Journal
JOURNAL OF CLINICAL PATHOLOGY
Volume 74, Issue 10, Pages 646-649Publisher
BMJ PUBLISHING GROUP
DOI: 10.1136/jclinpath-2020-206956
Keywords
cell proliferation; lymphoma; immunohistochemistry; image processing; computer-assisted
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Funding
- National Institute for Health Research Imperial Biomedical Research Centre [RDF01]
- Pathological Society of Great Britain and Ireland
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PHH3 immunohistochemistry is found to be a reliable mitosis-specific marker in MCL, making it easier to perform precise counts and evaluate proliferation indices compared to traditional Ki-67 estimation.
Aims 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. Methods and results We investigated phosphohistone H3 (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&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). Conclusions 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 'eye-balling'.
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