ArticleHistopathology2023
Improving mitotic cell counting accuracy and efficiency using phosphohistone-H3 (PHH3) antibody counterstained with haematoxylin and eosin as part of breast cancer grading.
Article in Histopathology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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9 citing papers in PubMed.
- Evaluation of Phosphohistone H3 in Assessment of Mitotic Activity in Invasive Breast Carcinoma: A Correlative Study With Ki-67 and Histologic Grade.International journal of surgical pathology · 2026Article
- Phospho-Histone H3 as a Tool for Improved Mitotic Counting and Risk Assessment in Gastrointestinal Stromal Tumors: A Study of 241 Cases.Medical science monitor : international medical journal of experimental and clinical research · 2026Article
- Cranial neural crest shortage leads to extensive craniofacial anomalies in mice mutant for the NR2F1/2 nuclear receptors.Developmental biology · 2026Article
- From traditional to deep learning approaches in whole slide image registration: A methodological review.Journal of pathology informatics · 2025Review
- Establishment of the Prognostic Signature with Genes Related to G2/M Checkpoint in Hepatocellular Carcinoma.Biochemical genetics · 2025Article
- The 1000 Mitoses Project: A Consensus-Based International Collaborative Study on Mitotic Figures Classification.International journal of surgical pathology · 2024Article
- Information mismatch in PHH3-assisted mitosis annotation leads to interpretation shifts in H&E slide analysis.Scientific reports · 2024Article
- Diagnostic and prognostic assessments of adrenocortical carcinomas by pathological features, immunohistochemical markers and reticular histochemistry staining.Diagnostic pathology · 2024Article
- Breast Cancer Molecular Subtyping in Practice: A Real-World Study of the APIS Breast Cancer Subtyping Assay in a Consecutive Series of Breast Core Biopsies.International journal of molecular sciences · 2024Article
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6 authors.
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Abstract
backgroundMitotic count in breast cancer is an important prognostic marker. Unfortunately, substantial inter- and intraobserver variation exists when pathologists manually count mitotic figures. To alleviate this problem, we developed a new technique incorporating both haematoxylin and eosin (H&E) and phosphorylated histone H3 (PHH3), a marker highly specific to mitotic figures, and compared it to visual scoring of mitotic figures using H&E only.
methodsTwo full-face sections from 97 cases were cut, one stained with H&E only, and the other was stained with PHH3 and counterstained with H&E (PHH3-H&E). Counting mitoses using PHH3-H&E was compared to traditional mitoses scoring using H&E in terms of reproducibility, scoring time, and the ability to detect mitosis hotspots. We assessed the agreement between manual and image analysis-assisted scoring of mitotic figures using H&E and PHH3-H&E-stained cells. The diagnostic performance of PHH3 in detecting mitotic figures in terms of sensitivity and specificity was measured. Finally, PHH3 replaced the mitosis score in a multivariate analysis to assess its significance.
resultsPathologists detected significantly higher mitotic figures using the PHH3-H&E (median ± SD, 20 ± 33) compared with H&E alone (median ± SD, 16 ± 25), P < 0.001. The concordance between pathologists in identifying mitotic figures was highest when using the dual PHH3-H&E technique; in addition, it highlighted mitotic figures at low power, allowing better agreement on choosing the hotspot area (k = 0.842) in comparison with standard H&E (k = 0.625). A better agreement between image analysis-assisted software and the human eye was observed for PHH3-stained mitotic figures. When the mitosis score was replaced with PHH3 in a Cox regression model with other grade components, PHH3 was an independent predictor of survival (hazard ratio [HR] 5.66, 95% confidence interval [CI] 1.92-16.69; P = 0.002), and even showed a more significant association with breast cancer-specific survival (BCSS) than mitosis (HR 3.63, 95% CI 1.49-8.86; P = 0.005) and Ki67 (P = 0.27).
conclusionUsing PHH3-H&E-stained slides can reliably be used in routine scoring of mitotic figures and integrating both techniques will compensate for each other's limitations and improve diagnostic accuracy, quality, and precision.
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