Lymphatic mapping establishes the role of BRAF gene mutation in papillary thyroid carcinoma.
OBJECTIVE
To define the role of BRAF gene mutation in the progression of papillary thyroid carcinoma.


BACKGROUND
BRAF gene mutation is frequently detected in papillary thyroid carcinoma. Its role in pathogenesis or progression is under investigation.


METHODS
Patients who underwent thyroidectomy and sentinel lymph node biopsy for papillary thyroid cancer were accrued. BRAF mutation was assessed in primary tumors and matched sentinel lymph nodes by a quantitative real-time PCR assay.


RESULTS
Tissue specimens from 103 consecutive patients were evaluated. BRAF mutation of the primary tumor was detected in 34 (33%) patients. In 26 of 34 (76%) patients with BRAF mutation, concomitant lymph node metastasis was detected. On the contrary, in 69 patients with BRAF mutation-negative primary tumors, only 12 (17%) patients had lymph node metastasis (chi, P < 0.0001). BRAF mutation was detected in 20 of 26 (77%) lymph node metastases matched to BRAF mutation-positive primary tumors; it was not detected in lymph node metastases matched to BRAF mutation-negative primary tumors. Univariate analysis identified age, stage, tumor size, and BRAF mutation as prognostic factors for lymph node metastasis. In multivariate analysis, only BRAF mutation remained a significant prognostic factor for lymph node metastasis (odds ratio = 10.8, 95% confidence interval, 3.5-34.0, P < 0.0001).


CONCLUSIONS
BRAF mutation may be a key genetic factor for the metastatic progression of papillary thyroid carcinoma. The study demonstrates that this gene mutation is a significant risk factor for locoregional lymph node metastasis and has potential utility as a surrogate marker.
Kim
Joseph
J
Department of Molecular Oncology, John Wayne Cancer Institute at Saint Johns Hospital, Santa Monica, CA 90404, USA.
Giuliano
Armando E
AE
Turner
Roderick R
RR
Gaffney
Robyn E
RE
Umetani
Naoyuki
N
Kitago
Minoru
M
Elashoff
David
D
Hoon
Dave S B
DS
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002291:Carcinoma, Papillary / Q000235:genetics* / Q000556:secondary; D002648:Child; D004273:DNA, Neoplasm / Q000235:genetics*; D005260:Female; D006801:Humans; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009367:Neoplasm Staging; D016133:Polymerase Chain Reaction; D011379:Prognosis; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics*; D021701:Sentinel Lymph Node Biopsy; D013964:Thyroid Neoplasms / Q000235:genetics* / Q000473:pathology
D004273:DNA, Neoplasm; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf