Evidence map›Paper›PMID 26690310›Full record

ArticleThe Journal of pathology2016

HER2 overexpression and amplification as a potential therapeutic target in colorectal cancer: analysis of 3256 patients enrolled in the QUASAR, FOCUS and PICCOLO colorectal cancer trials.

Susan D Richman, Katie Southward, Philip Chambers, Debra Cross, Jennifer Barrett, Gemma Hemmings, Morag Taylor, Henry Wood, Gordon Hutchins, Joseph M Foster and 9 more

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

Article in The Journal of pathology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 141 papers, 5 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
141citing papers in PubMed, 5 pooled it
5.6field-weighted citation impact, top 3% 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

141 citing papers in PubMed, 5 syntheses or guidelines pooled it, 234 citations in OpenAlex.

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  6. Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2024
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81 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

19 authors at 5 institutions in 1 country.

Susan D RichmanSection of Pathology and Tumour Biology, Leeds Institute of Cancer and Pathology, University of Leeds, UK.
Katie SouthwardSection of Pathology and Tumour Biology, Leeds Institute of Cancer and Pathology, University of Leeds, UK.
Philip ChambersSection of Pathology and Tumour Biology, Leeds Institute of Cancer and Pathology, University of Leeds, UK.
Debra CrossHistopathology and Molecular Pathology, St James University Hospital, Leeds, UK.
Jennifer BarrettSection of Epidemiology and Biostatistics, Leeds Institute of Cancer and Pathology, University of Leeds, UK.
Gemma HemmingsSection of Pathology and Tumour Biology, Leeds Institute of Cancer and Pathology, University of Leeds, UK.
Morag TaylorSection of Pathology and Tumour Biology, Leeds Institute of Cancer and Pathology, University of Leeds, UK.
Henry WoodSection of Pathology and Tumour Biology, Leeds Institute of Cancer and Pathology, University of Leeds, UK.
Gordon HutchinsSection of Pathology and Tumour Biology, Leeds Institute of Cancer and Pathology, University of Leeds, UK.
Joseph M FosterAffymetrix UK Ltd, High Wycombe, UK.
Assa OumieAffymetrix UK Ltd, High Wycombe, UK.
Karen G SpinkAffymetrix UK Ltd, High Wycombe, UK.
Sarah R BrownClinical Trials Research Unit, University of Leeds, Leeds, UK.
Marc JonesClinical Trials Research Unit, University of Leeds, Leeds, UK.
David KerrCancer Medicine, University of Oxford, UK.
Kelly HandleyBirmingham Clinical Trials Unit, University of Birmingham, UK.
Richard GrayClinical Trials Service Unit and Epidemiology Studies Unit, University of Oxford, UK.
Matthew SeymourSection of Oncology, Leeds Institute of Cancer and Pathology, University of Leeds, UK.
Philip QuirkeSection of Pathology and Tumour Biology, Leeds Institute of Cancer and Pathology, University of Leeds, UK.
University of Leeds · GBMRC Clinical Trials Unit at UCL · GBSt James's University Hospital · GBUniversity of Birmingham · GBUniversity of Oxford · GB

Funding

Cancer Research UK C37059/A11941Medical Research Council
6 · The paper itself

Abstract

HER2 overexpression/amplification is linked to trastuzumab response in breast/gastric cancers. One suggested anti-EGFR resistance mechanism in colorectal cancer (CRC) is aberrant MEK-AKT pathway activation through HER2 up-regulation. We assessed HER2-amplification/overexpression in stage II-III and IV CRC patients, assessing relationships to KRAS/BRAF and outcome. Pathological material was obtained from 1914 patients in the QUASAR stage II-III trial and 1342 patients in stage IV trials (FOCUS and PICCOLO). Tissue microarrays were created for HER2 immunohistochemistry. HER2-amplification was assessed using FISH and copy number variation. KRAS/BRAF mutation status was assessed by pyrosequencing. Progression-free survival (PFS) and overall survival (OS) data were obtained for FOCUS/PICCOLO and recurrence and mortality for QUASAR; 29/1342 (2.2%) stage IV and 25/1914 (1.3%) stage II-III tumours showed HER2 protein overexpression. Of the HER2-overexpressing cases, 27/28 (96.4%) stage IV tumours and 20/24 (83.3%) stage II-III tumours demonstrated HER2 amplification by FISH; 41/47 (87.2%) also showed copy number gains. HER2-overexpression was associated with KRAS/BRAF wild-type (WT) status at all stages: in 5.2% WT versus 1.0% mutated tumours (p < 0.0001) in stage IV and 2.1% versus 0.2% in stage II-III tumours (p = 0.01), respectively. HER2 was not associated with OS or PFS. At stage II-III, there was no significant correlation between HER2 overexpression and 5FU/FA response. A higher proportion of HER2-overexpressing cases experienced recurrence, but the difference was not significant. HER2-amplification/overexpression is identifiable by immunohistochemistry, occurring infrequently in stage II-III CRC, rising in stage IV and further in KRAS/BRAF WT tumours. The value of HER2-targeted therapy in patients with HER2-amplified CRC must be tested in a clinical trial. © 2015 The Authors. Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.

Indexed as

Antineoplastic Combined Chemotherapy ProtocolsClinical Trials as TopicColorectal NeoplasmsDNA Copy Number VariationsErb-b2 Receptor Tyrosine KinasesFemaleGene Expression Regulation, NeoplasticHumansImmunohistochemistryMaleMutationNeoplasm Recurrence, LocalNeoplasm StagingERBB2 protein, humanErb-b2 Receptor Tyrosine Kinasesamplificationcolorectal cancerHER2overexpression, copy number variation

Identifiers

PMID26690310
PMCPMC4785607
OpenAlexW2212171768

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.