Abstract
INTRODUCTION: Encapsulated follicular variant of papillary thyroid carcinoma (EFVPTC) has been reclassified into noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) and invasive EFVPTC. NIFTP is considered a low-risk neoplasm. Therefore, follicular variant of papillary thyroid cancer (FVPTC) presently has two distinct histopathological subtypes - invasive EFVPTC and infiltrative/diffuse FVPTC. Molecular characteristics of these groups remain unclear. METHODOLOGY: Thirty FVPTCs (10 NIFTPs, 12 invasive EFVPTCs, and 8 infiltrative/diffuse variants) were reviewed and screened for BRAF and RAS mutations by restriction fragment length morphism-polymerase chain reaction (PCR) and Sanger sequencing. The mRNA expression levels of iodine-metabolizing genes were analyzed using real-time PCR. The mutations status and mRNA expression levels were correlated with clinicopathological features. RESULTS: All 10 NIFTPs had predominant follicular pattern. One case showed NRAS mutation, whereas none showed BRAF mutation. All invasive EFVPTC had capsular and/or lymphovascular invasion and 4/12 showed lymph node metastasis. BRAF and NRAS were seen in three cases each of invasive FVPTC. All eight infiltrating/diffuse FVPTCs showed infiltration into adjacent thyroid parenchyma and lymph node metastasis. CONCLUSION: BRAF mutation was observed in 62.5% of cases; however, no NRAS mutation was found. Sodium iodide symporter (NIS) expressions in NIFTP were similar to that of normal thyroid tissue, whereas it was downregulated in invasive and infiltrative/diffuse FVPTC. Our study supports the argument that NIFTP can be considered as low-risk follicular thyroid neoplasm. Those tumors that harbor BRAF mutations may be offered a complete thyroidectomy because they show decreased expression of NIS gene which confers a tendency to lose radioactive iodine avidity and further recurrence of the tumor.