Evidence map›Paper›PMID 25649416›Full record

ArticleBMC gastroenterology2015

Heterogeneity of amplification of HER2, EGFR, CCND1 and MYC in gastric cancer.

Phillip Stahl, Carsten Seeschaaf, Patrick Lebok, Asad Kutup, Maximillian Bockhorn, Jakob R Izbicki, Carsten Bokemeyer, Ronald Simon, Guido Sauter, Andreas H Marx

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in BMC gastroenterology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 77 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
77citing papers in PubMed, 2 pooled it
12.7field-weighted citation impact, top 1% 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

77 citing papers in PubMed, 2 syntheses or guidelines pooled it, 126 citations in OpenAlex.

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17 more citing papers are in PubMed but not listed here.

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 at 2 institutions in 1 country.

Phillip StahlInstitute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany. p.stahl@uke.de.
Carsten SeeschaafInstitute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany. seeschaaf@gmx.de.
Patrick LebokInstitute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany. p.lebok@uke.de.
Asad KutupGeneral, Visceral and Thoracic Surgery Department and Clinic, University Medical Center Hamburg-Eppendorf, Hamburg, Germany. a.kutup@uke.de.
Maximillian BockhornGeneral, Visceral and Thoracic Surgery Department and Clinic, University Medical Center Hamburg-Eppendorf, Hamburg, Germany. m.bockhorn@uke.de.
Jakob R IzbickiGeneral, Visceral and Thoracic Surgery Department and Clinic, University Medical Center Hamburg-Eppendorf, Hamburg, Germany. izbicki@uke.de.
Carsten BokemeyerII Med. Klinik, Oncology, Hematology with section Pneumology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany. c.bokemeyer@uke.de.
Ronald SimonInstitute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany. r.simon@uke.de.
Guido SauterInstitute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany. g.sauter@uke.de.
Andreas H MarxInstitute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany. a.marx@uke.de.
Universität Hamburg · DEUniversity Medical Center Hamburg-Eppendorf · DE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundIntra-tumor heterogeneity is a potential cause for failure of targeted therapy in gastric cancer, but the extent of heterogeneity of established (HER2) or potential (EGFR, CCND1) target genes and prognostic gene alterations (MYC) had not been systematically studied.

methodsTo study heterogeneity of these genes in a large patient cohort, a heterogeneity tissue microarray was constructed containing 0.6 mm tissue cores from 9 different areas of the primary gastric cancers of 113 patients and matched lymph node metastases from 61 of these patients. Dual color fluorescence in-situ hybridization was performed to assess amplification of HER2, EGFR, CCND1 and MYC using established thresholds (ratio ≥ 2.0). Her2 immunohistochemistry (IHC) was performed in addition.

resultsAmplification was found in 17.4% of 109 interpretable cases for HER2, 6.4% for EGFR, 17.4% for CCND1, and 24.8% for MYC. HER2 amplification was strongly linked to protein overexpression by IHC in a spot-by-spot analysis (p < 0.0001). Intra-tumor heterogeneity was found in the primary tumors of 9 of 19 (47.3%) cancers with HER2, 8 of 17 (47.0%) cancers with CCND1, 5 of 7 (71.4%) cancers with EGFR, and 23 of 27 (85.2%) cancers with MYC amplification. Amplification heterogeneity was particularly frequent in case of low-level amplification (<10 gene copies). While the amplification status was often different between metastases, unequivocal intra-tumor heterogeneity was not found in individual metastases.

conclusionThe data of our study demonstrate that heterogeneity is common for biomarkers in gastric cancer. Given that both TMA tissue cores and clinical tumor biopsies analyze only a small fraction of the tumor bulk, it can be concluded that such heterogeneity may potentially limit treatment decisions based on the analysis of a single clinical cancer biopsy.

Indexed as

Gene AmplificationGenes, erbB-1Genes, erbB-2Genes, mycAdultAgedAged, 80 and overBiomarkers, TumorCyclin D1Genetic HeterogeneityHumansImmunohistochemistryIn Situ Hybridization, FluorescenceLymphatic MetastasisMiddle AgedStomach NeoplasmsBiomarkers, TumorCCND1 protein, humanCyclin D1

Identifiers

PMID25649416
PMCPMC4324419
OpenAlexW2104581112

What OpenQuestion holds

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LicenceCC BY
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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.