Circulating thyroid cancer biomarkers: Current limitations and future prospects

Differentiated thyroid cancer (DTC) is the most common malignancy of the endocrine system. There has been a significant increase in its incidence over the past two decades attributable mainly to the use of more sensitive diagnostic modalities. Ultrasound-guided fine needle aspiration cytology is the mainstay of diagnosis of benign disorders and malignancy. However, approximately 20% of lesions cannot be adequately categorized as benign or malignant. In the postoperative setting, monitoring of thyroglobulin (Tg) levels has been employed for the detection of disease recurrence. Unfortunately, Tg antibodies are common and interfere with Tg measurement in this subset of patients. Despite this limitation, Tg remains the sole widely used thyroid cancer biomarker in the clinical setting. In an attempt to bypass antibody interference, research has focused mainly on mRNA targets thought to be exclusively expressed in thyroid cells. Tg and thyroid stimulating hormone receptor (TSHR) mRNA have been extensively studied both for discerning between benign disease and malignancy and in postoperative disease surveillance. However, results among reports have been inconsistent probably reflecting considerable differences in methodology. Recently, microRNA (miRNA) targets are being investigated as potential biomarkers in DTC. MiRNAs are more stable molecules and theoretically are not as vulnerable as mRNA during manipulation. Initial results have been encouraging but large-scale studies are warranted to verify and elucidate their potential application in diagnosis and postoperative surveillance of thyroid cancer. Several other novel targets, primarily mutations and circulating cells, are currently emerging as promising thyroid cancer circulating biomarkers. Although interesting and intriguing, data are limited and derive from small-scale studies in specific patient cohorts. Further research findings demonstrating their value are awaited with anticipation.