Abstract 5402: A panel of miRNAs for diagnosis of wild-type thyroid nodules with pre-surgical indeterminate cytology
Authors: Denaro Maria , Condello Vincenzo , Ugolini Clara , Macerola Elisabetta , Poma Anello Marcello , Materazzi Gabriele , Vitti Paolo , Basolo Fulvio 
Published: August 2018

Abstract
Fine-needle aspiration (FNA) cytology is the gold standard for the evaluation of thyroid nodules, but about 30% are cytologically indeterminate. The inability to resolve preoperative thyroid nodules as benign or malignant is therefore a challenge. Molecular tests in FNA are useful to assist the diagnosis and the management of patients. However, if a thyroid nodule is indeterminate and genetic tests are inconclusive, surgical excision may be considered for definitive diagnosis. To overcome these limitations, novel diagnostic procedures and molecular tests are required. Among these, miRNAs have been reported as promising molecular markers in thyroid cancer.
The aim of this study was to evaluate the potential diagnostic utility of miRNA expression in preoperative diagnosis of thyroid nodules with indeterminate cytology and wild type in RAS family genes and BRAF gene.
The miRNA expression profile was evaluated in a small cohort of 12 wild-type Follicular Adenomas (FAs) and 4 wild-type Infiltrative Follicular Variant of Papillary Thyroid Carcinomas (IFVPTCs) with pre-surgical indeterminate cytology or in patients with cytological diagnosis not available. The two groups have been selected with similar characteristics in terms of age of patients, nodules size and with a ratio Male-Female 1:3. The expression of 798 miRNAs has been evaluated by using nCounter Nanostring technology, a sensitive and reproducible method. The differential miRNAs expression between FAs and IFVPTCs was investigated by applying the non-parametric Mann-Whitney U-test. In addition, an unsupervised hierarchical clustering analysis by Pearson correlation was performed.
We found a set of 13 miRNAs differentially expressed between malignant and benign lesions. miR-222-3p, miR-30d-5p, miR-100-5p, miR-1972, miR-125b-5p, miR-155-5p were significantly up-regulated, whereas miR-574-5p, let-7f-5p, miR-148a-3p, miR-598-3p, miR-195-5p, miR-301a-3p, miR-5196-3p+hsa-miR-6732-3p were significantly down-regulated in IFVPTCs compared to FAs (p-value&lt;0,05). The unsupervised hierarchical clustering analysis has identified 2 main clusters: the first one consisted of 9 FAs, whereas the second one consisted of 4 IFVPTCs and 3 FAs. The 4 IFVPTCs are grouped in an unique sub-cluster with a correlation of 0,74. This miRNA expression profile could distinguish malignant from benign lesions. If these results will be confirmed in a wide cohort of patients and in FNA cytology, this strategy could increase the diagnostic yield and improve the preoperative diagnosis of wild-type thyroid nodules with indeterminate cytology.
Although this is a preliminary study, the deregulation of this set of miRNAs might help identify malignant nodules that are negative for well-known gene alterations in preoperative FNAs.
Citation Format: Maria Denaro, Vincenzo Condello, Clara Ugolini, Elisabetta Macerola, Anello Marcello Poma, Gabriele Materazzi, Paolo Vitti, Fulvio Basolo. A panel of miRNAs for diagnosis of wild-type thyroid nodules with pre-surgical indeterminate cytology [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 5402.