Evidence map›Paper›PMID 39104219›Full record

ArticleHistopathology2025

Advancing Ki67 hotspot detection in breast cancer: a comparative analysis of automated digital image analysis algorithms.

Mieke C Zwager, Shibo Yu, Henk J Buikema, Geertruida H de Bock, Thomas W Ramsing, Jeppe Thagaard, Timco Koopman, Bert van der Vegt

Abstract readComparative Study
In one paragraph

Article in Histopathology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing 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

7 citing papers in PubMed.

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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

8 authors.

Mieke C ZwagerDepartment of Pathology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.ORCID https://orcid.org/0000-0002-4470-7628
Shibo YuDepartment of Pathology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.ORCID https://orcid.org/0000-0001-5646-5710
Henk J BuikemaDepartment of Pathology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.ORCID https://orcid.org/0009-0007-3234-4595
Geertruida H de BockDepartment of Epidemiology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.ORCID https://orcid.org/0000-0003-3104-4471
Thomas W RamsingVisiopharm, Hørsholm, Denmark.
Jeppe ThagaardVisiopharm, Hørsholm, Denmark.ORCID https://orcid.org/0000-0003-0201-2243
Timco KoopmanDepartment of Pathology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.ORCID https://orcid.org/0000-0001-5695-0126
Bert van der VegtDepartment of Pathology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.ORCID https://orcid.org/0000-0002-2613-1506

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

aimManual detection and scoring of Ki67 hotspots is difficult and prone to variability, limiting its clinical utility. Automated hotspot detection and scoring by digital image analysis (DIA) could improve the assessment of the Ki67 hotspot proliferation index (PI). This study compared the clinical performance of Ki67 hotspot detection and scoring DIA algorithms based on virtual dual staining (VDS) and deep learning (DL) with manual Ki67 hotspot PI assessment.

methodsTissue sections of 135 consecutive invasive breast carcinomas were immunohistochemically stained for Ki67. Two DIA algorithms, based on VDS and DL, automatically determined the Ki67 hotspot PI. For manual assessment; two independent observers detected hotspots and calculated scores using a validated scoring protocol.

resultsAutomated hotspot detection and assessment by VDS and DL could be performed in 73% and 100% of the cases, respectively. Automated hotspot detection by VDS and DL led to higher Ki67 hotspot PIs (mean 39.6% and 38.3%, respectively) compared to manual consensus Ki67 PIs (mean 28.8%). Comparing manual consensus Ki67 PIs with VDS Ki67 PIs revealed substantial correlation (r = 0.90), while manual consensus versus DL Ki67 PIs demonstrated high correlation (r = 0.95).

conclusionAutomated Ki67 hotspot detection and analysis correlated strongly with manual Ki67 assessment and provided higher PIs compared to manual assessment. The DL-based algorithm outperformed the VDS-based algorithm in clinical applicability, because it did not depend on virtual alignment of slides and correlated stronger with manual scores. Use of a DL-based algorithm may allow clearer Ki67 PI cutoff values, thereby improving the clinical usability of Ki67.

Indexed as

AlgorithmsBreast NeoplasmsKi-67 AntigenBiomarkers, TumorDeep LearningFemaleHumansImage Processing, Computer-AssistedImmunohistochemistryBiomarkers, TumorKi-67 Antigenartificial intelligence (AI)breast cancerdigital image analysis (DIA)hotspotKi67 proliferation index

Identifiers

PMID39104219
PMCPMC11649514

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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.