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Pathol Res Pract. 2015 Feb;211(2):162-70. doi: 10.1016/j.prp.2014.10.005. Epub 2014 Oct 27.

Clinicopathologic correlations of the BRAFV600E mutation, BRAF V600E immunohistochemistry, and BRAF RNA in situ hybridization in papillary thyroid carcinoma.

Author information

1
Department of Pathology and Translational Genomics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea.
2
Department of Pathology, Chung-Ang University Hospital, Chung-Ang University College of Medicine, Seoul, South Korea.
3
Department of Internal Medicine, Division of Endocrinology, Chung-Ang University Hospital, Chung-Ang University College of Medicine, Seoul, South Korea; Thyroid Center, Chung-Ang University Hospital, Chung-Ang University College of Medicine, Seoul, South Korea.
4
Department of Surgery, Chung-Ang University Hospital, Chung-Ang University College of Medicine, Seoul, South Korea; Thyroid Center, Chung-Ang University Hospital, Chung-Ang University College of Medicine, Seoul, South Korea.
5
Department of Pathology, Chung-Ang University Hospital, Chung-Ang University College of Medicine, Seoul, South Korea; Thyroid Center, Chung-Ang University Hospital, Chung-Ang University College of Medicine, Seoul, South Korea. Electronic address: hkim1967@gmail.com.

Abstract

BACKGROUND:

The BRAF(V600E) mutation is the most common genetic alteration in papillary thyroid carcinoma (PTC). The aim of this study is to analyze the clinicopathologic correlations of the BRAF(V600E) mutation, BRAF V600E immunohistochemistry (IHC) and BRAF RNA in situ hybridization (ISH) in PTC.

METHODS:

This study included 467 patients with PTC who underwent surgical resection. We studied the BRAF(V600E) mutation using real-time PCR and BRAF V600E and BRAF RNA ISH using tissue microarray (TMA).

RESULTS:

The frequencies of a positive BRAF(V600E) mutation by real-time PCR, positive BRAF V600E IHC, and high BRAF RNA ISH were 84%, 86%, and 70%, respectively, in PTC. Conventional PTC had higher positive rates in all three tests than other histologic types. The BRAF(V600E) mutation, BRAF V600E IHC, low ΔCt, and high BRAF RNA ISH were significantly associated with lymph node metastasis. The BRAF(V600E) mutation was significantly associated with positive immunostaining for BRAF V600E mutant protein (P<0.001) overall, with high BRAF RNA ISH only in the follicular variant (P=0.035). No significant correlation was noted between BRAF V600E IHC and BRAF RNA ISH. The sensitivity of BRAF V600E IHC for the BRAF(V600E) mutation was 95%, and the specificity was 61% overall, 96% and 54% in the conventional type, and 85% and 70% in the follicular variant.

CONCLUSIONS:

Our results showed that positive BRAF V600E IHC significantly correlated with the BRAF(V600E) mutation. This suggests its clinical utility as a screening tool for the BRAF(V600E) mutation. In addition, a high BRAF RNA ISH score could be a candidate marker of aggressive behavior in BRAF(V600E) mutation-positive cases of PTC.

KEYWORDS:

BRAF V600E mutation; Immunohistochemistry; Papillary carcinoma; RNA in situ hybridization

PMID:
25468810
DOI:
10.1016/j.prp.2014.10.005
[Indexed for MEDLINE]

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