Immunohistochemical Detection of the BRAF V600E-mutated... : The American Journal of Surgical Pathology (original) (raw)

Original Articles

Immunohistochemical Detection of the BRAF V600E-mutated Protein in Papillary Thyroid Carcinoma

Koperek, Oskar MD*; Kornauth, Christoph MD*; Capper, David MD†,‡; Berghoff, Anna Sophie MD§; Asari, Reza MD∥; Niederle, Bruno MD∥; von Deimling, Andreas MD†,‡; Birner, Peter MD, MSc*; Preusser, Matthias MD§

*Clinical Institute of Pathology

§Department of Medicine I and Comprehensive Cancer Center

∥Section of Endocrine Surgery, Division of General Surgery, Department of Surgery, Medical University of Vienna, Vienna, Austria

†Department of Neuropathology, Institute of Pathology, Ruprecht-Karls University

‡Clinical Cooperation Unit Neuropathology, DKFZ, Heidelberg, Germany

Conflicts of Interest and Source of Funding: This study was partly supported by the Medical Scientific Fund of the Mayor of the City of Vienna (Project# 10069) and an EANO fellowship grant. Andreas von Deimling and David Capper declare shared inventorship of anti-BRAF V600E antibody clone VE1. A patent for diagnostic application of VE1 has been applied for. All terms are being managed by the German Cancer Research Center in accordance with its conflict of interest policies. For the remaining authors none were declared.

Correspondence: Peter Birner, MD, MSc, Clinical Institute of Pathology, Medical University of Vienna, Währinger Gürtel 18-20, A-1090 Vienna, Austria (e-mail: [email protected]).

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Erratum

Abstract

The V600E mutation of the B-type Raf kinase (BRAF) gene is a common event in papillary thyroid carcinoma (PTC) and seems to play a key role in the development and progression of this disease. We evaluated the expression of the mutated BRAF V600E protein in 144 cases of PTC using a novel mutation-specific antibody. Seventy-six PTCs (52.8%) showed unequivocal diffuse cytoplasmic expression of the mutated BRAF protein, and the T1799A point mutation was confirmed by sequencing analysis in selected cases. No statistical difference in V600E BRAF protein expression was seen between microcarcinomas and macrocarcinomas. Further, no significant correlation of V600E expression with clinicopathologic parameters of aggressiveness such as lymph node metastasis, peritumoral infiltration, or perithyroidal infiltration was found. BRAF V600E protein expression was significantly more common in tumors with tall cell or oncocytic features but was less common in tumors with follicular growth pattern. Diffuse sclerosing, solid and follicular variants did not show the mutated BRAF protein. Immunohistochemical detection of the mutated V600E BRAF protein in PTC may facilitate mutational analysis in the clinical setting. Our data show that the expression of the mutated BRAF V600 protein and thus the corresponding BRAF mutation seems not to be per se a marker of aggressiveness but is already seen in clinically indolent microcarcinomas. Nevertheless, the investigation of BRAF V600E protein expression might be of clinical interest especially in therapy-resistant disease, as new therapeutics inhibiting the mutated protein are clinically available.

Erratum

This article had a minor systematic error affecting both subgroups equally. In several patients age at time of data collection, not at surgery was used for calculations.

The mean age of all patients at time of surgery was 48.2±16.6 years (5-79), in patients with mutated BRAF 51.8±14.6 years (21-79), and 44.1±18 years (5-79) in patients without BRAF mutation (Table 1). BRAF mutation was significantly associated with higher age of patients (_P_=0.01, Mann Whitney U-test).

The rest of the results and all conclusions remain unchanged.

The American Journal of Surgical Pathology. 36(10):1578, October 2012.