Zhijiang Chen1, Weiran Wang2, Jiajie Xu3, Yuntao Song4, Honglin Zhu2, Tonghui Ma5, Minghua Ge6, Haixia Guan7. 1. Department of Endocrinology, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong Province, China. 2. Department of Translational Medicine, Genetron Health (Beijing) Technology, Co. Ltd., Beijing, China. 3. Key Laboratory of Endocrine Gland Diseases of Zhejiang Province, Otolaryngology & Head and Neck Center, Cancer Center, Department of Head and Neck Surgery, Zhejiang Provincial People's Hospital (Afliated People's Hospital, Hangzhou Medical College), Hangzhou, Zhejiang Province, China. 4. Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Head and Neck Surgery, Peking University Cancer Hospital and Institute, Beijing, China. 5. Department of Translational Medicine, Genetron Health (Beijing) Technology, Co. Ltd., Beijing, China. tonghuima0818@sina.com. 6. Key Laboratory of Endocrine Gland Diseases of Zhejiang Province, Otolaryngology & Head and Neck Center, Cancer Center, Department of Head and Neck Surgery, Zhejiang Provincial People's Hospital (Afliated People's Hospital, Hangzhou Medical College), Hangzhou, Zhejiang Province, China. gemingh@163.com. 7. Department of Endocrinology, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong Province, China. hxguan@vip.126.com.
Abstract
PURPOSE: Although papillary thyroid cancer (PTC) has a low mortality rate, the rate of recurrence remains relatively high. This study aims to develop a molecular signature to predict the recurrence of PTC. METHODS: A total of 333 PTC patients' data from The Cancer Genome Atlas (TCGA) were included. We calculated tumor mutation burden (TMB) and analyzed the mutation status of BRAF and TERT promoter. RESULTS: Tumor recurrence occurred in 17 of 263 cases in TMB-L patients versus 14 of 70 cases in TMB-H patients (hazard ratio [HR], 3.55; 95% confidence interval [CI], 1.75-7.21; P < 0.001). The HR for recurrence in TMB-H patients remained significant after adjustment for classical clinicopathologic factors (patient age, gender, extrathyroidal extension and lymph node metastasis). These clinical factors had no effect on recurrence rate in TMB-L patients, but had a strong adverse effect on the prognosis of TMB-H patients. Compared with TMB-L patients lacking mutation, the HR (95% CI) of recurrence for TMB-H patients with coexisting BRAF V600E and/or TERT C228/250 T mutations was 6.68 (2.41-18.57), which remained significant after adjustment for clinicopathological factors. The mutation status of BRAF V600E and TERT C228/250 T had little effect on PTC recurrence in TMB-L patients. Either of the mutation was associated with high recurrence rate in TMB-H patients. CONCLUSIONS: The presence of BRAF V600E and/or TERT promoter mutations denotes a high risk of recurrence in TMB-H patients. This represents a powerful molecular prognostic genotype that can help predict patients with the highest risk of recurrence.
PURPOSE: Although papillary thyroid cancer (PTC) has a low mortality rate, the rate of recurrence remains relatively high. This study aims to develop a molecular signature to predict the recurrence of PTC. METHODS: A total of 333 PTC patients' data from The Cancer Genome Atlas (TCGA) were included. We calculated tumor mutation burden (TMB) and analyzed the mutation status of BRAF and TERT promoter. RESULTS: Tumor recurrence occurred in 17 of 263 cases in TMB-L patients versus 14 of 70 cases in TMB-H patients (hazard ratio [HR], 3.55; 95% confidence interval [CI], 1.75-7.21; P < 0.001). The HR for recurrence in TMB-H patients remained significant after adjustment for classical clinicopathologic factors (patient age, gender, extrathyroidal extension and lymph node metastasis). These clinical factors had no effect on recurrence rate in TMB-L patients, but had a strong adverse effect on the prognosis of TMB-H patients. Compared with TMB-L patients lacking mutation, the HR (95% CI) of recurrence for TMB-H patients with coexisting BRAF V600E and/or TERT C228/250 T mutations was 6.68 (2.41-18.57), which remained significant after adjustment for clinicopathological factors. The mutation status of BRAF V600E and TERT C228/250 T had little effect on PTC recurrence in TMB-L patients. Either of the mutation was associated with high recurrence rate in TMB-H patients. CONCLUSIONS: The presence of BRAF V600E and/or TERT promoter mutations denotes a high risk of recurrence in TMB-H patients. This represents a powerful molecular prognostic genotype that can help predict patients with the highest risk of recurrence.
Authors: Ted Gansler; Patricia A Ganz; Marcia Grant; Frederick L Greene; Peter Johnstone; Martin Mahoney; Lisa A Newman; William K Oh; Charles R Thomas; Michael J Thun; Andrew J Vickers; Richard C Wender; Otis Webb Brawley Journal: CA Cancer J Clin Date: 2010 Nov-Dec Impact factor: 508.702
Authors: Ahmedin Jemal; Freddie Bray; Melissa M Center; Jacques Ferlay; Elizabeth Ward; David Forman Journal: CA Cancer J Clin Date: 2011-02-04 Impact factor: 508.702