Evidence map›Paper›PMID 34555047›Full record

ArticlePloS one2021

Looking for more reliable biomarkers in breast cancer: Comparison between routine methods and RT-qPCR.

Emanuele Caselli, Cristina Pelliccia, Valeria Teti, Guido Bellezza, Martina Mandarano, Ivana Ferri, Kerstin Hartmann, Mark Laible, Ugur Sahin, Zsuzsanna Varga and 3 more

Abstract readComparative Study
In one paragraph

Article in PloS one, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.

0numbers the graph read from it
0cells of the map it votes in
9citing 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

9 citing papers in PubMed.

  1. Article
  2. Review
  3. Deep learning algorithm on H&E whole slide images to characterizeComputational and structural biotechnology journal · 2024
    Article
  4. Article
  5. Article
  6. Review
  7. Article
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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

13 authors.

Emanuele CaselliDepartment of Medicine and Surgery, Section of Anatomic Pathology and Histology, Medical School, University of Perugia, Perugia, Italy.ORCID 0000-0002-9515-0209
Cristina PellicciaDepartment of Medicine and Surgery, Section of Anatomic Pathology and Histology, Medical School, University of Perugia, Perugia, Italy.
Valeria TetiDepartment of Medicine and Surgery, Section of Anatomic Pathology and Histology, Medical School, University of Perugia, Perugia, Italy.
Guido BellezzaDepartment of Medicine and Surgery, Section of Anatomic Pathology and Histology, Medical School, University of Perugia, Perugia, Italy.
Martina MandaranoDepartment of Medicine and Surgery, Section of Anatomic Pathology and Histology, Medical School, University of Perugia, Perugia, Italy.ORCID 0000-0001-5019-4825
Ivana FerriDepartment of Medicine and Surgery, Section of Anatomic Pathology and Histology, Medical School, University of Perugia, Perugia, Italy.
Kerstin HartmannBioNTech Diagnostics GmbH, Mainz, Germany.
Mark LaibleBioNTech Diagnostics GmbH, Mainz, Germany.
Ugur SahinBioNTech Diagnostics GmbH, Mainz, Germany.
Zsuzsanna VargaInstitute for Pathology and Molecular Pathology, Universitätsspital Zürich, Zürich, Switzerland.
Chiara LupiUmbria Cancer Registry, Perugia, Italy.ORCID 0000-0001-8695-008X
Fabrizio StracciUmbria Cancer Registry, Perugia, Italy.
Angelo SidoniDepartment of Medicine and Surgery, Section of Anatomic Pathology and Histology, Medical School, University of Perugia, Perugia, Italy.ORCID 0000-0002-8458-5901

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

purposeDecades of quality control efforts have raised the standards of immunohistochemistry (IHC), the principle method used for biomarker testing in breast cancer; however, computational pathology and reverse transcription quantitative PCR (RT-qPCR) may also hold promise for additional substantial improvements.

methodsHerein, we investigated discrepancies in the assessment of estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2) and marker of proliferation Ki67 comparing routinely obtained IHC (and FISH) data (ORI) with the results of manual (REV) and semi-automated (DIA) re-evaluation of the original IHC slides and then with RNA expression data from the same tissue block using the MammaTyper® (MT) gene expression assay.

resultsCorrelation for ER and PR was high between ORI IHC and the other three study methods (REV, DIA and RT-qPCR). For HER2, 10 out of 96 discrepant cases can be detected between ORI and REV that involved at least one call in the equivocal category (except for one case). For Ki67, 22 (29.1%) cases were categorized differently by either REV alone (n = 17), DIA alone (n = 15) or both (n = 10) and 28 cases (29.2%) for RT-qPCR. Most of the discrepant Ki67 cases changed from low to high between the original and following assessment and belonged to the intermediate Ki67 expression range (between 9 and 30%).

conclusionsDetermination of the breast cancer biomarkers ER, PR, HER2 and Ki67 at the mRNA level shows high degree of correlation with IHC and compares well with correlations between original with subsequent independent manual or semi-automated IHC assessments. The use of methods with wider dynamic range and higher reproducibility such as RT-qPCR may offer more precise assessment of endocrine responsiveness, improve Ki67 standardization and help resolve HER2 cases that remain equivocal or ambiguous by IHC/FISH. In summary, our findings seem to configure RT-qPCR as a complementary method to be used in cases of either equivocal results or presenting, at the traditional determination assays, biomarkers expressions close to the cut-off values.

Indexed as

Biomarkers, TumorBreast NeoplasmsDiagnostic Tests, RoutineErb-b2 Receptor Tyrosine KinasesFemaleHumansImmunohistochemistryIn Situ Hybridization, FluorescenceReal-Time Polymerase Chain ReactionReceptors, EstrogenReceptors, ProgesteroneReproducibility of ResultsBiomarkers, TumorERBB2 protein, humanErb-b2 Receptor Tyrosine KinasesReceptors, EstrogenReceptors, Progesterone

Identifiers

PMID34555047
PMCPMC8460001

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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.