Evidence map›Paper›PMID 30181553›Full record

ArticleLaboratory investigation; a journal of technical methods and pathology2019

Ki67 reproducibility using digital image analysis: an inter-platform and inter-operator study.

Balazs Acs, Vasiliki Pelekanou, Yalai Bai, Sandra Martinez-Morilla, Maria Toki, Samuel C Y Leung, Torsten O Nielsen, David L Rimm

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In one paragraph

Article in Laboratory investigation; a journal of technical methods and pathology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 70 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
70citing papers in PubMed, 2 pooled it
–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

70 citing papers in PubMed, 2 syntheses or guidelines pooled it.

  1. Guideline
  2. Pooled it
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  11. Comparison of QuPath and HALO Platforms for Analysis of the Tumor Microenvironment in Prostate Cancer.Laboratory investigation; a journal of technical methods and pathology · 2025
    Article
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  14. Digital pathology in tau research: A comparison of QuPath and HALO.Journal of neuropathology and experimental neurology · 2025
    Article
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  19. Biomarkers in breast cancer 2024: an updated consensus statement by the Spanish Society of Medical Oncology and the Spanish Society of Pathology.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2024
    Article
  20. Article

10 more citing papers are in PubMed but not listed here.

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

8 authors.

Balazs AcsDepartment of Pathology, Yale School of Medicine, New Haven, CT, USA.ORCID http://orcid.org/0000-0002-0972-4633
Vasiliki PelekanouDepartment of Pathology, Yale School of Medicine, New Haven, CT, USA.
Yalai BaiDepartment of Pathology, Yale School of Medicine, New Haven, CT, USA.
Sandra Martinez-MorillaDepartment of Pathology, Yale School of Medicine, New Haven, CT, USA.
Maria TokiDepartment of Pathology, Yale School of Medicine, New Haven, CT, USA.
Samuel C Y LeungDepartment of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC, Canada.
Torsten O NielsenDepartment of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC, Canada.
David L RimmDepartment of Pathology, Yale School of Medicine, New Haven, CT, USA. david.rimm@yale.edu.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Ki67 expression has been a valuable prognostic variable in breast cancer, but has not seen broad adoption due to lack of standardization between institutions. Automation could represent a solution. Here we investigate the reproducibility of Ki67 measurement between three image analysis platforms with supervised classifiers performed by the same operator, by multiple operators, and finally we compare their accuracy in prognostic potential. Two breast cancer patient cohorts were used for this study. The standardization was done with the 30 cases of ER+ breast cancer that were used in phase 3 of International Ki67 in Breast Cancer Working Group initiatives where blocks were centrally cut and stained for Ki67. The outcome cohort was from 149 breast cancer cases from the Yale Pathology archives. A tissue microarray was built from representative tissue blocks with median follow-up of 120 months. The Mib-1 antibody (Dako) was used to detect Ki67 (dilution 1:100). HALO (IndicaLab), QuantCenter (3DHistech), and QuPath (open source software) digital image analysis (DIA) platforms were used to evaluate Ki67 expression. Intraclass correlation coefficient (ICC) was used to measure reproducibility. Between-DIA platform reproducibility was excellent (ICC: 0.933, CI: 0.879-0.966). Excellent reproducibility was found between all DIA platforms and the reference standard Ki67 values of Spectrum Webscope (QuPath-Spectrum Webscope ICC: 0.970, CI: 0.936-0.986; HALO-Spectrum Webscope ICC: 0.968, CI: 0.933-0.985; QuantCenter-Spectrum Webscope ICC: 0.964, CI: 0.919-0.983). All platforms showed excellent intra-DIA reproducibility (QuPath ICC: 0.992, CI: 0.986-0.996; HALO ICC: 0.972, CI: 0.924-0.988; QuantCenter ICC: 0.978, CI: 0.932-0.991). Comparing each DIA against outcome, the hazard ratios were similar. The inter-operator reproducibility was particularly high (ICC: 0.962-0.995). Our results showed outstanding reproducibility both within and between-DIA platforms, including one freely available DIA platform (QuPath). We also found the platforms essentially indistinguishable with respect to prediction of breast cancer patient outcome. Results justify multi-institutional DIA studies to assess clinical utility.

Indexed as

Image Processing, Computer-AssistedAdultAgedAged, 80 and overBreast NeoplasmsCohort StudiesHumansKi-67 AntigenMiddle AgedObserver VariationReproducibility of ResultsKi-67 AntigenMKI67 protein, human

Identifiers

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

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.