Evidence map›Paper›PMID 27499923›Full record

ArticleThe journal of pathology. Clinical research2016

High-throughput automated scoring of Ki67 in breast cancer tissue microarrays from the Breast Cancer Association Consortium.

Mustapha Abubakar, William J Howat, Frances Daley, Lila Zabaglo, Leigh-Anne McDuffus, Fiona Blows, Penny Coulson, H Raza Ali, Javier Benitez, Roger Milne and 33 more

Abstract read
In one paragraph

Article in The journal of pathology. Clinical research, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.

0numbers the graph read from it
0cells of the map it votes in
12citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

12 citing papers in PubMed.

  1. Article
  2. Review
  3. Article
  4. Article
  5. Combined quantitative measures of ER, PR, HER2, and KI67 provide more prognostic information than categorical combinations in luminal breast cancer.Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc · 2019
    Article
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  7. Article
  8. Article
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

43 authors.

Mustapha AbubakarDivision of Genetics and Epidemiology The Institute of Cancer Research London UK.
William J HowatCancer Research UK Cambridge Institute, University of Cambridge Cambridge UK.
Frances DaleyBreakthrough Breast Cancer Research Centre, Division of Breast Cancer Research, The Institute of Cancer Research London UK.
Lila ZabagloAcademic Department of Biochemistry, Royal Marsden Hospital Fulham Road London.
Leigh-Anne McDuffusCancer Research UK Cambridge Institute, University of Cambridge Cambridge UK.
Fiona BlowsCentre for Cancer Genetic Epidemiology, Department of Oncology, University of Cambridge Cambridge UK.
Penny CoulsonDivision of Genetics and Epidemiology The Institute of Cancer Research London UK.
H Raza AliCancer Research UK Cambridge Institute, University of Cambridge Cambridge UK.
Javier BenitezHuman Genetics Group, Human Cancer Genetics Program, Spanish National Cancer Research Centre (CNIO)MadridSpain; Centro de Investigacion en Red de Enfermedades Raras (CIBERER)ValenciaSpain.
Roger MilneCancer Epidemiology Centre, Cancer Council VictoriaMelbourneAustralia; Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global health, The University of MelbourneMelbourneAustralia.
Herman BrennerDivision of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ)HeidelbergGermany; Division of Preventive Oncology, German Cancer Research Center (DKFZ), and National Center for Tumor Diseases (NCT)HeidelbergGermany; German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ)HeidelbergGermany.
Christa StegmaierSaarland Cancer Registry Saarland Germany.
Arto MannermaaSchool of Medicine, Institute of Clinical Medicine, Pathology and Forensic Medicine, Cancer Center of Eastern Finland, University of Eastern FinlandKuopioFinland; Imaging Center, Department of Clinical Pathology, Kuopio University HospitalKuopioFinland.
Jenny Chang-ClaudeDivision of Cancer Epidemiology, German Cancer Research Center (DKFZ)HeidelbergGermany; University Cancer Center Hamburg (UCCH), University Medical Center Hamburg-EppendorfHamburgGermany.
Anja RudolphDivision of Cancer Epidemiology, German Cancer Research Center (DKFZ) Heidelberg Germany.
Peter SinnDepartment of Pathology Institute of Pathology, Heidelberg University Hospital Germany.
Fergus J CouchDepartment of Laboratory Medicine and Pathology Mayo Clinic Rochester, MN USA.
Rob A E M TollenaarDepartment of Surgery Leiden University Medical Center The Netherlands.
Peter DevileeDepartment of Human Genetics & Department of Pathology Leiden University Medical Center Leiden The Netherlands.
Jonine FigueroaUsher Institute of Population Health Sciences and Informatics, The University of Edinburgh Scotland UK.
Mark E ShermanDivision of Cancer Epidemiology and Genetics National Cancer Institute Rockville Maryland USA.
Jolanta LissowskaDepartment of Cancer Epidemiology and Prevention M. Sklodowska-Curie Memorial Cancer Center and Institute of Oncology Warsaw Poland.
Stephen HewittLaboratory of Pathology National Cancer Institute, National Institutes of Health Rockville MD USA.
Diana EcclesFaculty of Medicine Academic Unit of Cancer Sciences Southampton General Hospital Southampton UK.
Maartje J HooningFamily Cancer Clinic, Department of Medical Oncology, Erasmus MC Cancer Institute Rotterdam The Netherlands.
Antoinette HollestelleFamily Cancer Clinic, Department of Medical Oncology, Erasmus MC Cancer Institute Rotterdam The Netherlands.
John Wm MartensFamily Cancer Clinic, Department of Medical Oncology, Erasmus MC Cancer Institute Rotterdam The Netherlands.
Carolien Hm van DeurzenDepartment of Pathology Erasmus MC Cancer Institute Rotterdam The Netherlands.
kConFab InvestigatorsDepartment of Genetics QIMR Berghofer Medical Research Institute Brisbane Australia.
Manjeet K BollaCentre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge Cambridge UK.
Qin WangCentre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge Cambridge UK.
Michael JonesDivision of Genetics and Epidemiology The Institute of Cancer Research London UK.
Minouk SchoemakerDivision of Genetics and Epidemiology The Institute of Cancer Research London UK.
Annegien BroeksDivision of Molecular Pathology Netherlands Cancer Institute, Antoni van Leeuwenhoek Hospital Amsterdam The Netherlands.
Flora E van LeeuwenDivision of Psychosocial Research and Epidemiology Netherlands Cancer Institute, Antoni van Leeuwenhoek Hospital Amsterdam The Netherlands.
Laura Van't VeerDivision of Molecular Pathology Netherlands Cancer Institute, Antoni van Leeuwenhoek Hospital Amsterdam The Netherlands.
Anthony J SwerdlowDivision of Genetics and EpidemiologyThe Institute of Cancer ResearchLondonUK; Division of Breast Cancer ResearchThe Institute of Cancer ResearchLondonUK.
Nick OrrBreakthrough Breast Cancer Research Centre, Division of Breast Cancer Research, The Institute of Cancer Research London UK.
Mitch DowsettBreakthrough Breast Cancer Research Centre, Division of Breast Cancer Research, The Institute of Cancer ResearchLondonUK; Academic Department of Biochemistry, Royal Marsden HospitalFulham RoadLondon.
Douglas EastonCentre for Cancer Genetic Epidemiology, Department of Oncology, University of CambridgeCambridgeUK; Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of CambridgeCambridgeUK.
Marjanka K SchmidtDivision of Molecular PathologyNetherlands Cancer Institute, Antoni van Leeuwenhoek HospitalAmsterdamThe Netherlands; Division of Psychosocial Research and EpidemiologyNetherlands Cancer Institute, Antoni van Leeuwenhoek HospitalAmsterdamThe Netherlands.
Paul D PharoahCentre for Cancer Genetic Epidemiology, Department of Oncology, University of CambridgeCambridgeUK; Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of CambridgeCambridgeUK.
Montserrat Garcia-ClosasDivision of Cancer Epidemiology and Genetics National Cancer Institute Rockville Maryland USA.

Funding

Hormone-Related CancersZIACP010126 · NCI · DIVISION OF CANCER EPIDEMIOLOGY AND GENETICS · PI GIERACH, GRETCHEN · 2009 to 2025
$103.5M
The Role of CHFR in Tumorigenesis and Paclitaxel-Sensitivity in Breast CancerP50CA116201 · NCI · MAYO CLINIC ROCHESTER · PI PETER C LUCAS · 2005 to 2026
$49.9M
Cancer Research UK 10119Cancer Research UK 10124Cancer Research UK 16561NCI NIH HHS P50 CA116201
6 · The paper itself

Abstract

Automated methods are needed to facilitate high-throughput and reproducible scoring of Ki67 and other markers in breast cancer tissue microarrays (TMAs) in large-scale studies. To address this need, we developed an automated protocol for Ki67 scoring and evaluated its performance in studies from the Breast Cancer Association Consortium. We utilized 166 TMAs containing 16,953 tumour cores representing 9,059 breast cancer cases, from 13 studies, with information on other clinical and pathological characteristics. TMAs were stained for Ki67 using standard immunohistochemical procedures, and scanned and digitized using the Ariol system. An automated algorithm was developed for the scoring of Ki67, and scores were compared to computer assisted visual (CAV) scores in a subset of 15 TMAs in a training set. We also assessed the correlation between automated Ki67 scores and other clinical and pathological characteristics. Overall, we observed good discriminatory accuracy (AUC = 85%) and good agreement (kappa = 0.64) between the automated and CAV scoring methods in the training set. The performance of the automated method varied by TMA (kappa range= 0.37-0.87) and study (kappa range = 0.39-0.69). The automated method performed better in satisfactory cores (kappa = 0.68) than suboptimal (kappa = 0.51) cores (p-value for comparison = 0.005); and among cores with higher total nuclei counted by the machine (4,000-4,500 cells: kappa = 0.78) than those with lower counts (50-500 cells: kappa = 0.41; p-value = 0.010). Among the 9,059 cases in this study, the correlations between automated Ki67 and clinical and pathological characteristics were found to be in the expected directions. Our findings indicate that automated scoring of Ki67 can be an efficient method to obtain good quality data across large numbers of TMAs from multicentre studies. However, robust algorithm development and rigorous pre- and post-analytical quality control procedures are necessary in order to ensure satisfactory performance.

Indexed as

automated algorithmbreast cancerimmunohistochemistryKi67tissue microarrays

Identifiers

PMID27499923
PMCPMC4958735

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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.