Relevance of BRAF and NRAS mutations in the primary tumor and metastases of papillary thyroid carcinomas

Abstract

BRAF but not NRAS mutations were heterogeneously distributed among primary tumor, nodal sites, and recurrent disease. The BRAF status of metastases generated during the follow-up can differ from the status of foci at diagnosis. © 2016 Wiley Periodicals, Inc. Head Neck 38: 1772-1779, 2016.

Intratumoral Genetic Heterogeneity in Papillary Thyroid Cancer: Occurrence and Clinical Significance

“…A discordant mutational status between the primary site and the metastases supports this mechanism and it was recorded in several human tumors (including lung, melanoma, colorectal, gastric, breast) [4]. In TC, discordant patterns were reported for BRAF V600E , TERT, RAS and other mutations [27,39,40,51,52,[58][59][60][61][62][63][64][65]. Data related to PTC are reviewed in Table 3.…”

“…Data related to PTC are reviewed in Table 3. In particular, the BRAF mutational status between primary tumor and metastases, mainly loco regional, was found to be discordant in up to 50% of cases, by different techniques [39,40,51,52,59,61,62]. In a recent study, it was shown that 14/27 TERT mutated primary tumors had wild-type TERT lymph node or distant metastases [52].…”

Cytologic, histologic and molecular findings of papillary thyroid carcinoma variants, one institution’s experience

“…[6,10,12,33] BRAF mutations are associated with a poor prognosis and tumor aggressiveness (extrathyroidal extension, lymph node metastasis, radioiodine treatment failure, and recurrence) and may be associated with the tumor being more often bilateral. [3,34] Without other coexisting genetic alterations, RAS mutated PTC lacks an aggressive behavior. [35] TERT promoter mutations correlate with aggressive clinicopathological features and poor outcomes.…”

“…[1,2] More than 80% of thyroid carcinomas are PTC, and its incidence is steadily increasing at a rate of 3% per year. [3] The age-standardized incidence rate of thyroid cancer per year in developed countries is 6.62 for men and 20.8 per women per 100,000. PTC accounts for 1.5% of all cancers in the United States (US).…”

“…[22] NRAS mutations are seen in approximately 40% of FVPTC and only rarely in PTCC. [3,4,7,23] NRAS is a member of the RAS family of GTPase and plays an important role as a mediator of cellular growth signals generated by upstream receptor tyrosine kinases. In addition to PTC, activating mutations of NRAS are found in various types of cancers, including 15%-25% of melanomas, 3%-5% of colorectal cancers, and 5%-10% of hepatocellular carcinomas.…”