A MALDI-TOF mass spectrometry (MassARRAY) mutation-detection 26-gene panel shows promise for improving the presurgical diagnosis of thyroid cancers with fine needle aspirations (FNAs), according to a pilot study presented at the 86th Annual Meeting of the American Thyroid Association (ATA), held September 21–25 in Denver, Colorado. The results were published in Thyroid.
“Our data show that mutation detection by MassARRAY can be successfully applied to minute amounts of degraded DNA from routine air-dried FNA smears,” reported lead study author Markus Eszlinger, PhD, of the Arnie Charbonneau Cancer Institute, University of Calgary, in Alberta, Canada. “The application of a 53-mutation panel resulted in a promising detection rate of 74% of cancers in the indeterminate category.”
FNA of thyroid nodules allows detection of numerous point-mutations and gene-fusion mutations that are common in papillary and follicular thyroid carcinomas. Targeted next-generation sequencing 300-gene mutation panels are “very promising,” Dr. Eszlinger noted, but are time- and cost-intensive for the presurgical diagnosis of these malignancies.
Dr. Eszlinger and his coauthors therefore developed a “cost-efficient” alternative thyroid FNA mutation–detection panel that employs MassARRAY. The panel was designed to identify the 53 most-prevalent point mutations in thyroid cancers, using RNA and DNA from air-dried FNAs.
They used 48 FNAs, including 27 cytologically indeterminate, 13 suspicious of malignancy, and 8 determined to be malignant, which had previously undergone next-generation pyrosequencing to determine BRAF, NRAS, HRAS, and KRAS mutation status.
“All the mutations previously identified by pyrosequencing (15 BRAF, 6 NRAS, 1 HRAS) were also identified by MassARRAY,” Dr. Eszlinger reported. “A high correlation of the BRAF mutation percentage detected by MassARRAY and pyrosequencing was observed” (r2 = 0.89, P < .0001).
But in indeterminate FNAs, the MassARRAY panel outperformed the pyrosequencing 7-gene panel. It identified the BRAF, NRAS, and HRAS mutations detected in 10 indeterminate FNAs with pyrosequencing—and 13 additional, pyrosequencing-undetected mutations in 10 more of the 27 indeterminate FNAs, raising the proportion of mutation-positive indeterminate FNAs from 37% to 74%. The additional MassARRAY-detected mutations included 1 BRAF, 1 NRAS, 1 HRAS, 6 TERT, 3 IDH1, and 1 PIK3CA mutation.
Prospective study is needed for a thyroid FNA gene panel that includes prevalent gene fusions, Dr. Eszlinger said.
Eszlinger M, Müller S, Bösenberg E, et al. Oral abstract 10. Application of MALDI-TOF Mass Spectrometry Based Molecular Testing to Indeterminate Thyroid Fine Needle Aspirations Improves Pre-Surgical Diagnosis. Thyroid. 2016;26(suppl 1).