Department of Oncology, University of Turin, Orbassano, Turin, Italy.
Pathology Unit, San Luigi Hospital, Turin, Italy.
Cancer Cytopathol. 2022 Sep;130(9):695-704. doi: 10.1002/cncy.22585. Epub 2022 May 2.
The molecular characterization of thyroid nodules in cytological samples has so far been focused on discriminating between benign and malignant forms in a purely diagnostic setting. The evidence on the impact of molecular biomarkers to determine the risk of aggressiveness in cytologically "neoplastic" lesions is limited to genomic alterations (such as BRAF and TERT mutations). The aim of our study was to assess the preoperative role of microRNAs (miRNAs) in predicting the nodal status of patients with papillary thyroid cancer.
A pilot series of histological samples of papillary thyroid carcinoma with (6 cases) or without (6 cases) lymph node metastases, matched for other major clinical and pathological features, was analyzed for global miRNA expression in a screening phase. A set of miRNAs was then validated in a series of 63 consecutive cytological samples of papillary carcinomas: 48 pN-negative and 15 pN-positive at histology.
Unsupervised cluster analysis segregated surgical pN-negative and pN-positive samples, except for 1 case. The 45 differentially expressed miRNAs in pN-positive versus pN-negative cases were predicted to regulate a wide range of cellular pathways, enriched for Wnt, gonadotropin-releasing hormone receptor, and cerulein/cholecystokinin receptor signaling. In agreement with their profiles in surgical samples, 4 miRNAs of the 10 selected for validation (miR-154-3p, miR-299-5p, miR-376a-3p, and miR-302E) had a significant differential expression in cytological samples of papillary carcinoma with lymph node metastases and predicted the positive nodal status with a relatively good performance.
MiRNA profiling is a potential promising strategy to define papillary carcinoma aggressiveness in the preoperative setting.
迄今为止，甲状腺结节的分子特征主要集中在纯诊断环境中区分良性和恶性形式。关于分子生物标志物确定细胞学“肿瘤性”病变侵袭性风险的证据仅限于基因组改变（如 BRAF 和 TERT 突变）。我们的研究旨在评估 microRNAs (miRNAs) 在预测甲状腺乳头状癌患者淋巴结状态中的术前作用。
在筛选阶段，对有（6 例）或无（6 例）淋巴结转移的甲状腺乳头状癌组织学样本进行了全 miRNA 表达的初步系列分析，这些样本匹配了其他主要临床和病理特征。然后，在一系列 63 例连续的甲状腺乳头状癌细胞学样本中验证了一组 miRNA：48 例 pN 阴性和 15 例组织学 pN 阳性。
未监督聚类分析将手术 pN 阴性和 pN 阳性样本分开，除了 1 例。在 pN 阳性与 pN 阴性病例中，45 个差异表达的 miRNA 被预测调节广泛的细胞途径，富集 Wnt、促性腺激素释放激素受体和蓝斑/胆囊收缩素受体信号。与手术样本中的表达谱一致，在验证中选择的 10 个 miRNA 中的 4 个（miR-154-3p、miR-299-5p、miR-376a-3p 和 miR-302E）在具有淋巴结转移的甲状腺乳头状癌细胞学样本中具有显著的差异表达，并具有相对较好的性能预测阳性淋巴结状态。
miRNA 谱分析是术前确定甲状腺乳头状癌侵袭性的一种很有前途的策略。
