Papillary thyroid carcinomas (PTCs) that invade into local structures are associated with a poor prognosis, but the mechanisms for PTC invasion are incompletely defined, limiting the development of new therapies. To characterize biological processes involved in PTC invasion, we analyzed the gene expression profiles of microscopically dissected intratumoral samples from central and invasive regions of seven widely invasive PTCs and normal thyroid tissue by oligonucleotide microarray and performed confirmatory expression and functional studies. In comparison with the central regions of primary PTCs, the invasive fronts overexpressed TGF β, NFκB and integrin pathway members, and regulators of small G proteins and CDC42. Moreover, reduced levels of mRNAs encoding proteins involved in cell–cell adhesion and communication were identified, consistent with epithelial-to-mesenchymal transition (EMT). To confirm that aggressive PTCs were characterized by EMT, 34 additional PTCs were examined for expression of vimentin, a hallmark of EMT. Overexpression of vimentin was associated with PTC invasion and nodal metastasis. Functional, in vitro studies demonstrated that vimentin was required both for the development and maintenance of a mesenchymal morphology and invasiveness in thyroid cancer cells. We conclude that EMT is common in PTC invasion and that vimentin regulates thyroid cancer EMT in vitro .

Background: Obesity has been implicated as a predisposing and disease-modifying factor in cancer. Epidemiological studies suggest that obesity is associated with an increased risk of thyroid cancer; however, the relationships between obesity and thyroid cancer stage or behavior are uncertain. We hypothesized that a higher body mass index (BMI) would be associated with aggressive thyroid cancer features and a higher incidence of persistent/recurrent disease. Methods: Two hundred fifty-nine consecutive patients with thyroid cancer were enrolled in this retrospective cohort study. Histopathological tumor features, stage at diagnosis, and disease status during and at the end of the study were determined based on chart review. BMI was calculated at the first clinical visit to our institution. The relationships between BMI and these parameters were assessed. Results: Mean follow-up time for the group was 6.2 yr (0.11–46 yr). No positive associations were identified between BMI and T, N, or M stage at diagnosis, vascular invasion, or recurrent or persistent disease on univariate or multivariate analyses. The absence of an association was also demonstrated on analysis by BMI quartiles. An unexpected inverse association was identified between BMI and nodal metastasis and tumor invasion on both univariate and multivariate analyses, suggesting that obesity may be associated with less aggressive tumor features, a finding that requires confirmatory studies. Conclusion: Although obesity has been associated with increased thyroid cancer incidence, a higher BMI was found not to be associated with more aggressive tumor features or a greater likelihood of recurrence or persistence over the analyzed time period.

Activating mutations in the gene encoding BRAF are the most commonly identified oncogenic abnormalities in papillary thyroid cancer. In vitro and in vivo models have demonstrated that overexpression of activated BRAF induces malignant transformation and aggressive tumour behaviour. BRAF and other RAF kinases are frequently activated by other thyroid oncogenes and are important mediators of their biological effects including dedifferentiation and proliferation. Because current therapeutic options for patients with thyroid cancers that are aggressive and/or do not respond to standard therapies are limited, BRAF and its downstream effectors represent attractive therapeutic targets. In this review, data supporting a role for BRAF activation in thyroid cancer development and establishing the potential therapeutic efficacy of BRAF-targeted agents in patients with thyroid cancer will be reviewed.

Thyroid cancer is an increasingly prevalent malignancy throughout the world. Management guidelines for both thyroid nodules and thyroid cancer have been published and updated by a number of societies internationally. All of these guidelines recognize this increasing incidence, particularly of small papillary thyroid cancers, due in part to improved technology enabling early or even ‘over’ diagnosis. Recent advances in molecular imaging and molecular methods have been developed to better characterize thyroid nodules, and a number of studies that have clarified risk stratification systems that can be modified over time allow for individualization of diagnosis, initial treatment, and subsequent follow-up strategies. Advances in surgical approaches and new treatments for patients with the most aggressive forms of thyroid cancer have all influenced management guidelines. Despite substantial similarities, there also are important differences between recent guidelines for some of the common clinical scenarios encountered by physicians in clinical practice. In the present manuscript, we will highlight similarities and differences between several of the most recently published guidelines focused on key areas of importance to clinical care and controversy. These are key areas for future research to strengthen the data to support future guideline recommendations.