Abstract
Objective Detection of circulating tumor DNA (ctDNA) in cancer patients can potentially serve as a noninvasive, sensitive test of disease status. The purpose of this study was to determine the ability to detect BRAF (V600E) mutations in the plasma of patients with thyroid nodules, with the goal of distinguishing between benign and malignant nodules. Methods Consecutive patients with thyroid nodules who consented for surgery were recruited. Plasma samples were obtained preoperatively and one month postoperatively. Quantitative PCR was used to determine the levels of the BRAF (V600E) mutation preoperatively and postoperatively. Results A total of 109 patients were recruited. On final pathology, 38 (32.8%) patients had benign thyroid nodules, 45 (38.8%) had classical papillary thyroid cancer (PTC), 23 (19.8%) had nonclassical PTC, and 3 (2.6%) had follicular thyroid cancer. 15/109 patients had detectable BRAF (V600E) ctDNA in their preoperative samples—all of them having classical PTC. Higher T-stage and extrathyroidal extension in PTC were associated with positive BRAF (V600E) ctDNA (p < 0.05). Eighty-eight pairs of preoperative and postoperative plasma samples were collected and analyzed. Of these eighty-eight paired samples, a total of 13/88 (14.8%) patients had detectable BRAF (V600E) ctDNA in their preoperative samples—all of them having classical PTC. 12 of these 13 patients had no detectable BRAF (V600E) postoperatively, while one remaining patient had a significant decline in his levels (p < 0.05). ConclusionBRAF (V600E) circulating thyroid tumor DNA can be detected in plasma and is correlated with a final diagnosis of the classical variant of PTC. Given that a postoperative drop in BRAF (V600E) ctDNA levels was observed in all cases suggests its utility as a tumor marker.
Highlights
Sequential patients referred to the Otolaryngology-Head and Neck Surgery Clinic for thyroid nodules at London Health Sciences Centre (LHSC) from April 2014 to March 2015 were approached for participation in the study
We successfully detected BRAF (V600E) circulating tumor DNA (ctDNA) in 15 (13.8%) out of the 109 patients with thyroid nodular disease selected for surgery, all of which had classical papillary thyroid cancer (PTC) in the index nodule
In our study, we demonstrated a correlation of ctDNA levels with advanced T-stage and extrathyroidal extension supporting this hypothesis
Summary
Sequential patients referred to the Otolaryngology-Head and Neck Surgery Clinic for thyroid nodules at London Health Sciences Centre (LHSC) from April 2014 to March 2015 were approached for participation in the study. Approval was obtained through the Lawson Health Research Institute research ethics board (REB 103985). Inclusion criteria included patients over the age of 18 and those scheduled to undergo partial or total thyroidectomy for their thyroid nodules. Exclusion criteria included a previous cancer known to be positive for the BRAF (V600E) mutation (such as melanoma, lung cancer, and colon cancer)
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