Session: OR14-Thyroid Cancer: Insights into Diagnosis & Treatment
Room 103 (Moscone Center)
DNA from formalin-fixed paraffin-embedded sections of 131 PTCs was subjected to a panel of 23 multiplexed assays interrogating 286 mutations in 23 genes on a MassARRAY platform (Sequenom). Mutation calling was determined using TyperAnalyzer software and manual analysis. Mutational status was compared with histological architecture, pTNM stage, MACIS score, and recurrence rate.
There were 68 mutations in 65 tumors: BRAFV600E (n: 40), BRAFK601E (n:1), EGFRS768I (n: 2); HRASQ61K (n:5), KRASG12C (n:4), KRASG12D (n:1), KRASQ61R (n: 2), NRASQ61K (n:3), NRASQ61R (n:8), STK11W332 (n:1) and STK11F354L (n: 1). Three samples revealed more than one mutation. Classical (papillary) and follicular architecture was seen in 67 and 64 PTCs, respectively. Complete pathologic data was available in 128 patients allowing complete pTNM stage and MACIS assignment. Thirteen patients received were not followed at our institution after surgical and radioactive iodine treatment; the remaining 115 patients had a mean follow up of 6.26 years. Our results demonstrate that the BRAFV600E mutation correlates strongly with classical architecture (p=0.001). While BRAFV600E mutation was associated with increasing frequency of lymph-nodal involvement and hence pTNM score (p=0.002), this relationship was abolished when histologic architecture was accounted for. Moreover, within the classic variant PTC group, BRAF status was not associated with pTNM or MACIS scores. In contrast, FV-PTC was more frequently associated with the RAS mutations (p=0.05). However, RAS mutations were not associated with clinical outcomes including staging and recurrence.
Our results highlight the importance of morphologic classification of PTC tissue architecture. Tumors with classical papillary architecture are more likely to feature a predominantly BRAFV600E signature, however, they display more aggressive clinical behavior independent of mutation status. In contrast, FV-PTCs are more frequently associated with an RAS signature whose contribution to the relatively more benign behavior of this tumor type requires longer-term outcome studies.
Nothing to Disclose: KG, SC, SZE, SLA, OM
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