Context: BRAF mutations are common in papillary thyroid carcinomas (PTCs). By affecting the expression of genes critically related to the development and differentiation of thyroid cancer, they may influence the prognosis of these tumors. Objective: Our objective was to characterize the expression of thyroid-specific genes associated with BRAF mutation in PTCs. Design/Setting and Patients: We examined the expression of key markers of thyrocyte differentiation in 56 PTCs with BRAF mutations (BRAF-mut) and 37 with wild-type BRAF (BRAF-wt). Eight samples of normal thyroid tissue were analyzed as controls. Quantitative PCR was used to measure mRNA levels for the sodium/ iodide symporter (NIS), apical iodide transporter (AIT-B), thyroglobulin (Tg), thyroperoxidase (TPO), TSH receptor (TSH-R), the transcription factor PAX8, and glucose transporter type 1 (Glut1). NIS protein expression and localization was also analyzed by immunohistochemistry. Results: mRNA levels for all thyroid-specific genes were reduced in all PTCs vs. normal thyroid tissues. NIS, AIT-B, Tg, and TPO expression was significantly lower in BRAF-mut tumors than in the BRAF-wt group. Glut-1 transcript levels were increased in all PTCs, and additional increases were noted in BRAF-mut tumors. In both tumor subsets, the NIS protein that was expressed was abnormally retained in the cytoplasm. Conclusion: BRAF V600E mutation in PTCs is associated with reduced expression of key genes involved in iodine metabolism. This effect may alter the effectiveness of diagnostic and/or therapeutic use of radioiodine in BRAF-mut PTCs.

BRAF mutations in papillary thyroid carcinomas inhibit genes involved in iodine metabolism / Durante, Cosimo; E., Puxeddu; Ferretti, Elisabetta; Roberta, Morisi; S., Moretti; R., Bruno; F., Barbi; N., Avenia; Scipioni, Angela; Verrienti, Antonella; Emanuele, Tosi; A., Cavaliere; Gulino, Alberto; Filetti, Sebastiano; D., Russo. - In: THE JOURNAL OF CLINICAL ENDOCRINOLOGY AND METABOLISM. - ISSN 0021-972X. - 92:7(2007), pp. 2840-2843. [10.1210/jc.2006-2707]

BRAF mutations in papillary thyroid carcinomas inhibit genes involved in iodine metabolism

DURANTE, COSIMO;FERRETTI, ELISABETTA;SCIPIONI, Angela;VERRIENTI, Antonella;GULINO, Alberto;FILETTI, SEBASTIANO;
2007

Abstract

Context: BRAF mutations are common in papillary thyroid carcinomas (PTCs). By affecting the expression of genes critically related to the development and differentiation of thyroid cancer, they may influence the prognosis of these tumors. Objective: Our objective was to characterize the expression of thyroid-specific genes associated with BRAF mutation in PTCs. Design/Setting and Patients: We examined the expression of key markers of thyrocyte differentiation in 56 PTCs with BRAF mutations (BRAF-mut) and 37 with wild-type BRAF (BRAF-wt). Eight samples of normal thyroid tissue were analyzed as controls. Quantitative PCR was used to measure mRNA levels for the sodium/ iodide symporter (NIS), apical iodide transporter (AIT-B), thyroglobulin (Tg), thyroperoxidase (TPO), TSH receptor (TSH-R), the transcription factor PAX8, and glucose transporter type 1 (Glut1). NIS protein expression and localization was also analyzed by immunohistochemistry. Results: mRNA levels for all thyroid-specific genes were reduced in all PTCs vs. normal thyroid tissues. NIS, AIT-B, Tg, and TPO expression was significantly lower in BRAF-mut tumors than in the BRAF-wt group. Glut-1 transcript levels were increased in all PTCs, and additional increases were noted in BRAF-mut tumors. In both tumor subsets, the NIS protein that was expressed was abnormally retained in the cytoplasm. Conclusion: BRAF V600E mutation in PTCs is associated with reduced expression of key genes involved in iodine metabolism. This effect may alter the effectiveness of diagnostic and/or therapeutic use of radioiodine in BRAF-mut PTCs.
2007
01 Pubblicazione su rivista::01a Articolo in rivista
BRAF mutations in papillary thyroid carcinomas inhibit genes involved in iodine metabolism / Durante, Cosimo; E., Puxeddu; Ferretti, Elisabetta; Roberta, Morisi; S., Moretti; R., Bruno; F., Barbi; N., Avenia; Scipioni, Angela; Verrienti, Antonella; Emanuele, Tosi; A., Cavaliere; Gulino, Alberto; Filetti, Sebastiano; D., Russo. - In: THE JOURNAL OF CLINICAL ENDOCRINOLOGY AND METABOLISM. - ISSN 0021-972X. - 92:7(2007), pp. 2840-2843. [10.1210/jc.2006-2707]
File allegati a questo prodotto
Non ci sono file associati a questo prodotto.

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/357675
 Attenzione

Attenzione! I dati visualizzati non sono stati sottoposti a validazione da parte dell'ateneo

Citazioni
  • ???jsp.display-item.citation.pmc??? 125
  • Scopus 323
  • ???jsp.display-item.citation.isi??? 295
social impact