TERT Promoter Mutations and the 8th Edition TNM Classification in Predicting the Survival of Thyroid Cancer Patients.

Jun Park,Tae Hyuk Kim,Chang-Seok Ki,Sungjoo Lee,Hyunju Park,Jae Hoon Chung,Sun Wook Kim,Jung Hee Shin,Kyunga Kim,Young Lyun Oh,Jee Soo Kim

doi:10.3390/cancers13040648

Abstract

Our research group has previously shown that the presence of TERT promoter mutations is an independent prognostic factor, by applying the TERT mutation status to the variables of the AJCC 7th edition. This study aimed to determine if TERT mutations could be independent predictors of thyroid cancer-specific mortality based on the AJCC TNM 8th edition, with long-term follow-up. This was a retrospective study of 393 patients with pathologically confirmed differentiated thyroid carcinoma (DTC) after thyroidectomy at a tertiary Korean hospital from 1994 to 2004. The thyroid cancer-specific mortality rate was 6.9% (5.2% for papillary and 15.2% for follicular cancers). TERT promoter mutations were identified in 10.9% (43/393) of DTC cases (9.8% of papillary and 16.7% of follicular cancer) and were associated with older age (p < 0.001), the presence of extrathyroidal invasion (p < 0.001), distant metastasis (p = 0.001), and advanced stage at diagnosis (p < 0.001). The 10-year survival rate in mutant TERT was 67.4% for DTC patients (vs. 98% for wild-type; adjusted hazard ratio (HR) of 9.93, (95% CI: 3.67-26.90)) and 75% for patients with papillary cancer (vs. 99%; 18.55 (4.83-71.18)). In addition, TERT promoter mutations were related to poor prognosis regardless of histologic type (p < 0.001 for both papillary and follicular cancer) or initial stage (p < 0.001, p = 0.004, and p = 0.086 for stages I, II, and III and IV, respectively). TERT promoter mutations comprise an independent poor prognostic factor after adjusting for the clinicopathological risk factors of the AJCC TNM 8th edition, histologic type, and each stage at diagnosis, which could increase prognostic predictability for patients with DTC.

Highlights

Differentiated thyroid carcinoma (DTC), which includes papillary thyroid carcinoma (PTC) and follicular thyroid carcinoma (FTC), accounts for 90% of all thyroid cancers
We examined whether the analysis of Telomerase reverse transcriptase (TERT) mutations could improve the prediction of mortality for differentiated thyroid carcinoma (DTC) patients based on the TNM-8 system
TNM 7th edition (TNM-7) has been revised to TNM-8 and prognostic predictability has increased [22,23], there is still no concept of molecular marker-based risk stratification, which has emerged based on prognostic genetic markers such as v-Raf murine sarcoma viral oncogene homolog B (BRAF) and TERT mutations [23]

Summary

Introduction

Differentiated thyroid carcinoma (DTC), which includes papillary thyroid carcinoma (PTC) and follicular thyroid carcinoma (FTC), accounts for 90% of all thyroid cancers. The American Joint Committee on Cancer/Union for International Cancer Control (AJCC/UICC) staging is a classification system developed to describe the extent of disease and predict mortality, based on a tumor–node–metastasis (TNM) scoring system. It is the most commonly used staging system for thyroid cancer and was recently revised from the TNM 7th edition (TNM-7) to the 8th edition (TNM-8) [4,5]. Manzardo et al recently reported that the risk of structural recurrence of DTC patients downstaged by tumor classification in TNM-8 may be overlooked [8], and the concept of a molecular profile that has recently emerged in the prognosis is still missing [10]

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