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Departments of¹ Endocrinology and Metabolism² Oncology³ Surgery, University of Pisa, 56100 Pisa, Italy⁴ Department of Internal Medicine, Endocrinology and Metabolism, and Biochemistry, University of Siena, 53100 Siena, Italy⁵ AMBISEN Center, High Technology Center for the Study of the Environmental Damage of the Endocrine and Nervous Systems, University of Pisa, 56124 Pisa, Italy

(Correspondence should be addressed to R Elisei, Department of Endocrinology, University of Pisa, Via Paradisa 2, 56124 Pisa, Italy; Email: relisei{at}endoc.med.unipi.it)

A low sodium iodide symporter (NIS) expression has been shown in papillary thyroid carcinomas (PTCs) harboring the BRAF^V600E mutation. In the present study, we analyzed the mRNA expression of thyroid differentiation genes, glucose transporter (GLUT)-1 and GLUT-3, in 78 PTCs according to the presence of BRAF^V600E or RET/PTC rearrangements. We found BRAF^V600E and RET/PTC rearrangements in 35.8 and 19.4% of PTCs respectively. The mRNA expression of NIS and thyroperoxidase (TPO) genes were significantly lower (P<0.0001 and P=0.004 respectively) in BRAF^V600E-positive PTC with respect to non-mutated samples. In support of this result, immunohistochemistry showed that the percentage of NIS-positive cells was significantly lower (P=0.005) in BRAF^V600E-mutated PTC (mean 53.5%) than in negative cases (mean 72.6%). In contrast, no difference either in NIS or in any other thyroid differentiation genes' mRNA expression was found in PTC with or without RET/PTC rearrangements. When GLUT-1 and GLUT-3 mRNA expression was considered, no correlation was found either in BRAF^V600E- nor in RET/PTC-mutated cases. In conclusion, this study confirmed the presence of a genetic alteration of BRAF and/or RET oncogenes in 64% of PTC cases and revealed a significant correlation of BRAF^V600E mutation with a lower expression of both NIS and TPO. This latter finding could indicate that an early dedifferentiation process is present at the molecular level in BRAF^V600E-mutated PTC, thus suggesting that the previously demonstrated poor prognostic significance of BRAF^V600E mutation could be related to the dedifferentiation process more than to a more advanced stage at diagnosis.

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