THU683 TERT Promoter Mutations, But Not BRAFV600EMutation, Correlate With The American Thyroid Association And TNM Staging Systems And Predict Outcome Of Differentiated Thyroid Cancer

Abstract

Abstract Disclosure: N. Mukhtar: None. K. Alhamoudi: None. M. Alswailem: None. H. Al-Hindi: None. A.K. Murugan: None. B. Alghamdi: None. A.S. Alzahrani: None. Context: The American Thyroid Association risk stratification (ATA) and the American Joint Committee on Cancer Tumor Node Metastases (TNM) predict recurrence and mortality of differentiated thyroid cancer (DTC). BRAFV600E and TERT promoter mutations have been shown to predict DTC outcome. Our objectives were to study these molecular markers in terms of their interaction and potential incremental prognostic values over the ATA and TNM staging systems. Patients and Methods: We studied 315 non-selected patients, 229 females, 86 males with a median age of 36 years (IQR 24-49). Data were extracted from medical records. BRAFV600E and TERT promoter mutations were tested by PCR-based Sanger sequencing. Persistent disease (PD) included all patients in structurally or biochemically incomplete and indeterminate response as defined by the 2015 ATA guidelines. Data were analysed using Chi-Square and Fisher Exact test and Kaplan Meier analysis. Results: Of 315 patients tested, 138 (43.8%) had BRAFV600E-positive tumors and 77 (24.5%) were positive for TERT promoter mutations. The BRAFV600E mutation did not correlate with the ATA and TNM staging, being non-significantly different in various stages of these systems and did not predict the development of PD (P 0.11). Unlike BRAFV600E, TERT promoter mutations were more frequent in the ATA high-risk than in intermediate- or low-risk tumors (P 0.01) and in TNM stages III and IV than in lower stages (P <0.001). TERT promoter mutations also predicted the outcome being present in 36.4% of patients with PD compared to only 15.6% in those without evidence of disease (P <0.0001). The same pattern was also seen when BRAFV600E and TERT promoter mutations were combined. TERT promoter mutations alone or TERT promoter + BRAFV600E mutations predicted the development of PD in 100% of patients in TNM stage IV or high-risk ATA stage. Conclusions:TERT promoter mutations alone or in combination with BRAFV600E mutation, but not BRAFV600E mutation alone, correlated well with the ATA and TNM staging and predicted development of PD, especially in higher stages of these systems. The combination of high-risk ATA or TNM stage IV with TERT promoter mutations is highly predictive of development of PD predicting PD in 100% of cases with these combinations. Presentation: Thursday, June 15, 2023