**1. Introduction**

Thyroid cancer is relatively infrequent malignancy, which accounts for about 1–5% of the cancer cases in women and less than 2% in men [1]. Although, it is one of the most common cancer among endocrine malignancies accounting for more than 95% of new cases in the United States [2, 3], according to American Cancer Society, thyroid cancer in the United States in 2019

© 2016 The Author(s). Licensee InTech. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. © 2019 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

is estimated to be about 53,070 new cases (40,260 in men and 37,810 in woman), and more than 2000 people will die from the disease [3]. As well as in the rest of the world, the incidence of thyroid cancer has increased threefold over the past 30 years and is expected to increase by 50–60% between 2010 and 2020 [3–5]. The increase in thyroid cancer incidence rates could be explained by thyroid ultrasound screening with improved technical performance of the equipment, as well as better access to medical examination [1, 6].

also from non-tumor cells after exercise, trauma, or inflammation [10]. Extraction of circulating tumor DNA (ctDNA) alone is a difficult process; therefore mutation in cfDNA particles is being searched and indicates the presence of tumor. A lot of mutation has been analyzed in different types of tumors, for example, epidermal growth factor receptor mutation in nonsmall cell lung cancer. At present, it is the only liquid biopsy test that has granted and has

Liquid Biopsy in Patients with Thyroid Carcinoma http://dx.doi.org/10.5772/intechopen.85356 89

By liquid biopsy, cfRNA can be analyzed but this particle is not as stable as cfDNA, therefore it is harder to investigate. Another circulating cell-free nucleic acid—microRNAs—is a new and more stable tumor marker in the blood. Exosomes are microvesicles (40–150 nm) that are released in the blood from tumors and normal cells as well. Exosomes contain proteins, DNA, RNA, miRNA, lipids, and metabolites. Tumor-educated platelets (TEPs) are anucleated cell fragments that can be educated by the transfer of tumor-associated particles, mostly

The large increase in the incidence of thyroid cancer is seen in papillary thyroid cancer (PTC) which represents the major histological type [12]. PTC accounts for 85% of thyroid malignancy [13]. World Health Organization has defined PTC as a malignant epithelial tumor showing follicular cell differentiation and a specific signs of nuclear features which include nuclear enlargement and overlapping, irregular nuclear contours, and nuclear pseudoinclusions or nuclear grooves, as well as optically clear nuclei [14]. PTC measuring 1 cm or smaller in the greatest dimension is defined as papillary thyroid microcarcinoma (PTMC). It is suggested that incidence of PTC increased largely due to an increase in the incidence of PTMC, probably due to thyroid ultrasound screening with improved technical performance of the equipment, as well as better access to medical examination. Foci of PTMC have been reported in up to 22%

The main therapeutic method which is used after the diagnosis of PTC is a total of subtotal thyroidectomy with or without radioactive iodine (RAI) and thyroid hormone suppression. Afterward monitorization of disease status is necessary for all the PTC patients which is carried out by measuring levels of serum thyroid-stimulating hormone (TSH) and serum thyroglobulin (Tg) in the blood. Neck ultrasonography is also performed to detect persistent or recurrent PTC nodules in the thyroid gland after treatment [16]. However, if thyroglobulin antibodies (TgAb) are found in the blood, serum thyroglobulin could not be used as a reliable tumor marker because of false negative rate. Furthermore, long time period is needed to observe the changes in the levels of serum TgAb, and this may lead to late diagnosis [17]. Therefore, other biomarkers need to be discovered and used to monitor persistent or recur-

A new diagnostic tool—liquid biopsy—can be used to analyze circulating tumor cells (CTCs) or circulating epithelial cells (CECs) and circulating cell-free tumor DNA (ctDNA) in the blood

FDA approval [9, 11].

RNA [9, 10].

rent disease.

**3. Papillary thyroid cancer and liquid biopsy**

of surgical thyroid specimens and up to 36% of autopsy series [6, 15].

Although, there are no significant rise in thyroid cancer mortality rates, growing detection of indolent forms may lead to overtreatment of the patients by performing unnecessary thyroidectomies [7]. General postoperative complications, such as fever, hemorrhages, infection, or cardiopulmonary and thromboembolic events, as well as specific complicationssuch as hypoparathyroidism/hypocalcemia and vocal cord/fold paralysis can be seen. In large population-based study, 27,912 patients were included and analyzed. General postoperative complications were observed in 6.5% of the patients and surgery-specific complications in 12.3% [8]. The diagnostic gold standard for thyroid cancer is the evaluation of histological features, although there still are some differential diagnostic difficulties. To avoid complications, a new, more precise diagnostic tool is necessary to diagnose and manage thyroid cancer patients.

Liquid biopsy is a usual blood sampling method, referred to as a noninvasive procedure to detect components of the tumor which circulates in the bloodstream, for example, circulating tumor cells (CTCs), cell-free nucleic acids, exosomes, or tumor-educated platelets (TEPs); thus it can be a promising method in tumor diagnostics prior to surgery, as well as in monitoring of the disease [9].
