OR14-6 DISTINCT GENOTYPIC SIGNATURES CORRELATE WITH MORPHOLOGY BUT DO NOT INDEPENDENTLY PREDICT BEHAVIOUR IN PAPILLARY THYROID CANCER

Program: Abstracts - Orals, Featured Poster Presentations, and Posters
Session: OR14-Thyroid Cancer: Insights into Diagnosis & Treatment
Clinical
Saturday, June 15, 2013: 11:30 AM-1:00 PM
Presentation Start Time: 12:45 PM
Room 103 (Moscone Center)
Karen Gomez-Hernandez, Sonia Cheng, Shereen Z Ezzat, Sylvia L. Asa and Ozgur Mete*
University Health Network, Toronto, ON, Canada
The diagnosis and classification of papillary carcinoma (PTC) is challenging because of variable criteria. There are limited data on the relationship between somatic mutational profiling and tumor behaviour. In this study, we aimed to identify genetic signatures of the major morphologic thyroid cancer histotypes and their relationships with pTNM status and MACIS scoring.

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

*Please take note of The Endocrine Society's News Embargo Policy at http://www.endo-society.org/endo2013/media.cfm

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