Evidence map›Paper›PMID 29739401›Full record

ArticleJournal of translational medicine2018

Limited utility of tissue micro-arrays in detecting intra-tumoral heterogeneity in stem cell characteristics and tumor progression markers in breast cancer.

Pascale Kündig, Charlotte Giesen, Hartland Jackson, Bernd Bodenmiller, Bärbel Papassotirolopus, Sandra Nicole Freiberger, Catharine Aquino, Lennart Opitz, Zsuzsanna Varga

Erratum issuedOpen access · goldAbstract read
In one paragraph

Article in Journal of translational medicine, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 19 papers.

0numbers the graph read from it
0cells of the map it votes in
19citing papers in PubMed
1.1field-weighted citation impact, top 18% 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

19 citing papers in PubMed, 21 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Article
  6. Slide-to-Slide Tissue Transfer and Array Assembly From Limited Samples for Comprehensive Molecular Profiling.Laboratory investigation; a journal of technical methods and pathology · 2023
    Article
  7. Article
  8. Review
  9. Review
  10. Review
  11. Article
  12. Article
  13. Article
  14. Article
  15. Emerging Role of SOX Proteins in Breast Cancer Development and Maintenance.Journal of mammary gland biology and neoplasia · 2019
    Review
  16. Article
  17. Article
  18. Article
  19. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

9 authors at 3 institutions in 1 country.

Pascale KündigInstitute of Pathology and Molecular Pathology, University Hospital Zurich, Schmelzbergstrasse 12, 8091, Zurich, Switzerland.
Charlotte GiesenInstitute of Molecular Life Sciences, University of Zurich, Zurich, Switzerland.
Hartland JacksonInstitute of Molecular Life Sciences, University of Zurich, Zurich, Switzerland.
Bernd BodenmillerInstitute of Molecular Life Sciences, University of Zurich, Zurich, Switzerland.
Bärbel PapassotirolopusBreast Center Seefeld, Zurich, Switzerland.
Sandra Nicole FreibergerInstitute of Pathology and Molecular Pathology, University Hospital Zurich, Schmelzbergstrasse 12, 8091, Zurich, Switzerland.
Catharine AquinoFunctional Genomics Center Zurich, Zurich, Switzerland.
Lennart OpitzFunctional Genomics Center Zurich, Zurich, Switzerland.
Zsuzsanna VargaInstitute of Pathology and Molecular Pathology, University Hospital Zurich, Schmelzbergstrasse 12, 8091, Zurich, Switzerland. zsuzsanna.varga@usz.ch.ORCID 0000-0002-2855-983X
University Hospital of Zurich · CHUniversity of Zurich · CHBreast Center · CH

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundIntra-tumoral heterogeneity has been recently addressed in different types of cancer, including breast cancer. A concept describing the origin of intra-tumoral heterogeneity is the cancer stem-cell hypothesis, proposing the existence of cancer stem cells that can self-renew limitlessly and therefore lead to tumor progression. Clonal evolution in accumulated single cell genomic alterations is a further possible explanation in carcinogenesis. In this study, we addressed the question whether intra-tumoral heterogeneity can be reliably detected in tissue-micro-arrays in breast cancer by comparing expression levels of conventional predictive/prognostic tumor markers, tumor progression markers and stem cell markers between central and peripheral tumor areas.

methodsWe analyzed immunohistochemical expression and/or gene amplification status of conventional prognostic tumor markers (ER, PR, HER2, CK5/6), tumor progression markers (PTEN, PIK3CA, p53, Ki-67) and stem cell markers (mTOR, SOX2, SOX9, SOX10, SLUG, CD44, CD24, TWIST) in 372 tissue-micro-array samples from 72 breast cancer patients. Expression levels were compared between central and peripheral tumor tissue areas and were correlated to histopathological grading. 15 selected cases additionally underwent RNA sequencing for transcriptome analysis.

resultsNo significant difference in any of the analyzed between central and peripheral tumor areas was seen with any of the analyzed methods/or results that showed difference. Except mTOR, PIK3CA and SOX9 (nuclear) protein expression, all markers correlated significantly (p < 0.05) with histopathological grading both in central and peripheral areas.

conclusionOur results suggest that intra-tumoral heterogeneity of stem-cell and tumor-progression markers cannot be reliably addressed in tissue-micro-array samples in breast cancer. However, most markers correlated strongly with histopathological grading confirming prognostic information as expression profiles were independent on the site of the biopsy was taken.

Indexed as

Disease ProgressionBiomarkers, TumorBreast NeoplasmsFemaleHumansNeoplasm GradingNeoplastic Stem CellsPrognosisTissue Array AnalysisTranscriptomeBiomarkers, TumorBreast cancerIntratumoral heterogeneityStem cellsTissue micro arrayTumor progression

Identifiers

PMID29739401
PMCPMC5941467
OpenAlexW4234497884

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

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.