Abstract 652: Mutational profile of papillary thyroid microcarcinoma with extensive lymph node metastasis: Comparison of primary thyroid cancer and metastatic lymph nodes

Abstract

Abstract Introduction: Papillary thyroid microcarcinoma (PTMC) has excellent clinical outcomes, but distant metastasis of PTMC can be fatal. We previously reported that change to an aggressive pathologic subtype of metastatic lymph nodes (LNs) were associated with distant metastasis of PTMC. This study aimed to evaluate and compare the mutational profile of primary tumor and metastatic LNs of PTMC. Method: We included 16 PTMC patients with lateral cervical LN metastases. One of them has distant metastases. DNAs from formalin-fixed, paraffin-embedded archival samples of 16 sets of the normal thyroid tissue, primary PTMC, and the largest metastatic LN were used for targeted next-generation sequencing by Oncopanel AMC version 2.0. Results: A total of 7 somatic variants were confirmed in primary PTMC compared to normal thyroid tissue. BRAF V600E mutation was the most common and seen in 12 primary PTMCs (75%) and 11 metastatic LNs (69%). Missense mutation of KMT2A, RAF1, and ROS1 was detected only in one primary PTMC (6.3%), respectively. Frame-shift mutation of JAK2, inframe deletion of ACVR2A and nonsense mutation of AR was detected one primary PTMC (6.3%) with its metastatic LN, respectively. When we compare the mutational profile of primary tumor and metastatic LNs, there were no newly developed somatic mutations in metastatic LNs. We also found ALK/STRN rearrangement in one PTMC with its metastatic LN (6.3%). CCDC6/RET rearrangement and RET intergenic rearrangement was detected only in 2 metastatic LNs (12.5%) and one metastatic LN (6.3%), respectively. BARD1 deletion was detected in one primary PTMC with its metastatic LNS (6.3%) and FLT4 deletion was detected only in one primary PTMC (6.3%). We also found JAK1, AURKC, and TP53 deletions, which were detected only in one metastatic LN, respectively (6.3%). Conclusion: The mutation frequency of PTMC was really low even in patients with extensive LN metastasis. The mutational status of primary tumor and their regional metastatic LNs were not significantly different and this suggests the minor role of genetic mutations in the process of LN metastases. Citation Format: Min Ji Jeon, Won Gu Kim, Sung Min Chun, Dong Eun Song, Tae Yong Kim, Young Kee Shong, Won Bae Kim. Mutational profile of papillary thyroid microcarcinoma with extensive lymph node metastasis: Comparison of primary thyroid cancer and metastatic lymph nodes [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 652.