The preoperative diagnostics of medullary thyroid carcinoma (MTC), including the measuring of the blood calcitonin level, has a number of limitations. Particular focus has recently been placed on the role of miRNAs in the development of various malignant tumors; a comparative analysis of accuracy of the existing methods for MTC diagnosis with a novel diagnosis method, evaluation of the miRNA-375 expression level, was performed in this study. The expression level of miRNA-375 in cytology samples from 555 patients with the known histological diagnosis, including 41 patients with confirmed postoperative diagnosis of MTC, was assessed. The diagnostic parameters of the basal calcitonin level, calcitonin in wash-out fluid from the FNAB needle, and miRNA-375 were compared. An assessment of the miRNA-375 expression level made it possible to detect all the MTC samples with a 100% accuracy among all the 555 cytology specimens, as well as in non-informative FNAB specimens, and specimens from the ipsilateral thyroid lobe. Parameters such as sensitivity, specificity, PPV, and NPV were 100%. The miRNA-375 level, unlike calcitonin, does not correlate with tumor volume, so it does not have the so-called “gray zone”. An assessment of the miRNA-375 expression allows one to accurately distinguish MTC from other malignant and benign thyroid tumors.

Molecular genetic events are among the numerous factors affecting the clinical course of papillary thyroid carcinoma (PTC). Recent studies have demonstrated that aberrant expression of miRNA, as well as different thyroid-related genes, correlate with the aggressive clinical course of PTC and unfavorable treatment outcomes, which opens up new avenues for using them in the personalization of the treatment strategy for patients with PTC. In the present work, our goal was to assess the applicability of molecular markers in the preoperative diagnosis of aggressive variants of papillary thyroid cancer. The molecular genetic profile (expression levels of 34 different markers and BRAF mutations) was studied for 108 cytology specimens collected by fine-needle aspiration biopsy in patients with PTC having different clinical manifestations. Statistically significant differences with adjustment for multiple comparisons (p < 0.0015) for clinically aggressive variants of PTC were obtained for four markers: miRNA-146b, miRNA-221, fibronectin 1 (FN1), and cyclin-dependent kinase inhibitor 2A (CDKN2A) genes. A weak statistical correlation (0.0015 < p < 0.05) was observed for miRNA-31, -375, -551b, -148b, -125b, mtDNA, CITED1, TPO, HMGA2, CLU, NIS, SERPINA1, TFF3, and TMPRSS4. The recurrence risk of papillary thyroid carcinoma can be preoperatively predicted using miRNA-221, FN1, and CDKN2A genes.

Introduction. Post-transcriptional mechanisms play a crucial role in the biological course and clinical manifestations of papillary thyroid cancer (PTC). Recent studies show that an increased content of oncogenic or reduced content of oncosuppressive microRNAs increases the aggressiveness of the tumor and correlates with an unfavorable prognosis of treatment, which allows them to be used in personalizing the treatment tactics of patients with PTC. The study objective is to compare the level of expression of 12 PTC-specific microRNAs and the frequency of V600E mutation of the BRAF gene in patients with different risk of relapse. Materials and methods. The study included 175 patients with PTC. For quantitative analysis of microRNA expression, a reverse transcription reaction followed by a real-time polymerase chain reaction in formalin-fixed paraffin blocks was used. Correlations between 12 microRNA expression and BRAF mutation with different clinical and anatomical features of PTC the risk of relapse according to the American Thyroid Association Risk Stratification System (2009) were analyzed. Results. We demonstrated that miR-146b, miR-221, miR-144, miR-451a, and miR-7 expression correlated with features such as extrathyroid tumor growth, larger size, multifocus, lymph node metastasis, and the presence of distant metastases of the PTC. Most importantly, miR-221, miR-144, miR-451a, and miR-7 expression correlated with risk levels, suggesting their potential significance in stratifying the risk of relapsing PTC. The dependence of the clinical behavior of PTC on the BRAF mutation has not been established.Conclusion. The result of the study will contribute to the individual choice of preoperative treatment tactics for patients with PTC.

Background. Anaplastic thyroid cancer (ATC) is one of the most aggressive human tumors. Since median survival of ATC patients is only 4 months, its early diagnosis is very important. Although ATC has specific clinical manifestations, the analysis of expression of different microRNAs can facilitate preoperative diagnostics and help to detect its potential precursors among differentiated cancers and other thyroid malignancies.The study objective is to identify microRNAs specific for ATC that are different from microRNAs in other thyroid cancers.Materials and methods. We analyzed the expression of 14 microRNAs in histological specimens of 67 patients with ATC. The control groups included 25 patients with benign nodules, 36 patients with follicular adenomas, 32 patients with follicular cancer, and 152 patients with papillary thyroid cancer. For 7 out of 67 ATC patients, we compared mi-croRNA levels in histological and cytological specimens.Results. Patients with ATC demonstrated a statistically significant decrease in the expression of miR-145, miR-125b and increase in the expression of miR-155 and miR-21 compared to all control groups. We found two reliable diagnostic markers of ATC: relative miR-21 expression (at a cutoff of 14.9, sensitivity was 0.955 and specificity was 0.837) and the miR-21/miR-145 ratio (at a cutoff of 122, sensitivity was 0.955 and specificity was 0.955). The level of miR-21 expression and miR-21/miR-145 ratio in cytological specimens were accurate in all 7 cases (100 %).Conclusion. the level of expression of specific microRNAs can be used as a reliable biomarker for ATC. The consistency between the results obtained in cytological and histological specimens enables the use of stained cytological samples for this analysis.

Among the unsolved problems in the treatment of patients with nodular thyroid pathology, there is a large number of diagnostic operations associated with difficulties in cytological diagnostics of follicular neoplasia, limited by opportunities in preoperative assessment of the malignant potential of thyroid cancer. A decrease in the effectiveness of targeted therapy in patients with radioiodresistant thyroid cancer occurs due to the ability of the tumor to activate parallel proliferative signaling pathways. It is assumed that the key to solving these problems lies in understanding various genetic changes in the tumor cell, such as point mutations, insertions and deletions, gene merges, rearrangements or gene translocations. A special place in this list is occupied by microRNAs. It is a class of small non-coding RNAs, which regulate post-transcriptional gene expression and thereby participate in cell differentiation, proliferation, angiogenesis, apoptosis resistance and activation of thyroid cancer metastasis. This review contains information about microRNAs detected in various types of thyroid tumors of diagnostic, prognostic and therapeutic interest. While some of them have been introduced into routine practice, others are new and require additional research before clinical use.