A Systematic Review and Meta-Analysis of the Diagnostic Performance of BRAF V600E Immunohistochemistry in Thyroid Histopathology

  • Ranjit Singarayer
  • Ozgur Mete
  • Laure Perrier
  • Lehana Thabane
  • Sylvia L. Asa
  • Stan Van Uum
  • Shereen Ezzat
  • David P. Goldstein
  • Anna M. SawkaEmail author


Immunohistochemistry (IHC) in evaluating thyroid surgical specimens may facilitate diagnostic and prognostic evaluation, with potential therapeutic implications. We performed a systematic review and meta-analysis examining the analytic validity of IHC in detecting BRAFV600E mutations in thyroid cancer (primary or metastatic). We screened citations from three electronic databases (until December 20, 2018), supplemented by a hand search of authors’ files and cross-references of reviews. Citations and full-text papers were independently reviewed in duplicate, and consensus was achieved on inclusion of papers. Two reviewers independently critically appraised and abstracted data from included papers. Random-effect meta-analyses were conducted for sensitivity and specificity estimates. We reviewed 1499 unique citations and 93 full-text articles. We included 1 systematic review and 30 original articles. The published review (from 2015) needed to be updated as there were multiple subsequent original studies. The pooled sensitivity of IHC in detecting a BRAFV600E mutation was 96.8% (95% confidence interval [CI] at 94.1%, 98.3%) (29 studies, including 2659 BRAFV600E mutant tumors). The IHC pooled specificity was 86.3% (95% CI 80.7%, 90.4%) (28 studies, including 1107 BRAFV600E wild-type specimens). These meta-analyses were subject to statistically significant heterogeneity, partly explained by antibody type (sensitivity and specificity) and tissue/tumor type (specificity). In conclusion, BRAF IHC is highly sensitive and reasonably specific in detecting the BRAFV600E mutation; however, there is some variability in analytic performance.


BRAFV600E Thyroid cancer Diagnostic accuracy Systematic review Meta-analysis Papillary thyroid carcinoma 



The authors would like to thank Mrs. Coreen Marino, for assistance in retrieving full-text papers.

Funding information


Compliance with Ethical Standards

Conflict of Interest

None declared.


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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • Ranjit Singarayer
    • 1
    • 2
  • Ozgur Mete
    • 3
    • 4
  • Laure Perrier
    • 5
  • Lehana Thabane
    • 6
    • 7
  • Sylvia L. Asa
    • 3
    • 4
  • Stan Van Uum
    • 8
    • 9
  • Shereen Ezzat
    • 10
    • 11
  • David P. Goldstein
    • 12
    • 13
  • Anna M. Sawka
    • 14
    • 15
    Email author
  1. 1.Thyroid FellowUniversity of TorontoTorontoCanada
  2. 2.Toronto General HospitalTorontoCanada
  3. 3.Department of PathologyUniversity Health Network and University of TorontoTorontoCanada
  4. 4.Toronto General HospitalTorontoCanada
  5. 5.University of Toronto LibrariesUniversity of TorontoTorontoCanada
  6. 6.Department of Health Research Methods, Evidence, and ImpactMcMaster UniversityHamiltonCanada
  7. 7.St. Joseph’s Healthcare HamiltonHamiltonCanada
  8. 8.Division of EndocrinologyWestern UniversityLondonCanada
  9. 9.Division of Endocrinology & MetabolismSt Joseph’s Health Care LondonLondonCanada
  10. 10.Department of Endocrine OncologyPrincess Margaret Cancer CentreTorontoCanada
  11. 11.Toronto General HospitalTorontoCanada
  12. 12.Department of Otolaryngology, Head and Neck SurgeryUniversity Health Network and University of TorontoTorontoCanada
  13. 13.Princess Margaret Cancer CentreTorontoCanada
  14. 14.Division of EndocrinologyUniversity Health Network and University of TorontoTorontoCanada
  15. 15.Toronto General HospitalTorontoCanada

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