Circulating BRAF^V600E in the Diagnosis and Follow-Up of Differentiated Papillary Thyroid Carcinoma

Context:

Cell-free nucleic acids circulating in plasma are considered a promising noninvasive tool for cancer monitoring. BRAF^V600E mutation in cell-free DNA (cfDNA) could represent an appropriate marker for papillary thyroid carcinoma (PTC).

Objective:

Our aim is to investigate the role of BRAF^V600E-mutated allele in cfDNA as a marker for the diagnosis and follow-up of PTC.

Study Design:

BRAF^V600E allele was detected and quantified by an allele-specific real-time quantitative PCR assay in plasma from 103 patients affected by nodular goiter. As control populations, we enrolled 49 healthy subjects and 16 patients with non-nodular thyroid diseases.

Results:

The percentage of circulating BRAF^V600E was significantly different between patients and controls and throughout different cytological categories of ultrasound-assisted fine-needle aspiration. Patients with a histopathological diagnosis of PTC showed a higher percentage of circulating BRAF^V600E (P = .035) compared to those with benign histology. In 19 patients, a second blood draw, taken 3–6 months after surgery, showed a lower percentage of BRAF^V600E in cfDNA than the presurgical sample (P < .001). The diagnostic performance of circulating BRAF^V600E was assessed by receiver operating characteristic curve analysis resulting in an area under the curve of 0.797. A cutoff value was chosen corresponding to maximum specificity (65%) and sensitivity (80%). On this basis, we evaluated the predictive value of BRAF^V600E in Thy 3 patients with a resulting positive predictive value of 33% and a negative predictive value of 80%.

Conclusions:

The results of the present study provide encouraging data supporting the possibility to take advantage of circulating BRAF^V600E in the management of PTC.