Hulya Iliksu Gozu

Introduction: BRAF V600E substitution is one of the most common mutation in PTC in different populations, and is associated with poor prognosis of the classical variant of PTC (CVPTC) such as extrathyroidal expansion, vascular invasion, lymph node metastasis and recurrence of the disease. The purpose of this study is to determine the prevalence of BRAF V600E mutation in subcell- types of the PTCs in Turkish population. Materials and methods: A total of 191 patients diagnosed with PTC admitted to Dr. Lutfi Kirdar Kartal Education and Research Hospital, Istanbul, were retrospectively analyzed. Clinical and pathologic factors including age, gender, PTC subtype, thyroid capsule invasion, extrathyroidal tissue invasion, and lymph node metastasis were obtained from patients’ medical records. DNA was extracted from FFPE tissue samples. The BRAF gene region including V600E mutation was screened by using high resolution melting curve analysis (HRMA) and the precise localisation of mutations were confirmed by using DNA sequencing with Sanger method. Results: One hundred and nine patients were diagnosed as CVPTC, 37 were macrocarcinoma and 72 were microcarcinoma. Sixty-five were diagnosed as Follicular variant of PTC (FVPTC), seventeen were diagnosed as Oncocytic variant of PTC (OVPTC). A mutation at 15th exon of the BRAF gene was detected in 23 of the 37 macroCVPTC patients. Nineteen out of twenty- three of these mutations were BRAF V600E, 1/23 was BRAF V600V and 3/23 were BRAF F583Y. Seventeen of the 72 microCVPTC cases were harbored with one of the BRAF mutations. Fifteen of them were BRAF V600E (20.8%) and only two of them were V600V mutation. Two mutations were detected in 37 macroFVPTC patients, one being BRAF V600V, while the other was BRAF V600E mutation (2.7%). Besides, two of the 28 microFVPTC cases (7.1%) were harbored with BRAFV600E mutation. Four of 12 macroOVPTC cases had one of the BRAF mutation. One of them was BRAFF595L and the others were BRAFV600E (25%). One of the microOVPTC case had BRAFV600V mutation. When mutation positive tumor samples were compared with mutation negative ones in classical variant group(CVPTC), thyroid capsule invasion, extrathyroidal tissue invasion, and lymph node metastasis were associated with BRAF mutations independent from tumor size (P<0.05 for each). Conclusion: Considering that BRAF V600E mutation is correlated with poor prognosis of the disease according to the obtained data, larger population based studies are necessary in order to follow up the prognosis of the PTC patients in Turkish population.

In the last decade, studies were first done to determine the frequency of G_sα and later thyrotropin receptor (TSHR) mutations in benign autonomously functioning thyroid nodules (AFTN). Different frequencies ranging from 0% to 38% for GSp mutations and from 20% to 86% for TSHR mutations were found. There were only some limited case reports related to TSHR genetic alterations in malignant AFTN. Their role in autonomously functioning thyroid carcinomas is not well established. We present a patient who had thyroidectomy for toxic multinodular goiter and a papillary carcinoma was demonstrated histopathologically. Genomic DNA was isolated from two solid areas in the hot nodule and peripheral leukocytes of the patient. After amplifying the related regions, TSHR and G_Sα genes were analyzed by single-strand conformation polymorphism (SSCP) analysis. The precise localization of the mutations was identified by automatic DNA sequence analysis. An activating mutation of the TSHR gene (Leu 512 Arg) was found in the autonomously functioning papillary carcinoma. It is believed that this mutation causes constitutive activation of the cyclic adenosine monophosphate (cAMP) signal transduction pathway and thereby causes thyrotoxicosis and a hot thyroid nodule in an autonomously functioning papillary carcinoma.