BRAF V600E/TERT promoter mutations and NIS/TSHR expression in differentiated thyroid carcinoma and their clinical significance ⁎

Abstract

Abstract Objective Telomerase reverse transcriptase (TERT) promoter mutations have recently been described in thyroid carcinoma. The purpose of this study was to investigate the clinical significance of (v-raf murine sarcoma viral oncogene homolog B1) BRAF V600E and TERT promoter mutations in differentiated thyroid carcinoma (DTC). The relationship between the two mutations and NIS/TSHR expression was also analyzed. Methods We have detected BRAF V600E and TERT promoter mutations by direct sequencing and NIS/TSHR expression by immunohistochemistry in 229 cases of DTC, 52 cases of benign nodular goiter, and 31 cases of normal thyroid tissue. Results The BRAF V600E mutation was detected in 142 (62.0%) of 229 cases of DTC [141 cases of papillary thyroid carcinoma (PTC) and 1 case of follicular thyroid carcinoma (FTC)]. TERT promoter mutations were detected in 18 (7.9%) of 229 cases of DTC (14 cases of PTC and 4 cases of FTC), including the mutations C228T (0.9%) and C250T (7.0%), which were mutually exclusive. Moreover, 11 (61.1%) cases also harbored the BRAF V600E mutation, which was not associated with gender, age, tumor size, lymph node metastasis, and recurrence risk stratification (P >0.05). The rate of TERT promoter mutation was higher in males, age ≥45, and in the middle/high-risk group (P <0.05), and the rate of simultaneous BRAF V600E and TERT promoter mutations were higher in the middle/high-risk group (P <0.05). In addition, NIS positive rate in the concurrent BRAF V600E and TERT promoter mutation group (45.5 %) was lower than in other groups (that is, the DTC group with BRAF V600E or TERT promoter mutations (55.1%), the DTC group with no BRAF V600E or TERT promoter mutation (57.5%), the nodules and normal group (75.9%); | r | = 0.171, P = 0.002). Conclusion TERT promoter mutations were lower in patients with DTC, with the C250T mutation being the most common. The detection of BRAF V600E mutation combined with TERT promoter mutations was instructive for the prognosis assessment and treatment of DTC.