Preoperative detection of the TERT promoter mutations in papillary thyroid carcinomas.

Tomoe Nakao,Miyoko Higuchi,Keiji Suzuki,Michiko Matsuse,Mitsuyoshi Hirokawa,Tatiana Rogounovitch,Tsutomu Sano,Vladimir Saenko,Akira Miyauchi,Norisato Mitsutake,Hisanori Sasai,Atsushi Kawakami,Aya Tanaka

doi:10.1111/cen.14567

Abstract

Telomerase reverse transcriptase promoter (TERT-p) mutations are strongly associated with tumour aggressiveness and worse prognosis in papillary thyroid carcinomas (PTCs). Since the TERT-p mutations have been reported to be subclonal, it is unclear how accurately they can be detected by preoperative fine-needle aspiration (FNA). The objective of this study was to analyse the concordance rate of the TERT-p mutations between preoperative FNA and corresponding postoperative surgical specimens. Ninety-six cases of PTC aged 55 years or older were studied. The mutational status of TERT-p was detected by droplet digital polymerase chain reaction assay. The mutational status of the TERT-p in FNA samples was highly concordant with that in postoperative formalin-fixed and paraffin-embedded (FFPE) specimens. The TERT-p mutation was significantly associated with age, tumour size, extrathyroidal extensionand the Ki-67 labelling index in multivariate analysis in both FNA and FFPE samples. The detection of the TERT-p mutations using FNA samples has a good ability to predict disease aggressiveness and, therefore, could be clinically useful in the determination of PTC management.

Highlights

The incidence of thyroid cancers has increased in recent years
Telomerase reverse transcriptase promoter (TERT-p) mutations are strongly associated with tumor aggressiveness and worse prognosis in papillary thyroid carcinomas (PTCs)
The mutational status of the telomerase reverse transcriptase (TERT)-p in fine needle aspiration (FNA) samples detected by our Droplet digital PCR (ddPCR) assay was highly concordant with that in postoperative formalin-fixed and paraffin-embedded (FFPE) specimens

Summary

Introduction

The incidence of thyroid cancers has increased in recent years. This increase is mostly attributed to papillary thyroid carcinomas (PTCs) 1. PTCs usually have a favorable prognosis, 10–15% of patients have recurrences, some of which become refractory to treatments 2,3. The BRAFV600E mutation is the most common genetic alteration in PTCs. Its prevalence varies from 30– 80% 4, which seems to be dependent on the study population. Many studies have reported an association between the presence of the BRAFV600E mutation and aggressive clinicopathological features in PTCs 5– 7. There are studies, especially from Japan, demonstrating no such relationship 8,9. The clinicopathological significance of BRAFV600E is not universal and still remains controversial

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