{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T13:50:33Z","timestamp":1791899433706,"version":"4.3.4"},"reference-count":25,"publisher":"BMJ","issue":"10","funder":[{"DOI":"10.13039\/501100013342","name":"NIHR Imperial Biomedical Research Centre","doi-asserted-by":"publisher","award":["RDF01"],"award-info":[{"award-number":["RDF01"]}],"id":[{"id":"10.13039\/501100013342","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["J Clin Pathol"],"accepted":{"date-parts":[[2020,8,6]]},"published-print":{"date-parts":[[2021,10]]},"abstract":"<jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>Mantle cell lymphoma (MCL) has a highly heterogeneous clinical course ranging from indolent, to aggressive and rapidly progressive disease. Proliferation is a strong predictor for disease outcome. In routine clinical practice, Ki-67 expression is used as a measure of proliferation. However, several studies have documented a high degree of inter-laboratory and inter-observer variation with Ki-67 immunohistochemistry. Phosphorylation of histone H3 occurs specifically during mitosis and hence serves as a specific marker for cells in mitosis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and results<\/jats:title>\n                    <jats:p>We investigated phosphohistone\nH3 (PHH3) immunohistochemistry as a proliferation maker in 28 tissue biopsies of MCL and compared the PHH3 results (as evaluated by direct microscopic visualisation and image analysis-aided scoring) with morphological subtyping, mitotic counts and Ki-67 index. We found PHH3-mitotic count was about sixfold higher than H&amp;E-mitotic count (mitoses in 10 high power fields). Furthermore, PHH3-mitotic count in aggressive morphological variants of MCL was significantly higher than in usual MCL. The PHH3-mitotic count showed a strong linear correlation with PHH3-mitotic index (percentage positive cells).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>We found PHH3 immunohistochemistry, a reliable mitosis-specific marker, in MCL. Performing precise counts and evaluating precise proliferation indices is easier with PHH3 immunohistochemistry. This contrasts with the conventional estimation of Ki-67 percentages by \u2018eye-balling\u2019.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/jclinpath-2020-206956","type":"journal-article","created":{"date-parts":[[2020,9,1]],"date-time":"2020-09-01T17:21:36Z","timestamp":1598980896000},"page":"646-649","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":6,"title":["Improving precise counting of mitotic cells in mantle cell lymphoma using phosphohistone H3 (PHH3) antibody"],"prefix":"10.1136","volume":"74","author":[{"given":"Hanine","family":"Medani","sequence":"first","affiliation":[{"name":"Department of Cellular & Molecular Pathology, Northwest London Pathology, Imperial College Healthcare NHS Trust, London, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohamed","family":"Elshiekh","sequence":"additional","affiliation":[{"name":"Department of Cellular & Molecular Pathology, Northwest London Pathology, Imperial College Healthcare NHS Trust, London, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3807-3638","authenticated-orcid":false,"given":"Kikkeri N","family":"Naresh","sequence":"additional","affiliation":[{"name":"Department of Cellular & Molecular Pathology, Northwest London Pathology, Imperial College Healthcare NHS Trust, London, London, UK"},{"name":"Centre for Haematology, Department of Immunology & Inflammation, Imperial College London, London, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[2020,9,1]]},"reference":[{"key":"2025112108115800000_74.10.646.1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2015.63.5904"},{"key":"2025112108115800000_74.10.646.2","doi-asserted-by":"publisher","DOI":"10.1016\/S1535-6108(03)00028-X"},{"key":"2025112108115800000_74.10.646.3","doi-asserted-by":"crossref","first-page":"1668","DOI":"10.1200\/JCO.2016.70.7901","article-title":"New molecular assay for the proliferation signature in mantle cell lymphoma applicable to formalin-fixed paraffin-embedded biopsies","volume":"35","author":"Scott","year":"2017","journal-title":"J Clin Oncol"},{"key":"2025112108115800000_74.10.646.4","unstructured":"Swerdlow SH , Campo E , Seto M , et al . Mantle cell lymphoma. In: Swerdlow S , Campo E , Harris NL , et al , eds. WHO classification of tumours of haematopoietic and lymphoid tissues. 4th edn. Lyon: IARC, 2017."},{"key":"2025112108115800000_74.10.646.5","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2015.63.8387"},{"key":"2025112108115800000_74.10.646.6","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2006.09.4490"},{"key":"2025112108115800000_74.10.646.7","doi-asserted-by":"publisher","DOI":"10.1139\/O09-053"},{"key":"2025112108115800000_74.10.646.8","doi-asserted-by":"publisher","DOI":"10.1016\/j.biochi.2012.04.018"},{"key":"2025112108115800000_74.10.646.9","doi-asserted-by":"crossref","first-page":"542","DOI":"10.1093\/ajcp\/aqz003","article-title":"The Utility of Phosphohistone H3 (PHH3) in Follicular Lymphoma Grading: A Comparative Study With Ki-67 and H&E Mitotic Count","volume":"151","author":"Khieu","year":"2019","journal-title":"Am J Clin Pathol"},{"key":"2025112108115800000_74.10.646.10","doi-asserted-by":"crossref","first-page":"579","DOI":"10.1097\/PAI.0000000000000481","article-title":"Mitotic index determined by phosphohistone H3 immunohistochemistry for precise grading in follicular lymphoma","volume":"26","author":"Bedekovics","year":"2018","journal-title":"Appl Immunohistochem Mol Morphol"},{"key":"2025112108115800000_74.10.646.11","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.2019"},{"key":"2025112108115800000_74.10.646.12","doi-asserted-by":"publisher","DOI":"10.1309\/AJCPAPH28VHZEKNQ"},{"key":"2025112108115800000_74.10.646.13","doi-asserted-by":"publisher","DOI":"10.1038\/bjc.2012.198"},{"key":"2025112108115800000_74.10.646.14","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1007\/s10549-019-05396-5","article-title":"Evaluation of phospho-histone H3 in Asian triple-negative breast cancer using multiplex immunofluorescence","volume":"178","author":"Lai","year":"2019","journal-title":"Breast Cancer Res Treat"},{"key":"2025112108115800000_74.10.646.15","doi-asserted-by":"publisher","DOI":"10.1097\/PAT.0000000000000248"},{"key":"2025112108115800000_74.10.646.16","doi-asserted-by":"crossref","DOI":"10.1016\/j.prp.2019.152753","article-title":"Potential pitfalls in diagnostic digital image analysis: experience with Ki-67 and PHH3 in gastrointestinal neuroendocrine tumors","volume":"216","author":"Hacking","year":"2020","journal-title":"Pathol Res Pract"},{"key":"2025112108115800000_74.10.646.17","doi-asserted-by":"publisher","DOI":"10.1097\/01.pas.0000202048.28203.25"},{"key":"2025112108115800000_74.10.646.18","doi-asserted-by":"publisher","DOI":"10.1097\/01.pas.0000141389.06925.d5"},{"key":"2025112108115800000_74.10.646.19","doi-asserted-by":"publisher","DOI":"10.1097\/DAD.0b013e31823135a3"},{"key":"2025112108115800000_74.10.646.20","doi-asserted-by":"publisher","DOI":"10.1007\/s00412-018-0659-8"},{"key":"2025112108115800000_74.10.646.21","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2018.06.110"},{"key":"2025112108115800000_74.10.646.22","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1038\/bjc.1987.41","article-title":"Mitotic activity in non-Hodgkin's lymphoma. Relation to the Kiel classification and to prognosis","volume":"55","author":"Akerman","year":"1987","journal-title":"Br J Cancer"},{"key":"2025112108115800000_74.10.646.23","doi-asserted-by":"publisher","DOI":"10.1016\/0277-5379(90)90216-G"},{"key":"2025112108115800000_74.10.646.24","first-page":"63","article-title":"Differential diagnosis between T-cell lymphoma and Hodgkin's disease: the value of mitotic counts and pericapsular infiltration","volume":"3","author":"Nguyen","year":"1989","journal-title":"Hematol Pathol"},{"key":"2025112108115800000_74.10.646.25","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2141.2005.05716.x"}],"container-title":["Journal of Clinical Pathology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1136\/jclinpath-2020-206956","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,11,21]],"date-time":"2025-11-21T16:12:11Z","timestamp":1763741531000},"score":1,"resource":{"primary":{"URL":"https:\/\/jcp.bmj.com\/lookup\/doi\/10.1136\/jclinpath-2020-206956"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,9,1]]},"references-count":25,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2021,9,20]]},"published-print":{"date-parts":[[2021,10]]}},"alternative-id":["10.1136\/jclinpath-2020-206956"],"URL":"https:\/\/doi.org\/10.1136\/jclinpath-2020-206956","relation":{},"ISSN":["0021-9746","1472-4146"],"issn-type":[{"value":"0021-9746","type":"print"},{"value":"1472-4146","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,9,1]]}}}