Endocrine Abstracts

Papillary thyroid carcinoma (PTC) is the most frequent histological subtype of thyroid cancers and BRAF^V600E genetic alteration is found in 60% of this endocrine cancer. BRAF^V600E tumors are associated with poor prognosis resistance to radioiodine therapy and tumor progression. Histological follow-up by anatomo-pathologists reveals that 2/3 of surgically-removed thyroid do not present malignant lesions. Continued fundamental research into the molecular mechanisms of thyroid cancer downstream of BRAF^V600E remains thus central to better understand the clinical behaviour of tumours, to improve differential diagnosis between thyroid cancer subtypes, to propose new therapies, and to avoid unnecessary surgery. To study PTC we used a mouse model in which expression of BRAF^V600E is specifically switched on in thyrocytes by doxycycline administration. Upon daily IP doxycycline injection thyroid tissue rapidly acquired histological features mimicking human PTC. Transcriptomic analysis revealed that two pathways: cytokine/cytokine receptor interaction and immune system were highly enriched upon BRAF^V600E induction. Multiplex immunofluorescence indeed confirmed the recruitment of abundant macrophages among which a population of CD206 ⁺/lyve-1⁺/Stab-1⁺ was dramatically increased. We decided to focus on this subpopulation of alternatively-activated macrophages by genetically inactivating the gene coding for the scavenger receptor Stabilin-1. We will present the results of our inactivation of Stabilin-1 in the context of in situ BRAF^V600E- dependent thyroid cancer and of the expression of Stabilin-1 in human thyroid cancers and other thyroid pathologies.