Preoperative detection of papillary and medullary thyroid cancer metastases in the lymph nodes of the neck lateral cellular tissue using a molecular classifier

Abstract

Introduction. The main method of preoperative diagnosis of thyroid tumors and the identification of possible metastasis is a cytological examination of smears obtained by fine-needle aspiration biopsy. However, the cytological material of the lymph nodes may not be adequate, and the detection of metastases faces a number of difficulties. In our recent study, we described a variant of the molecular classifier that allows the detection and typing of malignant thyroid tumors by analyzing several molecular markers in cytological preparations.The study objective was to assess the applicability of the developed method for the preoperative detection of metastases of papillary and medullary thyroid cancer in the lymph nodes of the neck lateral cellular tissue.Materials and methods. A total of 86 cytological samples were used, obtained from individual lymph nodes of 62 patients who had a diagnosis – thyroid cancer. Samples were analyzed by real-time polymerase chain reaction regarding the preselected set of molecular markers: the BRAF V600E mutation, the normalized concentration of HMGA2, FN1 and SERPINA1 mRNA, 5 miRNAs and the mitochondrial/nuclear DNA ratio. The decision tree-based classifier was used to discriminate between benign and malignant samples.Results. The previously described classifier, based on the analysis of the BRAF V600E mutation, the content of HMGA2 mRNA, 3 miRNAs and the mitochondrial/nuclear DNA ratio, revealed metastases of thyroid cancer with good specificity (98 %) but less sensitivity (83 %). Therefore, a new classifier was built, including three markers – HMGA2 and FN1 mRNA, and miRNA-375, which, with regard to the detection of metastases, showed good sensitivity – 93 % with a slight decrease in specificity (up to 96 %).Conclusion. Thus, we demonstrated the possibility of preoperative detection of thyroid cancer metastases in the lymph nodes of the neck lateral cellular tissue by analyzing several molecular markers in cytological material.