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.
目的： 探讨甲状腺滤泡型乳头状癌(FVPTC)、滤泡性腺瘤(FTA)及滤泡癌(FTC)的分子生物学特征，并分析其基因变异状态在甲状腺滤泡性肿瘤发生起源、鉴别诊断及预后评估中的意义。 方法： 提取50例甲状腺滤泡性肿瘤组织的DNA，进行二代基因测序(NGS)，分析50个癌症相关热点基因的变异状态。 结果： NGS基因检测结果质控合格47例。29例FVPTC中，22例检测到基因突变，BRAF V600E基因突变最常见(9例)，其次是TP53基因突变(8例)和NRAS基因突变(4例)。8例FTA中，NRAS Q61R突变3例，BRAF G466E突变1例。10例FTC中，NRAS Q61R突变2例，TP53基因突变2例。BRAF V600E基因突变只出现于FVPTC中，与患者发病年龄(P＝0.022)、淋巴结转移(P＝0.015)有关，RAS基因突变与各临床病理特征无关，TP53突变与淋巴结转移有关(P＝0.009)。 结论： BRAF V600E基因突变可用于辅助鉴别诊断FVPTC与FTA、FTC，N/KRAS基因突变不能作为甲状腺滤泡性肿瘤良恶性鉴别诊断的唯一指标。TP53基因突变在甲状腺滤泡性肿瘤的发生发展过程中起着重要作用，可能提示肿瘤侵袭性更高，患者预后更差。.
Keywords: Follicular thyroid adenoma; Follicular thyroid carcinoma; Follicular variant papillary thyroid carcinoma; Gene mutation; Next-generation sequencing.