A molecular diagnostic panel for thyroid cancer disease management.

Head and Neck Cancer
Session Type and Session Title: 
Clinical Science Symposium, Targeting Therapeutics for Thyroid Cancers
Abstract Number: 



J Clin Oncol 30, 2012 (suppl; abstr 5510)


Shih-Min Cheng, Kevin Qu, Adam Abdool, Anthony Sferruzza, Frederic Waldman, Richard E Reitz; Quest Diagnostics Nichols Institute, San Juan Capistrano, CA; Quest Diagnostics, San Juan Capistrano, CA

Abstracts that were granted an exception in accordance with ASCO's Conflict of Interest Policy are designated with a caret symbol (^).

Abstract Disclosures


Background: In 2009, the American Thyroid Association revised its guidelines for patients with thyroid nodules and differentiated thyroid cancers, recommending BRAF, RAS, RET/PTC, and PAX8-PPARγ molecular testing in patients with indeterminate fine-needle aspirate (FNA) cytology. Alterations in any of these markers in thyroid nodules are strongly associated with malignancy. We studied the prevalence of these alterations in thyroid FNA specimens in order to establish a strategy to improve disease management. Methods: DNA and RNA were extracted from thyroid FNA specimens (N=149) and tested for BRAF mutations using allele-specific PCR (V600E and K601E); for RAS (H-, K-, N-) mutations using pyrosequencing (codons 12, 13, and 61); and for RET/PTC1 and RET/PTC3 rearrangements and PAX8-PPARγ translocations using RT-PCR. Results: Overall, 90 (60.4%) of the specimens had alterations in ≥1 of the 4 molecular markers (Table). BRAF V600E mutations (54.4%) were the most prevalent mutations in papillary thyroid cancer (PTC); no K601E mutations were found. RAS mutations were found in PTC, follicular adenoma (FA), and follicular thyroid cancer (FTC) specimens; half of these mutations involved N-RAS Q61. RET/PTC rearrangements were detected in 3.5% of PTC specimens and were evenly distributed between the 2 major subtypes, RET/PTC1 and RET/PTC3. PAX8/PPARγ translocations were detected in 18.8% of FTC but not in FA, probably due to small sample size. Out of 7 indeterminate thyroid nodules, 2 had BRAF mutations and 2 had RAS mutations. The presence of the 4 markers was generally mutually exclusive; only 1 PTC specimen had concurrent RAS and RET/PTC1 alterations. Conclusions: The prevalence of BRAF, RAS, RET/PTC, and PAX8/PPARγ alterations in thyroid cancer specimens highlights the potential for targeted therapeutic strategies. The mutually exclusive pattern of alterations also suggests a hierarchical screening strategy for samples with limited availability.
Prevalence of marker alterations in thyroid FNA specimens (NT = not tested).
Diagnosis # BRAF
PTC 114 62 (54.4) 11 (9.6) 4 (3.5) NT 77 (67.5)
FA 12 NT 2 (16.7) NT 0 2 (16.7)
FTC 16 NT 5 (31.3) NT 3 (18.8) 8 (50%)
Indeterminate 7 2 (28.6) 2 (28.6) 0 0 4 (57.1)