Prognostic utility of BRAF mutation in papillary thyroid cancer

Abstract

Papillary thyroid cancer (PTC) is a common endocrine malignancy that frequently harbors the oncogenic T1799A BRAF mutation. As a novel prognostic molecular marker, this mutation has received considerable attention in recent years for its potential utility in the risk stratification and management of PTC. In PTC, BRAF mutation is closely associated with extrathyroidal extension, lymph node metastasis, advanced tumor stages, disease recurrence, and even patient mortality. Many of the responsible molecular derangements promoted by, or associated with, BRAF mutation have been identified, including over-expression of tumor-promoting genes, suppression of tumor-suppressor genes, and silencing of thyroid iodide-handling genes, resulting in impairment or loss of radioiodine avidity and hence the failure of radioiodine treatment of PTC. BRAF mutation can be readily tested on thyroid fine needle aspiration biopsy specimens, with high preoperative predictive probabilities for clinicopathological outcomes of PTC. As such, the knowledge of BRAF mutation status can facilitate more accurate risk stratification and better decision making at various steps in the management of PTC, from preoperative planning of initial surgical scale to postoperative decisions about appropriate radioiodine treatment and thyroid-stimulating hormone suppression, and to selections of appropriate surveillance modalities for PTC recurrence. The greatest utility of BRAF mutation status is in those cases where traditional clinicopathological criteria alone would otherwise be unreliable in the risk stratification and management of PTC. Use of this unique molecular marker, in conjunction with conventional clinicopathological risk factors, to assist the prognostication of PTC is likely to improve the efficiency of contemporary management of thyroid cancer.

Figure 1

A. Association of BRAF mutation with PTC recurrence -- Odds ratios for PTC recurrence with BRAF mutation in various studies. The line of odds ratio for Riesco-Ezaguirre et al data is truncated at the value of 16. The data from reference 55 included here has no overlap with the data in reference 51. B. Association of BRAF mutation with decreased survival probability of PTC patients. Fig 1B is adapted from Elisei et al with permission.