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The presence of the BRAF V600E mutation is significantly associated with increased cancer-related death among patients with papillary thyroid cancer, according to the results of a study published in the Journal of the American Medical Association.

The thyroid gland is located in the front of the neck and is attached to the lower part of the voice box (larynx) and to the upper part of the windpipe (trachea). It has two sides, or lobes, that are connected by a narrow neck. The thyroid gland produces thyroid hormones, which regulate metabolism, growth, and development and are essential for life.

Papillary thyroid cancer is the most common type of thyroid cancer, accounting for more than 70 percent of all cases. Papillary cancers are typically irregular or solid masses that arise from otherwise normal thyroid tissue. More than half of papillary cancers have spread to lymph nodes in the neck. However, papillary cancers rarely spread to distant locations in the body. Papillary thyroid cancer is highly curable with currently available treatment techniques.

The BRAF gene is known to play a part in cell growth, and mutations in BRAF are common in several types of cancer. BRAF V600E mutation is common in papillary thyroid cancer. To investigate the relationship between BRAF V600E mutation and mortality, researchers conducted a retrospective study of 1,849 patients (1411 women and 438 men) with a median age of 46 years and an overall median follow-up time of 33 months after initial treatment at 13 centers in 7 countries between 1978 and 2011.

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The study results indicated that 47.5 percent of patients had the BRAF V600E mutation—and overall mortality was significantly higher among mutation carriers (5.3%) than in those who did not have the mutation (1.1%). Among patients who died, 80.4% had the BRAF V600E mutation. The researchers found significantly higher mortality in patients with the BRAF V600E mutation, even after adjusting for diagnosis, gender, and medical center. What’s more, they found higher mutation-associated mortality in two clinicopathological subcategories: lymph node metastasis and distant tumor metastasis.

The researchers concluded that BRAF V600E mutation was significantly associated with increased mortality in patients with papillary thyroid cancer. However, overall mortality is low in this disease and questions still remain as to how to use information regarding BRAF V600E mutation to manage mortality risk. More research will be necessary to determine how BRAF testing can be used to improve the prognosis of patients with papillary thyroid cancer.


Xing M, Alzahrani AS, Carson KA, et al. Association between BRAF V600E mutation and mortality in patients with papillary thyroid cancer. JAMA. 2013; 309(14): 1493-1501.

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