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 could not completely predict the final outcome of each patient.
Molecular marker-based risk stratification of thyroid cancer has been recently proposed to better estimate its prognostic risk. The BRAF mutation has drawn much attention since 2000. However, cancer-related mortality has been low although the BRAF mutation is common in thyroid cancer. In many studies, the BRAF mutation was reported to be associated with an increased cancer-specific mortality, but it was no longer significant after the adjustment of risk factors.
Telomere reverse transcription (TERT) activation, one of the hallmarks of cancer, enables unlimited proliferation and is driven by oncogenes. In 2013, two point mutations (C228T and C250T) in the TERT promoter have been found in 71% of melanomas and have also been identified in over 50 cancer types including thyroid cancer. These somatic mutations enhanced promoter activity which might immortalize proliferative cancer cells by maintaining telomere length.
The TERT promoter mutation was found in approximately 10% of papillary thyroid carcinoma, 17% of follicular thyroid carcinoma, and more than 40% of poorly differentiated or anaplastic thyroid carcinoma. It has been reported to be associated with large tumor size, old age, dedifferentiation, aggressive histology, advanced stages, distant metastasis, recurrence and mortality in thyroid cancer. 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. Its prognostic strength highlights its potential use as a clinical biomarker in thyroid cancer.