Next-generation sequencing tool shows 96% specificity in thyroid cancer detection

SAN JUAN, Puerto Rico — A next-generation sequencing tool allows for improved accuracy in diagnosis of thyroid nodules and treatment of thyroid cancer, according to a presenter here.

“The ThyroSeq next-generation sequencing approach allows simultaneous testing for multiple mutations with high accuracy and sensitivity. It requires a minimal amount of nucleic acids and can be performed on [fine needle aspiration] and tissue samples,” Marina Nikiforova, MD, FCAP, director of the University of Pittsburgh Medical Center Molecular Oncology and Personalized Diagnostics laboratory, said. “ThyroSeq can be used for high-throughput genotyping of thyroid samples, helping to improve accuracy of diagnosis of thyroid nodules and prognostication of thyroid cancer.”

Marina Nikiforova

This tool was launched at the University of Pittsburgh on Oct. 1, 2013, and Nikiforova and colleagues published some data in the Journal of Clinical Endocrinology & Metabolism this year. These results indicated that ThyroSeq’s accuracy for mutation detection was 100% with a sensitivity of 3% to 5% of mutant alleles or fusion transcripts. They also showed that the next-generation tool detected mutations in a significant number of carcinomas, including in more than 70% of papillary, anaplastic and medullary thyroid cancers, whereas mutations were detected in only 6% of benign nodules. The most common mutations were BRAF and RAS and a number of additional, more rare mutations was found in thyroid cancer samples.

In this presentation, Nikiforova expanded her previous observation and discussed an examination of 61 FNA samples with the most common type of indeterminate cytology, ie, follicular neoplasm, using both ThyroSeq and surgical excision. ThyroSeq and surgical pathology agreed on all but four specimens. Of those four, two were found malignant by ThyroSeq but benign by surgical biopsy, and two were found benign by ThyroSeq but malignant by surgical biopsy.

“Only two tumors were missed, for 96% specificity and 93% of overall accuracy,” Nikiforova said.

Overall, she added, Thyroseq is able to detect mutations in 12 genes and 45 gene fusions and only required 10 ng of DNA and RNA, so that more than 98% of all thyroid FNA samples worked. Importantly, a number of mutational markers added to the ThyroSeq panel can allow to identify those tumors that are likely to be more aggressive and therefore need to be treated more extensively.

“This will bring management of thyroid cancer to the next level,” she said. – by Katrina Altersitz

For more information: Nikiforova MN. Oral Abstract 13. Presented at: the 83rd Annual Meeting of the American Thyroid Association; Oct. 16-20, 2013; San Juan, Puerto Rico.

Disclosure: Nikiforova reports no relevant financial disclosures.