TERT mRNA Expression as a Novel Prognostic Marker in Papillary Thyroid Carcinomas

Area of Science:

• Oncology
• Genetics
• Molecular Biology

Background:

• Telomerase reverse transcriptase (TERT) promoter mutations are associated with aggressive papillary thyroid carcinomas (PTCs) and poor prognosis.
• The role of TERT mRNA expression, particularly in relation to TERT promoter mutations and clinicopathological features in PTC, remains largely unexplored.

Purpose of the Study:

• To investigate the status of TERT mRNA expression in PTC.
• To determine the relationship between TERT promoter mutations, TERT mRNA expression, and clinicopathological features, including tumor aggressiveness and recurrence risk.

Main Methods:

• Analysis of 159 PTC samples for TERT promoter mutations using direct DNA sequencing.
• Quantification of TERT mRNA expression via quantitative reverse transcription polymerase chain reaction.
• High-sensitivity detection of low allelic frequency TERT promoter mutations using droplet digital polymerase chain reaction (ddPCR).
• Statistical analysis of TERT mutation/expression status against clinicopathological features and recurrence risk.

Main Results:

• TERT promoter mutations were identified in 12.6% of PTC cases, correlating with aggressive features.
• TERT expression was present in mutation-positive tumors and also in 40.3% of mutation-negative tumors.
• Low allelic frequency TERT promoter mutations were detected in a subset of mutation-negative tumors using ddPCR.
• TERT mutation-negative/expression-positive tumors exhibited a significantly higher recurrence risk compared to mutation-negative/expression-negative tumors.
• TERT expression levels in mutation-negative PTCs inversely correlated with patient age and BRAF mutation status.

Conclusions:

• TERT promoter mutations strongly correlate with aggressive clinicopathological features in PTC.
• High TERT mRNA expression, even without promoter mutations, is associated with a significantly higher recurrence rate in PTC.
• TERT mRNA expression serves as a valuable prognostic marker, particularly for younger PTC patients who are less likely to harbor TERT promoter mutations.