Association between TERT promoter mutations and clinical behaviors in differentiated thyroid carcinoma: a systematic review and meta-analysis

Abstract

Background The association between telomerase reverse transcriptase (TERT) promoter mutations and some clinical behaviors in thyroid cancer remains controversial and requires additional investigation. This study aimed to evaluate the association between TERT promoter mutations and clinical behaviors (including clinicopathological features and prognosis) in differentiated thyroid carcinomas (DTC). Methods We performed an up-to-date systematic review and current comprehensive meta-analysis. We searched three electronic databases for relevant studies. We used fixedor random-effect models to calculate pooled estimated odds ratios (ORs) or standardized mean differences (SMDs) and corresponding 95% confidence intervals (CIs). Results We included 51 eligible studies incorporating 11,382 cases. Average frequencies of TERT promoter mutations in DTC, papillary (PTC), and follicular (FTC) thyroid carcinomas were 10.9%, 10.6%, and 15.1%, respectively. In DTC and PTC, TERT promoter mutations were significantly associated with sex, age, tumor size, vascular invasion, extrathyroidal extension, lymph node and distant metastases, advanced tumor, nodes, and metastasis (TNM) stage, persistence/recurrence, and disease-specific mortality. In FTC, TERT promoter mutations were significantly associated with age, distant metastases, advanced TNM stage, persistence/recurrence, and disease-specific mortality. Conclusions TERT promoter mutations could be considered as biomarkers assisting in risk stratification, prognostic prediction, and individualizing therapeutic options for DTC (PTC and FTC).

Multidisciplinary Diagnosis of Subcutaneous Soft Tissue Metastasis of Follicular Thyroid Carcinoma: A Case Report

“…In thyroid cancer, TERT promoter mutations are usually presented in follicular-derived thyroid carcinoma and associated with more aggressiveness, distant metastasis, tumor recurrence and poor prognosis (18,19). In our case, the metastasis nodules harbored TERT C228T mutation (Figure 4), which implies it may contribute to the aggressiveness of the FTC and distant metastasis.…”

Molecular Markers Guiding Thyroid Cancer Management

“…The most common mutation in FTC are RAS and PAX8/PPARG fusion oncogenes, found in 27-50% [110] and 12-53% [21] respectively. However, additional genetic mutations, such as PTEN, PIK3CA, EIF1AX, DICER1, TSH Receptor, but also TERT promotor mutations are thought to be required to promote carcinogenesis and transformation of a follicular adenoma to FTC [21,120,121]. Although, some authors suggest an improved prognosis with PAX8/PPARG [122] rearrangement and worsened outcome with RAS mutation, only the total mutational burden seems to be an independent predictor of worse outcome, rather than single mutation alone [120,123,124].…”

“…However, additional genetic mutations, such as PTEN, PIK3CA, EIF1AX, DICER1, TSH Receptor, but also TERT promotor mutations are thought to be required to promote carcinogenesis and transformation of a follicular adenoma to FTC [21,120,121]. Although, some authors suggest an improved prognosis with PAX8/PPARG [122] rearrangement and worsened outcome with RAS mutation, only the total mutational burden seems to be an independent predictor of worse outcome, rather than single mutation alone [120,123,124]. Hürtle cell carcinomas (HCC), a variant of FTC, are genetically distinct with mainly CNAs and mutations in mitochondrial DNA or non-mitochondrial genes that interact with mitochondrial function.…”

Actualities in Genetics of Differentiated Thyroid Cancer

“…Increased TERT expression occurs in cancer due to several genetic anomalies: point mutations in the TERT promoter (C228T, C250T), increased number of copies or aberrant methylation of certain regions of the TERT promoter (14, 15). In differentiated thyroid cancer, these mutations are frequently associated with aggressive clinical and pathological features (older age, tumor size, extra-thyroidal extension, lymph node invasion, vascular invasion, metastatic disease) (3,16) and are less prevalent in micropapillary thyroid carcinomas (6). In multiple prospective studies TERT promoter mutations were associated with advanced age, features of tumor aggression (advanced stage, extra-thyroidal extension, metastatic disease), persistent or recurrent disease and increased disease-specific mortality (16).…”

“…In differentiated thyroid cancer, these mutations are frequently associated with aggressive clinical and pathological features (older age, tumor size, extra-thyroidal extension, lymph node invasion, vascular invasion, metastatic disease) (3,16) and are less prevalent in micropapillary thyroid carcinomas (6). In multiple prospective studies TERT promoter mutations were associated with advanced age, features of tumor aggression (advanced stage, extra-thyroidal extension, metastatic disease), persistent or recurrent disease and increased disease-specific mortality (16). Even in PTC patients without pathological features of aggressive and metastatic disease, TERT promoter mutations can select the subgroup of patients with a poorer prognosis (17).…”