The BRAF mutation is useful for prediction of clinical recurrence in low-risk patients with conventional papillary thyroid carcinoma.
BACKGROUND
The activating BRAF(V600E) mutation is the most common genetic alteration reported in papillary thyroid carcinoma (PTC). While some reports suggest the BRAF(V600E) mutation is associated with factors predicting a poor prognosis and recurrence, this remains a controversial issue.


OBJECTIVE
To determine whether the presence of the BRAF(V600E) mutation is a prognostic indicator for clinical recurrence in low-risk patients with conventional PTC.


METHODS
The study involved 203 conventional PTC patients who underwent total or near-total thyroidectomy followed by immediate 131I ablation of the remnants. Patients with antithyroglobulin antibodies and those with extracervical metastases at presentation were excluded. DNA was extracted from paraffin-embedded tumour specimens, and the presence of the BRAF(V600E) mutation was evaluated using PCR amplification and direct sequencing.


RESULTS
The BRAF(V600E) mutation was found to be present in 149 (73.4%) of 203 patients. The BRAF(V600E) mutation was correlated with male gender (P = 0.006) and with tumour size (P = 0.005). While there appeared to be an association between the BRAF(V600E) mutation and extrathyroid extension, this did not reach statistical significance (P = 0.062). During follow-up of the 203 patients (median 7.3 years; range 0.7-10.0 years), 36 (18%) patients experienced recurrence. While univariate analysis showed the BRAF(V600E) mutation was associated with tumour recurrence (21% with mutation vs 7% without mutation; P = 0.037), this association was not shown following multivariate analyses adjusting for the clinicopathological prognostic factors of age, gender, tumour size, extrathyroid extension, multifocality and lymph node metastasis.


CONCLUSIONS
Although the BRAF(V600E) mutation was found to be associated with a higher clinical recurrence of disease in low-risk conventional PTC patients, it was not an independent predictor.
Kim
Tae Yong
TY
Department of Internal Medicine, Asan Medical Centre, University of Ulsan College of Medicine, Seoul, Korea.
Kim
Won Bae
WB
Rhee
Yoon Soo
YS
Song
Ja Young
JY
Kim
Jung Min
JM
Gong
Gyungyub
G
Lee
Seungkoo
S
Kim
Sang Yoon
SY
Kim
Seong Chul
SC
Hong
Suck Joon
SJ
Shong
Young Kee
YK
D000328:Adult; D002291:Carcinoma, Papillary / Q000235:genetics* / Q000401:mortality / Q000601:surgery; D005260:Female; D019788:Fluorodeoxyglucose F18; D005500:Follow-Up Studies; D006801:Humans; D007457:Iodine Radioisotopes / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009364:Neoplasm Recurrence, Local / Q000235:genetics* / Q000401:mortality; D017354:Point Mutation; D049268:Positron-Emission Tomography; D011379:Prognosis; D016016:Proportional Hazards Models; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics*; D019275:Radiopharmaceuticals / Q000627:therapeutic use; D016019:Survival Analysis; D013964:Thyroid Neoplasms / Q000235:genetics* / Q000401:mortality / Q000601:surgery; D013965:Thyroidectomy
D007457:Iodine Radioisotopes; D019275:Radiopharmaceuticals; D019788:Fluorodeoxyglucose F18; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf