Coexistence of TERT Promoter Mutations and the BRAF V600E Alteration and Its Impact on Histopathological Features of Papillary Thyroid Carcinoma in a Selected Series of Polish Patients

Abstract

<i>TERT</i> promoter (<i>TERT</i>p) mutations are important factors in papillary thyroid carcinomas (PTCs). They are associated with tumor aggressiveness, recurrence, and disease-specific mortality and their use in risk stratification of PTC patients has been proposed. In this study we investigated the prevalence of <i>TERT</i>p mutations in a cohort of Polish patients with PTCs and the association of these mutations with histopathological factors, particularly in coexistence with the <i>BRAF</i> V600E mutation. A total of 189 consecutive PTC specimens with known <i>BRAF</i> mutational status were evaluated. <i>TERT</i>p mutations were detected in 8.5% of cases (16/189) with the C228T mutation being the most frequent. In six of the PTC specimens (3.2%), four additional <i>TERT</i>p alterations were found, which included one known polymorphism (rs2735943) and three previously unreported alterations. The association analysis revealed that the <i>TERT</i>p hotspot mutations were highly correlated with the presence of the <i>BRAF</i> V600E mutation and their coexistence was significantly associated with gender, advanced patient age, advanced disease stage, presence of lymph node metastases, larger tumor size, and tumor-capsule infiltration. While correlations were identified, the possibility of <i>TERT</i>p mutations being key molecular modulators responsible for PTC aggressiveness requires further studies.