Abstract
Objective: Fine needle aspiration (FNA) is a procedure used in the diagnosis of thyroid nodules. A definitive diagnosis is not possible when FNA shows follicular cells, and therefore a surgical intervention is necessary. Identifying genetic expression patterns in FNA samples of indeterminate thyroid nodules could assist in distinguishing benign from malignant follicular thyroid lesions. Methods: Patients with follicular cells on FNA and a pathologic diagnosis of either follicular thyroid adenoma (FTA) or carcinoma (FTC) were included. Thyroid tissue was collected at the time of definitive surgery. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) was used with an array profiler including 84 genes involved in transformation and tumorigenesis. RT2 Profiler PCR array data analysis software identified fold-change based upon ΔΔCt calculations. Gene expression was normalized to five housekeeping genes. Results: Nineteen patients were included: 10 with FTA and 9 with FTC on post-operative pathology. In the FTC group, 11 genes had greater than 2-fold up or down-regulation relative to the adenoma group; and two genes reached statistical significance, caspase-8 and IL-8 (p ≤ 0.05). Utilizing the Sub-Network Enrichment Analysis (SNEA) algorithm, sub-networks of genes involving the transforming growth factor (TGF) family and peroxisome proliferator-activated receptor delta (PPARδ) family were both highly regulated. Conclusions: Our preliminary data identify two potential genes that may aid in differentiating FTC from FTA, and demonstrates a potential role for qRT-PCR of FNA samples. This may contribute to the workup of thyroid nodules to ultimately guide the treatment of indeterminate follicular lesions.
Highlights
5-10% of the general population is diagnosed with a thyroid nodule in their lifetime
This study aims to identify candidate genetic markers using a wide array of previously identified genes implicated in carcinogenesis that may potentially distinguish between follicular thyroid adenoma (FTA) and follicular thyroid carcinoma (FTC), thereby leading to their potential use in a biomarker panel that may be used in the pre-operative clinical setting of indeterminate thyroid nodules
Patients were recommended surgical intervention by a single surgeon in the form of a thyroid lobectomy, total thyroidectomy, or lobectomy followed by completion thyroidectomy, based on current guidelines and a discussion between the patient and surgeon
Summary
5-10% of the general population is diagnosed with a thyroid nodule in their lifetime. Most thyroid nodules are benign; ruling out malignancy is necessary as this affects patient treatment and outcomes [1]. Fine needle aspiration (FNA) remains an integral component in the evaluation of a thyroid nodule, and has reduced the rate of thyroid surgery for patients with benign nodules. Previous experience has demonstrated that up to 86% of resected nodules were benign [2]. The benefits of FNA-directed evaluation of a nodule include simplicity of the procedure, economic efficiency and overall reliability to distinguish between benign and malignant disease [2,3,4]. While FNA is simple and accurate, there are particular scenarios where differentiation of benign and malignant cytology becomes difficult
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