Immunohistochemical analysis of thyroid follicular neoplasms and BRAF mutation correlation.

BACKGROUND: The accurate diagnosis of benign and malign thyroid tumors is very important for the clinical management of patients. The distinction of thyroid papillary carcinoma follicular variant and follicular adenoma can be difficult. AIM: To investigate the alternative methods like immunohistochemistry and exon 15 in the BRAF gene 1799 T/A mutation analyses for distinguishing thyroid tumors. MATERIALS AND METHODS: We applied immunohistochemical markers; CK19, HMWCK, Galectin‑3, HBME‑1 and Fibronectin and mutant allelespecific PCR amplification technique was used to determine 1799 T/A mutation within the BRAF gene. Formalin‑fixed parafin embedded tissues from 45 surgically total resected thyroids, included 26 thyroid papillary carcinoma follicular variant (FV‑TPC), 8 Follicular Adenoma (FA), 6 Minimal invasive follicular carcinoma (MIFC) and 5 Follicular Carcinoma (FC). STATISTICAL ANALYSES USED: Pearson Chi‑Square and Kruskal Wallis tests were performed. RESULTS: There was a positive correlation between FV‑TPC and HMWCK, CK 19, HBME1, Galectin 3, fibronectin (P < 0.05), but there was no correlation with FV‑TPC and BRAF gene mutation (P > 0.05). HBME‑1 and CK 19 stained strong and diffuse positive in FV‑TPCs but weak and focal in FAs. CONCLUSION: Our study suggests that morphologic features combined with immunohistochemical panel of HMWCK, CK19, HBME‑1, Galectin‑3 and fibronectin can help to distinguish benign and malign thyroid neoplasms and FV‑TPC from follicular adenomas. BRAF gene 1799 T/A mutation has been non‑specific but its detection can be a useful tool combined with immunohistochemistry for diagnosing FV‑TPC.

The importance of sodium/iodide symporter (NIS) for thyroid cancer management

The thyroid gland has the ability to uptake and concentrate iodide, which is a fundamental step in thyroid hormone biosynthesis. Radioiodine has been used as a diagnostic and therapeutic tool for several years. However, the studies related to the mechanisms of iodide transport were only possible after the cloning of the gene that encodes the sodium/iodide symporter (NIS). The studies about the regulation of NIS expression and the possibility of gene therapy with the aim of transferring NIS gene to cells that normally do not express the symporter have also become possible. In the majority of hypofunctioning thyroid nodules, both benign and malignant, NIS gene expression is maintained, but NIS protein is retained in the intracellular compartment. The expression of NIS in non-thyroid tumoral cells in vivo has been possible through the transfer of NIS gene under the control of tissue-specific promoters. Apart from its therapeutic use, NIS has also been used for the localization of metastases by scintigraphy or PET-scan with 124I. In conclusion, NIS gene cloning led to an important development in the field of thyroid pathophysiology, and has also been fundamental to extend the use of radioiodine for the management of non-thyroid tumors.

A glândula tireóide tem capacidade de captar e concentrar iodeto, etapa fundamental na biossíntese dos hormônios tireóideos. O uso de iodo radioativo para fins de diagnóstico e terapia das doenças da tireóide vem sendo feito há muitos anos. Entretanto, somente após a clonagem do gene que codifica o co-transportador de sódio/iodeto (NIS) houve aumento significativo dos estudos relacionados ao mecanismo de transporte de iodeto. Os estudos sobre a regulação da expressão do NIS e a possibilidade de terapia gênica visando à transferência do gene NIS para células que normalmente não expressam esse transportador, foram também viabilizados. Na maior parte dos nódulos tireóideos hipofuncionantes, tanto benignos quanto malignos, a expressão do gene do NIS está presente, mas a proteína NIS fica retida no compartimento intracelular. A transferência do gene usando-se promotores tecido-específicos possibilitou a expressão do NIS em células tumorais não-tireóideas in vivo. Além do seu uso terapêutico, o NIS também vem sendo usado para a localização de metástases tumorais através da cintilografia ou do PET-scan usando-se 124I. Em conclusão, a clonagem do NIS possibilitou enorme avanço na área de fisiopatologia tireóidea e foi também fundamental para estender o uso do radioiodo para tumores não tireóideos.