ThyroSeq Assay Shows High Sensitivity and Specificity in Detecting Thyroid Cancer

Commentary by Yuri E. Nikiforov, MD, PhD; Sally E. Carty, MD; and, Priyathama Vellanki, MD

microscope, dna double helix and human cellThe ThyroSeq v2.1 multigene next generation sequencing test showed a high sensitivity and specificity in the detection of cancer in thyroid nodules with atypia of undetermined significance/follicular lesion of undermined significance (AUS/FLUS) cytology. The assay may reduce the need for multiple invasive diagnostic procedures, the study authors reported in the November issue of Thyroid.

“The clinical implications of the findings are that most advanced multigene molecular panels such as ThyroSeq provide both high positive predictive value and negative predictive value for cancer detection in thyroid nodules and are in position to eliminate indeterminate cytologic diagnosis of thyroid nodules,” said lead author Yuri E. Nikiforov, MD, PhD, Professor of Pathology and Director of the Division of Molecular Anatomic Pathology at the University of Pittsburgh School of Medicine.

“The expansion of knowledge on thyroid cancer genetics and availability of new revolutionary technology (ie, next-generation  sequencing), finally allow us to improve management of patients who had to undergo diagnostic surgery because existing tools were not able to determine if a given nodule benign or malignant,” Dr. Nikiforov said.

The researchers examined 465 consecutive fine-needle aspiration (FNA) samples with AUS/FLUS cytology with the ThyroSeq v2.1 panel, which analyzed 14 genes for point mutations and tested for 42 types of gene fusions that occur in thyroid cancer. Assay performance was determined using data from 98 nodules that have definitive surgical (n=96) or nonsurgical (n=2) outcome information.

High Sensitivity and Specificity Found With ThyroSeq Test
Among the 98 nodules with known outcome, the ThyroSeq test correctly classified 20 out of 22 cancers with high precision and accuracy. The test had a sensitivity of 90.9%, specificity of 92.1%, positive predictive value of 76.9%, and negative predictive value of 97.2%, with an overall accuracy of 91.8%.

Of the 465 nodules, 3 were composed of parathyroid cells and the remaining 462 contained thyroid follicular cells. Thirty-one of the thyroid follicular cells (6.7%) were positive for mutations, most commonly in NRAS and HRAS genes. Point mutations were found in 7 different genes and 5 types of gene fusions were identified in these nodules.

“This molecular testing panel holds great promise for streamlining and eliminating unnecessary surgery, not just here, but nationwide,” said co-author Sally E. Carty, MD, Professor and Chief of Endocrine Surgery, University of Pittsburgh School of Medicine, and co-director of the UPMC/UPCI Multidisciplinary Thyroid Center, in a statement to the press.

Clinical Implications
“This test had a high a negative and positive predictive value for diagnosing thyroid cancer,” Priyathama Vellanki, MD, Assistant Professor in the Division of Endocrinology, Metabolism and Lipids at Emory University School of Medicine in Atlanta, GA. “In other words, this test will test negative for malignancy most of the time when a patient does not have thyroid cancer and positive most of the time when a patient has thyroid cancer. However, positive and negative predictive values depend on the prevalence of cancer.”

“When using these tests, clinicians should take into account the prevalence of thyroid cancer in their population,” Dr. Vellanki said. “This test was validated in a single center and is therefore, applicable to centers with similar prevalence of thyroid cancer. This test still needs to be validated at multiple centers.”

“Nevertheless, this test could be useful in helping the clinician decide on a more definitive course of action when a patient has indeterminate cytology.” Dr. Vellanki told

December 10, 2015


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