Predicting malignancy in thyroid nodules: molecular advances

Over the last several years, a clearer understanding has developed of the genetic alterations underlying thyroid carcinogenesis. This knowledge can be used to tackle 1 of the challenges facing thyroidologists: management of the indeterminate thyroid nodule. Despite the accuracy of fine-needle aspiration cytology, many patients undergo surgery to diagnose malignancy and better diagnostic tools are required. A number of biomarkers have recently been studied and show promise in this setting. In particular, BRAF, RAS, PAX8-PPARγ, microRNAs, and loss of heterozygosity have each been demonstrated as useful molecular tools for predicting malignancy and can potentially guide decisions regarding surgical management of nodular thyroid disease. This review summarizes the current literature surrounding each of these markers, highlights our institution's prospective analysis of these markers, and describes the subsequent incorporation of molecular markers into a management algorithm for thyroid nodules.