The analysis of genetic and clinicopathologic characteristics in patients with follicular thyroid neoplasm

Abstract

Objective: To explore the molecular characteristics of follicular variant papillary thyroid carcinoma (FVPTC), follicular thyroid adenoma (FTA) and follicular thyroid carcinoma (FTC), and investigate their role in tumorigenesis, differential diagnosis and prognosis evaluation in patients with follicular thyroid neoplasm. Methods: We retrospectively analyzed 50 surgical resection samples of follicular thyroid neoplasm. DNA was obtained from formalin-fixed, paraffin-embedded tissue, and subjected to next-generation sequencing (NGS) to analyze 50 hotspots for mutation in genes. Results: 47 samples passed quality control, including 29 FVPTCs, 8 FTAs and 10 FTCs. 75.9% of FVPTCs harbored mutated genes: BRAF V600E (31.0%, 9/29) was the most frequent, followed by TP53 (27.6%, 8/29), and N/KRAS (20.7%, 6/29). In contrast, 37.5% (3/8) FTAs carried NRAS Q61R mutation with 12.5% (1/8) FTA carrying mutated BRAF G466E. 20% (2/10) FTCs harbored NRAS Q61R mutation, and 20% (2/10) FTCs with TP53 mutations. BRAF V600E gene mutation only appeared in FVPTC, and was associated with age of onset and lymph node metastasis. There was no significant correlation between N/KRAS mutations and clinical pathologic features. Patients with lymph node metastasis group seems to have more TP53 mutation. Conclusions: BRAF V600E gene mutation can be used to identity FVPTC from FTA/FTC. N/KRAS mutations cannot be used as the exclusive indicator of benign and malignant in thyroid follicular tumor. TP53 mutations play an important role in the process of follicular thyroid neoplasm, indicating more aggressive behavior and poor prognosis.