Evidence map›Paper›PMID 28219109›Full record

ArticleHematological oncology2018

The use of BRAF V600E mutation-specific immunohistochemistry in pediatric Langerhans cell histiocytosis.

Leomar Y Ballester, Miguel D Cantu, Karen P H Lim, Stephen F Sarabia, Lizmery Suarez Ferguson, C Renee Webb, Carl E Allen, Kenneth L McClain, Carrie A Mohila, Jyotinder N Punia and 4 more

Abstract read
In one paragraph

Article in Hematological oncology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.

0numbers the graph read from it
0cells of the map it votes in
19citing papers in PubMed
3.3field-weighted citation impact, top 8% 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

19 citing papers in PubMed, 52 citations in OpenAlex.

  1. Review
  2. Article
  3. Article
  4. Article
  5. Review
  6. Review
  7. Article
  8. Review
  9. Article
  10. Histiocytic disorders.Nature reviews. Disease primers · 2021
    Review
  11. Article
  12. Article
  13. A mutation in POLR3E impairs antiviral immune response and RNA polymerase III.Proceedings of the National Academy of Sciences of the United States of America · 2020
    Article
  14. Article
  15. High frequency of BRAF V600E mutation in Iranian population ameloblastomas.Medicina oral, patologia oral y cirugia bucal · 2020
    Article
  16. Blood advances · 2019
    Article
  17. Article
  18. Article
  19. Review
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

14 authors at 2 institutions in 1 country.

Leomar Y BallesterDepartment of Pathology, Texas Children's Hospital, Houston, TX, USA.
Miguel D CantuDepartment of Pediatrics, Texas Children's Hospital, Houston, TX, USA.
Karen P H LimDepartment of Pediatrics, Texas Children's Hospital, Houston, TX, USA.
Stephen F SarabiaDepartment of Pathology & Immunology, Baylor College of Medicine, Houston, TX, USA.
Lizmery Suarez FergusonDepartment of Pathology, Texas Children's Hospital, Houston, TX, USA.
C Renee WebbDepartment of Pathology, Texas Children's Hospital, Houston, TX, USA.
Carl E AllenDepartment of Pediatrics, Texas Children's Hospital, Houston, TX, USA.
Kenneth L McClainDepartment of Pediatrics, Texas Children's Hospital, Houston, TX, USA.
Carrie A MohilaDepartment of Pathology, Texas Children's Hospital, Houston, TX, USA.
Jyotinder N PuniaDepartment of Pathology, Texas Children's Hospital, Houston, TX, USA.
Angshumoy RoyDepartment of Pathology, Texas Children's Hospital, Houston, TX, USA.
Dolores H López-TerradaDepartment of Pathology, Texas Children's Hospital, Houston, TX, USA.
M John HicksDepartment of Pathology, Texas Children's Hospital, Houston, TX, USA.
Kevin E FisherDepartment of Pathology, Texas Children's Hospital, Houston, TX, USA.ORCID http://orcid.org/0000-0002-6179-0937
Baylor College of Medicine · USTexas Children's Hospital · US

Funding

Tissue ResourceP50CA126752 · NCI · BAYLOR COLLEGE OF MEDICINE · PI MALCOLM K. BRENNER, HELEN E HESLOP · 2007 to 2026
$51.4M
Hematology Training ProgramT32DK060445 · NIDDK · BAYLOR COLLEGE OF MEDICINE · PI GOODELL, MARGARET A. · 2002 to 2023
$8.3M
ERK control of Dendritic Cell Differentiation, Homeostasis and DiseaseR01CA154947 · NCI · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI CARL E ALLEN, MIRIAM MERAD · 2011 to 2026
$7.0M
NCI NIH HHS L30 CA189034NCI NIH HHS P50 CA126752NCI NIH HHS R01 CA154947NIDDK NIH HHS T32 DK060445
6 · The paper itself

Abstract

BRAF p.V600E mutations are detected in greater than 50% of pediatric Langerhans cell histiocytosis (LCH) lesions. However, the use of mutation-specific BRAF V600E immunohistochemistry (IHC) as a surrogate for molecular testing in pediatric LCH is unknown. We tested the mutation-specific BRAF V600E monoclonal antibody (clone VE1) in formalin-fixed, paraffin-embedded LCH samples from 26 pediatric patients (14 males and 12 females, ages 7 mo-17 y) using allele-specific real-time polymerase chain reaction (PCR) with a limit of detection of 0.5% as the comparative gold standard. BRAF VE1 staining was scored for both intensity (0-3+) and percentage of immunoreactive tumor cells (0%-100%). BRAF VE1 immunoreactivity was determined using both lenient (≥1+, ≥1%) and stringent (≥2+, ≥10%) scoring criteria. Using lenient-scoring criteria, we found that the sensitivity and specificity of IHC compared with allele-specific real-time PCR were 100.0% and 18.2%, respectively. The poor specificity of lenient IHC analysis was attributable to weak, 1+ staining in both BRAF-mutated and wild-type LCH. Using stringent-scoring criteria, we found that specificity improved to 100.0% at the expense of sensitivity that decreased to 80.0%. Stringent scoring generated 3 false-negative results, but in all cases, neoplastic tissue comprised less than 5% of the stained section and/or the specimen was decalcified. In conclusion, highly sensitive molecular assays remain the gold standard for BRAF mutation analysis in LCH paraffin-embedded lesions. To avoid false-positive results, unequivocal VE1 staining of 2+ intensity in greater than or equal to 10% neoplastic histiocytes is required. However, negative VE1 results require additional studies to exclude false-negatives, and stringent-scoring criteria may not be optimal for scant or decalcified specimens.

Indexed as

MutationAdolescentChildChild, PreschoolFemaleHistiocytosis, Langerhans-CellHumansImmunohistochemistryInfantMaleProto-Oncogene Proteins B-rafBRAF protein, humanProto-Oncogene Proteins B-rafBRAFimmunohistochemistryLCHpediatricV600EVE1

Identifiers

PMID28219109
PMCPMC6886693
OpenAlexW2590225456

What OpenQuestion holds

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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.