Department of Surgical, Medical, Molecular Pathology and Critical Area (Anatomical Pathology Section), University of Pisa, via Savi 10, 56126, Pisa, Italy.
Department of Clinical and Experimental Medicine (Endocrinology Section), University of Pisa, via Paradisa 2, 56124, Pisa, Italy.
J Endocrinol Invest. 2019 Feb;42(2):157-166. doi: 10.1007/s40618-018-0895-z. Epub 2018 Apr 27.
Fine-needle aspiration (FNA) cytology is a mainstay in the evaluation of thyroid nodules, but fails to reach reliable results in 25-30% of cases. The role of molecular markers in helping clinical decisions has been investigated for the last years, but their clinical usefulness is still unsettled.
Mutation analysis of BRAF, RAS genes and TERT promoter was performed in a series of 617 consecutive cytological specimens undergoing FNA.
The 617 nodules had the following cytological diagnosis: non diagnostic 22 (3.6%), benign 425 (68.9%), indeterminate 114 (18.5%), suspicious 11 (1.8%) and malignant 45 (7.3%). BRAF mutations were found in 31 cases (5.0%), all but two in suspicious and malignant nodules. RAS mutations were detected in 47 samples (7.6%): 25 benign (5.9%) and 19 indeterminate nodules (16.7%). TERT promoter mutation alone was detected in three samples. Histological outcome was available for 167 nodules, 81 of which proved malignant: all the 48 with suspicious or malignant cytology; 25 out of 56 (44.6%) with indeterminate and 8 out of 57 (14%) with benign cytology. BRAF mutations were associated with worse tumors pathological features. The presence of RAS mutations was indicative of follicular-patterned malignancies in 5 out of 8 benign nodules and 9 out of 11 indeterminate nodules.
Our study established mutational rates for BRAF and RAS genes in a large series of FNA specimens. BRAF mutations were confirmed as highly specific but not able to improve cytological diagnosis, while RAS testing proved effective in assessing malignancy in nodules with indeterminate and benign cytology.
细针穿刺细胞学检查（FNA）是评估甲状腺结节的主要方法，但在 25-30%的病例中无法得出可靠的结果。近年来，人们一直在研究分子标志物在辅助临床决策方面的作用，但它们的临床实用性仍未确定。
对 617 例连续进行 FNA 的细胞学标本进行 BRAF、RAS 基因和 TERT 启动子的突变分析。
617 个结节的细胞学诊断如下：非诊断性 22 例（3.6%），良性 425 例（68.9%），不典型 114 例（18.5%），可疑 11 例（1.8%）和恶性 45 例（7.3%）。31 例（5.0%）发现 BRAF 突变，均位于可疑和恶性结节中。47 例（7.6%）检测到 RAS 突变：25 例良性（5.9%）和 19 例不典型结节（16.7%）。单独检测到 TERT 启动子突变 3 例。167 个结节有组织学结果，其中 81 个为恶性：所有 48 个具有可疑或恶性细胞学特征的结节；56 个不典型结节中的 25 个（44.6%）和 57 个良性结节中的 8 个（14%）。BRAF 突变与肿瘤恶性程度较高有关。RAS 突变在 8 个良性和 9 个不典型结节中提示滤泡模式恶性肿瘤。
本研究在大量 FNA 标本中确定了 BRAF 和 RAS 基因突变率。BRAF 突变被证实具有高度特异性，但不能改善细胞学诊断，而 RAS 检测在评估不典型和良性细胞学结节的恶性程度方面是有效的。
