Molecular Testing for Thyroid Nodules Recommended as Adjunct to Fine Needle Aspiration

In September 2010, Dr. Haugen presented data on the test’s efficacy at the 14th International Thyroid Congress in Paris, France. The data were based on a prospective, multicenter study and showed that among 43 indeterminate thyroid FNA samples, the mRNA test had an NPV of greater than 95 percent, according to a press release issued by Veracyte. “A test with this high of [an NPV] will help [physicians] rule out malignancy and confidently monitor many patients with ambiguous thyroid nodules, enabling these patients to avoid unnecessary surgery,” Dr. Haugen stated in the press release.

In his interview with ENT Today, Dr. Haugen confirmed that he is still very much a proponent of the mRNA expression test, adding that the full results of the multicenter study he presented in Paris will be published in a major endocrinology publication “in the next month or two.” But he stressed that each molecular test, the panel of mutations in use at UPMC and the mRNA expression assay “has its strengths, and both in fact are used at our institution.”

Another Vote for Veracyte

Paul Ladenson, MD, director of the division of endocrinology and metabolism, Johns Hopkins University School of Medicine in Baltimore, prefers the mRNA approach. “The strategy of mRNA expression profiling in Veracyte’s Afirma test is to identify benign nodules, not cancers. This is its real strength,” Dr. Ladenson told ENT Today. “Currently, the limitation of any technique that primarily focuses on mutation detection to identify cancers is that at least one in five thyroid cancer patients don’t have any mutation we know about yet and can look for. And so there is going to be an inherent lack of negative predictive value in any test that seeks only known cancer-associated mutations.”

Dr. Nikiforov acknowledged that roughly 30 percent of thyroid cancers are caused by as yet undefined mutations. In the 2009 study, that gap was underscored by the fact that the sensitivity of the panel, when used alone, was only 62 percent, he noted. That’s why he stressed the value of doing the mutational panel in concert with cytologic testing, which can help nail down the pathology of thyroid nodules and yield a more definitive diagnosis. In the 2009 study, he noted, that approach yielded an NPV of between 92.9 percent and 97.4 percent. “And the NPV of this test is only going to get better in the next few years,” he stressed, “when I am confident that the incredibly powerful genetic research tools we currently have will reveal the remaining mutations that cause thyroid cancer.”

Caveats

A slightly more tempered view of molecular testing was taken by Constantine Theoharis, MD, assistant professor of pathology at Yale University School of Medicine in New Haven. In a review paper focusing on the molecular diagnosis and management of thyroid nodules (Curr Opin Oncol. 2012;24(1):35-41), he challenged the idea that BRAF mutations detected with the panel used by Dr. Nikiforov and others can serve not only as a diagnostic marker for malignancy but also as a prognostic indicator of aggressive disease that requires more extensive surgery. “While there may be some empirical evidence supporting this approach, there are no long-term prospective studies that I’ve seen in the literature that link any of these clinical strategies to BRAF status. Such studies would be exceptionally difficult to conduct,” he said.