BRAF(V600E) mutation is associated with an increased risk of nodal recurrence requiring reoperative surgery in patients with papillary thyroid cancer.
BACKGROUND
The role of the B-isoform of the Raf kinase (BRAF) mutation BRAF(V600E) as an independent prognostic factor in papillary thyroid cancer (PTC) remains controversial. Some studies suggest that tumors containing BRAF(V600E) have decreased radioiodine avidity and present a greater risk of nodal recurrence and distant metastases.


METHODS
Paraffin-embedded specimens from consecutive patients who underwent surgery for PTC before 2003 were independently reviewed by an endocrine pathologist. DNA was extracted, amplified by polymerase chain reaction, and the presence of the BRAF(V600E) mutation was determined by restriction digest. Tumor characteristics and long-term disease outcomes were analyzed according to BRAF(V600E) status.


RESULTS
BRAF(V600E) was identified in 60 (59%) of 101 patients. At a median follow-up of 106 months, the overall disease-free survival was 78%. Clinically evident nodal recurrence occurred in 11% of BRAF(V600E)-positive patients, and all patients required lateral neck dissection (P = .02). In contrast, subclinical nodal recurrence occurred in 7% of BRAF(V600E)-negative patients, and all recurrences were successfully ablated with radioactive iodine. There was a trend toward poorer disease-free survival among patients with stage III/IV PTC and BRAF(V600E) mutation (P = .08). All 5 disease-related deaths occurred in patients with BRAF(V600E)-positive primary tumors (P = .06).


CONCLUSIONS
The BRAF(V600E) mutation in PTC is associated with an increased risk of palpable nodal recurrence and the need for reoperative surgery.
Endocrine Surgical Unit, University of Sydney, St Leonards, New South Wales, Australia.
Christine J
CJ
O'Neill
Martyn
M
Bullock
Angela
A
Chou
Stan B
SB
Sidhu
Leigh W
LW
Delbridge
Bruce G
BG
Robinson
Anthony J
AJ
Gill
Diana L
DL
Learoyd
Roderick
R
Clifton-Bligh
Mark S
MS
Sywak
D000328:Adult; D000368:Aged; D002277:Carcinoma; D002291:Carcinoma, Papillary; D017931:DNA Primers; D018572:Disease-Free Survival; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000401:mortality / Q000601:surgery*; D012150:Polymorphism, Restriction Fragment Length; D020641:Polymorphism, Single Nucleotide; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics*; D012086:Reoperation / Q000706:statistics & numerical data*; D015183:Restriction Mapping; D012307:Risk Factors; D012727:Sex Characteristics; D015996:Survival Rate; D000077273:Thyroid Cancer, Papillary; D013964:Thyroid Neoplasms / Q000401:mortality / Q000473:pathology / Q000601:surgery
D017931:DNA Primers; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf