IN HYPOPHOSPHATASIA (HPP), DEFICIENT ALP can ruin bones, bodies, and lives. Alexion Endocrinology, Diabetes & Metabolism Case Reports

ISSN 1470-3947 (print)
ISSN 1479-6848 (online)

Searchable abstracts of presentations at key conferences in endocrinology

Published by BioScientifica
Endocrine Abstracts (2007) 14 OC5.4 

BRAFV600E mutations but not RET/PTC rearrangements are correlated with a lower expression of NIS mRNA expression in papillary thyroid cancer (PTC)

Cristina Romei1, Pamela Piampiani1, Pinuccia Faviana3, Fulvio Basolo3, Valeria Bottici1, Mariangela Sculli1, Piero Berti2, Gabriele Materazzi2, Aldo Pinchera1 & Rossella Elisei1

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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 BRAFV600E 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 BRAFV600E and RET/PTC rearrangements were present in 32.2% and 19.7% of cases respectively. BRAFV600E 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 BRAFV600E 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 BRAFV600E 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.