Annals of Surgical Oncology

, Volume 25, Issue 6, pp 1775–1781 | Cite as

Comparison of Immunohistochemistry and Direct Sequencing Methods for Identification of the BRAFV600E Mutation in Papillary Thyroid Carcinoma

  • Jong-kyu Kim
  • Chan Yong Seong
  • In Eui Bae
  • Jin Wook Yi
  • Hyeong Won Yu
  • Su-jin Kim
  • Jae-Kyung WonEmail author
  • Young Jun Chai
  • June Young Choi
  • Kyu Eun LeeEmail author
Endocrine Tumors



BRAFV600E mutation is the most common somatic variant in papillary thyroid carcinoma (PTC) and is associated with aggressive prognostic factors. The conventional detection method for BRAF mutations is polymerase chain reaction followed by Sanger sequencing. Recently, an immunohistochemistry (IHC) method using a BRAFV600E-specific antibody (VE1) has been developed and widely adopted in the clinics; however, there is a lack of evidence regarding the comparability of the IHC and Sanger sequencing methods.


Our institution began using the BRAFV600E IHC test in January 2013. We retrospectively analyzed 697 samples that were tested using both the IHC and sequencing methods, and evaluated their concordance.


BRAF mutation was detected in 90.0% (627/697) of samples using IHC and 83.4% (581/697) of samples using direct sequencing. The diagnostic parameters of IHC compared with Sanger sequencing were as follows: 100% sensitivity (581/581), 60.3% specificity (70/116), 92.7% positive predictive value (581/627), and 100% negative predictive value (70/70). No false negative results were recorded using IHC. The overall concordance rate between the two methods was 93.4% (651/697). Discordant results were found in 46 samples (6.6%), 29 of which were from cases with small tumors (< 6 mm), 8 were from cases with low tumor cellularity, and 9 were specimens yielding low-quality DNA.


IHC using the VE1 antibody is a reliable and highly sensitive method for detecting the BRAFV600E mutation in classic PTC.



Jong-kyu Kim, Chan Yong Seong, In Eui Bae, Jin Wook Yi, Hyeong Won Yu, Su-jin Kim, Jae-Kyung Won, Young Jun Chai, June Young Choi, and Kyu Eun Lee declare no conflicts of interest.


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Copyright information

© Society of Surgical Oncology 2018

Authors and Affiliations

  • Jong-kyu Kim
    • 1
  • Chan Yong Seong
    • 2
  • In Eui Bae
    • 3
  • Jin Wook Yi
    • 2
  • Hyeong Won Yu
    • 3
  • Su-jin Kim
    • 2
  • Jae-Kyung Won
    • 4
    Email author
  • Young Jun Chai
    • 5
  • June Young Choi
    • 3
  • Kyu Eun Lee
    • 2
    Email author
  1. 1.Department of General SurgeryEwha Womans University College of Medicine and Graduate School of MedicineSeoulKorea
  2. 2.Department of SurgerySeoul National University Hospital and College of MedicineSeoulKorea
  3. 3.Department of Surgery, Seoul National University College of MedicineSeoul National University Bundang HospitalSeongnamKorea
  4. 4.Department of PathologySeoul National University Hospital and College of MedicineSeoulKorea
  5. 5.Department of SurgerySeoul National University Boramae Medical CenterSeoulKorea

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