Objective: BRAFV600E causes up-regulation of TIMP-1, promoting cell invasion in papillary thyroid carcinoma (PTC). HIF-1α is regulated by hypoxia but also by BRAFV600Emediated signaling pathway in PTC. We assessed the impact on clinical behavior in PTC of TIMP-1, HIF-1α and the hypoxia-inducible CAIX and CAXII. Method: The protein expression was assessed by Western blot in two cell lines, TPC-1/BRAFWT and BCPAP/ BRAFV600E. TMA-immunohistochemistry analysis was used to study protein expression in 114 PTC samples. BRAF status was analyzed by pyrosequencing. Data were correlated with clinicopathological variables of patients. Results: Higher expression of all proteins was detected in BCPAP exposed to hypoxia. TIMP-1 expression displayed 87 % sensitivity and 83 % specificity for identifying BRAF mutation (P<0.001), and was associated with pT-stage (P= 0.001), pN-stage (P= 0.02), and multifocality (P=0.03). HIF-1α expression was correlated to pT-stage (P=0.05). CAIX expression was related to pN-stage (P=0.02), and both CAIX (P=0.004) and CAXII (P=0.05) were highly associated with vascular invasion. Conclusion: TIMP-1 protein expression is reliable surrogate of BRAF mutated status in PTC. TIMP-1 and hypoxiaregulated proteins have potential for future use as predictors of the malignant change in PTC, and warrant further investigation as new therapeutic targets for the treatment of highly aggressive form of PTC. Objective: MTC are usually aggressive tumours which account for 3-5 % of all thyroid carcinomas. Most of MTC are sporadic, the remaining tumours are due to hereditary forms with germline activating mutations of the RET proto-oncogene. The aim of this study was to assess the microRNA profiling expression in both sporadic and hereditary forms of MTC. Method: A total of 40 frozen MTC from patients with welldocumented clinico-pathological parameters were used for microarray analyses (14 HMTC and 26 SMTC) using Human MicroRNA Mircoarray Kit version 2 (Agilent Technologies). After identification of a set of miRNA of interest, validation was done using qPCR. Results: When comparing HMTC harbouring germinal RET mutation with SMTC, seven miRNAwere significantly deregulated (miR-96, −10a, −376c, −15a, −7-2*, −106b, −132). The most highly discriminative miRNA in tumoral samples (>3 fold change) identify miR-375, −129-3p, −136, −376c and −451. Moreover, 5 miRNA could segregate MTC with good prognosis and better clinical outcome (miR-137, −144, −224, −144 and −224) . Conclusion: A specific microRNA signature in HMTC can be identified. Moreover, detection of microRNAs in tissue samples might be of interest for improved clinical management and treatment of patients with MTC.