Comprehensive Assessment of TERT mRNA Expression across a Large Cohort of Benign and Malignant Thyroid Tumours

Abstract

<jats:p>The presence of TERT promoter (TERTp) mutations in thyroid cancer have been associated with worse prognosis features, whereas the extent and meaning of the expression and activation of TERT in thyroid tumours is still largely unknown. We analysed frozen samples from a series of benign and malignant thyroid tumours, displaying non-aggressive features and low mutational burden in order to evaluate the presence of TERTp mutations and TERT mRNA expression in these settings. In this series, TERTp mutations were found in 2%, only in malignant cases, in larger cancers, and from older patients. TERT mRNA expression was detected in both benign and malignant tumours, with increased frequencies in the malignant tumours with aggressive histotypes, larger tumours, and from older patients. In benign tumours, TERT mRNA expression was found in 17% of the follicular thyroid adenoma (FTA) with increased levels of expression in smaller tumours and associated with the presence of thyroiditis. TERTp mutations and TERT mRNA expression are correlated with worse prognosis features in malignant thyroid tumours, whereas TERT mRNA expression in the benign tumours is associated with the presence of thyroiditis.</jats:p>

Comprehensive molecular analysis of immortalization hallmarks in thyroid cancer reveals new prognostic markers

“…The high percentage of clinically aggressive tumours that we observed showed promoter methylation, but the absence of promoter mutations (60%, 12/20) denotes the limited prognostic predictive value of testing only TERT promoter mutations, which is in consonance with previous studies 17,46 . On the other hand, tumour‐lymphocytic infiltrates could lead to a misinterpretation of TERT expression results in some particular cases, as this cell lineage can maintain TERT expression after differentiation 20 . In fact, this feature could explain the positivity of TERT expression of most of the tumours in our series with an exceptional response to primary treatment, and without other molecular or clinical evidence related to poor prognosis.…”

“…17,46 On the other hand, tumour-lymphocytic infiltrates could lead to a misinterpretation of TERT expression results in some particular cases, as this cell lineage can maintain TERT expression after differentiation. 20 In fact, this feature could explain the positivity of TERT expression of most of the tumours in our series with an exceptional response to primary treatment, and without other molecular or clinical evidence related to poor prognosis. Thus, our results underscore the need to consider TERT promoter methylation in screening tools for the stratification of thyroid tumours according to their malignant potential and to report TERT gene expression results along with tumour cellular composition.…”

“…17,18 Altogether, these findings suggest that alterations related to TERT re-expression are late events in thyroid tumourigenesis. However, the prognostic specificity of TERT promoter mutations and expression has been questioned as they have also been reported in benign forms of thyroid 19,20 and other types of cancer, 21 highlighting the need of further studies to refine the prognostic value of these immortalization markers.…”

TERT Promoter Mutation and Extent of Thyroidectomy in Patients with 1–4 cm Intrathyroidal Papillary Carcinoma

“…They are known as effective risk factors for patients with PTC. Several investigators have shown that TERT promoter mutations are significantly more common among older patients, bigger tumor size, more aggressive subtype, tumors with extrathyroidal invasion, distant metastasis or higher stage at diagnosis, and are related to poor outcomes [7,[23][24][25][26][27][28]. In addition, Xing et al reported that coexisting BRAF V600E and TERT promoter mutations represented a strong predictor for the most aggressive PTCs with the highest recurrence rate [29].…”

Significance of DMBT1 in Papillary Thyroid Carcinoma Concurrent With Hashimoto’s Thyroiditis

“…As an aggressive marker, the BRAF-V600E mutation was less frequently detected in PTC patients concurrent with HT than non-HT ( 15 ). The mRNAs have exhibited a great potential in both physiological and pathological processes of PTC ( 16 – 18 ). Thus, dysregulated expression mRNAs may be a promising predictor of poor prognosis in PTC.…”