Evidence map›Paper›PMID 37568162›Full record

ArticleCancer cell international2023

ADAM8 is expressed widely in breast cancer and predicts poor outcome in hormone receptor positive, HER-2 negative patients.

Stefania Pianetti, Kathy D Miller, Hannah H Chen, Sandra Althouse, Sha Cao, Steven J Michael, Gail E Sonenshein, Nora D Mineva

Open access · goldAbstract read
In one paragraph

Article in Cancer cell international, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
0.9field-weighted citation impact, top 20% 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

5 citing papers in PubMed, 4 citations in OpenAlex.

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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 at 7 institutions in 2 countries.

Stefania PianettiDepartment of Developmental, Molecular, and Chemical Biology, Tufts University School of Medicine, 136 Harrison Ave., Boston, MA, 02111, USA.
Kathy D MillerIndiana University Melvin and Bren Simon Comprehensive Cancer Center, Indianapolis, IN, USA.
Hannah H ChenDepartment of Pathology and Laboratory Medicine, Tufts Medical Center, Boston, MA, USA.
Sandra AlthouseDepartment of Biostatistics and Health Data Science, Indiana University School of Medicine, Indianapolis, IN, USA.
Sha CaoDepartment of Biostatistics and Health Data Science, Indiana University School of Medicine, Indianapolis, IN, USA.
Steven J MichaelDepartment of Developmental, Molecular, and Chemical Biology, Tufts University School of Medicine, 136 Harrison Ave., Boston, MA, 02111, USA.
Gail E SonensheinDepartment of Developmental, Molecular, and Chemical Biology, Tufts University School of Medicine, 136 Harrison Ave., Boston, MA, 02111, USA.
Nora D MinevaDepartment of Developmental, Molecular, and Chemical Biology, Tufts University School of Medicine, 136 Harrison Ave., Boston, MA, 02111, USA. nora.mineva@adectopharma.com.
Tufts University · USAgricultural Development Advisory Service (United Kingdom) · GBAVEO Oncology (United States) · USIndiana University Melvin and Bren Simon Comprehensive Cancer CenterIndiana University – Purdue University Indianapolis · USIndiana University School of MedicineTufts Medical Center · US

Funding

Development of a Companion Diagnostic Assay for Detection of ADAM8-Positive CancersR43CA239942 · NCI · ADECTO PHARMACEUTICALS, INC. · PI SONENSHEIN, GAIL E. · 2019 to 2019
$300k
NCI NIH HHS R43 CA239942NCI NIH HHS R43CA239942
6 · The paper itself

Abstract

backgroundBreast malignancies are the predominant cancer-related cause of death in women. New methods of diagnosis, prognosis and treatment are necessary. Previously, we identified the breast cancer cell surface protein ADAM8 as a marker of poor survival, and a driver of Triple-Negative Breast Cancer (TNBC) growth and spread. Immunohistochemistry (IHC) with a research-only anti-ADAM8 antibody revealed 34.0% of TNBCs (17/50) expressed ADAM8. To identify those patients who could benefit from future ADAM8-based interventions, new clinical tests are needed. Here, we report on the preclinical development of a highly specific IHC assay for detection of ADAM8-positive breast tumors.

methodsFormalin-fixed paraffin-embedded sections of ADAM8-positive breast cell lines and patient-derived xenograft tumors were used in IHC to identify a lead antibody, appropriate staining conditions and controls. Patient breast cancer samples (n = 490) were used to validate the assay. Cox proportional hazards models assessed association between survival and ADAM8 expression.

resultsADAM8 staining conditions were optimized, a lead anti-human ADAM8 monoclonal IHC antibody (ADP2) identified, and a breast staining/scoring control cell line microarray (CCM) generated expressing a range of ADAM8 levels. Assay specificity, reproducibility, and appropriateness of the CCM for scoring tumor samples were demonstrated. Consistent with earlier findings, 36.1% (22/61) of patient TNBCs expressed ADAM8. Overall, 33.9% (166/490) of the breast cancer population was ADAM8-positive, including Hormone Receptor (HR) and Human Epidermal Growth Factor Receptor-2 (HER2) positive cancers, which were tested for the first time. For the most prevalent HR-positive/HER2-negative subtype, high ADAM8 expression identified patients at risk of poor survival.

conclusionsOur studies show ADAM8 is widely expressed in breast cancer and provide support for both a diagnostic and prognostic value of the ADP2 IHC assay. As ADAM8 has been implicated in multiple solid malignancies, continued development of this assay may have broad impact on cancer management.

Indexed as

ADAM8BiomarkerBreast cancerDiagnosisImmunohistochemistryPrognosis

Identifiers

PMID37568162
PMCPMC10422820
OpenAlexW4385759636

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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.