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. 2022 Mar 11:13:808298.
doi: 10.3389/fendo.2022.808298. eCollection 2022.

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

Sandeep Kumar Parvathareddy  1 , Abdul K Siraj  1 , Kaleem Iqbal  1 , Zeeshan Qadri  1 , Saeeda O Ahmed  1 , Maha Al-Rasheed  1 , Ahmed A AlQatie  2 , Saif S Al-Sobhi  3 , Fouad Al-Dayel  4 , Khawla S Al-Kuraya  1
Affiliations

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

Sandeep Kumar Parvathareddy et al. Front Endocrinol (Lausanne). .

Abstract

Background: Papillary 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.

Methods: We 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.

Results: Among 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.

Conclusions: Our 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.

Keywords: TERT promoter mutations; distant metastasis; metastasis-free survival; papillary thyroid microcarcinoma; predictor.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Radiologic images of distant metastasis in papillary thyroid microcarcinoma cases. (A) Computed tomography of the lung showing extensive pulmonary metastases with classic canon-ball metastases (arrows) and miliary metastatic nodules (arrow heads). (B) Positron emission tomography (PET) scan and (C) X-ray, showing expansile lytic metastatic lesion in the left humerus (arrows) with pathologic fracture related to metastasis. PET scan also shows a metastatic focus in the skull bone (arrow head).
Figure 2
Figure 2
(A) Kaplan-Meier survival curve showing shorter metastasis-free survival in TERT mutant cases compared to TERT wildtype (p = 0.0002). (B) Kaplan-Meier survival curve showing shorter metastasis-free survival in TERT mutant only cases compared to TERT+BRAF mutant cases (p = 0.0364). (C) Significantly higher frequency of TERT mutation was noted in the distant metastatic cases compared to the overall cohort of papillary thyroid microcarcinomas (p < 0.0001).
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