Analysis of BRAFV600E mutation and DNA methylation improves the diagnostics of thyroid fine needle aspiration biopsies

Diagnostic Pathology

Bingyin Shi¹  Peng Hou¹  Qi Yang¹  Kexia Wu¹  Yiping Qu¹  Jing Wei¹  Zhaoxia Zhang¹  Shu Liu¹  Bingfei Zhang¹ 

[1] Department of Endocrinology, The First Affiliated Hospital of Xi’an Jiaotong University School of Medicine, Xi’an 710061, P. R. China

关键词: Papillary thyroid cancer (PTC);    Thyroid nodules;    Fine needle aspiration biopsy (FNAB);    DNA methylation;    BRAF^V600E mutation;   

Others  :  802757
DOI  :  10.1186/1746-1596-9-45

 received in 2013-12-03, accepted in 2014-02-21,  发布年份 2014

【 摘 要 】

Background

Thyroid nodules with indeterminate cytological features on fine needle aspiration biopsy specimens (FNABs) have a ~20% risk of thyroid cancer. BRAF^V600E mutation and DNA methylation are useful markers to distinguish malignant thyroid neoplasm from benign. The aim of this study was to determine whether combined detection of BRAF^V600E mutation and methylation markers on FNABs could improve the diagnostic accuracy of thyroid cancer.

Methods

Using pyrosequencing and quantitative methylation-specific PCR (Q-MSP) methods, FNABs from 79 and 38 patients with thyroid nodules in training and test groups, respectively, were analyzed for BRAF^V600E mutation and gene methylation.

Results

BRAF^V600E mutation was found in 30/42 (71.4%) and 14/20 (70%) FNABs in training and test groups, respectively. All BRAF^V600E-positive samples were histologically diagnosed as papillary thyroid cancer (PTC) after thyroidectomy. As expected, BRAF mutation was not found in all benign nodules. Moreover, we demonstrated that the five genes, including CALCA, DAPK1, TIMP3, RAR-beta and RASSF1A, were aberrantly methylated in FNABs. Of them, methylation level of DAPK1 in PTCs was significantly higher than that in benign samples (P <0.0001). Conversely, methylation level of RASSF1A in PTCs was significantly lower than that in benign samples (P =0.003). Notably, compared with BRAF mutation testing alone, combined detection of BRAF mutation and methylation markers increased the diagnostic sensitivity and accuracy of PTC with excellent specificity.

Conclusion

Our data have demonstrated that combine analysis of BRAF mutation and DNA methylation markers on FNABs may be a useful strategy to facilitate the diagnosis of malignant thyroid neoplasm, particularly PTC.

Virtual slides

The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/6080878071149177 webcite.

【 授权许可】

   
2014 Zhang et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

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