BRAF and RAS Mutational Status in Noninvasive Follicular Thyroid Neoplasm with Papillary-Like Nuclear Features and Invasive Subtype of Encapsulated Follicular Variant of Papillary Thyroid Carcinoma in Korea

Abstract

Background: Noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) is an indolent thyroid tumor previously known as noninvasive subtype of encapsulated follicular variant of papillary thyroid carcinoma (EFVPTC). The absence of BRAF^V600E mutations has been considered characteristic of NIFTPs. However, a recent study from Korea found that 28.6% of NIFTPs harbored a BRAF mutation. This study evaluated BRAF and RAS mutations in NIFTPs and invasive subtype of EFVPTCs.

Methods: This study enrolled 32 patients with NIFTP and 48 with invasive EFVPTC. BRAF, NRAS, HRAS, and KRAS mutations were evaluated by direct sequencing using DNA from fresh-frozen tissues and formalin-fixed, paraffin-embedded tissue samples.

Results: The primary tumor size of NIFTP was smaller than that of invasive EFVPTC (median 2.8 cm vs. 3.2 cm; p = 0.03). Cervical lymph node metastases were found in only four (8%) patients with invasive EFVPTC. There was no BRAF mutation in NIFTPs, whereas invasive EFVPTCs had three (6%) BRAF^V600E mutations and one (2%) BRAF^K601E mutation. RAS mutations were detected in 15 (47%) NIFTPs and 22 (46%) invasive EFVPTCs. NRAS mutations in codon 61 were the most common mutations in NIFTPs (34%) and invasive EFVPTCs (27%). There was no significant difference in the frequency of RAS mutations between the two groups.

Conclusions: There was no BRAF mutation in any of the NIFTPs. RAS mutations, particularly mutations in codon 61 of NRAS, were the most common mutations in both NIFTPs and invasive EFVPTCs. The presence of a RAS mutation is not helpful for preoperative differentiation between NIFTPs and invasive EFVPTCs.

Keywords: BRAF; RAS; biomarker; encapsulated follicular variant papillary thyroid carcinoma; mutation.