Preoperative Assessment of TERT Promoter Mutation on Thyroid Core Needle Biopsies Supports Diagnosis of Malignancy and Addresses Surgical Strategy.

ABSTRACT

In the last decade, several molecular markers have been proposed to improve the diagnosis of thyroid nodules. Among these, mutations in the telomerase reverse transcriptase (TERT) promoter have been correlated to malignant tumors, characterized by highest recurrence and decreased patients' survival. This suggests an important role of TERT mutational analysis in the clinical diagnosis and management of thyroid cancer patients. The aim of the study was to demonstrate the adequacy of core needle biopsy (CNB) for the preoperative assessment of TERT mutational status, to reach a more accurate definition of malignancy and a more appropriate surgical planning. Indeed, CNB is gaining momentum for improving diagnosis of thyroid nodules deemed inconclusive by fine needle aspirate (FNA). The study included 50 patients submitted to CNB due to inconclusive FNA report. TERT mutational status was correlated with BRAF mutation, definitive histology, and post-operative TNM staging of the neoplasia. C228T mutation of the TERT promoter was reported in 10% of the papillary carcinomas (PTC) series. When compared with final histology, all cases harboring TERT mutation resulted as locally invasive PTCs. The prevalence of TERT mutated cases was 17.6% among locally advanced PTCs. TERT analysis on CNB allows the assessment of the pathological population on paraffin sections before DNA isolation, minimizing the risk of false negatives due to poor sampling that affects FNA, and gathering aggregate information about morphology and TERT mutational status. Data indicating a worse outcome of the tumor might be used to individualize treatment decision, surgical option, and follow-up design.