Telomerase reverse transcriptase promoter mutation and its clinical implication in thyroid cancer

Considering the long-term survival in most patients with thyroid cancer, it is very important to distinguish patients who need aggressive treatment from those who do not. Clinicopathological prognostic factors have been used to predict their prognoses, but they could not completely predict the final outcome of each patient. Recently, molecular marker-based risk stratification of thyroid cancer has been proposed to better estimate the risk. BRAF mutation has drawn much attention based on its high prevalence. However, its association with recurrence/mortality is not clear, and it is debatable. Telomerase reverse transcriptase (TERT) promoter mutation has been identified in over 50 human cancers including thyroid cancer after its first discovery in melanoma. It increases telomerase activity, which allows cancer cells to immortalize. It was found in approximately 10% of papillary thyroid carcinoma, 17% of follicular thyroid carcinoma, and 40% of poorly differentiated or anaplastic thyroid carcinoma. It is highly prevalent in old age, large tumors, aggressive histology, advanced stages, and distant metastasis. It is associated with increased recurrence and mortality. Concomitant TERT and BRAF mutations diminished the survival rate. Inclusion of TERT promoter mutation analysis with conventional clinicopathological evaluation could lead to better prognostication and management for individual patients.