The incidence of papillary thyroid cancer (PTC) is markedly higher in women than men during the reproductive years. In vitro studies have suggested that estrogen may play an important role in the development and progression of PTC through estrogen receptors (ERs). This study aimed to investigate the expression patterns of the two main ER subtypes, α and β1 (wild-type ERβ), in PTC tissue and their clinical significance.

Background: MicroRNAs (miRNAs) are important diagnostic and prognostic markers in cancer. In the study reported here, we analyzed the potential relationship between miRNA expression and extrathyroidal invasion in papillary thyroid carcinoma (PTC). Methods: Samples from 91 patients with PTC were collected from January 2008 to April 2012 at our hospital. To detect the levels of miRNA expression in fresh frozen tissues from patients with extrathyroidal invasion (n = 3) and non-extrathyroidal invasion (n = 3), miRNA array was carried out. The upregulated miRNAs between the two groups were confirmed by using real-time reverse transcriptase polymerase chain reaction. Results: The levels of miR-146b, miR-221, miR-222, and miR-135b were significantly higher in the extrathyroidal invasion group than in the non-extrathyroidal invasion group (P = 0.001, 0.019, 0.004, and 0.006, respectively). In addition, the miR-146b expression level was significantly higher in the massive extrathyroidal invasion group than in the minimal extrathyroidal invasion group (P = 0.016). The expression levels of miR-146b, miR-222, and miR-135b were significantly associated with tumor size (P = 0.018, 0.008, and 0.024, respectively). The upregulation of miR-146b and miR-222 was significantly associated with higher tumor-node-metastasis stage (P = 0.004 and 0.0001, respectively). The expression level of miR-222 was also correlated with age and sex (P = 0.048 and 0.002, respectively). Conclusion: Our results reveal that the expression of four miRNAs correlated with extrathyroidal invasion and other clinicopathologic features in PTCs, which may support their potential clinical value as prognostic biomarkers for PTCs.

Certain epidemiological studies have suggested exposure to polybrominated diphenyl ethers (PBDEs) affect the production and secretion of thyroid hormones (TH); however, conflicting results have been reported in different studies. There is not a convincing conclusion about this debate to date. To perform a meta-analysis determining if there are correlations between PBDEs exposure and the serum levels of TH. Medical and scientific literature databases were searched for articles that met the eligibility criteria. The included articles were assessed for methodological quality. The correlation coefficient values or regression coefficient values between PBDEs and thyroid stimulating hormone (TSH) or total thyroxine (TT4) from each article were used for analysis. Sixteen articles were included in this meta-analysis. Pearson correlation coefficients (r) were directly collected or calculated from data given in the articles. Then, Fisher’s z transformation was performed to convert each correlation coefficient to an approximately normal distribution. For z values between PBDEs exposure and TSH levels, the pooled z value for 18 studies was 0.08 (95% CI: -0.06, 0.22), and indicated significant heterogeneity (I² values = 90.7%). Subgroup analysis was performed based on the median values of serum PBDEs in each study, there was not significant heterogeneity in each of the four subgroups (I² values <30%). In meta-analysis of z values between PBDEs exposure and the levels of TT4, the pooled z value for 11 studies was -0.02 (95% CI: -0.11, 0.08), and also indicated significant heterogeneity (I² values = 57.6%). Similar subgroup analysis was done for the PBDEs exposures and the levels of TT4. No significant heterogeneity was shown in either of the two subgroups (I² values = 0). The findings in our meta-analysis indicate the effects of PBDEs on thyroid function may mainly depend on PBDEs exposure and their levels found in serum. The relationship between PBDEs exposure and changes in thyroid function seem to fit an approximate u-shaped curve. These predictions await further verification, namely a prospective longitudinal study.

Estradiol (E2) promotes metastatic propensity. However, the detailed mechanism remains largely unknown. E-cadherin, vimentin, and MMP-9 play a dominant role in the metastatic process. We aimed to investigate the effects of E2 on metastatic potential of PTC cell line BCPAP and on E-cadherin, vimentin, and MMP-9 protein expression. PTC cell line BCPAP was evaluated for the presence of estrogen receptor (ER) by western blot analysis. The effects of E2, PPT (a potent ERα-selective agonist), and DPN (a potent ERβ-selective agonist) on modulation of metastatic phenotype were determined by usingin vitroscratch wound assay and invasion assay. In addition, the effects on E-cadherin, vimentin, and matrix metalloproteinase-9 (MMP-9) protein expression were evaluated by Western blot analysis. We found that BCPAP cells expressed ERαand ERβ. E2 and PPT enhanced, but DPN inhibited, the migration and invasion of BCPAP cells in anin vitroexperimental model system that is modulated by E-cadherin, vimentin, and MMP-9. These findings indicate that E2 induces the metastatic potential of BCPAP cells through ERαand ERβ. The two ER subtypes play differential roles in modulation of BCPAP cell metastasis and the related molecule expressions including E-cadherin, vimentin, and MMP-9.