New Technologies for the Biomolecular Characterization of Thyroid Carcinoma

Abstract

In the last decades the epidemiology of the nodular thyroid pathology has been modified, with a progressive increase in the finding of nodules in the adult population associated with a similar tendency to the growth of the incidence of thyroid tumors. Nowadays, the fine-needle aspiration cytology (FNAC) is the most used diagnostic procedure to investigate the nature of thyroid nodules, however the success rate is varying between 70-95% of cases. The remaining 5-30% results in an indeterminate diagnosis, that needs to be followed by a diagnostic surgery, unnecessary for about the 70% of the cases, since the histological examination demonstrates its benign nature. BRAF V600E in papillary thyroid carcinoma (PTC) and NRAS Q61R in the follicular variant, can provide not only a diagnosis, but also a targeted therapeutic approach. The aim of the work, is to reduce the indeterminate cases of FNA (Fine Needle Aspiration) through the use of biomarkers by comparing routine cytology with molecular diagnostics. But usually this is quite insufficient and technically not optimal for in-depth investigations. From these limits CytoMatrix is born. It is a synthetic matrix that above all has the property of capturing and preserving the primitive aspirative cells within a three-dimensional structure, optimizing the management of lacking biological material such as the thyroid needle aspiration. The results were compared with the traditional cytology and then confirmed by the post-surgery histological examination: 83% diagnosed with Papillary carcinomas, falling within the estimate of Thyroid Carcinomas, which predicts the PTC between 80-90% , with mutational expression BRAF (V600E) between 45-80% and NRAS (Q61R) between 0-15%. The research of mutational markers with IHC, FISH and PCR Real-Time, shows an increase of success rate of 67%. This demonstrates not only the compatibility of the matrix with this type of examination, but also the potential application of CytoMatrix to support the differential diagnosis in Thyroid Pathology, for reducing the percentage of indeterminate cases. A more accurate diagnosis can steer the patient toward therapeutic follow-up or clinical surgery, thanks to the predictability of lesions associated with usage of molecular markers.