Current status of the prognostic molecular markers in medullary thyroid carcinoma

Abstract

Medullary thyroid cancer (MTC) is a rare thyroid malignancy, which arises from parafollicular C-cells. It occurs in the hereditary or sporadic form. Hereditary type is a consequence of activation of the RET proto-oncogene by germline mutations, whereas about 80% of sporadic MTC tumors harbor somatic, mainly RET or rarely RAS mutations. According to the current ATA guidelines, a postoperative MTC risk stratification and long-term follow-up are mainly based on histopathological data, including tumor stage, the presence of lymph node and/or distant metastases (TNM classification), and serum concentration of two biomarkers: calcitonin (Ctn) and carcinoembryonic antigen (CEA). The type of RET germline mutation also correlates with MTC clinical characteristics. The most common and the best known RET mutation in sporadic MTC, localized at codon 918, is related to a more aggressive MTC course and poorer survival. However, even if histopathological or clinical features allow to predict a long-term prognosis, they are not sufficient to select the patients showing aggressive MTC courses requiring immediate treatment or those, who are refractory to different therapeutic methods. Besides the RET gene mutations, there are currently no other reliable molecular prognostic markers. This review summarizes the present data of genomic investigation on molecular prognostic factors in medullary thyroid cancer.

Novel Inhibitor-Based Therapies for Thyroid Cancer—An Update

“…In case of widespread regional or metastatic disease, surgical interventions are not associated with a higher cure rate, therefore, less aggressive local treatment procedures should be preferred. Systemic therapy is employed in multi-metastatic and rapidly progressing malignancies [ 61 , 104 , 105 ].…”

“…As already mentioned, current guidelines on management of MTC patients recommend cabozantinib and vandetanib as the first-line single-agent systemic therapy in patients with advanced progressive MTC, based on their documented ability to improve PFS ( Table 1 ). Both drugs inhibit RET kinase activity to some extent, however, their major anticancer effect is due to their strong inhibition of angiogenesis [ 13 , 61 , 105 , 155 ]. The list of on-going clinical trials for treatment of MTC is provided in Table 4 .…”

“…The RET alteration determines distinct phenotypes of MTC that may differ in terms of age of disease onset and aggressiveness. For example, malignancies harboring the RET M918T somatic mutation that is the most frequent genetic change in sporadic MTCs, are related to a more aggressive MTC course and worse survival [ 61 , 62 ].…”

Prognosis of radiotherapy in medullary thyroid carcinoma patients without distant metastasis

“…Prognosis of radiotherapy in medullary thyroid carcinoma patients without distant metastasis MTC currently has a poor prognosis and few clinical treatments, and it presents more advanced disease symptoms and a worse prognosis than well-differentiated thyroid carcinoma (5). On presentation, half of patients have local lesions, while 35% of patients extend to surrounding tissues and 13% of patients have distant metastases (6).…”

Papillary Thyroid Carcinoma Landscape and Its Immunological Link With Hashimoto Thyroiditis at Single-Cell Resolution

“…Single-cell transcriptomes provided new insights into cell-cell interactions in multiple types of cancer (Zhang et al, 2019;Davis et al, 2020;Wieland et al, 2020). Some molecular studies reported the advances in follicular thyroid carcinoma and medullary thyroid carcinoma (Ceolin et al, 2012;Mohammadi and Hedayati, 2017;Borowczyk et al, 2019;Oczko-Wojciechowska et al, 2020). A recent scRNA-seq study made a comparison of tumor microenvironment (TME) in PTC between genders (Peng et al, 2021).…”