EN19 - Organoids of Canine Medullary Thyroid Carcinoma and Feline Thyroid Adenomatous Hyperplasia (ESVE Award Winner)

Abstract: Background - Aetiology and pathophysiology of canine medullary thyroid carcinoma (cMTC) and functional feline thyroid adenomatous hyperplasia (fTAH) remain poorly understood. 3D organoid culture could constitute an excellent in vitro model.

Hypothesis/Objectives - Establish and characterize patient-derived organoid cultures of cMTC and fTAH, explore new therapeutic options for cMTC in cMTC organoids and evaluate the effect of TSH on growth and thyroid hormone (TH) production in fTAH organoids.

Animals - One frozen cMTC and fTAH patient-derived tissue sample.

Methods - Organoids from one cMTC and fTAH were cultured. Histology and immunohistochemistry for thyroglobulin, calcitonin, vimentin and Ki-67 were performed. While immunohistochemistry for thyroid transcription factor-1 (TTF-1) and synaptophysin was also performed on cMTC organoids. CellTiter-Blue^® viability assays were used to evaluate the effect of carboplatin, meloxicam and toceranib phosphate on cMTC organoid growth and to evaluate the effect of different concentrations of TSH on fTAH organoid growth. TH production by fTAH organoids was evaluated after incubation with sodium iodide and different TSH-concentrations.

Results - Organoids were cultured for 99 (cMTC) and 65 (fTAH) days. Organoids resembled the primary tissue histologically. TTF-1 and calcitonin immunolabeling in cMTC organoids confirmed thyroid and C-cell origin. fTAH organoid cells showed thyroglobulin immunolabeling (5-10%) and no calcitonin immunolabeling. No drug had effect on cMTC organoid growth. TSH had no effect on fTAH organoid growth and no TH production was detected.

Conclusions and clinical importance - Organoid cultures provide a promising in vitro model to explore pathophysiology and new treatment modalities for cMTC and fTAH.