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Accurate detection of BRAF p.V600E mutations in challenging melanoma specimens requires stringent immunohistochemistry scoring criteria or sensitive molecular assays

Overview of attention for article published in Human Pathology, August 2014
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  • In the top 25% of all research outputs scored by Altmetric
  • High Attention Score compared to outputs of the same age (87th percentile)
  • High Attention Score compared to outputs of the same age and source (97th percentile)

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1 news outlet
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Title
Accurate detection of BRAF p.V600E mutations in challenging melanoma specimens requires stringent immunohistochemistry scoring criteria or sensitive molecular assays
Published in
Human Pathology, August 2014
DOI 10.1016/j.humpath.2014.07.014
Pubmed ID
Authors

Kevin E. Fisher, Cynthia Cohen, Momin T. Siddiqui, John F. Palma, Edward H. Lipford, John W. Longshore

Abstract

Malignant melanoma patients require BRAF mutation testing prior to initiating BRAF inhibitor therapy. Molecular testing remains the diagnostic gold standard, but recent work suggests that BRAF immunohistochemistry (IHC) confers comparable results. Sample attributes and scoring criteria that may affect BRAF IHC interpretation, however, are poorly defined. We investigated formalin-fixed, paraffin-embedded samples with variable challenging interpretative attributes: metastases, core needle biopsies, sample tissues less than 60 mm(2), samples with greater than 50% necrosis, and/or samples with greater than 10% melanin pigmentation. Three pathologists independently scored 122 BRAF V600E IHC-labeled melanoma samples for percentage (0%-100%) of staining intensity (0-3+). Interscorer BRAF IHC discrepancies were resolved by consensus review. Lenient (≥1+, >0%) and stringent (≥2+, ≥10%) IHC scoring criteria were compared to BRAF V600 mutation (cobas) results (n = 118). Specimens with greater than 10% melanin pigmentation and metastatic samples produced the majority of interobserver IHC and IHC/cobas scoring discrepancies. Consensus review using stringent scoring criteria decreased the number of discrepant results, yielded very good interobserver reproducibility, and improved specificity and positive predictive value for BRAF p.V600E detection. BRAF p.V600K mutations accounted for 57.1% of false-negative IHC results when stringent, consensus criteria scoring were used. The cobas test detected 75.0% (8/12) of BRAF IHC-negative BRAF p.V600K mutations confirmed by next-generation sequencing. Molecular BRAF testing is the preferred screening test for BRAF inhibitor therapy eligibility because of superior sensitivity in challenging interpretative melanoma specimens. However, BRAF V600E IHC has excellent specificity and positive predictive value when stringent, consensus scoring criteria are implemented. To decrease IHC scoring discrepancies, pathologists should interpret metastatic and pigmented samples with caution.

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Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 21 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 21 100%

Demographic breakdown

Readers by professional status Count As %
Other 4 19%
Researcher 3 14%
Professor 2 10%
Student > Master 2 10%
Student > Doctoral Student 1 5%
Other 4 19%
Unknown 5 24%
Readers by discipline Count As %
Medicine and Dentistry 7 33%
Agricultural and Biological Sciences 4 19%
Unspecified 1 5%
Environmental Science 1 5%
Biochemistry, Genetics and Molecular Biology 1 5%
Other 2 10%
Unknown 5 24%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 11. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 03 February 2023.
All research outputs
#3,201,746
of 25,371,288 outputs
Outputs from Human Pathology
#306
of 3,380 outputs
Outputs of similar age
#31,139
of 241,596 outputs
Outputs of similar age from Human Pathology
#1
of 43 outputs
Altmetric has tracked 25,371,288 research outputs across all sources so far. Compared to these this one has done well and is in the 87th percentile: it's in the top 25% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 3,380 research outputs from this source. They typically receive a little more attention than average, with a mean Attention Score of 5.1. This one has done particularly well, scoring higher than 90% of its peers.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 241,596 tracked outputs that were published within six weeks on either side of this one in any source. This one has done well, scoring higher than 87% of its contemporaries.
We're also able to compare this research output to 43 others from the same source and published within six weeks on either side of this one. This one has done particularly well, scoring higher than 97% of its contemporaries.