Molecular Diagnostics Focus on Thyroid Nodule Classification

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New data being presented at the 84th Annual Meeting of the American Thyroid Association show promise for two molecular tests that help identify indeterminate thyroid nodules as either benign or malignant.

The methods may help patients who have thyroid nodules to avoid diagnostic surgery, authors of the studies said.

The first test is a microRNA-based assay being developed by Rosetta Genomics, Ltd. The test was developed by screening more than 2000 microRNAs to identify microRNA biomarkers that could stratify tissue from thyroid lesions, captured in pre-operative fine needle aspirate (FNA) samples, as benign or malignant.¹

To investigate the microRNA-based test, researchers collected more than 150 thyroid FNA samples representing various histological subtypes, the majority of which had been deemed indeterminate. The samples were processed and profiled using Rosetta's microarray platform.

Differential expression of microRNAs was found between benign and malignant neoplasms. In addition, next-generation sequencing was performed on a set of 11 thyroid follicular resection samples, in which 386 novel candidate microRNAs were found; 27 of them were also measured using quantitative polymerase chain reaction.

“We demonstrated the feasibility of extracting and profiling miRNAs from cell blocks and smears stained with different cytological stains,” the authors stated. “We also identified novel microRNAs using proprietary small-RNA next-generation sequencing, which may serve as new biomarkers for the classification of thyroid nodules. Using the expression levels of just two microRNAs, we can reach an accuracy of over 85% in discriminating benign from malignant thyroid nodules.”

Kenneth A. Berlin, president and chief executive officer of Rosetta Genomics, said the test is currently under development and is expected to launch in the third quarter of 2015.

“These data corroborate the results from our earlier studies, which have demonstrated that microRNA expression levels can differentiate malignant nodules from benign nodules, and also demonstrated the ability to extract and profile microRNAs from thyroid FNAs,” he continued. “We are in the process of conducting larger validation studies, as we plan for the launch of our thyroid assay in the U.S. in 2015.”

Results from two different studies also demonstrated the utility of Veracyte, Inc’s Afirma Gene Expression Classifier (GEC), which analyzes fine needle aspirations.

In the first study², 16 patients whose nodules were found to be benign through GEC were evaluated for long-term follow-up. Of those 16 patients, 3 underwent surgery, where it was confirmed that the nodules were benign.

The remaining 13 GEC-benign patients were followed with physical exam and ultrasound. Of those 13 patients, 3 were followed for 2.5 to 3 years, 4 patients were followed for 1 to 2.5 years, and 3 patients were followed for 6 to 12 months. All have shown no significant change in nodules by exam or serial sonography.

"This is the first known study to assess the durability and safety of Afirma GEC results for up to three years," Brian Michael, MD, of Wellspan Health in Gettysburg, Pennsylvania, said in a statement. "In this relatively small sample, 13 patients who would have previously been referred for surgery were able to safely avoid it. These findings should give physicians further confidence in moving patients with benign Afirma GEC results from diagnostic surgery to routine monitoring."

In another study³ that examined Afirma GEC’s ability to perform accurately regardless of nodule size, all 5 nodules (≥3 cm) that were identified as benign by the test were confirmed by surgery to be benign.

"These two new studies add to the growing body of evidence supporting the ability of Veracyte's Afirma GEC to accurately rule out cancer in thyroid nodules that are deemed indeterminate by traditional cytopathology," Bonnie Anderson, president and CEO of Veracyte, said in a statement. "These findings are consistent with findings from the pivotal clinical validation study published in the New England Journal of Medicine in 2012, and taken together reinforce the Afirma GEC as a new standard for helping thyroid nodule patients avoid unnecessary thyroid surgery and the anxiety, costs and need for lifelong thyroid hormone therapy that can accompany such surgery."

References

Benjamin H, Lithwick Yanai G, Kushnir M, et al. MicroRNAs as a powerful diagnostic tool for thyroid nodule classification in pre-operative samples. Presented at: the 84^th Annual Meeting of the American Thyroid Association; October 29-November 2, 2014; Coronado, CA. Poster #284.
Michael BE. Long term clinical and imaging follow-up of an office-based gene expression classifier used to manage thyroid nodules. Presented at: the 84^th Annual Meeting of the American Thyroid Association; October 29-November 2, 2014; Coronado, CA. Poster #269.
Mize JR, Monroe RJ. Performance of the Afirma Gene Expression Classifier on indeterminate thyroid fine needle aspirates from large nodules. Presented at: the 84^th Annual Meeting of the American Thyroid Association; October 29-November 2, 2014; Coronado, CA. Poster #39.

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