POSSIBILITIES OF PREOPERATIVE DIAGNOSIS OF IODINE RESISTANCE REGIONAL LYMPH NODES METASTASES OF DIFFERENTIATED THYROID CANCER

Abstract

Recently, there has been an increase in the incidence and detectability of patients with differentiated thyroid cancer. At the same time in a number of patients in the combined treatment, initially low susceptibility of regional metastases to radioiodine therapy is revealed, or iodine resistance develops during treatment, which significantly worsens the prognosis. The need to identify patients with radioiodine resistance at the preoperative stage to justify the scope of surgical treatment is an extremely important task.

Objective of research. The research was developed to examine the possibility of preoperation diagnostics of iodine-refractory regional metastases for in patients with differentiated thyroid cancer. A number of patients with differentiated thyroid cancer develop iodine-refractory regional metastases, which significantly worsens the prognosis. Given contradictory attitude towards prophylactic lymph node dissection in the central neck area and an increase in the number of organ-preserving operations, we have searched for a method of preoperative diagnosis of radioiodine-resistance.

Materials and methods. The results of treatment of 67 patients with differentiated thyroid cancer were analyzed, which after radioiodine therapy metastases in cervical lymph nodes were revealed. Depending on the results of post-therapy scintigraphy, patients were divided into two groups: with iodine-positive (n = 32) (first group) and iodine-negative (n = 35) metastases (second group). All patients were operated on again, the presence of metastases was confirmed morphologically, and the expression of the TERT, TG, SLC5, KRT19, KRT5, ERBB2, 2 reference genes GUSB and B2M was analyzed and the status of the BRAF gene (mutation search V600E).

Results. When comparing the results of molecular genetic studies in both groups, differences in the average expression of the SLC5 gene (NIS), the frequency of the wild-type BRAF gene, and, in addition, the ratios of the mutant (V600E) and non-mutated alleles of the BRAF gene (p = 0,05; p = 0,013 and p = 0,034). The combination of 5 indicators: the expression level of SLC5, KRT5, ERBB2, the non-mutated status of the BRAF gene, the proportion of the mutant (V600E) / non-mutant alleles of the BRAF gene, predict the probability of resistance of regional metastases to radioiodine - in 90,9% of cases, and in 75,0% of cases - preservation of their ability to fix the radionuclide.

The conclusion. The level of SLC5, KRT5, ERBB2 gene expression, the non-mutated status of the BRAF gene, the ratio of the number of mutant (V600E) / non-mutant alleles of the BRAF gene in the biopsy material allow before the operation to predict the effectiveness of the forthcoming radioiodine therapy and, and at supposed resistance radioiodine therapy to form indications to prophylactic lymph node dissection in the central neck area. The possibility of such a prognosis based on the results of a primary tumor study requires further clarification.