Prognostic Stratification of Highly Differentiated Thyroid Cancer Based on Molecular Genetic Studies.

[BACKGROUND] The aim of this literature review was to identify the critical role of molecular-genetic and epigenetic factors in predicting the course of differentiated thyroid carcinoma (DTC), to improve diagnostic and therapeutic strategies for this disease.

[METHODS] Analytical and comparative review methods of publications available in the databases of Scopus, Web of Science, and PubMed were employed.

[RESULTS] The results demonstrated that the presence of specific mutations and epigenetic modifications significantly influenced the likelihood of recurrence, metastatic potential, and tumour sensitivity to conservative treatment, including radioactive iodine therapy. Mutations in the  B-Raf kinase family protein, telomerase reverse transcriptase, rat sarcoma genes, and rearranged during transfection/papillary thyroid carcinoma rearrangements were shown to be associated with an increased risk of recurrence, metastatic activity, and reduced efficacy of radioiodine treatment. Epigenetic markers such as promoter methylation of tumour suppressor genes, global hypomethylation, and microRNAs (miR-146b, miR-221, miR-375) emerged as promising predictors of aggressive disease progression. The review outcomes indicate that a personalized approach based on identifying the molecular profile of the tumour allows for more accurate risk assessment of adverse outcomes and determination of prospects for targeted therapy.

[CONCLUSION] The practical significance of this work lies in the possibility of considering the identified genomic and epigenomic features when choosing surgical intervention and adjuvant therapy, thereby increasing the chances for long-term remission. Additionally, it emphasizes the standardization of analytical methods and the development of a unified system for evaluating the combined genetic alterations, which could enhance the quality of prognostic stratification and more effectively tailor treatment strategies.