Activating mutations in the BRAF kinase gene have recently been reported in human cancers. The aim of the present study was to determine the frequency of BRAF mutations in thyroid cancer and their correlation with clinicopathological parameters. We analyzed exons 11 and 15 of BRAF gene in six human thyroid cancer cell lines and 207 paraffin-embedded thyroid tumor tissues. A missense mutation was found at T1796A (V599E) in exon 15 in four of the six cell lines and 51 of 207 thyroid tumors (24.6%; 0 of 20 follicular adenoma, 0 of 11 follicular carcinoma, 49 of 170 papillary carcinomas, and 2 of 6 undifferentiated carcinomas). Activation of MAPK kinase-MAPK pathway was observed in cell lines harboring BRAF mutation. BRAF mutation-associated enhanced cell growth was suppressed by MAPK kinase inhibitor, U0126. Examination of 126 patients with papillary thyroid cancer showed that BRAF mutation correlated significantly with distant metastasis (P = 0.033) and clinical stage (P = 0.049). Our results indicate that activating mutation of BRAF gene could be a potentially useful marker of prognosis of patients with advanced thyroid cancers.

To investigate the relationship between thyroid function and carotid intima-media thickness (CIMT) in a relatively large general population with euthyroid status we initially enrolled 1772 Japanese adults (421 men and 1351 women) who participated in a medical screening program for the general population over 40 years old. To evaluate only euthyroid subjects without vascular diseases and/or its major risk factors, 1129 were excluded and 643 participants (175 men and 468 women) were included for further analysis. Simple and multivariate linear regression analyses were performed to evaluate free thyroxine (fT4) and thyroid-stimulating hormone (TSH) levels and other existing parameters, including carotid intima-media thickness. By multivariate linear regression analysis adjusted for age and sex, free thyroxine was significantly correlated with triglycerides (beta=0.07, p=0.015), carotid intima-media thickness (beta=-0.091, p=0.049), and thyroid-stimulating hormone (beta=-0.091, p=0.003). Thyroid-stimulating hormone was significantly correlated with high-density lipoprotein cholesterol (HDL-C) (beta=-0.001, p=0.015), HbA(1c) (beta=0.038, p=0.045), carotid intima-media thickness (beta=0.27, p=0.001), and free thyroxine (beta=-0.15, p=0.003). When adjusted for confounding factors, free thyroxine was significantly correlated only with carotid intima-media thickness (beta=-0.13, p=0.043) and thyroid-stimulating hormone was significantly correlated with HDL-C (beta=-0.001, p<0.001), HbA(1c) (beta=0.04, p=0.021), and carotid intima-media thickness (beta=0.29, p=0.001). We have demonstrated that carotid intima-media thickness is independently associated with thyroid function within the normal reference range, which suggests an increased cardiovascular risk in subjects with low normal thyroid function.

The Great East Japan Earthquake in March 2011 destroyed the Fukushima Dai-ichi Nuclear Power Plant (FNPP) and almost all residents in a 20 km radius from the plant eventually evacuated. FNPP reactors had stabilized in December 2011 and some evacuees decided to return to their hometowns, the other evacuees remain. We tried to identify the determinants that affect the decision to return home in order to promote recovery of the surrounding area of FNPP. We selected 71 residents who had not returned to home town and 56 residents who had returned. Logistic regression analysis adjusted for confounding factors showed that being female (OR: 2.43, p=0.03), living in areas with relatively higher ambient doses (OR: 3.60, p=0.01) and expressing anxiety over radiation exposure (OR: 8.91, p<0.01) were independently associated with decisions not to return. Our current results suggest the importance of active participation by scientists and local authorities in communicating the risk to the general population involved in returning home.

Due to the likelihood of physical and mental health impacts following the unprecedented accident at the Fukushima Dai-ichi Nuclear Power Plant, the Fukushima prefectural government decided to conduct the Fukushima Health Management Survey to assist in the long-term health management of residents. This included thyroid ultrasound examination for all children in Fukushima. For appropriate evaluation of ultrasound screening of the thyroid, it is important to understand its reference data of thyroid findings in children in general. In order to analyze the frequencies of specific thyroid findings, we conducted ultrasound screening of the thyroid by the same procedures as used in Fukushima in 4,365 children, aged 3 to 18 years, from three Japanese prefectures. Overall, thyroid cysts were identified in 56.88% and thyroid nodules in 1.65% of the participants. Thyroid cysts and nodules with a maximum diameter of more than 5 mm were identified in 4.58% and 1.01%, respectively, and age-adjusted prevalences were 3.82% and 0.99%, respectively. Although the prevalence of cysts and nodules varied among the examination areas, no significant differences were observed among the three examination areas in the prevalence of cysts and nodules with a maximum diameter of more than 5 mm. Also, the prevalence of thyroid cysts and nodules, especially those with a maximum diameter of more than 5 mm, significantly increased with age, and showed a female predominance. We also identified ectopic thymus (1.95%), diffuse goiter (1.40%), ultimobranchial body (0.73%), lymph node swelling (0.21%) and thyroid agenesis (0.05%). This is the first ultrasound description of the age-adjusted prevalence of thyroid cysts and nodules, or of the prevalence of abnormalities other than cysts and nodules, such as ectopic thymus, in relation to age, in the general Japanese child population. We contend that this can provide relevant information for the Fukushima Health Management Survey and future population studies.

Fine-needle aspiration biopsy (FNAB) samples from thyroid tumor tissues were analyzed for the presence of the BRAF(T1796A) mutation by polymerase chain reaction (PCR)-restriction fragment length polymorphism (RFLP) analysis. This assay utilized a specific mismatched primer and has proved to be a relatively simple, accurate, and highly sensitive method. The analysis of 130 aspirated samples from thyroid tumors (18 follicular adenomas, 72 papillary carcinomas [PTCs], 8 follicular carcinomas, 2 undifferentiated carcinomas, 1 medullary carcinoma, 2 malignant lymphomas, and 27 adenomatous goiters) revealed BRAF(T1796A) mutations in 37 (51.4%) of 72 PTCs, supporting the usefulness of this method. We examined BRAF(T1796A) in 21 patients with thyroid tumors using leftover cells in the needle at the preoperative FNAB. BRAF(T1796A) was detected in 4 patients, of which 3 cases were diagnosed as positive and 1 case as suspicious by cytologic examination. Furthermore, BRAF(T1796A) mutations were found to occur more often in tumors of 3 cm or larger in size. Our results indicate that the preoperative determination of the presence of a BRAF(T1796A) mutation by conventional PCR-RFLP may be potentially useful in the diagnosis of the most common thyroid malignancies.