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Algorithm to test microRNA on fine needle aspiration could improve molecular cytology diagnostic yield
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SAN DIEGO — Multicategorical testing for DNA, messengerRNA and microRNA on fine needle aspirations of thyroid nodules could increase preoperative diagnostic yield of molecular cytology, according to research presented at The Endocrine Society annual meeting.
With high positive and negative predictive values (PPV/NPV), the testing algorithm can identify more benign or malignant nodules and thereby reduce both unnecessary surgeries and two-step total thyroidectomies, according to researchers.
“By combining direct genotyping for the common driver mutations with gene expression for selected microRNAs, the molecular assessment of benign and malignant tumors is significantly improved,” Thomas J Giordano, MD, PhD, of the University of Michigan Health System, told Endocrine Today.
Thomas J. Giordano
Giordano, with Emmanuel Labourier, PhD, of Interpace Diagnostics and Asuragen, and colleagues measured microRNA (miRNA) expression in surgically resected thyroid lesions and preoperative fine needle aspirations (FNAs) by reverse transcription-quantitative polymerase chain reaction (PCR); the scientists used the miRCURY LNA Universal RT microRNA PCR system.
The investigators then performed qualitative analyses for 17 distinct oncogenic gene alterations in the BRAF, HRAS, KRAS, NRAS, PAX8 and RET genes; this was done through the miRInform Thyroid testing service.
Based on a set of 254 unique thyroid lesions, the researchers identified miRNA that were differentially expressed in papillary or follicular carcinomas and benign conditions (adenoma, diffuse hyperplasia, chronic thyroiditis) and developed linear classification models capable of discriminating between malignant and benign lesions with sensitivity and specificity above 90%.
The scientists optimized a multistep, 10-miRNA algorithm in a surgical training set and 235 preoperative FNAs by targeting compatibility for high sensitivity and specificity and actionable PPV/NPV when added to gene mutation testing.
In an independent cross-sectional cohort study of 109 nodules collected from endocrinology practices, mutations were detected in 68.6% with a malignant histology outcome; further, among mutation-negative specimens, the miRNA classifier identified 63.6% of malignant cases and 98.4% of benign cases.
The combined algorithm demonstrated sensitivity of 88.6% (95% CI, 73.3-96.8%) and specificity of 85.1% (95% CI, 75-92.3%). The NPV was similar to that previously reported for the Afirma gene expression classifier (95.6% at 24% prevalence vs. 94.3% at 24% prevalence) with a 65% increase in true benign call rate.
“The results from this improved dual molecular approach represent an important advance in the preoperative evaluation of thyroid nodules,” Giordano said. – by Allegra Tiver
Reference:
Labourier E. Poster Board SAT-344. Presented at: The Endocrine Society Annual Meeting; March 5-8, 2015, San Diego.
Disclosure: Giordano reports financial relationships with Asuragen and Interpace Diagnostics.