The panel includes seven main types of mutations that account for most thyroid cancers, according to Dr. Nikiforov: BRAF, NRAS, HRAS, KRAS, RET/PTC1, RET/PTC3 and PAX8/PPARg. The mutation with the strongest correlation to malignancy was BRAF, he added, pointing to another important benefit of the test: its prognostic value. “Research has shown that BRAF-positive thyroid cancers tend to be very aggressive [J Clin Endocrinol Metab. 2008;93(10):3943:-3949],” he explained. In such cases, he noted, surgeons at his institution will keep a sharp eye out for lymph node involvement and, in some instances, opt for a larger excision.
Explore This IssueApril 2012
More Recent Evidence
In 2011, Dr. Nikiforov and his colleagues at UPMC published another study aimed at measuring the diagnostic value of the molecular panel (J Clin Endocrinol Metab. 96(11):3390-3397), but with a tighter focus on patients with FNA samples of indeterminate cytology. A total of 967 FNA samples collected from 729 patients whose nodules were found to fit into one of three categories of indeterminate cytology were subjected to mutational analysis. Of that total, 479 patients underwent thyroidectomy, either because repeat FNA testing had previously indicated an elevated risk for cancer or based on the results of molecular testing. The mutational status of those patients was then correlated with surgical pathology.
The investigators found that a positive test for any of the mutations included in their panel correlated with a surgical finding of malignancy in 87 percent to 97 percent of cases, depending on the type of indeterminate findings present. Conversely, the rate of cancer found in mutation-negative nodules ranged between 6 percent and 28 percent.
“The results confirmed the central benefit of this test: For patients with indeterminate cytology, it enabled us to give them definitive treatment recommendations very early in their evaluations,” Dr. Nikiforov said. “If they are positive for any of the mutations, we recommend total thyroidectomy rather than a two-phase surgical approach. On the other hand, if the nodules are negative for these mutations and belong to the lowest-risk category of FNA cytology, they do not need a partial lobectomy or any other type of diagnostic surgery and can be followed by annual routine thyroid examination.”
Dr. Nikiforov added that both studies had some limitations. In the 2009 study, for example, molecular testing was performed without checking for the adequacy of thyroid nodule material collected for molecular analysis. “This could have lessened the chances for mutation detection,” he said. In the 2011 study, the adequacy issue was addressed by refining the collection process, but other potential biases were present, including the fact that the pathologists were sometimes aware of the results of molecular analysis.
Cost-Effectiveness Data in Press
An even more recent study co-authored by Dr. Nikiforov showed that testing for tumor-specific mutations is not only clinically effective; it can be cost effective as well. In the study, which has been published in the Journal of Clinical Endocrinology and Metabolism (2012 Mar 14. [epub ahead of print]), the researchers determined that if the cost of the testing is less than $870 per patient, then savings from reduced interventions offset the cost of the test.