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

Introduction

Thyroid cancer is the most common among endocrine malignancies, and its incidence has been increasing rapidly over the years.¹ Papillary thyroid cancer (PTC) is the most common histological type, accounting for about 90% of thyroid cancer.^2,3 Generally, the prognosis of PTC patients is excellent with a survival rate of more than 95% and usually a good response to initial treatment.³ Nonetheless, there is a small group of PTCs that behave aggressively at presentation, develop distant metastasis (DM), and are associated with an increased rate of mortality.⁴ DM is not a frequent event in PTCs, accounting about 2%–5% of cases,^5–8 but the presence of DM has been well known as an adverse prognostic factor in PTCs.^5,9–11 In the latest guidelines of the American Thyroid Association (ATA), differentiated thyroid cancers (DTCs) with DM are classified as ATA high risk.⁴

Several clinicopathological factors such as old age, large size, vascular invasion, and extrathyroidal extension have been demonstrated to be risk factors for DM in DTC.^5,12,13 However, there are ongoing debates in other studies on this topic.^14–17 There has been rapid development in understanding the pathogenesis and genetic profiles of thyroid cancer in recent years. A few genetic events have been shown to be associated with aggressive behaviors and poor outcomes in PTC.^6,18,19 In addition to having worse impact on patients’ survival, the survival rate of thyroid cancer patients with DM has not improved over the last two decades despite the fact that there have been huge improvements in patient management and treatment strategies.²⁰ Therefore, it is really needful to identify reliable molecular markers that are predictive of DM in PTCs.

In this study, we aimed to perform a systematic review and meta-analysis of observational studies to investigate the role of molecular markers in predicting DM in PTCs.

Methods

Literature search

We searched for relevant studies in four electronic databases including PubMed, Scopus, Web of Science, and Virtual Health Library from inception to November 2016. We used the following search terms: “BRAF or TERT or RAS or RET/PTC”; “papillary thyroid”; and “carcinoma or cancer.” Additional studies were found by reviewing the citations within the included publications and other reviews. Our study protocol is...