Endocrine Abstracts

Oxidative stress (OS) can have an impact both in the pathogenesis and in the progression of TC, as it has been shown to induce oncogenes and inhibit tumor suppressors. The main source of cellular ROS is represented by NADPH oxidases (NOXs). Aims of the study were to investigate the NOX-derived OS in TC samples, benign nodules and corresponding normal tissues, and to correlate the level of OS with histological classification, genetic profile and clinical and prognostic features of patients. Twenty-four papillary (PTCs), 6 follicular (FTCs) and 3 anaplastic thyroid tumors (ATCs), 4 noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFPTs), 8 follicular adenomas (FAs), 4 Hurtle adenomas (HAs) and contra-lateral normal tissues were included in the study. H2O2 generation by NOXs in the cytoplasmic fraction of tumoral and normal tissues was measured using the fluorescent Amplex Red Reagent. The molecular profile of tumor samples was characterized by a custom AmpliSeq DNA/RNA NGS panel (Illumina) in which the most common mutations/fusions found in TC are included. The median of H2O2 generation considering all tumors and benign lesions was significantly higher than that obtained in all normal tissues analyzed. When compared with the corresponding normal tissues, differences in H2O2 production were found only in PTCs and FTCs (P = 1.2*10-6, 5.8*10-5, respectively). Interestingly, when we stratified PTCs for genetic variants, only PTCs with mutations in TERT and BRAF or BRAF alone showed an increased H2O2 generation compared with the corresponding normal tissues (P = 0.03 and 6.1*10-5, respectively). Moreover, H2O2 production in FTCs resulted higher compared to FA and to PTCs (P = 0.003). Finally, the H2O2 production in PTCs with high/intermediate ATA risk resulted significantly higher compared with that obtained in low ATA risk PTCs (P = 0.02). In conclusion, our data indicate that thyroid tumors are exposed to a higher OS compared to normal tissues. Moreover, the level of NOX4-generated ROS correlates with BRAF and TERT mutations and with worst tumor presentation in PTCs. The high OS associated with thyroid tumors may have diagnostic, prognostic and therapeutic relevance.