Department of Cellular & Molecular Pathology, Northwest London Pathology, Imperial College Healthcare NHS Trust, London, London, UK.
Department of Cellular & Molecular Pathology, Northwest London Pathology, Imperial College Healthcare NHS Trust, London, London, UK
J Clin Pathol. 2021 Oct;74(10):646-649. doi: 10.1136/jclinpath-2020-206956. Epub 2020 Sep 1.
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.
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).
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'.
套细胞淋巴瘤（MCL）具有高度异质性的临床病程，从惰性、侵袭性到快速进展性疾病不等。增殖是疾病预后的强有力预测指标。在常规临床实践中，Ki-67 表达被用作增殖的衡量标准。然而，多项研究记录了 Ki-67 免疫组化检测存在高度的实验室间和观察者间变异。组蛋白 H3 的磷酸化仅在有丝分裂期间发生，因此可作为有丝分裂细胞的特异性标志物。
我们研究了磷酸化组蛋白 H3（PHH3）免疫组化为 28 例 MCL 组织活检中的增殖标志物，并将 PHH3 结果（通过直接显微镜观察和图像分析辅助评分进行评估）与形态学分型、有丝分裂计数和 Ki-67 指数进行比较。我们发现 PHH3-有丝分裂计数比 H&E-有丝分裂计数高约六倍（10 个高倍视野中的有丝分裂数）。此外，侵袭性形态学变异型 MCL 中的 PHH3-有丝分裂计数明显高于普通 MCL。PHH3-有丝分裂计数与 PHH3-有丝分裂指数（阳性细胞百分比）呈强线性相关。
我们在 MCL 中发现了 PHH3 免疫组化，这是一种可靠的有丝分裂特异性标志物。使用 PHH3 免疫组化进行精确计数和评估精确的增殖指数更容易。这与传统的 Ki-67 百分比的“目测”估计形成对比。
