Clinicopathological Risk Factors for Distant Metastasis in Differentiated Thyroid Carcinoma: A Meta-analysis.

INTRODUCTION: Distant metastasis (DM) is not a frequent event in differentiated thyroid carcinoma (DTC) but has an adverse impact on mortality of patients with DTC. In the current study, we aimed to conduct a comprehensive systematic review and meta-analysis to investigate the risk factors for DM in DTCs and for each histological subtype. METHODS: Five electronic databases were searched from inception to December 2016 for relevant articles. Pooled odd ratios and 95% confidence interval were calculated using random-effect model. RESULTS: Thirty-four articles with 73,219 patients were included for meta-analyses. In DTCs, male gender, age ≥45 years, tumor size ≥4 cm, multifocality, vascular invasion (VI), extrathyroidal extension (ETE), lymph node metastasis (LNM), and lateral LNM were demonstrated to be associated with significant risks for DM. In addition, several clinicopathological factors such as age ≥45 years, VI, ETE, and LNM were shown to be significant risk factors for DM in both PTC and FTC subgroups. CONCLUSION: Our study demonstrated the promising value of several clinicopathological factors such as male gender, older age, VI, ETE, and LNM in predicting DM in PTCs and FTCs. Our study affirms the value of the selected clinicopathological factors for tumor risk stratification and assessment of patients' prognosis.

Role of molecular markers to predict distant metastasis in papillary thyroid carcinoma: Promising value of TERT promoter mutations and insignificant role of BRAF mutations-a meta-analysis.

The presence of distant metastasis is associated with an adverse outcome in papillary thyroid cancer. We performed a meta-analysis to investigate the role of molecular markers as predictors for distant metastasis in papillary thyroid cancer. Four electronic databases including PubMed, Web of Science, Scopus, and Virtual Health Library were searched, and odds ratio and its 95% confidence interval concerning the association of BRAF, RAS, and TERT promoter mutations and RET/PTC rearrangements with distant metastasis were calculated using random-effects model. In total, 42 studies with 11,109 papillary thyroid cancers were included for meta-analyses. Overall, the presence of TERT promoter (odds ratio = 5.95; 95% confidence interval = 2.95-11.99), RAS mutations (odds ratio = 2.5; 95% confidence interval = 1.00-6.22), and RET/PTC rearrangements (odds ratio = 1.92; 95% confidence interval = 1.03-3.56) were found to be associated with a significantly increased risk for distant metastasis. BRAF mutations were not associated with an elevated risk for distant metastasis (odds ratio = 0.79; 95% confidence interval = 0.54-1.16). In conclusion, our study demonstrated the promising value of few molecular biomarkers, especially TERT promoter mutations in predicting distant metastasis in papillary thyroid cancers, while BRAF mutations showed no association with distant metastasis. Our study affirms the value of selected mutations for tumor risk stratification and assessment of patients' prognosis.

A meta-analysis of prognostic roles of molecular markers in papillary thyroid carcinoma.

The prognostic role of molecular markers in papillary thyroid carcinoma (PTC) is a matter of ongoing debate. The aim of our study is to investigate the impact of RAS, BRAF, TERT promoter mutations and RET/PTC rearrangements on the prognosis of PTC patients. We performed a search in four electronic databases: PubMed, Scopus, Web of Science and Virtual Health Library (VHL). Data of hazard ratio (HR) and its 95% confidence interval (CI) for disease-specific survival (DSS) and disease-free survival (DFS) were directly obtained from original papers or indirectly estimated from Kaplan-Meier curve (KMC). Pooled HRs were calculated using random-effect model weighted by inverse variance method. Publication bias was assessed by using Egger's regression test and visual inspection of funnel plots. From 2630 studies, we finally included 35 studies with 17,732 patients for meta-analyses. TERT promoter mutation was significantly associated with unfavorable DSS (HR = 7.64; 95% CI = 4.00-14.61) and DFS (HR = 2.98; 95% CI = 2.27-3.92). BRAF mutations significantly increased the risk for recurrence (HR = 1.63; 95% CI = 1.27-2.10) but not for cancer mortality (HR = 1.41; 95% CI = 0.90-2.23). In subgroup analyses, BRAF mutation only showed its prognostic value in short-/medium-term follow-up. Data regarding RAS mutations and RET/PTC fusions were insufficient for meta-analyses. TERT promoter mutation can be used as an independent and reliable marker for risk stratification and predicting patient's outcomes. The use of BRAF mutation to assess patient prognosis should be carefully considered.