Profile of BRAF V600E, BRAF K601E, NRAS, HRAS, and KRAS Mutational Status, and Clinicopathological Characteristics of Papillary Thyroid Carcinoma in Indonesian National Referral Hospital

Abstract

Introduction: BRAFV600E and RAS mutations are the most common gene mutations in papillary thyroid carcinoma (PTC) that may be correlated with its biological behavior. There are still limited data about BRAFV600E and RAS mutations in Indonesia. This study aims to determine the prevalence of BRAFV600E and RAS mutations, and their association with clinicopathologic characteristics.

Methods: Patients who had total thyroidectomy from 2019 to 2021 and those who met our study criteria underwent PCR and DNA sequencing analysis for BRAFV600E, BRAFK601E, exon 2 and 3 of NRAS, HRAS, and KRAS. Analyses were performed to determine the associations of BRAFV600E and RAS mutations with clinicopathologic characteristics.

Results: Of 172 PTC patients, BRAFV600E mutation was observed in 37.8% of the patients and RAS mutations were found in 21.5%. One patient harbored BRAFK601E mutation. There was a significant association of BRAFV600E with a high-stage (p = 0.033, OR: 3.279; 95% CI: 1.048-10.259), tall-cell variants (p ≤0.001, OR: 41.143; 95% CI: 11.979-141.308), non-encapsulated (p = 0.001, OR: 4.176; 95% CI: 2.008-8.685), lymphovascular invasion (p = 0.043, OR: 1.912; 95% CI: 1.018-3.592), extrathyroidal extension (p = <0.001, OR: 3.983; 95% CI: 1.970-8.054), and lymph node metastasis (p = 0.009, OR: 2.301; 95% CI: 1.224-4.326). Follicular variant (p = 0.001, OR: 7.011; 95% CI: 2.690-18.268), encapsulated (p = 0.017, OR: 2.433; 95% CI: 1.161-5.100), and absent of extrathyroidal extension (p = 0.033, OR: 2.890; 95% CI: 1.052-7.940) were associated with RAS mutations.

Conclusion: A significant association between BRAFV600E mutation and high clinical stage, tall-cell variants, non-encapsulated morphology, lymphovascular invasion, extrathyroidal extension, and lymph node metastasis in PTC was observed. RAS mutations were associated with the follicular variant, encapsulated tumor, and no extrathyroidal extension. HRAS-mutated PTC frequently exhibited tumor multifocality.

Keywords: BRAFK601E; BRAFV600E; RAS; clinicopathological characteristics; papillary thyroid carcinoma.