Activity of Ecto-5'-nucleotidase (NT5E/CD73) is Increased in Papillary Thyroid Carcinoma and Its Expression is Associated with Metastatic Lymph Nodes

The incidence of papillary thyroid carcinoma (PTC) has been increasing, which raised the interest in its molecular pathways. Although the high expression of ecto-5'-nucleotidase (NT5E) gene expression and NT5E enzymatic activity in several types of cancer is associated with tumor progression, its role in PTC remains unknown. Here, we investigated the AMP hydrolysis in human normal thyroid cells and PTC cells, in primary culture, and the association of NT5E expression with clinical aspects of PTC patients. AMPase activity was higher in thyroid cells isolated from PTC, as compared to normal thyroid (P = 0.0063). Significant correlation was observed between AMPase activity and NT5E levels in primary thyroid cell cultures (r = 0.655, P = 0.029). NT5E expression was higher in PTC than in the adjacent non-malignant thyroid tissue (P = 0.0065) and were positively associated with metastatic lymph nodes (P = 0.0007), risk of recurrence (P = 0.0033), tumor size (P = 0.049), and nodular hyperplasia in the adjacent thyroid parenchyma, when compared to normal thyroid or lymphocytic thyroiditis (P = 0.0146). After adjusting for potential confounders, the malignant/non-malignant paired expression ratio of NT5E mRNA was independently associated with metastatic lymph nodes (P = 0.0005), and tumor size (P=0.0005). In addition, the analysis of PTC described in the TCGA database also showed an association between higher expression of NT5E and metastatic lymph nodes, and tumor microinvasion. These results support the hypothesis that NT5E have a role in PTC microenvironment and might be a potential target for PTC therapy.