Interpace Diagnostics, Parsippany, NJ, has recently released new data supporting the use of combination platform testing with ThyraMIR, the only microRNA expression classifier, and the ThyGenX thyroid oncogene panel, for DNA and RNA mutational analysis, to improve thyroid cancer diagnosis.
Presented at the 2015 annual meeting of the Endocrine Society, in San Diego, the study showed that the system can identify benign and malignant nodules with high sensitivity and specificity, resulting in a clinically actionable negative predictive value (NPV) of 94% and positive predictive value (PPV) of 74%.1 Combining nucleic acid sequencing with a gene classifier significantly improved the tests’ ability to correctly identify both benign and malignant nodules, which could result in fewer unnecessary surgeries.
The histologically blinded, multicenter, cross-sectional cohort study analyzed data from 109 nodules with indeterminate cytology, and surgical outcomes of primary benign or malignant thyroid lesions, as established by local pathology experts from 12 representative endocrinology centers across the United States. Following fine-needle aspiration, combined use of mutation testing and ThyraMIR resulted in an overall test sensitivity of 89% and specificity of 85%. Importantly, researchers noted that the improvements relative to current molecular classification methods are applicable regardless of the local prevalence of thyroid cancer.
“These promising results support the addition of microRNA testing to oncogene mutational analysis,” says study author Thomas J. Giordano, MD, PhD, a professor of pathology and director of the molecular pathology research laboratory at the University of Michigan. “This combined gene expression and genotyping approach is designed to more accurately diagnose and characterize thyroid nodules,” he adds. “This can help clinicians to make the most appropriate management recommendations for their patients, and hopefully avoid unnecessary surgeries on benign nodules.”
Approximately 525,000 thyroid nodule fine-needle aspiration procedures are performed each year in the United States. Prevalence of thyroid cancer in the clinical setting is often not known and varies among institutions. Indeterminate cytology diagnoses are common and represent approximately 15% to 30% of cases. Guidelines issued by the National Comprehensive Cancer Network and American Thyroid Association currently recommend consideration of molecular testing on such indeterminate cases to help inform treatment decisions and avoid unnecessary surgery on benign nodules, which may occur in 70% to 80% of all cases.
The ThyGenX thyroid oncogene panel is a molecular diagnostic test used to improve risk-stratification and surgical decision-making when standard cytopathology does not provide a clear diagnosis of thyroid cancer. ThyGenX assists physicians in distinguishing between benign and malignant genotypes in indeterminate thyroid nodules by utilizing next-generation sequencing (NGS) to identify more than 100 genetic alterations associated with papillary and follicular thyroid carcinomas, the two most common forms of thyroid malignancies. The design of the panel is based on the miRInform test, whose high predictive value has been validated in a recent prospective clinical study involving more than 600 patients. Interpace Diagnostics acquired the miRInform test from Asuragen in 2014, and has now enhanced it by upgrading to a NGS platform, providing greater genomic insights and increased panel content.
The ThyraMIR thyroid miRNA classifier is the first and only microRNA gene expression classifier. MicroRNAs are small, non-coding RNAs that bind to messenger RNA and regulate the expression of genes involved in human cancers, including every subtype of thyroid cancer. ThyraMIR measures the expression of 10 microRNAs and, when used in combination with ThyGenX, yields both high negative predictive value and high positive predictive value. This results in improved molecular classification of both benign and malignant thyroid nodules independent of thyroid cancer prevalence in the clinical setting.
“We are excited about these compelling data and that the use of this first and only microRNA gene expression classifier, combined with our thyroid oncogene mutational panel, can potentially further advance the diagnosis and treatment of thyroid lesions beyond currently available tests,” says Nancy Lurker, CEO of PDI Inc, the parent company of Interpace Diagnostics.
PDI Inc is a healthcare commercialization company providing go-to-market strategy, execution, and outsourced sales teams to U.S. pharmaceutical, biotechnology, diagnostics, and healthcare companies. PDI’s Interpace Diagnostics subsidiary is focused on developing and commercializing molecular diagnostic tests, leveraging the latest technology and personalized medicine for better patient diagnosis and management. For more information visit PDI Inc.
Although previous studies have supported the value of mutational analysis, a growing amount of evidence is showing that detection of ever-increasing numbers of uncommon mutations does not by itself provide diagnostic clarity, but in fact contributes to diminishing specificity for cancer detection.
“A combined approach, fundamental to our testing, offers the most-effective means to guide individual patient management and optimize healthcare resources,” says Sydney Finkelstein, MD, chief scientific officer at Interpace Diagnostics.
- Labourier E, Beaudenon S, Wylie D, Giordano TJ. Multicategorical testing for miRNA, mRNA, and DNA on fine-needle aspiration improves the preoperative diagnosis of thyroid nodules with indeterminate cytology [poster presentation]. San Diego: The Endocrine Society annual meeting, March 5-8, 2015; abstract available at: https://endo.confex.com/endo/2015endo/webprogram/Paper18782.html.