TERT Promoter Mutations Are an Independent Predictor of Distant Metastasis in Middle Eastern Papillary Thyroid Microcarcinoma

Abstract

BackgroundPapillary thyroid microcarcinomas (PTMCs) have been attributed to the recent increased incidence of thyroid cancer. Although indolent, a subset of PTMC could potentially develop distant metastasis (DM). This study aimed to evaluate the clinico-pathological features and molecular characteristics of PTMC and identify the risk factors for DM in PTMC patients from Middle Eastern ethnicity.MethodsWe retrospectively analyzed 210 patients with histologically confirmed PTMC. Clinico-pathological associations for DM, BRAF mutation and TERT mutation were analyzed successfully in 184 patients. Multivariate analysis was performed using Cox proportional hazards model and logistic regression analysis.ResultsAmong the PTMC patients included in this cohort, DM was noted in 6.0% (11/184), whereas tumor relapse occurred in 29/184 (15.8%). Of the 11 cases with DM, lung metastasis occurred in 8 cases, bone metastasis in 2 cases and brain metastasis in 1 case. Presence of extrathyroidal extension and male sex were significantly associated with DM. Molecular analysis showed BRAF V600E mutations to be the most frequent, being detected in 45.7% (84/184). TERT promoter mutations were detected in 16 (8.7%) cases and were significantly associated with DM and shorter metastasis-free survival in multivariate analysis.ConclusionsOur study indicates a surprisingly high frequency of TERT promoter mutation in Saudi patients with PTMC. Identifying TERT promoter mutations as an independent predictor of DM in patients with microcarcinoma could explain the inherent aggressive nature of PTMC from Middle Eastern ethnicity and magnify its role in patient risk stratification, which might help in improving therapeutic strategy for these patients.

Risk Factors for Cervical Lymph Node Metastasis in Middle Eastern Papillary Thyroid Microcarcinoma

“…The incidence of PTC is higher in Saudi Arabia compared to Western populations and it ranks as the second most common malignancy among females in this ethnicity, accounting for 14.3% of all cancers [ 4 ]. Further, as reported by this study and in other studies on Middle Eastern populations, the incidence of recurrence (18.4%) [ 27 ], lymph node metastasis (53.0%) [ 28 ], and distant metastasis (7.5%) [ 29 ] is higher compared to other ethnicities. Another important difference is the earlier age of onset for PTC in Middle Eastern populations.…”

Multi-omics profiling of papillary thyroid microcarcinoma reveals different somatic mutations and a unique transcriptomic signature

“…2 b), which was consistent with the finding of a previous study that also compared the mutation rates between China and TCGA (72.4% & 59.7%) [ 12 ]. Parvathareddy et al showed BRAF V600E mutations were detected in 45.7% (84/184) Middle Eastern PTMCs, which was less than the PTMETA cohort [ 58 ]. Iodine-rich diets or chronic thyroiditis were suspected to be possible reasons for high BRAF V600E mutations in Chinese PTC [ 59 ].…”

BRAFV600E and TERT promoter C228T mutations on ThyroSeq v3 analysis of delayed skin metastasis from papillary thyroid cancer: a case report and literature review

“…Although BRAF mutation had been associated with lymph node metastases, extrathyroidal extension, tumor size, and advanced disease stage [16], more recent studies have questioned its impact on risk stratification and prognosis for PTC [17]. However, TERT promoter mutation has been found to be an independent predictor of distant metastasis, recurrence, and disease-free survival [18][19][20][21]. Moreover, its copresence with BRAF mutation has been associated with even more aggressive clinicopathological characteristics [22].…”