Evidence map›Paper›PMID 26916072›Full record

ArticleModern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc2016

Digital image analysis outperforms manual biomarker assessment in breast cancer.

Gustav Stålhammar, Nelson Fuentes Martinez, Michael Lippert, Nicholas P Tobin, Ida Mølholm, Lorand Kis, Gustaf Rosin, Mattias Rantalainen, Lars Pedersen, Jonas Bergh and 2 more

Open access · bronzeAbstract read
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In one paragraph

Article in Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 77 papers.

0numbers the graph read from it
0cells of the map it votes in
77citing papers in PubMed
8.0field-weighted citation impact, top 2% of its field
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

77 citing papers in PubMed, 179 citations in OpenAlex.

  1. Article
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  9. Use of AI Histopathology in Breast Cancer Diagnosis.Medicina (Kaunas, Lithuania) · 2025
    Review
  10. Can mutation abundance assess the biological behavior of BRAFJournal of translational medicine · 2025
    Article
  11. Article
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  13. Review
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17 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

12 authors at 4 institutions in 2 countries.

Gustav StålhammarDepartment of Oncology and Pathology, Karolinska Institutet, Stockholm, Sweden.
Nelson Fuentes MartinezDepartment of Oncology and Pathology, Karolinska Institutet, Stockholm, Sweden.
Michael LippertVisiopharm A/S, Hoersholm, Denmark.
Nicholas P TobinCancer Center Karolinska, Stockholm, Sweden.
Ida MølholmVisiopharm A/S, Hoersholm, Denmark.
Lorand KisDepartment of Clinical Pathology, Karolinska University Hospital, Stockholm, Sweden.
Gustaf RosinDepartment of Oncology and Pathology, Karolinska Institutet, Stockholm, Sweden.
Mattias RantalainenDepartment of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
Lars PedersenVisiopharm A/S, Hoersholm, Denmark.
Jonas BerghDepartment of Oncology and Pathology, Karolinska Institutet, Stockholm, Sweden.
Michael GrunkinVisiopharm A/S, Hoersholm, Denmark.
Johan HartmanDepartment of Oncology and Pathology, Karolinska Institutet, Stockholm, Sweden.
Karolinska Institutet · SEKarolinska University Hospital · SEKarolinska Development (Sweden) · SETechnical University of Denmark · DK

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

In the spectrum of breast cancers, categorization according to the four gene expression-based subtypes 'Luminal A,' 'Luminal B,' 'HER2-enriched,' and 'Basal-like' is the method of choice for prognostic and predictive value. As gene expression assays are not yet universally available, routine immunohistochemical stains act as surrogate markers for these subtypes. Thus, congruence of surrogate markers and gene expression tests is of utmost importance. In this study, 3 cohorts of primary breast cancer specimens (total n=436) with up to 28 years of survival data were scored for Ki67, ER, PR, and HER2 status manually and by digital image analysis (DIA). The results were then compared for sensitivity and specificity for the Luminal B subtype, concordance to PAM50 assays in subtype classification and prognostic power. The DIA system used was the Visiopharm Integrator System. DIA outperformed manual scoring in terms of sensitivity and specificity for the Luminal B subtype, widely considered the most challenging distinction in surrogate subclassification, and produced slightly better concordance and Cohen's κ agreement with PAM50 gene expression assays. Manual biomarker scores and DIA essentially matched each other for Cox regression hazard ratios for all-cause mortality. When the Nottingham combined histologic grade (Elston-Ellis) was used as a prognostic surrogate, stronger Spearman's rank-order correlations were produced by DIA. Prognostic value of Ki67 scores in terms of likelihood ratio χ(2) (LR χ(2)) was higher for DIA that also added significantly more prognostic information to the manual scores (LR-Δχ(2)). In conclusion, the system for DIA evaluated here was in most aspects a superior alternative to manual biomarker scoring. It also has the potential to reduce time consumption for pathologists, as many of the steps in the workflow are either automatic or feasible to manage without pathological expertise.

Indexed as

AdultAgedBiomarkers, TumorBreast NeoplasmsFemaleGene Expression ProfilingHumansImage Processing, Computer-AssistedImmunohistochemistryMiddle AgedSensitivity and SpecificityBiomarkers, Tumor

Identifiers

PMID26916072
OpenAlexW2287628440

What OpenQuestion holds

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Registered trials

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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.