Evidence map›Paper›PMID 40356444›Full record

ArticleHistopathology2025

ROS1 immunohistochemistry as a potential predictive biomarker for ROS1-targeted therapy in breast cancer: impact of antibody clone selection.

Anna Sokolova, Vaibhavi Joshi, Haarika Chittoory, Michael Walsh, Malcolm Lim, Jamie R Kutasovic, Kaltin Ferguson, Peter T Simpson, Sunil R Lakhani, Amy E McCart Reed

Abstract read
PubMed Full text at PMC Publisher
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 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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

1 citing paper in PubMed.

  1. Toward targeted therapeutics for lobular breast cancer.The Journal of clinical investigation · 2026
    Review
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

10 authors.

Anna SokolovaCentre for Clinical Research, Faculty of Medicine, The University of Queensland, Brisbane, Queensland, Australia.ORCID https://orcid.org/0000-0002-0347-6181
Vaibhavi JoshiCentre for Clinical Research, Faculty of Medicine, The University of Queensland, Brisbane, Queensland, Australia.ORCID https://orcid.org/0000-0002-1309-1664
Haarika ChittooryCentre for Clinical Research, Faculty of Medicine, The University of Queensland, Brisbane, Queensland, Australia.ORCID https://orcid.org/0000-0003-2793-3196
Michael WalshSullivan and Nicolaides Pathology, Brisbane, Queensland, Australia.ORCID https://orcid.org/0000-0002-2855-6743
Malcolm LimCentre for Clinical Research, Faculty of Medicine, The University of Queensland, Brisbane, Queensland, Australia.ORCID https://orcid.org/0000-0003-3691-4368
Jamie R KutasovicCentre for Clinical Research, Faculty of Medicine, The University of Queensland, Brisbane, Queensland, Australia.ORCID https://orcid.org/0000-0001-5410-3636
Kaltin FergusonMater Research Institute, The University of Queensland, Brisbane, Queensland, Australia.ORCID https://orcid.org/0009-0000-2148-4380
Peter T SimpsonCentre for Clinical Research, Faculty of Medicine, The University of Queensland, Brisbane, Queensland, Australia.ORCID https://orcid.org/0000-0002-4816-8289
Sunil R LakhaniCentre for Clinical Research, Faculty of Medicine, The University of Queensland, Brisbane, Queensland, Australia.ORCID https://orcid.org/0000-0003-4067-2760
Amy E McCart ReedCentre for Clinical Research, Faculty of Medicine, The University of Queensland, Brisbane, Queensland, Australia.ORCID https://orcid.org/0000-0001-5387-2791

Funding

Breast Cancer Trials
6 · The paper itself

Abstract

aimsInvasive lobular carcinoma (ILC) may show targetable vulnerabilities secondary to the characteristic loss of the cell adhesion protein E-cadherin. Specifically, a synthetic lethal interaction was identified between E-cadherin loss and ROS1 inhibition. Several clinical trials are currently under way to assess the efficacy of ROS1 inhibitors in ILC; however, ROS1 expression has not been confirmed in ILC tumours and ROS1 has not been validated as a biomarker in the breast cancer setting. This study aimed to (i) examine ROS1 expression in a large cohort of breast cancer cases and (ii) investigate the biology and clinical significance of ROS1 positivity in breast cancer. METHODS AND

resultsROS1 immunohistochemistry was performed on a large cohort of ILC (n = 274) and invasive carcinoma of no special type (NST; n = 431) cases with extensive clinicopathological data. The staining performance of four ROS1 antibody clones was compared. There was marked variation in ROS1 status according to antibody clone. D4D6 and SP384 were negative in almost all breast cancer cases, whereas EP282 and EPMGHR2 were positive in 37 and 47% of ILC cases, and 49 and 74% of NST cases, respectively. Only data from clones D4D6 and SP384 were highly concordant, while EP282 and EPMGHR2 were positive in distinct breast cancer subtypes.

conclusionsAssessment of ROS1 status in breast cancer appears to be highly antibody clone-dependent. ROS1 antibody clone selection will be an important consideration in the design of clinical trials investigating the clinical validity of ROS1 as a predictive biomarker in breast cancer.

Indexed as

Biomarkers, TumorBreast NeoplasmsCarcinoma, LobularProtein-Tyrosine KinasesProto-Oncogene ProteinsAdultAgedAged, 80 and overFemaleHumansImmunohistochemistryMiddle AgedBiomarkers, TumorProtein-Tyrosine KinasesProto-Oncogene ProteinsROS1 protein, humanbiomarkerbreast cancercrizotinibinvasive lobular carcinomaROS1

Identifiers

PMID40356444
PMCPMC12232189

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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.