Detection of BRAFV600E in Liquid Biopsy from Patients with Papillary Thyroid Cancer Is Associated with Tumor Aggressiveness and Response to Therapy

• Main Authors: Kirk Jensen, Shilpa Thakur, Aneeta Patel, Maria Cecilia Mendonca-Torres, John Costello, Cristiane Jeyce Gomes-Lima, Mary Walter, Leonard Wartofsky, Kenneth Dale Burman, Athanasios Bikas, Dorina Ylli, Vasyl V. Vasko, Joanna Klubo-Gwiezdzinska
• Format: Article
• Language: English
• Published: MDPI AG 2020-08-01
• Series: Journal of Clinical Medicine
• Subjects: COLD-PCR; digital PCR; BRAFV600E; papillary thyroid cancer; liquid biopsy
• Online Access: https://www.mdpi.com/2077-0383/9/8/2481

<b> </b>The detection of rare mutational targets in plasma (liquid biopsy) has emerged as a promising tool for the assessment of patients with cancer. We determined the presence of cell-free DNA containing the <i>BRAFV600E</i> mutations (cf<i>BRAFV600E</i>) in plasma samples from 57 patients with papillary thyroid cancer (PTC) with somatic <i>BRAFV600E</i> mutation-positive primary tumors using microfluidic digital PCR, and co-amplification at lower denaturation temperature (COLD) PCR. Mutant cf<i>BRAFV600E</i> alleles were detected in 24/57 (42.1%) of the examined patients. The presence of cf<i>BRAFV600E</i> was significantly associated with tumor size (<i>p</i> = 0.03), multifocal patterns of growth (<i>p</i> = 0.03), the presence of extrathyroidal gross extension (<i>p</i> = 0.02) and the presence of pulmonary micrometastases (<i>p</i> = 0.04). In patients with low-, intermediate- and high-risk PTCs, cf<i>BRAFV600E</i> was detected in 4/19 (21.0%), 8/22 (36.3%) and 12/16 (75.0%) of cases, respectively. Patients with detectable <i>cfBRAFV600E</i> were characterized by a 4.68 times higher likelihood of non-excellent response to therapy, as compared to patients without detectable cf<i>BRAF</i>V600E (OR (odds ratios), 4.68; 95% CI (confidence intervals)) 1.26–17.32; <i>p</i> = 0.02). In summary, the combination of digital polymerase chain reaction (dPCR) with COLD-PCR enables the detection of <i>BRAFV600E</i> in the liquid biopsy from patients with PTCs and could prove useful for the identification of patients with PTC at an increased risk for a structurally or biochemically incomplete or indeterminate response to treatment.