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

“Because our cost analysis was based on Medicare data, it is widely generalizable to other hospitals that use the molecular testing,” said lead author Linwah Yip, MD, an endocrine surgeon at the University of Pittsburgh. “Using molecular markers to help us determine the most appropriate initial operation can reduce health care costs and, more importantly, not having two operations is safer and more beneficial for patients”

“Using molecular markers to help us determine the most appropriate initial operation can reduce health care costs.”

—Linwah Yip, MD

ATA Treatment Guideline

Current treatment guidelines, issued in 2009 by the American Thyroid Association (Thyroid. 2009;19(11):1167-1214), give the molecular testing strategy employed by Dr. Nikiforov and his colleagues a “C” designation—that is, the test is recommended “based on expert opinion.” In contrast, tests and treatments given an “A” rating in the guidelines are “strongly” recommended because they have “well-designed, well-conducted studies in representative populations that directly assess effects on health outcomes.”

Bryan Haugen, MD, a co-author of the ATA guidelines and a co-investigator with Dr. Nikiforov in the 2009 prospective study, said there is probably a bit of a lag behind that “C” rating; evidence is starting to build, he said, showing that molecular testing as an adjunct to thyroid nodule FNA can benefit select patients. Still, “this is a relatively new technology, and we need the results replicated at other institutions,” said Dr. Haugen, who is head of pathology within the division of endocrinology, metabolism and diabetes and Mary Rossick Kern and Jerome H. Kern Chair in Endocrine Neoplasms Research at the University of Colorado School of Medicine in Denver.

Dr. Haugen said that, in his view, the greatest strength of the molecular panel used by Dr. Nikiforov is its PPV. “If surgery is at all a possibility based on cytological findings or ultrasound, then Yuri’s test is the way to go because it can really help guide the type and extent of surgery,” he said. For patients with indeterminate cytological and/or ultrasound findings, in contrast, “you’re in a gray zone, where I agree with Dr. Nikiforov that the risk for doing unnecessary surgery is quite high, because when you take out the nodule, anywhere from 60 percent to 80 percent of them are benign. But, in my view, I think there is a better test available for those scenarios.”

Specifically, Dr. Haugen was referring to Afirma, a proprietary gene expression test marketed by Veracyte. The test, like the one advocated by Dr. Nikiforov, is used to analyze FNA cell samples, but instead of employing a panel of tumor-specific mutations for analysis, Afirma assesses mRNA expression levels for 142 genes that have been shown to be expressed differently in benign and malignant thyroid nodules (J Clin Endocrinol Metab. 2010;95(12):5296-5304). The data are then analyzed with a proprietary algorithm that identifies whether a sample’s expression pattern conforms to these genetic markers for benign tumor growth. The test can only be done at a single lab, located at Veracyte’s headquarters in San Francisco, according to Dr. Haugen.