Endocrine Abstracts

Angiotensin-converting enzyme 2 (ACE2), Transmembrane serine protease 2 (TMPRSS2) and Furin were known to be key players for the SARS-CoV-2 infection. Thyroid gland was shown to be one of the relevant targets for SARS-CoV-2 infection allegedly due to the higher expression levels of these molecules in follicular cells. However, it remains to be fully determined the expression of ACE2, TMPRSS2 and Furin in normal follicular cell. In addition, the putative role of these molecules in the neoplastic transformation of the thyrocytes has never been explored. We aimed to characterize the expression of ACE2, TMPRSS2 and Furin in a series of thyroid lesions in comparison to adjacent thyroid. To attain this objective, we quantified the mRNA expression of these molecules by RT-qPCR in 191 samples that included, adjacent thyroid tissue (AT), and benign and malignant neoplasms. We also performed IHQ on 68 samples of FFPE thyroid tissues to understand the expression pattern of these proteins in situ. The results were correlated with the clinicopathological and molecular data available (https://doi.org/10.3390/cancers12071846). Our results revealed a significant decrease of ACE2 mRNA in all thyroid lesions when compared with ATs. On the other hand, Furin showed a significant increase in the mRNA levels, particularly in adenomas, but also in carcinomas, when compared with ATs. Interestingly, within carcinomas, follicular carcinomas seemed to have a decreased expression of Furin when compared with papillary carcinomas. Regarding the clinicopathological and molecular data, ACE2 expression was significantly increased in smaller adenomas (P < 0.05), with the presence of lymphocytic infiltrate (P < 0.005), specifically thyroiditis (P < 0.01), and positive expression of TERT mRNA. Furin mRNA expression was significantly increased in tumours from male patients (P = 0.005) and in cases that presented lymph node metastasis (P < 0.05). On the other hand, Furin expression was significantly decreased in tumours with NRAS mutations (P < 0.05). No significant differences were found concerning TMPRSS2. Regarding protein expression in the tissue samples, the pattern of expression observed for ACE2 was membranous, limited to the cells in small vessels. The expression was increased in benign lesions when compared to ATs and papillary carcinomas (P < 0.05). Cytoplasmic expression of TMPRSS2 was decreased in malignant lesions when compared to AT and Furin nuclear staining was significantly increased in adenomas when compared to thyroid carcinomas and ATs. Our study shows that the expression of these three molecules is altered in thyroid neoplastic lesions but further studies are needed to understand their putative role in tumorigenesis of the thyroid gland.