title: BRAFV600E mutation in papillary thyroid microcarcinoma: a meta-analysis.
abstract: The prognostic value of the BRAFV600E mutation, resulting in poor clinical outcomes of papillary thyroid carcinoma, has been generally confirmed. However, the association of BRAFV600E with aggressive clinical behaviors of papillary thyroid microcarcinoma (PTMC) has not been firmly established in individual studies. We performed this meta-analysis to examine the relationship between BRAFV600E mutation and the clinicopathological features of PTMC. We conducted a systematic search in PubMed, EMBASE, and the Cochrane library for relevant studies. We selected all the studies that reported clinicopathological features of PTMC patients with information available on BRAFV600E mutation status. Nineteen studies involving a total of 3437 patients met these selection criteria and were included in the analyses. The average prevalence of the BRAFV600E mutation was 47.48%, with no significant difference with respect to patient sex (male versus female) and age (younger than 45 years versus 45 years or older). Compared with the WT BRAF gene, the BRAFV600E mutation was associated with tumor multifocality (odds ratio (OR) 1.38; 95% CI, 1.04-1.82), extrathyroidal extension (OR 3.09; 95% CI, 2.24-4.26), lymph node metastases (OR 2.43; 95% CI, 1.28-4.60), and advanced stage (OR 2.39; 95% CI, 1.38-4.15) of PTMC. Thus, our findings from this large meta-analysis definitively demonstrate that BRAFV600E-mutation-positive PTMC are more likely to manifest with aggressive clinicopathological characteristics. In appropriate clinical settings, testing for the BRAFV600E mutation is likely to be useful in assisting the risk stratification and management of PTMC.
authors.affiliation: Department of EndocrinologyShanghai Tenth People's Hospital, Tongji University School of Medicine, 301 Yan Chang Middle Road, Shanghai 200072, ChinaFirst Clinical Medical CollegeNanjing Medical University, Nanjing 210029, ChinaJiangsu Institute of Nuclear MedicineWuxi 214063, ChinaDepartment of CardiologyShanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, ChinaDepartment of Neurology and NeuroscienceWeill Cornell Medical College, New York, New York 10065, USADepartments of Nuclear MedicineUltrasound MedicineShanghai Tenth People's Hospital, Shanghai 200072, ChinaThyroid InstituteTongji University, Shanghai 200072, ChinaDivision of EndocrinologyDiabetes and Metabolism, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21287, USA Department of EndocrinologyShanghai Tenth People's Hospital, Tongji University School of Medicine, 301 Yan Chang Middle Road, Shanghai 200072, ChinaFirst Clinical Medical CollegeNanjing Medical University, Nanjing 210029, ChinaJiangsu Institute of Nuclear MedicineWuxi 214063, ChinaDepartment of CardiologyShanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, ChinaDepartment of Neurology and NeuroscienceWeill Cornell Medical College, New York, New York 10065, USADepartments of Nuclear MedicineUltrasound MedicineShanghai Tenth People's Hospital, Shanghai 200072, ChinaThyroid InstituteTongji University, Shanghai 200072, ChinaDivision of EndocrinologyDiabetes and Metabolism, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21287, USA Department of EndocrinologyShanghai Tenth People's Hospital, Tongji University School of Medicine, 301 Yan Chang Middle Road, Shanghai 200072, ChinaFirst Clinical Medical CollegeNanjing Medical University, Nanjing 210029, ChinaJiangsu Institute of Nuclear MedicineWuxi 214063, ChinaDepartment of CardiologyShanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, ChinaDepartment o
authors.forename: Fei
authors.initials: F
authors.lastname: Li
authors.affiliation: Department of EndocrinologyShanghai Tenth People's Hospital, Tongji University School of Medicine, 301 Yan Chang Middle Road, Shanghai 200072, ChinaFirst Clinical Medical CollegeNanjing Medical University, Nanjing 210029, ChinaJiangsu Institute of Nuclear MedicineWuxi 214063, ChinaDepartment of CardiologyShanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, ChinaDepartment of Neurology and NeuroscienceWeill Cornell Medical College, New York, New York 10065, USADepartments of Nuclear MedicineUltrasound MedicineShanghai Tenth People's Hospital, Shanghai 200072, ChinaThyroid InstituteTongji University, Shanghai 200072, ChinaDivision of EndocrinologyDiabetes and Metabolism, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21287, USA.
authors.forename: Guangqi
authors.initials: G
authors.lastname: Chen
authors.affiliation: Department of EndocrinologyShanghai Tenth People's Hospital, Tongji University School of Medicine, 301 Yan Chang Middle Road, Shanghai 200072, ChinaFirst Clinical Medical CollegeNanjing Medical University, Nanjing 210029, ChinaJiangsu Institute of Nuclear MedicineWuxi 214063, ChinaDepartment of CardiologyShanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, ChinaDepartment of Neurology and NeuroscienceWeill Cornell Medical College, New York, New York 10065, USADepartments of Nuclear MedicineUltrasound MedicineShanghai Tenth People's Hospital, Shanghai 200072, ChinaThyroid InstituteTongji University, Shanghai 200072, ChinaDivision of EndocrinologyDiabetes and Metabolism, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21287, USA.
authors.forename: Chunjun
authors.initials: C
authors.lastname: Sheng
authors.affiliation: Department of EndocrinologyShanghai Tenth People's Hospital, Tongji University School of Medicine, 301 Yan Chang Middle Road, Shanghai 200072, ChinaFirst Clinical Medical CollegeNanjing Medical University, Nanjing 210029, ChinaJiangsu Institute of Nuclear MedicineWuxi 214063, ChinaDepartment of CardiologyShanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, ChinaDepartment of Neurology and NeuroscienceWeill Cornell Medical College, New York, New York 10065, USADepartments of Nuclear MedicineUltrasound MedicineShanghai Tenth People's Hospital, Shanghai 200072, ChinaThyroid InstituteTongji University, Shanghai 200072, ChinaDivision of EndocrinologyDiabetes and Metabolism, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21287, USA.
authors.forename: Aaron M
authors.initials: AM
authors.lastname: Gusdon
authors.affiliation: Department of EndocrinologyShanghai Tenth People's Hospital, Tongji University School of Medicine, 301 Yan Chang Middle Road, Shanghai 200072, ChinaFirst Clinical Medical CollegeNanjing Medical University, Nanjing 210029, ChinaJiangsu Institute of Nuclear MedicineWuxi 214063, ChinaDepartment of CardiologyShanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, ChinaDepartment of Neurology and NeuroscienceWeill Cornell Medical College, New York, New York 10065, USADepartments of Nuclear MedicineUltrasound MedicineShanghai Tenth People's Hospital, Shanghai 200072, ChinaThyroid InstituteTongji University, Shanghai 200072, ChinaDivision of EndocrinologyDiabetes and Metabolism, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21287, USA.
authors.forename: Yueye
authors.initials: Y
authors.lastname: Huang
authors.affiliation: Department of EndocrinologyShanghai Tenth People's Hospital, Tongji University School of Medicine, 301 Yan Chang Middle Road, Shanghai 200072, ChinaFirst Clinical Medical CollegeNanjing Medical University, Nanjing 210029, ChinaJiangsu Institute of Nuclear MedicineWuxi 214063, ChinaDepartment of CardiologyShanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, ChinaDepartment of Neurology and NeuroscienceWeill Cornell Medical College, New York, New York 10065, USADepartments of Nuclear MedicineUltrasound MedicineShanghai Tenth People's Hospital, Shanghai 200072, ChinaThyroid InstituteTongji University, Shanghai 200072, ChinaDivision of EndocrinologyDiabetes and Metabolism, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21287, USA Department of EndocrinologyShanghai Tenth People's Hospital, Tongji University School of Medicine, 301 Yan Chang Middle Road, Shanghai 200072, ChinaFirst Clinical Medical CollegeNanjing Medical University, Nanjing 210029, ChinaJiangsu Institute of Nuclear MedicineWuxi 214063, ChinaDepartment of CardiologyShanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, ChinaDepartment of Neurology and NeuroscienceWeill Cornell Medical College, New York, New York 10065, USADepartments of Nuclear MedicineUltrasound MedicineShanghai Tenth People's Hospital, Shanghai 200072, ChinaThyroid InstituteTongji University, Shanghai 200072, ChinaDivision of EndocrinologyDiabetes and Metabolism, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21287, USA.
authors.forename: Zhongwei
authors.initials: Z
authors.lastname: Lv
authors.affiliation: Department of EndocrinologyShanghai Tenth People's Hospital, Tongji University School of Medicine, 301 Yan Chang Middle Road, Shanghai 200072, ChinaFirst Clinical Medical CollegeNanjing Medical University, Nanjing 210029, ChinaJiangsu Institute of Nuclear MedicineWuxi 214063, ChinaDepartment of CardiologyShanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, ChinaDepartment of Neurology and NeuroscienceWeill Cornell Medical College, New York, New York 10065, USADepartments of Nuclear MedicineUltrasound MedicineShanghai Tenth People's Hospital, Shanghai 200072, ChinaThyroid InstituteTongji University, Shanghai 200072, ChinaDivision of EndocrinologyDiabetes and Metabolism, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21287, USA Department of EndocrinologyShanghai Tenth People's Hospital, Tongji University School of Medicine, 301 Yan Chang Middle Road, Shanghai 200072, ChinaFirst Clinical Medical CollegeNanjing Medical University, Nanjing 210029, ChinaJiangsu Institute of Nuclear MedicineWuxi 214063, ChinaDepartment of CardiologyShanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, ChinaDepartment of Neurology and NeuroscienceWeill Cornell Medical College, New York, New York 10065, USADepartments of Nuclear MedicineUltrasound MedicineShanghai Tenth People's Hospital, Shanghai 200072, ChinaThyroid InstituteTongji University, Shanghai 200072, ChinaDivision of EndocrinologyDiabetes and Metabolism, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21287, USA.
authors.forename: Huixiong
authors.initials: H
authors.lastname: Xu
authors.affiliation: Department of EndocrinologyShanghai Tenth People's Hospital, Tongji University School of Medicine, 301 Yan Chang Middle Road, Shanghai 200072, ChinaFirst Clinical Medical CollegeNanjing Medical University, Nanjing 210029, ChinaJiangsu Institute of Nuclear MedicineWuxi 214063, ChinaDepartment of CardiologyShanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, ChinaDepartment of Neurology and NeuroscienceWeill Cornell Medical College, New York, New York 10065, USADepartments of Nuclear MedicineUltrasound MedicineShanghai Tenth People's Hospital, Shanghai 200072, ChinaThyroid InstituteTongji University, Shanghai 200072, ChinaDivision of EndocrinologyDiabetes and Metabolism, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21287, USA Department of EndocrinologyShanghai Tenth People's Hospital, Tongji University School of Medicine, 301 Yan Chang Middle Road, Shanghai 200072, ChinaFirst Clinical Medical CollegeNanjing Medical University, Nanjing 210029, ChinaJiangsu Institute of Nuclear MedicineWuxi 214063, ChinaDepartment of CardiologyShanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, ChinaDepartment of Neurology and NeuroscienceWeill Cornell Medical College, New York, New York 10065, USADepartments of Nuclear MedicineUltrasound MedicineShanghai Tenth People's Hospital, Shanghai 200072, ChinaThyroid InstituteTongji University, Shanghai 200072, ChinaDivision of EndocrinologyDiabetes and Metabolism, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21287, USA.
authors.forename: Mingzhao
authors.initials: M
authors.lastname: Xing
authors.affiliation: Department of EndocrinologyShanghai Tenth People's Hospital, Tongji University School of Medicine, 301 Yan Chang Middle Road, Shanghai 200072, ChinaFirst Clinical Medical CollegeNanjing Medical University, Nanjing 210029, ChinaJiangsu Institute of Nuclear MedicineWuxi 214063, ChinaDepartment of CardiologyShanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, ChinaDepartment of Neurology and NeuroscienceWeill Cornell Medical College, New York, New York 10065, USADepartments of Nuclear MedicineUltrasound MedicineShanghai Tenth People's Hospital, Shanghai 200072, ChinaThyroid InstituteTongji University, Shanghai 200072, ChinaDivision of EndocrinologyDiabetes and Metabolism, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21287, USA Department of EndocrinologyShanghai Tenth People's Hospital, Tongji University School of Medicine, 301 Yan Chang Middle Road, Shanghai 200072, ChinaFirst Clinical Medical CollegeNanjing Medical University, Nanjing 210029, ChinaJiangsu Institute of Nuclear MedicineWuxi 214063, ChinaDepartment of CardiologyShanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, ChinaDepartment of Neurology and NeuroscienceWeill Cornell Medical College, New York, New York 10065, USADepartments of Nuclear MedicineUltrasound MedicineShanghai Tenth People's Hospital, Shanghai 200072, ChinaThyroid InstituteTongji University, Shanghai 200072, ChinaDivision of EndocrinologyDiabetes and Metabolism, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21287, USA Department of EndocrinologyShanghai Tenth People's Hospital, Tongji University School of Medicine, 301 Yan Chang Middle Road, Shanghai 200072, ChinaFirst Clinical Medical CollegeNanjing Medical University, Nanjing 210029, ChinaJiangsu Institute of Nuclear MedicineWuxi 214063, ChinaDepartment of CardiologyShanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, ChinaDepartment o
authors.forename: Shen
authors.initials: S
authors.lastname: Qu
mesh_terms: D002291:Carcinoma, Papillary / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology; D005260:Female; D006801:Humans; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009154:Mutation; D016017:Odds Ratio; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics*; D013964:Thyroid Neoplasms / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology
chemical_list: C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf
keywords: BRAFV600E mutation; meta-analysis; papillary thyroid microcarcinoma; prognosis; thyroid cancer