Evidence map›Paper›PMID 23657789›Full record

ArticleCancer2013

Mutation-specific antibody detects mutant BRAFV600E protein expression in human colon carcinomas.

Frank A Sinicrope, Thomas C Smyrk, David Tougeron, Stephen N Thibodeau, Shalini Singh, Andrea Muranyi, Kandavel Shanmugam, Thomas M Grogan, Steven R Alberts, Qian Shi

Open access · bronzeAbstract read
In one paragraph

Article in Cancer, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
29citing papers in PubMed, 2 pooled it
7.5field-weighted citation impact, top 2% 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

29 citing papers in PubMed, 2 syntheses or guidelines pooled it, 65 citations in OpenAlex.

  1. Molecular features in gangliogliomas: a systematic review.Child's nervous system : ChNS : official journal of the International Society for Pediatric Neurosurgery · 2026
    Pooled it
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  10. Sessile Serrated Polyps are Precursors of Colon Carcinomas With Deficient DNA Mismatch Repair.Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association · 2016
    Article
  11. Article
  12. Article
  13. A cautionary note on the immunohistochemical detection of BRAF v600e mutations in serrated lesions of the colon.Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc · 2015
    Article
  14. Article
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  16. Performance comparison of three BRAF V600E detection methods in malignant melanoma and colorectal cancer specimens.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2015
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  17. Review
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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

10 authors at 3 institutions in 1 country.

Frank A SinicropeDepartment of Medicine, Mayo Clinic, Rochester, MN 55905, USA. sinicrope.frank@mayo.edu
Thomas C Smyrk
David Tougeron
Stephen N Thibodeau
Shalini Singh
Andrea Muranyi
Kandavel Shanmugam
Thomas M Grogan
Steven R Alberts
Qian Shi
Mayo Clinic · USVentana Research Corporation (United States) · USWinnMed · US

Funding

Translational Research in Colon Cancer Prevention & TreatmentK05CA142885 · NCI · MAYO CLINIC ROCHESTER · PI SINICROPE, FRANK A. · 2009 to 2013
$808k
NCI NIH HHS K05 CA142885
6 · The paper itself

Abstract

backgroundA point mutation (V600E) in the BRAF oncogene is a prognostic biomarker and may predict for nonresponse to anti-EGFR antibody therapy in patients with colorectal carcinoma. BRAFV600E mutations are frequently detected in tumors with microsatellite instability and indicate a sporadic origin. We used a mutation-specific antibody to examine mutant BRAFV600E protein expression and its concordance with BRAFV600E mutation data.

methodsPrimary stage III colon carcinomas were analyzed for BRAFV600E mutations in exon 15, and 50 BRAFV600E mutation carriers and 25 wild-type tumors were selected for analysis of BRAF proteins by immunohistochemistry (IHC). IHC was performed in archival tissue specimens using a pan-BRAF antibody and a mutation-specific antibody against BRAFV600E proteins. Staining was scored by 2 pathologists who were blinded to clinical and mutation data.

resultsUsing a pan-BRAF antibody, total BRAF protein expression was observed in the tumor cell cytoplasm in 74 of 75 colon carcinomas. A mutation-specific antibody identified diffuse cytoplasmic staining of mutant BRAFV600E proteins in 49 of 74 cancers. Analysis using a polymerase chain reaction-based assay revealed that all 49 of these cancers carried BRAFV600E mutations. In contrast, BRAFV600E staining was absent in all 25 tumors that carried wild-type copies of BRAF.

conclusionsA BRAF mutation-specific (V600E) antibody detected tumors with BRAFV600E mutations and exhibited complete concordance with a DNA-based method. These results support the use of IHC as a simplified strategy to screen colorectal cancers for BRAFV600E mutations in clinical practice.

Indexed as

Point MutationAgedAntibodiesBiomarkers, TumorColonic NeoplasmsFemaleHumansImmunohistochemistryMaleMicrosatellite InstabilityMiddle AgedNeoplasm StagingPrognosisProspective StudiesProto-Oncogene Proteins B-rafAntibodiesBiomarkers, TumorBRAF protein, humanProto-Oncogene Proteins B-rafBRAFV600E mutationBRAFV600E proteincolon cancerimmunohistochemistrymicrosatellite instability

Identifiers

PMID23657789
PMCPMC3720760
OpenAlexW1664541800

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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.