Development of the Afirma Molecular ClassifierImplementing Rigorous ScienceVeracyte set out to develop a molecular assay to classify indeterminate* nodules as benign or suspicious for malignancy. The Veracyte clinical team launched patient sample collection efforts at more than 50 centers across the U.S., including 12 academic centers and more than 40 community-based clinics. The result was a sample library with “real world” characteristics representing the wide range of sample types the Afirma Gene Expression Classifier will encounter in clinical use.1,2Leveraging this large and rich sample collection set, Veracyte’s scientific team applied genomic technology and biostatistical approaches to scan the entire genome to find the biomarkers which best distinguished malignant from benign nodules. Applying an empirical approach, the team started by conducting whole-genome microarray analyses of the 22,000 genes (247,000 transcripts) in the human body. Several studies, including multiple cross-validation studies, ultimately narrowed the list of informative genes to 142. Measurements of the expression of the 142 genes in thyroid FNA samples were combined in a multi-dimensional algorithm to better determine whether a given thyroid nodule is likely benign or malignant.1,2 In two prospective, independent, multi-center validation studies, the Afirma Gene Expression Classifier has successfully identified benign nodules with a negative predictive value (NPV) of greater than 95% (the risk of malignancy for these nodules is less than 5%).1-2 In both studies, the Gene Expression Classifier result was compared to the "gold standard" of two blinded expert histopathology reviews of corresponding thyroidectomy specimens obtained through surgery. Based on these results Veracyte commercialized the Afirma Gene Expression Classifier as part of the Afirma Thyroid FNA Analysis, which is now offered through its CLIA licensed clinical laboratory.1-3 * Indeterminate includes Follicular Lesion of Undetermined Significance (FLUS)/Atypia of Undetermined Significance (AUS) and (suspicious for) Hürthle/Follicular Neoplasm.1. Haugen BR et al. abstract #LB137, ITC, Paris, FR 2010 [oral abstract].
|
