BRAF Analysis in Fine Needle Aspiration Biopsy (FNAB) of Papillary Thyroid Carcinoma (PTC).
Agnes Colanta, Maria Arcila, Laura Tafe, Ronald Ghossein, Marc Ladanyi, Oscar Lin. MSKCC, NY, NY
Background: BRAF mutation is the most common genetic alteration in papillary thyroid carcinoma (PTC) and has been associated with extrathyroidal extension, metastases and recurrence. It has been reported to be an independent prognostic factor that can be used to preoperatively identify PTC patients with aggressive disease. Thus, it may be useful in tailoring the initial surgical extent for these patients. Our objectives were to evaluate the BRAF status using archived cytology specimens from patients with histologically proven PTC and long term follow up and to correlate these results with the original cytology diagnosis, clinicopathological stage at surgery and long term outcome of these patients.
Design: Fine needle aspiration biopsy (FNAB) material from 24 cases of PTC with corresponding confirmatory thyroidectomy specimens and more than 10 years follow-up were used in this study. The slides were evaluated to confirm the presence of diagnostic cells and DNA was extracted from the previously-stained cytology slides. Standard PCR was performed for an amplicon in BRAF exon 15 that included the V600E mutation site. Locked nucleic acid (LNA) PCR was also performed to increase sensitivity. Cycle sequencing was performed using the BigDye Terminator kit and analysis was performed on an ABI automated sequencer (Applied Biosystems). The forward and reverse sequences were analyzed for point mutations.
Results: The frequency of BRAF mutation in PTC in our series was 38%. The correlation of the BRAF status with the cytology diagnosis, clinicopathological stage at surgery and recurrence are summarized in Table 1. Notably, only one patient died of disease. This case was BRAF(+), tall cell variant PTC, presented at high stage, developed recurrence and distant metastases. Eight of the nine (89%) BRAF(+) cases were of the tall cell and classical variants while 5 of the 15 (33%) BRAF(-) cases were of the follicular variant.
|BRAF Status||PTC (N=24)||FNAB Diagnosis||Clinicopathologic Feature|
|Positive [N=11/24 (46%)]||Suspicious [N=6/24 (25%)]||Atypical [N=7/24 (29%)]||> stage 1 [N=6/24 (25%)]||Recurrence [N=4/24 (17%)]|
|BRAF (+)||9 (38%)||8 (73%)||1 (17%)||0||4 (67%)||2 (50%)|
|BRAF(-)||15 (62%)||3 (27%)||5 (83%)||7 (100%)||2 (33%)||2 (50%)|