Прогностическое значение тестирования соматических мутаций и различных методов лечения при высокодифференцированном раке щитовидной железы низкого риска

Abstract

Background: Using molecular testing for prediction the course of the disease could possibly help doctors in making therapeutic decisions about the management of patients, because it remains controversial issues in low-risk differentiated thyroid cancer patients. The expert’s opinions are different on the volume of treatment of these patients: the adequacy of hemitireoidectomy, the need to remove the lymph nodes of the central zone (level VI) and the need for radioiodine therapy. Aims: to evaluate the frequency of recurrences in different complex treatment options of low-risk differentiated thyroid cancer; to evaluate the frequency of somatic mutations in the hot spots of BRAF, KRAS, KRAS, EIF1AX and TERT genes in histological material and to evaluate their prognostic value. Materials and methods: A prospective, observational, cohort, sample, single-center, open-label, controlled, nonrandomized clinical trial was performed, which included patients with the thyroid neoplasms, recruited in the period from 2012 to 2014. Samples of histological material were tested for the presence of somatic mutations in hot spots of the genes BRAF, KRAS, NRAS, TERT , and EIF1AX . After the treatment, the low-risk differentiated thyroid cancer patients group were observed for 43–68 months. Results: The study included 90 patients with low-risk well differentiated thyroid cancer. Mutations in the hot spots of the BRAF gene (exon 15, codon area 600-601) were found in 53 patients, mutations in the hot spots of the NRAS gene (exon 3, codon 61) – in 3 patients; mutations in the hot spots of the KRAS, TERT and EIF1AX genes were not detected. The median follow-up in the well differentiated thyroid cancer group was 56 months. Recurrence diagnosed in 12 patients (13.3%), significant differences in the frequency of recurrence depending on the surgical treatment option was not revealed, significant differences in the frequency of recurrence between the groups BRAF+/BRAF was not revealed. Conclusions: Low-risk well differentiated thyroid cancer patients have characterized a very favorable the course of disease and prognosis, even in the case of recurrence. In this study, complex treatment has not shown significant advantages over thyroidectomy in treating patients with thyroid microcarcinomas. Mutation testing of histological material in hot spots of genes BRAF, KRAS, NRAS, EIF1AX and TERT can’t be used as an additional marker in low-risk well differentiated thyroid cancer patients to predict the course of the disease, although the lack of detection of aggressive genes of the disease may indicate a favorable prognosis in these patients.