The Frequency and Clinical Implications of the BRAF^V600EMutation in Papillary Thyroid Cancer Patients in Korea Over the Past Two Decades

Abstract

BackgroundOver the past several decades, there has been a rapid worldwide increase in the prevalence of papillary thyroid cancer (PTC) as well as a number of changes in the clinicopathological characteristics of this disease. BRAFV600E, which is a mutation of the proto-oncogene BRAF, has become the most frequent genetic mutation associated with PTC, particularly in Korea. Thus, the present study investigated whether the prevalence of the BRAFV600E mutation has increased over the past two decades in the Korean population and whether various PTC-related clinicopathological characteristics have changed.MethodsThe present study included 2,624 patients who underwent a thyroidectomy for PTC during two preselected periods; 1995 to 2003 and 2009 to 2012. The BRAFV600E mutation status of each patient was confirmed using the polymerase chain reaction-restriction fragment length polymorphism method or by the direct sequencing of DNA.ResultsThe prevalence of the BRAFV600E mutation in Korean PTC patients increased from 62.2% to 73.7% (P=0.001) over the last two decades. Additionally, there was a greater degree of extrathyroidal extension (ETE) and lymph node metastasis in 2009 to 2012 patients with the BRAFV600E mutation and a higher frequency of thyroiditis and follicular variant-PTC in 2009 to 2012 patients with wild-type BRAF. However, only the frequency of ETE was significantly higher in 1995 to 2003 patients with the BRAFV600E mutation (P=0.047). Long-term recurrence rates during a 10-year median follow-up did not differ based on BRAFV600E mutation status.ConclusionThe BRAFV600E mutation rate in Korean PTC patients has been persistently high (approximately 70%) over the past two decades and continues to increase. The present findings demonstrate that BRAFV600E-positive PTC was associated with more aggressive clinicopathological features, especially in patients who were recently diagnosed, suggesting that BRAFV600E mutation status may be a useful prognostic factor for PTC in patients recently diagnosed with this disease.

Effect of Hashimoto thyroiditis on low‐dose radioactive‐iodine remnant ablation

“…Incidence of Hashimoto thyroiditis with concomitant PTC were reported as 4.7% in Spain, 26.8% to 38.1% in Italy, 7.1% in Ireland, 14.7% to 30.1% in the United States, and 31.1% in the present study of Korea . Furthermore, in Korea, B‐type Raf (BRAF) mutation was found in about 70% of patients with PTC, which was significantly higher than 46% in United States . As BRAF mutations were known to cause impaired expression of iodide‐handling genes, including NIS and radioiodine refractoriness of thyroid cancer, higher prevalence of the mutated BRAF gene in Korea may be one of the reasons for the difference in radioactive‐iodine remnant ablation success rate .…”

A meta-analysis of prognostic roles of molecular markers in papillary thyroid carcinoma

“…We received responses from authors of six studies in Korea, Italy, Poland and Turkey to provide their unpublished data (16, 17, 18, 19, 20, 21). …”

Genetic alterations of differentiated thyroid carcinoma in iodine‐rich and iodine‐deficient countries

“…BRAF mutations are the most common mutations in PTCs, and BRAF V600E constitutes 99% of all BRAF mutations 37. The increase in prevalence of BRAF mutations in accordance with iodine supplementation and increase in proportion of PTCs have been reported in different geographical areas 38, 39, 40. This association led to a hypothesis that iodine intake may play a role, at least to some extent, in tumorigenesis of PTC and influence the increase of the BRAF mutations in PTCs.…”