From Circulating Tumor Cells to Mirna: New Challenges in the Diagnosis and Prognosis of Medullary Thyroid Cancer

Abstract

Medullary thyroid carcinoma (MTC) is a malignant tumor that arises from parafollicular C cells, which are responsible for producing calcitonin. The majority (75%) of MTC cases are sporadic forms, while the remaining (25%) have a hereditary component. In these hereditary cases, MTC can occur in conjunction with other endocrine disorders (i.e., pheochromocytoma) or as an isolated condition known as familial medullary thyroid carcinoma. The primary genetic mutation associated with the development of MTC, regardless of its hereditary or sporadic nature, is a point mutation in the RET gene. Evaluation of serum calcitonin levels represents the most reliable and sensitive marker for both the initial diagnosis and the postsurgical monitoring of MTC. Unfortunately, most patients do not achieve normalization of postsurgical serum calcitonin (CT) levels after surgery. Therefore, there is a need to find new biomarkers to be used with serum CT in order to increase test sensitivity and specificity. In this review, we summarize the literature from 2010 to 2023 to review the role of circulating tumor cells, cell-free DNA, and miRNA and their application in diagnosis, outcome of MTC, and response to treatments.

Keywords: cell-free DNA; circulating tumor cells; extracellular vesicles; medullary thyroid cancer; miRNA.

Figure 1

RET gene domains and different mutation sites.

Figure 2

Graphical representation of distant site colonization by a circulating tumor cell (CTC) detached from a primary site (created in BioRender.com).

Figure 3

p.M918T represents the most common mutation found in cfDNA from medullary thyroid cancer. The scheme reports study results and the role of cfDNA in diagnosis or in outcome [29,30,31,32,33].