BRAFV600E mutation in papillary thyroid microcarcinoma: a meta-analysis

Fei Li; Guangqi Chen; Chunjun Sheng; Aaron M Gusdon; Yueye Huang; Zhongwei Lv; Huixiong Xu; Mingzhao Xing; Shen Qu

doi:10.1530/ERC-14-0531

BRAFV600E mutation in papillary thyroid microcarcinoma: a meta-analysis

Endocr Relat Cancer. 2015 Apr;22(2):159-68. doi: 10.1530/ERC-14-0531. Epub 2015 Jan 15.

Authors

Fei Li¹, Guangqi Chen², Chunjun Sheng², Aaron M Gusdon², Yueye Huang², Zhongwei Lv³, Huixiong Xu³, Mingzhao Xing³, Shen Qu¹

Affiliations

¹ 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
² 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.
³ 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.

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.

Keywords: BRAFV600E mutation; meta-analysis; papillary thyroid microcarcinoma; prognosis; thyroid cancer.

Publication types

Meta-Analysis
Research Support, Non-U.S. Gov't

MeSH terms

Carcinoma, Papillary / epidemiology
Carcinoma, Papillary / genetics*
Carcinoma, Papillary / pathology
Female
Humans
Lymphatic Metastasis
Male
Middle Aged
Mutation
Odds Ratio
Proto-Oncogene Proteins B-raf / genetics*
Thyroid Neoplasms / epidemiology
Thyroid Neoplasms / genetics*
Thyroid Neoplasms / pathology

Substances

BRAF protein, human
Proto-Oncogene Proteins B-raf

Supplementary concepts

Papillary Thyroid Microcarcinoma

Grants and funding

P30 CA006973/CA/NCI NIH HHS/United States