Diagnostic and Prognostic Molecular Markers in Thyroid Cancer

Abstract

Thyroid nodules are extremely common, which is accompanied with a rapidly rising incidence of diagnosed thyroid cancer in recent years. The main challenges currently encountered in the clinical management of thyroid nodule and thyroid cancer are the often indeterminate cytology on thyroid fine needle aspiration biopsy in the former case, which creates problematic diagnostic dilemmas, and the often prognostic uncertainty in the latter case, which causes much controversy in managing the risk-harm balance of treatment of thyroid cancer. Molecular markers have emerged to be highly promising in tackling these challenges. Considerable progress has occurred in recent years in the identification and development of diagnostic and prognostic molecular markers for thyroid nodule and thyroid cancer. Many such markers have been investigated and several of them are proven to be clinically useful and are increasingly used as adjunct diagnostic molecular tests with thyroid biopsy. The most prominent examples include the gene expression classifier, genetic panel of BRAF mutation, RAS mutations, RET-PTC and PAX8-PPARγ, and the protein marker galectin-3. The best characterized prognostic molecular maker is BRAF V600E mutation, which has been proven to be useful in assisting the risk stratification of PTC; this will now be further enhanced by the recently discovered TERT promoter mutations in thyroid cancer. Several other molecular markers, such as the peripheral blood-based DNA methylation markers and thyroid-stimulating hormone receptor mRNA, also hold promises as diagnostic and prognostic molecular markers for thyroid cancer. It is expected that further optimization and appropriate selection and application of the current and new molecular markers will significantly improve the management of thyroid nodule and thyroid cancer in various clinical settings.