Abstract
Simple SummaryOver the last couple of decades, the prognostic stratification systems of differentiated thyroid cancer (DTC) patients have been revised several times in an attempt to achieve a tailored clinical management reflecting the single patients’ needs. Such revisions are likely to continue in the near future, since the prognostic value of a number of promising clinicopathological features and new molecular biomarkers are being evaluated. Here, we will review the current staging systems of thyroid cancer patients and discuss the most relevant clinicopathological parameters and new molecular markers that are potentially capable of refining the prognosis.Over the last few years, a great advance has been made in the comprehension of the molecular pathogenesis underlying thyroid cancer progression, particularly for the papillary thyroid cancer (PTC), which represents the most common thyroid malignancy. Putative cancer driver mutations have been identified in more than 98% of PTC, and a new PTC classification into molecular subtypes has been proposed in order to resolve clinical uncertainties still present in the clinical management of patients. Additionally, the prognostic stratification systems have been profoundly modified over the last decade, with a view to refine patients’ staging and being able to choose a clinical approach tailored on single patient’s needs. Here, we will briefly discuss the recent changes in the clinical management of thyroid nodules, and review the current staging systems of thyroid cancer patients by analyzing promising clinicopathological features (i.e., gender, thyroid auto-immunity, multifocality, PTC histological variants, and vascular invasion) as well as new molecular markers (i.e., BRAF/TERT promoter mutations, miRNAs, and components of the plasminogen activating system) potentially capable of ameliorating the prognosis of PTC patients.
Highlights
The findings showed that the prevalence of papillary thyroid cancer (PTC) was higher in patients affected by chronic lymphocytic thyroiditis (CLT) and was associated with increased TSH levels [106]
The authors examined 71 articles for a total of 44,034 patients, among which 11,132 had CLT. They observed a negative association between CLT and extrathyroidal extension, lymph node metastases, distant metastases, and disease recurrence [108]. This evidence was further corroborated by a recent study performed on 2070 PTC patients, showing that those who were positive for thyroid peroxidase antibodies (TPOAb) before surgery had a significantly longer disease-free intervals (DFI) compared to patients negative for TPOAb [109]
The Connection BRAFV600E -TERTp Mutations. Since their initial identification in TC, it was evident that TERTp mutations, besides being more common in the most aggressive TC (i.e., TCPTC, poorly DTC (PDTC), anaplastic TC (ATC)), are associated with BRAFV600E PTC [20]
Summary
As for other types of solid cancers, the genetic instability is thought to represent the driving force by which transformed thyrocytes accumulate additional gene mutations during disease progression [24,25]. The Cancer Genome Atlas (TGCA) Research Network identified new oncogenic drivers and new driver events in known cancer genes, and considerably extended the somatic genetic landscape of PTC [11]. This further information was used to propose a reclassification of PTC into molecular subtypes with the aim to improve PTC staging and clinical management [11]
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