BRAF (V600E) mutation analysis in papillary thyroid carcinomas by peptide nucleic acid clamp real-time PCR

Abstract

BACKGROUND: Activating somatic mutation of the BRAF (V600E) has been identified as the most common genetic event in papillary thyroid carcinoma (PTC) with a variable frequency (32-87%) in different series by different methods. The BRAF (V600E) mutation is associated with various clinicopathological parameters. The mutation is an important factor for the management of the PTC patients. The objective of this study was to detect the BRAF (V600E) mutation in PTCs by peptide nucleic acid (PNA) clamp real-time PCR and to analyze the results with clinicopathological parameters. METHODS: We performed genetic analysis of BRAF (V600E) by PNA clamp real-time PCR in 211 PTCs in Korea, stratified by clinicopathological parameters. RESULTS: The BRAF (V600E) mutation was detected in 90% of PTC cases, and it occurred significantly more often in female patients than in male patients (p = 0.001). The clinicopathological parameters of age, tumor size, and disease stage were not associated with the BRAF (V600E) mutation, while extrathyroid invasion (p = 0.031), lymph nodal metastasis (p = 0.002), and tumor multiplicity (p = 0.020) were. CONCLUSIONS: The prevalence (90%) of the BRAF (V600E) mutation in this study is the highest ever reported, confirming the key role of this mutation in PTC tumorigenesis. The BRAF (V600E) mutation was associated with aggressive clinical behaviors including extrathyroid invasion, lymph nodal metastasis and tumor multifocality. The PNA clamp real-time PCR method for the BRAF (V600E) mutation detection is sensitive and is applicable in a clinical setting.