Optimizing surgical treatment of papillary thyroid carcinoma associated with BRAF mutation.
BACKGROUND
To date, a mutation of the BRAF oncogene is the most common genetic alteration found in papillary thyroid carcinoma (PTC) and is associated with extrathyroidal extension, lymph node metastasis, and tumor recurrence. It is not known whether pre-operative identification of BRAF mutations in cytologic specimens should alter surgical management.


METHODS
From 2006 to 2008, the clinical, cytologic, and pathologic parameters of 106 consecutive surgically treated patients with BRAF-positive PTC were compared with a concurrent cohort of 100 patients with BRAF-negative PTC.


RESULTS
In all, 99 BRAF-positive PTC patients underwent initial treatment, and 7 BRAF-positive patients had surgical resection of recurrent/persistent PTC. BRAF mutations were identified on preoperative cytologic samples (31 patients) or after thyroidectomy (75 patients). All 31 patients with BRAF-positive fine-needle aspiration (FNA) had PTC at thyroidectomy (specificity 100%). At short-term follow-up, 11/106 BRAF-positive patients have required reoperation for recurrent/persistent disease compared with 3 BRAF-negative patients (P = .04). Preoperative knowledge of BRAF mutation positivity could have productively altered initial PTC surgical management in 24% of patients.


CONCLUSIONS
In PTC, BRAF mutations are associated with cervical recurrence and with reoperation. Pre-operative cytologic identification of BRAF mutation has high specificity and may guide the initial extent of thyroidectomy and node dissection.
Yip
Linwah
L
Department of Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA. yipl@upmc.edu
Nikiforova
Marina N
MN
Carty
Sally E
SE
Yim
John H
JH
Stang
Michael T
MT
Tublin
Mitchell J
MJ
Lebeau
Shane O
SO
Hodak
Steven P
SP
Ogilvie
Jennifer B
JB
Nikiforov
Yuri E
YE
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D019943:Amino Acid Substitution; D002291:Carcinoma, Papillary / Q000235:genetics* / Q000556:secondary / Q000601:surgery*; D015331:Cohort Studies; D005260:Female; D006801:Humans; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000235:genetics / Q000601:surgery; D017354:Point Mutation; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics*; D012086:Reoperation; D013964:Thyroid Neoplasms / Q000235:genetics* / Q000601:surgery*; D013965:Thyroidectomy; D055815:Young Adult
C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf