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Oncotarget. 2017 Aug 24;8(43):74897-74909. doi: 10.18632/oncotarget.20451. eCollection 2017 Sep 26.

Immunohistochemistry cannot replace DNA analysis for evaluation of BRAF V600E mutations in papillary thyroid carcinoma.

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Endocrinology Clinic, Holycross Cancer Center, Kielce, Poland.
Department of Molecular Diagnostics, Holycross Cancer Center, Kielce, Poland.
Department of Surgical Pathology, Holycross Cancer Center, Kielce, Poland.
Cancer Epidemiology, Holycross Cancer Center, Kielce, Poland.
Department of Probability Theory and Statistics Institute of Mathematics, Faculty of Mathematics and Natural Science, Jan Kochanowski University, Kielce, Poland.
Oncology Clinic, Holycross Cancer Center, Kielce, Poland.
The Faculty of Health Sciences, Jan Kochanowski University in Kielce, Poland.



The BRAF V600E mutation is the most common genetic event occurring in papillary thyroid cancer (PTC). Recently, the possibility of using immunohistochemistry (IHC) to detect the BRAF V600E mutation has been reported.


In 140 patients with classical PTC, the status of the BRAF V600E mutation was determined by IHC (using two alternative staining protocols, IHC-1 and IHC-2) and molecular biology methods: Sanger sequencing (SEQ) and real-time PCR (qPCR).


The BRAF V600E mutation was detected in 57.1% (80/140) patients by IHC-1 and 62.9% (88/140) patients by IHC-2. The highest correlation in detecting the BRAF V600E mutation was found between IHC-2 and qPCR (94.2%), and between IHC-1 and qPCR (83.9%). Correlations between IHC-1 and SEQ and between IHC-2 and SEQ were 71.5% and 76.2%, respectively. The IHC-2 protocol had higher sensitivity, PPV, and NPV, and Cohen's kappa than IHC- 1. The presence of BRAF V600E mutation in IHC-2 statistically correlated with age at diagnosis, histopathological stage, and extrathyroidal extension.


The results obtained in this study indicate a lack of concordance between BRAF V600E detection by IHC and molecular methods. The IHC method cannot replace molecular methods for the detection of the BRAF V600E mutation.


BRAF V600E; Sanger sequencing; immunohistochemistry; papillary thyroid cancer; qPCR

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