]] and 33 (31.8%) were WHO grade II, [[World health organization grade 3 meningioma]]s were excluded from study due to small number of patients. Subtypes of [[meningioma]] includes 5 [[angiomatous meningioma]] (4,8%), 6 [[fibroblastic meningioma]] (5.7%), 1 [[meningothelial meningioma]] (0,9%), 11 [[psammomatous meningioma]] (10,5%), 3 [[secretory meningioma]] (2,8%), 43 [[transitional meningioma]] (41,3%) and 33 [[atypical meningioma]]s (31,7%). There is a strong correlation with [[Phosphohistone H3]] (PHH-3) and [[Ki-67]] (p:0,001>) and mitosis index (p:0,001 > ) although there is no correlation with [[STAT3]] (p:0,260). There is a strong correlation with STAT-3 and Ki-67 (p:0,013), although there is no correlation with mitosis index (p:0,085) and PHH-3 (p:0,260).

In the study they also obtain same results with Ki-67 and mitotic index, although correlation with PHH-3 and STAT-3 is firstly determined and there was no statistically significant relation were observed. Depends on the STAT-3 cell proliferation feature, inactivation of these pathways may predict new chemotherapies for grade II meningiomas
((Ozek E, Akdag H, Tosuner Z, Abdallah A, Hatiboglu MA. The correlation between 
phosphorylated Histone H3 (PHH3) and p-STAT3 in Meningiomas. Clin Neurol
Neurosurg. 2019 Jan 25;178:46-50. doi: 10.1016/j.clineuro.2019.01.016. [Epub
ahead of print] PubMed PMID: 30710729.
)).
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Elmaci et al. from the Department of Neurosurgery, Memorial Hospital, Sisli, [[Istanbul]], Turkey, review data on PHH3 proliferation markers in meningeal tumors. PHH3-staining highlights mitotic cells and makes easier of rapid grading by driving pathologist's attention on the most mitotically active areas. Thereby, it would function more sensitive in detecting MFs that might be otherwise overloked and more precise by reducing interobserver variability through allowing the pathologist to analyze if the stained nuclei exhibit morphologic features of mitosis
((Elmaci İ, Altinoz MA, Sari R, Bolukbasi FH. Phosphorylated Histone H3 (PHH3)
as a Novel Cell Proliferation Marker and Prognosticator for Meningeal Tumors: A
Short Review. Appl Immunohistochem Mol Morphol. 2017 Aug 2. doi:
10.1097/PAI.0000000000000499. [Epub ahead of print] PubMed PMID: 28777144.
)).

===== References =====