Evidence map›Paper›PMID 41374998›Full record

ArticleCancers2025

Tissue Microarray-Based Digital Spatial Profiling of Benign Breast Lobules and Breast Cancers: Feasibility, Biological Coherence, and Cross-Platform Benchmarks.

Mark E Sherman, Jodi C Carter, Robert A Vierkant, Melody Stallings-Mann, Laura Pacheco-Spann, Stacey J Winham, Celine M Vachon, Chen Wang, Matthew R Jensen, Melissa A Troester and 5 more

Abstract read
In one paragraph

Article in Cancers, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
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0citing papers in PubMed
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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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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

15 authors.

Mark E ShermanQuantitative Health Sciences, Mayo Clinic Alix School of Medicine and Health Sciences, Jacksonville, FL 32225, USA.
Jodi C CarterDepartment of Laboratory Medicine and Pathology, University of Alberta, 114 Street and 89 Avenue, Edmonton, AB T6G 2M7, Canada.
Robert A VierkantQuantitative Health Sciences, Mayo Clinic Alix School of Medicine and Health Sciences, Rochester, MN 55905, USA.ORCID 0000-0001-6242-5221
Melody Stallings-MannCancer Biology, Mayo Clinic, Jacksonville, FL 32225, USA.
Laura Pacheco-SpannQuantitative Health Sciences, Mayo Clinic Alix School of Medicine and Health Sciences, Jacksonville, FL 32225, USA.ORCID 0000-0002-6531-8840
Stacey J WinhamQuantitative Health Sciences, Mayo Clinic Alix School of Medicine and Health Sciences, Rochester, MN 55905, USA.
Celine M VachonDivision of Epidemiology, Mayo Clinic Alix School of Medicine and Health Sciences, Rochester, MN 55905, USA.
Chen WangQuantitative Health Sciences, Mayo Clinic Alix School of Medicine and Health Sciences, Rochester, MN 55905, USA.
Matthew R JensenQuantitative Health Sciences, Mayo Clinic Alix School of Medicine and Health Sciences, Rochester, MN 55905, USA.
Melissa A TroesterLineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
Amy C DegnimDepartment of Surgery, Mayo Clinic Alix School of Medicine and Health Sciences, Rochester, MN 55905, USA.
E Aubrey ThompsonCancer Biology, Mayo Clinic, Jacksonville, FL 32225, USA.
Jennifer KachergusCancer Biology, Mayo Clinic, Jacksonville, FL 32225, USA.
Ji ShiCancer Biology, Mayo Clinic, Jacksonville, FL 32225, USA.ORCID 0009-0001-9696-8627
Derek C RadiskyCancer Biology, Mayo Clinic, Jacksonville, FL 32225, USA.ORCID 0000-0002-1962-8784

Funding

NCI NIH HHS CA15083NCI NIH HHS CA234827
6 · The paper itself

Abstract

backgroundDiscovering risk biomarkers in small benign breast disease (BBD) biopsies is constrained by scarce tissue and microanatomic heterogeneity of terminal duct lobular units (TDLUs). We tested whether tissue-sparing tissue microarray (TMA)-based Digital Spatial Profiling (DSP) can deliver reproducible, biologically coherent protein measurements across benign lobules and breast cancers (BCs), and how well DSP aligns with standard immunoassays.

methodsWe performed a pilot using tissues from the Mayo Clinic BBD cohort using TMAs representing four contexts: terminal duct lobular units (TDLUs) from BBD biopsies preceding BC and matched BBD-controls, subsequent BCs, and BC-associated TDLUs. We profiled 79 proteins by DSP (37 retained after QC) and benchmarked against chromogenic IHC and OPAL immunofluorescence. Reproducibility was evaluated using intraclass correlation coefficients (ICCs), cross-platform agreement (weighted kappa), marker correlations, and mixed-effects models with false-discovery-rate (FDR) control.

resultsWe analyzed 368 BBD-TDLU cores (88 cases; 88 controls), 204 BC cores and 110 BC-associated TDLU cores. ICCs were highest in BC tissues, and lower in BC-associated TDLUs and BBD-TDLUs. Agreement was slight-to-fair in TDLUs but moderate (ER/PR) to substantial (BCL2) in BC. DSP recapitulated expected immunologic correlations (CD45 with T-cell, B-cell, and macrophage markers) and tissue-type gradients (BC > BC-associated TDLUs > BBD-TDLUs). Exploratory case-control differences in BBD-TDLUs did not persist after FDR control.

conclusionsTMA-based DSP is feasible in archival breast tissues and yields biologically coherent, cross-platform-benchmarked profiles that are particularly robust in BC, while conserving scarce TDLUS and clarifying current limits of single-marker risk stratification from benign lobules. These data provide a foundation for refined sampling and expanded panels in future TDLU-focused studies.

Indexed as

benign breast diseasebiomarker discoverybreast cancercross-platform agreementdigital spatial profilingimmunohistochemistrymultiplex immunofluorescence (OPAL)reproducibilityterminal duct lobular unittissue microarray

Identifiers

PMID41374998
PMCPMC12691068

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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.