ArticleVirchows Archiv : an international journal of pathology2016
Bimodality of intratumor Ki67 expression is an independent prognostic factor of overall survival in patients with invasive breast carcinoma.
Article in Virchows Archiv : an international journal of pathology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 37 citations in OpenAlex.
- Automated Image Analysis of HER2 Fluorescence In Situ Hybridization to Refine Definitions of Genetic Heterogeneity in Breast Cancer Tissue.BioMed research international · 2017Trial
- Integrated local and global Ki67 profiling for prognostic stratification and therapeutic guidance in high-grade neuroendocrine neoplasms: a multicenter validation study.International journal of surgery (London, England) · 2025Article
- Outcome prediction of oestrogen receptor-positive breast cancer based on a panel of oestrogen receptor-regulated genes.Histopathology · 2025Article
- Reproducibility of Ki67 Haralick entropy as a prognostic marker in estrogen receptor-positive HER2-negative breast cancer.American journal of clinical pathology · 2025Article
- Double-Multiplex Immunostainings for Immune Profiling of Invasive Breast Carcinoma: Emerging Novel Immune-Based Biomarkers.International journal of molecular sciences · 2025Review
- Intratumoral heterogeneity of Ki67 proliferation index outperforms conventional immunohistochemistry prognostic factors in estrogen receptor-positive HER2-negative breast cancer.Virchows Archiv : an international journal of pathology · 2025Article
- Advancing Ki67 hotspot detection in breast cancer: a comparative analysis of automated digital image analysis algorithms.Histopathology · 2025Article
- Characterization of Breast Cancer Intra-Tumor Heterogeneity Using Artificial Intelligence.Cancers · 2024Article
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- The state of the art for artificial intelligence in lung digital pathology.The Journal of pathology · 2022Review
- Artificial intelligence applied to breast pathology.Virchows Archiv : an international journal of pathology · 2022Review
- Clinical implication of low estrogen receptor (ER-low) expression in breast cancer.Frontiers in endocrinology · 2022Review
- Clinical validity and clinical utility of Ki67 in early breast cancer.Therapeutic advances in medical oncology · 2022Review
- How the variability between computer-assisted analysis procedures evaluating immune markers can influence patients' outcome prediction.Histochemistry and cell biology · 2021Article
- Machine-Learning-Based Evaluation of Intratumoral Heterogeneity and Tumor-Stroma Interface for Clinical Guidance.The American journal of pathology · 2021Review
- Intratumoral Heterogeneity and Immune Response Indicators to Predict Overall Survival in a Retrospective Study of HER2-Borderline (IHC 2+) Breast Cancer Patients.Frontiers in oncology · 2021Article
- Spatial transcriptomics inferred from pathology whole-slide images links tumor heterogeneity to survival in breast and lung cancer.Scientific reports · 2020Article
- Factors influencing agreement of breast cancer luminal molecular subtype by Ki67 labeling index between core needle biopsy and surgical resection specimens.Virchows Archiv : an international journal of pathology · 2020Article
- Independent Prognostic Value of Intratumoral Heterogeneity and Immune Response Features by Automated Digital Immunohistochemistry Analysis in Early Hormone Receptor-Positive Breast Carcinoma.Frontiers in oncology · 2020Article
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Authors and funding
14 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Proliferative activity, assessed by Ki67 immunohistochemistry (IHC), is an established prognostic and predictive biomarker of breast cancer (BC). However, it remains under-utilized due to lack of standardized robust measurement methodologies and significant intratumor heterogeneity of expression. A recently proposed methodology for IHC biomarker assessment in whole slide images (WSI), based on systematic subsampling of tissue information extracted by digital image analysis (DIA) into hexagonal tiling arrays, enables computation of a comprehensive set of Ki67 indicators, including intratumor variability. In this study, the tiling methodology was applied to assess Ki67 expression in WSI of 152 surgically removed Ki67-stained (on full-face sections) BC specimens and to test which, if any, Ki67 indicators can predict overall survival (OS). Visual Ki67 IHC estimates and conventional clinico-pathologic parameters were also included in the study. Analysis revealed linearly independent intrinsic factors of the Ki67 IHC variance: proliferation (level of expression), disordered texture (entropy), tumor size and Nottingham Prognostic Index, bimodality, and correlation. All visual and DIA-generated indicators of the level of Ki67 expression provided significant cutoff values as single predictors of OS. However, only bimodality indicators (Ashman's D, in particular) were independent predictors of OS in the context of hormone receptor and HER2 status. From this, we conclude that spatial heterogeneity of proliferative tumor activity, measured by DIA of Ki67 IHC expression and analyzed by the hexagonal tiling approach, can serve as an independent prognostic indicator of OS in BC patients that outperforms the prognostic power of the level of proliferative activity.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.