Ultrasound and clinicopathological features of papillary thyroid carcinomas with BRAF and TERT promoter mutations

// Soo Yeon Hahn 1, * , Tae Hyuk Kim 2, * , Chang Seok Ki 3 , Sun Wook Kim 2 , Soohyun Ahn 4 , Jung Hee Shin 1 and Jae Hoon Chung 2 1 Department of Radiology and Center for Imaging Science, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea 2 Division of Endocrinology and Metabolism, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea 3 Department of Laboratory Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea 4 Biostatistics and Clinical Epidemiology Center, Research Institute for Future Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea * These authors have contributed equally to this work Correspondence to: Jung Hee Shin, email: jhshin11@skku.edu Jae Hoon Chung, email: jaeh.chung@samsung.com Keywords: papillary thyroid carcinoma; BRAF mutation; TERT promoter mutation; ultrasound; prognosis Received: January 12, 2017      Accepted: July 26, 2017      Published: November 14, 2017 ABSTRACT This study is to investigate if any relationship exists between the telomerase reverse transcriptase (TERT) promoter or proto-oncogene BRAF mutation and ultrasound (US) and clinicopathological features of papillary thyroid carcinomas (PTCs). The study included 150 patients with surgically confirmed PTC from October 1994 to December 2004. According to the existence of TERT promoter or BRAF mutations, we categorized patients into three groups (no mutation, BRAF mutation alone, or TERT+BRAF mutations) and analyzed the relationships between TERT promoter or BRAF mutation and US and clinicopathological features. The rate of recurrence or death according to mutation analysis was estimated. There were 35 (23.3%) cases with no mutation, 104 (69.3%) with BRAF mutation alone, and 11 (7.3%) with TERT+BRAF mutations. As the number of genetic mutations increased from no mutation to BRAF mutation alone to both BRAF and TERT mutations, the proportions of hypoechogenicity, non-parallel orientation, spiculated/microlobulated margin, microcalcifications, and high suspicion category increased. PTCs with TERT+BRAF mutations recurred more frequently than other groups (odd ratio = 17.921 and 31.468). The intervals to recurrence and overall survival were significantly shorter in the TERT+BRAF mutation group than in the other groups ( P s <.0001). PTCs with no mutation, with BRAF mutation alone, and with both TERT and BRAF mutations linearly increase in the probability of displaying malignant US features. In PTCs, the coexistence of BRAF with TERT mutations is more strongly correlated with recurrence and mortality than BRAF mutation alone.