P82a

Abstract

Preoperative differential diagnosis of benign thyroid nodules and thyroid cancer is an important issue of endocrinology. Preoperative identification of a tumor type allows a surgeon to determine an adequate surgical treatment and reduce complications. The cytological analysis of samples obtained by the fine-needle aspiration biopsy is limited in sensitivity and specificity and the core biopsy is not safe to be used in patients with thyroid nodes smaller than 2 cm. The most promising area in the preoperative diagnosis of malignant tumors is molecular biomarkers, which can be used to determine the surgical treatment and indications for the target therapy. BRAF V600E is the most frequent genetic alteration in thyroid cancer. It activates the MAP-kinase pathway which causes changes in expression levels of extracellular matrix proteins and some of their receptors. Changes in the expression of integrin receptors and their ligands, such as osteopontin and thrombospondin-1, contribute to tumor cell proliferation and migration. The C-Jun pathway is also very important in pathogenesis of thyroid cancer. Changes in its activity can affect the expression of GSTP enzyme which participates in hormone metabolism. Altered MiRNA expression has been observed in a variety of cancer states allowing their potential use as cancer biomarkers. The aim of this study was to evaluate integrins, angiogenic factors, GSTP and MiRNAs as potential biomarkers for the diagnosis and prognosis of thyroid cancer. 112 samples of papillary thyroid cancer (PTC) and 120 samples of benign nodular neoplasms were analyzed. The expression levels of the studied genes were determined by RT-PCR. The results were confirmed by immunohistochemical analysis. The BRAF V600E mutation was determined by allele-specific real-time PCR. The results showed that GSTP can be used for clinical settings as a cancer-specific marker for thyroid neoplasms with 83–88% sensitivity, 70–80% specificity and 76–84% diagnostic accuracy. Higher expression levels of integrins α2, α5, αv, α9, β1, β3 and IL-8, angiogenin, and VEGF were observed in malignant tumors in comparison with the normal thyroid tissue (p < 0.05). The BRAF V600E mutation was detected in 70% of all PTC cases. In the BRAF V600E positive PTC samples the levels of ITGA3 and ITGAV expression were higher than in the BRAF V600E negative ones (p < 0.05). The expression of miRNA 21, 221, 222, 155 was significantly increased in the cancer samples compared to the benign neoplasms. Thus, the studied molecular markers could be used for preoperative diagnosis of thyroid neoplasms and the treatment approach.