Doerfler William R, Nikitski Alyaksandr V, Morariu Elena M, Ohori N Paul, Chiosea Simion I, Landau Michael S, Nikiforova Marina N, Nikiforov Yuri E, Yip Linwah, Manroa Pooja
Division of Endocrinology and Metabolism, University of Pittsburgh, Pittsburgh, Pennysylvania, USA.
Department of Pathology, University of Pittsburgh, Pittsburgh, Pennysylvania, USA.
Endocr Relat Cancer. 2021 Apr 27;28(5):301-309. doi: 10.1530/ERC-20-0435.
Hürthle cell carcinoma (HCC) is a distinct type of thyroid cancer genetically characterized by DNA copy number alterations (CNA), typically of genome haploidization type (GH-type). However, whether CNA also occurs in benign Hürthle cell adenomas (HCA) or Hürthle cell hyperplastic nodules (HCHN), and have diagnostic impact in fine-needle aspiration (FNA) samples, remains unknown. To address these questions, we (1) analyzed 26 HCC, 24 HCA, and 8 HCHN tissues for CNA and other mutations using ThyroSeq v3 (TSv3) next-generation sequencing panel, and (2) determined cancer rate in 111 FNA samples with CNA and known surgical outcome. We identified CNA, more often of the GH-type, in 81% of HCC and in 38% HCA, but not in HCHN. Among four HCC with distant metastasis, all had CNA and three TERT mutations. Overall, positive TSv3 results were obtained in 24 (92%) HCC, including all with ATA high risk of recurrence or metastasis. Among 111 FNA cases with CNA, 38 (34%) were malignant and 73 (66%) benign. A significant correlation between cancer rate and nodule size was observed, particularly among cases with GH-type CNA, where every additional centimeter of nodule size increased the malignancy odds by 1.9 (95% CI 1.3-2.7; P = 0.001). In summary, the results of this study demonstrate that CNA characteristic of HCC also occur in HCA, although with lower frequency, and probability of cancer in nodules with CNA increases with nodule size. Detection of CNA, in conjunction with other mutations and nodule size, is helpful in predicting malignancy in thyroid nodules.
许特尔细胞癌（HCC）是一种独特类型的甲状腺癌，其基因特征为DNA拷贝数改变（CNA），通常为基因组单倍体化类型（GH型）。然而，CNA是否也出现在良性许特尔细胞腺瘤（HCA）或许特尔细胞增生性结节（HCHN）中，以及对细针穿刺（FNA）样本是否具有诊断意义，仍不清楚。为了解决这些问题，我们（1）使用ThyroSeq v3（TSv3）下一代测序平台分析了26例HCC、24例HCA和8例HCHN组织的CNA及其他突变，（2）确定了111例有CNA且已知手术结果的FNA样本中的癌症发生率。我们在81%的HCC和38%的HCA中发现了CNA，HCHN中未发现，CNA更常为GH型。在4例有远处转移的HCC中，均有CNA，3例有TERT突变。总体而言，24例（92%）HCC的TSv3结果为阳性，包括所有ATA复发或转移高风险的病例。在111例有CNA的FNA病例中，38例（34%）为恶性，73例（66%）为良性。观察到癌症发生率与结节大小之间存在显著相关性，特别是在GH型CNA的病例中，结节大小每增加1厘米，恶性几率增加1.9（95%CI 1.3 - 2.7；P = 0.001）。总之，本研究结果表明，HCC特征性的CNA也出现在HCA中，尽管频率较低，且有CNA的结节中癌症发生概率随结节大小增加。检测CNA，并结合其他突变和结节大小，有助于预测甲状腺结节的恶性程度。
