Brachyury (Brachy) and Insulin Like Growth Factor Receptor I (IGF1R) Expression in Thyroid Nodular Pathology

MARTIN, AYELEN; FERNÁNDEZ, MARÍA CELIA; MASNATA, MARÍA EUGENIA; PAPENDIECK, PATRICIA; CLÉMENT, FLORENCIA; BARRIOS, EVELIN; DE MATTEO, ELENA; CHIESA, ANA; PENNISI PATRICIA

Congreso; Reunión Anual de Sociedades de Biociencias SAIC- SAI- SAFIS 2020; 2020

In pediatrics, thyroid tumor stratification is difficult to assess. Epithelial?mesenchymal transition (EMT), plays a role in tumor development. In human carcinomas Brachy has been identified as a regulator of EMT associated to malignancy. To date, no information about Brachy and IGF1R expression in pediatric thyroid nodular disease is available. Aim: To evaluate Brachy and IGF1R expression in thyroid nodular samples from pediatric patients and to study the effect of Brachy overexpression in a thyroid papillary carcinoma (TPC) cell line in vitro. Methods: Paraffin-embedded samples from pediatric patients with Thyroid Papillary Carcinomas (TPCa), Follicular Adenomas (FA) or Benign Thyroid Nodular disease (BTN) were processed for Brachy and IGF1R immunostaining. TPC cells were used to obtain clones overexpressing Brachy (TPC.BR50 and TPC.BR150). Gene expression was quantified by rqPCR. Proliferation assays (6 days) and wounding assays (24h) were carried out. Protein extracts were obtained from whole lysates and processed by western blot (WB). Results: 43 samples were analysed, 10 from BTN. Only TPCa and FA showed positive staining for Brachy (16/25TPCa;5/8FA) and IGF1R (12/25TPCa;3/8FA). In carcinomas, positivity for IGF1R was only detected when Brachy was present. Brachy overexpression in TPC cells (TPC50) increased proliferation vs parental cells (**p< 0.005,). Cell migration was also higher for Brachy overexpressing cells (**p< 0.005 TPC50 vs TPC), e-cadherin expression was diminished, and mesenchymal markers (vimentin-fibronectin) were increased. Finally, WB studies showed that Brachy overexpression was related to a higher IGF1R expression in TPC50 cells in comparison to parental cells. Conclusion: Brachy expression was associated to IGF1R expression in thyroid carcinomas. In vitro, Brachy overexpression had an impact on IGF1R expression, increased proliferation and migration. These results suggest a potential role for Brachy in the biology of thyroid tumors.