Abstract 4697: Quantitation of BRAF V600E alleles predicts papillary thyroid cancer progression

Abstract

Abstract BACKGROUND: BRAF V600E is the most common genetic alteration in thyroid cancer. However, there is still controversy regarding its clinicopathological significance and clonal mutation frequency. To clarify these inconsistent results, we investigated the association between the allelic frequency of BRAF V600E and the clinicopathological features in classic papillary thyroid carcinoma (PTC). DESIGN: Tumor tissues from 321 patients with classic PTC were microdissected under a dissecting microscope and analyzed for the presence or absence of the BRAF mutation and mutant allelic percentage using quantitative pyrosequencing. RESULTS: BRAF V600E was found in 264 (82.2%) of 321 classic PTC. In the BRAF V600E-positive tumors, the mutant allelic frequency varied from 8% to 41% of total BRAF alleles (median, 20%). The frequency of BRAF V600E alleles directly correlated with tumor size (R-squared = 0.162, P<0.001) and number of metastatic lymph nodes (R-squared = 0.063, P<0.001). Out of 264 BRAF-positive PTCs, 136 (51%) had ≥20% of BRAF mutant alleles. Extrathyroidal extension and lymph node metastasis were more frequent in PTCs with high (≥20%) abundance of mutant alleles than in those with low abundance of mutant alleles (55% vs 37%, P=0.003 and 62% vs 46%, P=0.012, respectively). However, if the mutant allelic percentage was not considered, the presence of BRAF V600E was only associated with extrathyroidal extension, but not with tumor size and lymph node metastasis. CONCLUSION: High abundance of BRAF V600E alleles predicts tumor progression in classic PTC. We suggest that the clonal, subclonal, or oligoclonal occurrence of BRAF V600E mutation may have different biological and clinicopathological significance in the PTC. Citation Format: Chan Kwon Jung, Min Hee Kim, Ja Seong Bae, Dong Jun Lim, Hyoungnam Lee, So Ra Jeon, Gyeong Sin Park. Quantitation of BRAF V600E alleles predicts papillary thyroid cancer progression. [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 4697. doi:10.1158/1538-7445.AM2014-4697