BRAF V600E mutation in papillary thyroid cancer is correlated with adverse clinicopathological features but not with iodine exposure.

INTRODUCTION: BRAFV600E activating mutation is the most frequent genetic abnormality in the pathogenesis of papillary thyroid carcinoma. We aimed to evaluate the association between BRAFV600E mutation and well-established prognostic clinicopathological characteristics as well as iodine exposure. MATERIAL AND METHODS: From 2000 to 2012, the data of PTC patients admitted to Dr. Lutfi Kirdar Kartal Education and Research Hospital in Turkey were reviewed retrospectively. Clinicopathological parameters were collected. BRAFV600E mutation was analysed by DNA sequencing method in tumour specimens. We hypothesised thatBRAFV600E mutation prevalence is positively correlated with prolonged iodine exposure and expected to be higher in the second half of the recruitment period due to the increment in time spent from the iodisation process of the table salt in our country. Thus, iodine exposure was categorised as short-term (2000-2006) and long-term (2006-2012). RESULTS: A total of 197 patients were accrued. The study population predominantly consisted of conventional variant. A statistically significant relationship was observed betweenBRAFV600E mutation presence and age (p = 0.03), conventional variant PTC (p = 0.00002), T4 stage (p = 0.002), vascular invasion (p = 0.036), thyroid capsule invasion (p < 0.00001), extrathyroidal tissue invasion (p < 0.00001), and lymph node metastasis (p < 0.00001). When categorised as long-term and short-term, iodine exposure was not statistically significantly related withBRAFV600E mutation; however, there were far more PTC cases in the long-term group (86.3% vs. 13.7%). CONCLUSION: We revealed that BRAFV600E mutation is associated with adverse clinicopathological parameters. There appeared to be no relation between long-term iodine exposure and BRAFV600E.

The Mitochondrial DNA Control Region Might Have Useful Diagnostic and Prognostic Biomarkers for Thyroid Tumors.

The literature suggests that mitochondrial DNA (mtDNA) defects are associated with a large number of diseases including cancers. The role of mtDNA variations in thyroid cancer is a highly controversial topic. Therefore, we investigated the role of mt-DNA control region (CR) variations in thyroid tumor progression and the influence of mtDNA haplogroups on susceptibility to thyroid tumors. For this purpose, in total, 108 hot thyroid nodules (HTNs), 95 cold thyroid nodules (CTNs), 48 papillary thyroid carcinoma (PTC) samples with their surrounding tissues and 104 healthy control subjects' blood samples were screened for all mtDNA CR variations using Sanger sequencing. We found that MtDNA haplogroup U was significantly associated with susceptibility to benign thyroid entities. In addition, eight single nucleotide polymorphisms (SNPs) (T146C, G185A, C194T, C295T, G16129A, T16304C, A16343G and T16362C) in the mtDNA CR were associated with the occurrence of benign and malign thyroid nodules in the Turkish population. As compared with samples taken from a healthy Turkish population and HTNs, the frequency of C7 repeats in D310 polycytosine sequence was found to be higher in CTNs and the PTC samples. In addition, the frequency of somatic mutations in mtMSI regions including T16189C and D514 CA dinucleotide repeats were found to be higher in PTC samples than benign thyroid nodules. Conversely, the frequency of somatic mutations in D310 was found to be higher in HTNs than CTNs and PTCs. In conclusion, mtDNA D310 instability does not play a role in the tumorigenesis of PTC but the results indicate that it might be used as a diagnostic clonal expansion biomarker for premalignant thyroid tumor cells. In addition, D514 CA instability might be considered as a prognostic biomarker for benign to malign transformation in thyroid tumors.

Cephalic vein thrombosis.

An 83-year-old male patient presented to the outpatient clinic with complaint of swelling at right antecubital area. Ultrasonographic examination of the right upper extremity revealed a mass lesion within the right cephalic vein, which was consistent with thrombus. A computed tomography (CT) venography showed contrast enhancement in cephalic vein at distal arm and an aneurysmatic thrombus area displaying regular borders with a size of 28*30 mm; there was no contrast enhancement at more proximal levels at the cephalic vein.

Limitation of apoptotic changes and crystal deposition by Tutukon following hyperoxaluria-induced tubular cell injury in rat model.

This study aimed at evaluating the protective effects of a herbal medication (Tutukon) on the hyperoxaluria induced apoptotic changes and crystal deposition in renal tubular epithelium in rat model. 60 male wistar rats were divided into three different groups (each group n: 20). In Group I severe hyperoxaluria was induced by ethylene glycol (EG) (0.75%) administration for 28 days. In Group II, in addition to hyperoxaluria induction, animals were treated with Tutukon for 28 days. Group III animals constituted the controls without any specific medication and/or intervention. While the presence and degree of crystal deposition in the tubular lumen were examined histopathologically under light microscopy, tubular apoptotic changes were evaluated using immunohistochemical staining for cysteine-aspartic acid protease-3 (Caspase-3) and tumor necrosis factor alpha (TNF-α) positivity on days 14 and 28, respectively. Evaluation of apoptotic changes by Caspase-3 positivity showed that while the majority of animals undergoing EG only showed evident apoptotic changes (n: 9), Tutukon application demonstrated a significant limitation with limited or no apoptosis (n: 7) in these animals. Similar data were noted for TNF alpha expression; while apoptotic changes were evident in 8 (80%) in Group I animals, limited changes were noted in Tutukon Group (n: 2). Regarding crystal deposition despite evident changes in Group I (9 animals), like apoptotic alterations, it was again significantly limited in animals receiving Tutukon (4 animals). Renal tubular crystal deposition and apoptotic changes induced by hyperoxaluria play a role in the pathogenesis of urolithiasis and the limitation of these changes might be instituted by Tutukon as a result of its antioxidant and antiinflammatory effects.