The presence of a RAS mutation, especially a NRAS codon 61 mutation, was significantly associated with the distant metastasis. The NRAS codon 61 mutation status might be a potential prognostic factor in FTC patients.

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Distant metastasis is a main cause of death in follicular thyroid carcinoma (FTC) patients. Factors related to distant metastasis in FTC had been known as age, primary tumor size, and invasiveness. Ras mutations were also supposed to be associated with poor clinical outcomes. We analyzed Ras mutations in FTC with a distant metastasis (FTC M1, n=28), size matched-FTC without a distant metastasis (FTC M0, n=28), follicular adenoma (FA, n=17), and nodular hyperplasia (NH, n=12) to figure out the roles of Ras mutations in follicular thyroid carcinogenesis and metastasis. In addition, we assess the relationship between Ras mutations and clinical outcomes in FTC patients. NRAS, HRAS, and KRAS mutations were assessed using direct sequencing method. Among 85 patients, 39 patients (46%) had Ras mutations. NRAS codon 61 mutation (n=21; 25%) was the most common point mutation. HRAS codon 61, KRAS codon 12/13, and KRAS codon 61 mutations were found in 7, 6, and 4 patients, respectively. NRAS codon 12/13 mutation was found in only 1 patient, and HRAS codon 12/13 mutation was not found. Ras mutations were significantly more common in the FTC than FA or NH groups. Especially, NRAS codon 61 mutation was associated with distant metastasis in patients with FTC. However, there was no significant difference in survival between the Ras mutation positive-FTC and Ras mutation negative-FTC patients. Ras mutation, especially NRAS codon 61 mutation, was significantly associated with the presence of distant metastases. NRAS codon 61 mutation status might be a potential prognostic factor in FTC patients. Citation Format: MinJi Jeon, Eun Kyung Jang, Dong Eun Song, So Young Sim, Eui Young Kim, Yun Mi Choi, Ji Min Han, Won Gu Kim, Tae Yong Kim, Young Kee Shong, Won Bae Kim. N-ras codon 61 mutation is associated with distant metastasis in patients with follicular thyroid carcinoma. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4009. doi:10.1158/1538-7445.AM2014-4009