MON-530 Local Lymph Node Metastasis Is Less Common in RAS- Mutated Thyroid Cancer Compared to BRAFV600E- Mutated Thyroid Cancer

Introduction: Somatic mutations of RAS- and BRAFV600E- are the most common driver mutation in thyroid cancer (TC) and in the majority of cases, these are mutually exclusive(1,2). Clinical characteristics of TC with either RAS or BRAFV600E mutation is not systemically studied. Methods: This is a retrospective study at the Ohio State University (OSU) from 1/2000 to 12/2018. Data were extracted from OSU Endocrine Neoplasia Repository (ENR). Medullary thyroid cancer was excluded. The treating physician determined patient management. Statistical analysis was performed with the chi-square test for categorical values and Mann-Whitney U test for continuous unpaired values. Two-sided P values of less than 0.05 were considered statistically significant. Results: Out of 320 patients, 152 patients had a positive mutational profile. Of these, 128 patients had a BRAFV600E mutation and 14 had a RAS mutation. Details of RAS mutation were as follows; NRASQ61K (n=2), NRASQ61R (n=1), HRASQ61R (n=1), HRASQ61K (n=1), NRAS without further details (n=9). Local lymph node metastasis was significantly less in RAS mutated cancer (58% vs 16%, p<0.05). Lymph node metastasis was limited to N1a in all RAS group, whereas 38% of BRAFV600E had N1b status. The number of positive lymph nodes were significantly fewer in the RAS group (mean 0.42 vs. 9.1, p=0.003). None of the patients in RAS group developed subsequent local neck recurrence, whereas 19% of BRAFV600E group developed a recurrence (p=0.05). Bone metastasis was more common in RAS compared to BRAFV600E group (21% vs 6%, p=0.04) but there were no differences in other distant metastases. Presence of extrathyroidal extension was significantly higher in BRAFV600E compared to RAS group (58 % vs 8%; p=0.04). Classic variant papillary thyroid cancer was the most common histologic diagnosis with both mutations, however, follicular-variant papillary thyroid cancer was more common in RAS than BRAFV600E group (29% vs 8%, p=0.04) and follicular thyroid cancer was only seen in the RAS group (25% vs 0%, p<0.05). There was no difference in gender, age at diagnosis, disease status after initial therapy, RAI treatment, RAI dosage, and mortality between the groups. Conclusion: Thyroid cancer associated with a RAS-mutation has less tendency to metastasize locally and has a higher incidence of bone metastasis compared to thyroid cancer with BRAFV600E-mutation. Individualized clinical follow up may be indicated depends on their mutational profile. References: 1. Cancer Genome Atlas Research N. Integrated genomic characterization of papillary thyroid carcinoma. Cell. 2014;159(3):676-690. 2. Nikiforova MN, Lynch RA, Biddinger PW, et al. RAS point mutations and PAX8-PPAR gamma rearrangement in thyroid tumors: evidence for distinct molecular pathways in thyroid follicular carcinoma. J Clin Endocrinol Metab. 2003;88(5):2318-2326.