Somatic mutation testing: the role in differential diagnosis of thyroid neoplasms

Background: In the preoperative diagnosis of thyroid tumors the cytological examination of the material of fine needle aspiration biopsy is the gold standard and serves as the basis for planning of treatment strategy. However, in 10–30% of cases, it cannot be clearly established by cytology whether the nature of thyroid neoplasm benign or malignant, which leads to the inability to choose the optimal treatment strategy in advance. For such cases, it is extremely important to search for methods of clarifying differential diagnosis, among which mutation testing is currently considered the most promising.

Aims: To evaluate the possibility of using mutation tests for clarifying differential diagnosis of thyroid neoplasms at the preoperative stage.

Materials and methods: We performed the prospective single center study, which included patients with the thyroid neoplasms, who had been treated in the Endocrinology Research Center, Moscow, Russia from 2012 to 2014. Samples of histological material, cytological material and blood plasma of these patients were tested for the presence of somatic mutations in hot spots of the genes BRAF, KRAS, NRAS, TERT, and EIF1AX.

Results: The study included 75 patients, 29 of them with low-risk papillary thyroid cancer, 29 with follicular neoplasm NA of the thyroid gland and 17 with colloid nodular goiter. Mutations in the “hot spots” of the BRAF gene (exon 15, codon area 600–601) were found in 29 patients, mutations in the “hot spots” of the NRAS gene (exon 3, codon 61) – in 8 patients; mutations in the hot spots of the KRAS, TERT and EIF1AX genes were not detected. Correlation of the results of mutational testing of cytological and histological material was 91.7%. Mutations of tumor origin in circulating blood plasma DNA were found in only 1 cases. The prognostic value of the positive result (PPV) of the mutation test on cytological material in relation to the malignant nature of the thyroid tumor was 100% for the BRAF gene and 0% for the NRAS gene.

Conclusions: The mutation test in the “hot spots” of the BRAF gene on cytological material can be used as an additional marker to clarify the nature of thyroid tumors, when the result of cytological examination are uncertain. Either in similar situations for mutation tests in the “hot spots” of genes KRAS, NRAS, EIF1AX and TERT on cytological material, or mutation testing of circulating DNA of blood plasma can’t be used as an additional marker.

thyroid neoplasms, thyroid cancer, differential diagnosis, indeterminate result of thyroid cytology, molecular testing, somatic mutations, genes BRAF, KRAS, NRAS, TERT, EIF1AX

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