BRAF<SUP>V600E</SUP> mutations but not RET/PTC rearrangements are correlated with a lower expression of NIS mRNA expression in papillary thyroid cancer (PTC)

Cristina Romei; Pamela Piampiani; Pinuccia Faviana; Fulvio Basolo; Valeria Bottici; Mariangela Sculli; Piero Berti; Gabriele Materazzi; Aldo Pinchera; Rossella Elisei

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Endocrine Abstracts (2007) 14 OC5.4

ECE2007 Oral Communications Thyroid basic (7 abstracts)

BRAF^V600E mutations but not RET/PTC rearrangements are correlated with a lower expression of NIS mRNA expression in papillary thyroid cancer (PTC)

Cristina Romei ¹ , Pamela Piampiani ¹ , Pinuccia Faviana ³ , Fulvio Basolo ³ , Valeria Bottici ¹ , Mariangela Sculli ¹ , Piero Berti ² , Gabriele Materazzi ² , Aldo Pinchera ¹ & Rossella Elisei ¹

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Author affiliations

¹Department of Endocrinology, University of Pisa, Pisa, Italy; ²Department of Surgery, University of Pisa, Pisa, Italy; ³Department of Oncology, University of Pisa, Pisa, Italy.

Several studies have identified a relationship between oncogene activation and dedifferentiation of PTC. Mutations of RAS, RET/PTC and BRAF modulate the expression of thyroid genes. An impaired NIS expression has been demonstrated in PTCs harboring the BRAF^V600E mutation.Aim of this study was to analyze BRAF and RET/PTC1-3 alterations and their influence on the expression of thyroid differentiation genes. Seventy-one PTC samples were studied. Quantitative analysis of TPO, Tg, TSH-R, TTF1 and NIS were performed by real time RT-PCR. Our results indicate that 44/71 cases (62%) were positive for one genetic alteration and 7/71 (9.8%) showed the simultaneous presence of 2 gene mutations. In particular BRAF^V600E and RET/PTC rearrangements were present in 32.2% and 19.7% of cases respectively. BRAF^V600E was more frequently found in the classical than in the follicular variant (P=0.02). At variance no correlation was identified between RET/PTC rearrangement and clinico-pathological features of PTCs. Genetic alterations were correlated with mRNA expression (ΔCt) of Tg, TPO, TSH-R, TTF-1, NIS. mRNA expression of NIS gene was significantly lower (P=0.0001) in PTCs harbouring the BRAF mutation with respect to not mutated samples. By immunohistochemistry we did not find any relationship between BRAF^V600E and NIS protein. No difference in NIS mRNA expression was found in PTC with or without RET/PTC rearrangements. We did not observe any significant difference in the expression of thyroid differentiation genes neither when compared with BRAF mutation or RET/PTC rearrangements. Furthermore no relationship was found between serum TSH and the expression of NIS mRNA in thyroid tumors. In conclusion our data indicate that (a) the frequency of BRAF^V600E mutations and RET/PTC rearrangements was 35% and 20% respectively; (b) in our series 10% of PTC cases harbored 2 different genetic alterations; (c) NIS mRNA expression was significantly lower in PTCs harboring a BRAF mutation but not a RET/PTC rearrangement; (d) the expression levels of other thyroid differentiation genes were not correlated with the presence of gene alterations.