Evidence map›Paper›PMID 26496026›Full record

ArticleOncotarget2015

VE1 immunohistochemistry predicts BRAF V600E mutation status and clinical outcome in colorectal cancer.

Christian Schafroth, José A Galván, Irene Centeno, Viktor H Koelzer, Heather E Dawson, Lena Sokol, Gregor Rieger, Martin D Berger, Marion Hädrich, Robert Rosenberg and 6 more

Abstract readMulticenter Study
In one paragraph

Article in Oncotarget, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
14citing papers in PubMed, 1 pooled it
–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

14 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
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  5. Nuclear interaction of Arp2/3 complex and BRAFAmerican journal of cancer research · 2022
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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

16 authors.

Christian SchafrothTranslational Research Unit, Institute of Pathology, Bern University Hospital, Bern, Switzerland.
José A GalvánTranslational Research Unit, Institute of Pathology, Bern University Hospital, Bern, Switzerland.
Irene CentenoTranslational Research Unit, Institute of Pathology, Bern University Hospital, Bern, Switzerland.
Viktor H KoelzerTranslational Research Unit, Institute of Pathology, Bern University Hospital, Bern, Switzerland.
Heather E DawsonTranslational Research Unit, Institute of Pathology, Bern University Hospital, Bern, Switzerland.
Lena SokolTranslational Research Unit, Institute of Pathology, Bern University Hospital, Bern, Switzerland.
Gregor RiegerTranslational Research Unit, Institute of Pathology, Bern University Hospital, Bern, Switzerland.
Martin D BergerDepartment of Medical Oncology, Bern University Hospital, Bern, Switzerland.
Marion HädrichVisceral Surgery and Medicine, Bern University Hospital, Bern, Switzerland.
Robert RosenbergDepartment of Surgery, Kantonsspital Baselland, Liestal, Switzerland.
Ulrich NitscheDepartment of Surgery, Klinikum rechts der Isar, Technische Universität München, Munich, Germany.
Beat SchnürigerVisceral Surgery and Medicine, Bern University Hospital, Bern, Switzerland.
Rupert LangerTranslational Research Unit, Institute of Pathology, Bern University Hospital, Bern, Switzerland.
Daniel InderbitzinVisceral Surgery and Medicine, Bern University Hospital, Bern, Switzerland.
Alessandro LugliTranslational Research Unit, Institute of Pathology, Bern University Hospital, Bern, Switzerland.
Inti ZlobecTranslational Research Unit, Institute of Pathology, Bern University Hospital, Bern, Switzerland.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

aimVE1 is a monoclonal antibody detecting mutant BRAFV(600E) protein by immunohistochemistry. Here we aim to determine the inter-observer agreement and concordance of VE1 with mutational status, investigate heterogeneity in colorectal cancers and metastases and determine the prognostic effect of VE1 in colorectal cancer patients.

methodsConcordance of VE1 with mutational status and inter-observer agreement were tested on a pilot cohort of colorectal cancers (n = 34), melanomas (n = 23) and thyroid cancers (n = 8). Two prognostic cohorts were evaluated (n = 259, Cohort 1 and n = 226, Cohort 2) by multiple-punch tissue microarrays. VE1 staining on preoperative biopsies (n = 118 patients) was compared to expression in resections. Primary tumors and metastases from 13 patients were tested for VE1 heterogeneity using a tissue microarray generated from all available blocks (n = 100 blocks).

resultsInter-observer agreement was 100% (kappa = 1.0). Concordance between VE1 and V600E mutation was 98.5%. Cohort 1: VE1 positivity (seen in 13.5%) was associated with older age (p = 0.0175) and MLH1 deficiency (p < 0.0001). Cohort 2: VE1 positivity (seen in 12.8%) was associated with female gender (p = 0.0016), right-sided tumor location (p < 0.0001), higher tumor grade (p < 0.0001) and mismatch repair (MMR)-deficiency (p < 0.0001). In survival analysis, MMR status and postoperative therapy were identified as possible confounding factors. Adjusting for these features, VE1 was an unfavorable prognostic factor. Preoperative biopsy staining matched resections in all cases except one. No heterogeneity was found across any primary/metastatic tumor blocks.

conclusionVE1 is highly concordant for V600E and homogeneously expressed suggesting staining can be analysed on resection specimens, preoperative biopsies, metastatic lesions and tissue microarrays.

Indexed as

Antibodies, MonoclonalImmunohistochemistryMutationAdultAgedAged, 80 and overBiomarkers, TumorBiopsyColorectal NeoplasmsDNA Mutational AnalysisFemaleGermanyHCT116 CellsHT29 CellsHumansKaplan-Meier EstimateAntibodies, MonoclonalBiomarkers, TumorBRAF protein, humanProto-Oncogene Proteins B-rafBRAFcolorectal cancerheterogeneitymetastasisPathology SectionprognosisVE1

Identifiers

PMID26496026
PMCPMC4747166

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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.