Molecular diagnostic “rule-in/rule‐out” tests to detect malignancy in thyroid nodules are either based upon the detection of oncogenic mutations and gene translocations or based upon mRNA and microRNA expression classiﬁers.
We have earlier reported a combined test, which incorporates the advantages of “rule‐in and rule-out” tests. In the combined test, specimens are initially tested using NGS‐based ThyGenX test to detect oncogenic driver mutations and gene fusions. If a mutation or fusion is detected, the specimen is called positive (malignant) and is not tested further. Otherwise, it is further tested by ThyraMIR miRNA classiﬁer to call samples malignant or benign. It is called malignant if either ThyGenX or ThyraMIR indicates malignancy, and is called benign if both ThyGenX and ThyraMIR indicate lack of malignancy. Using retrospectively collected FNA specimens, the combined ThyGenX/ThyraMIR test showed synergistic performance improvement over each test and resulted in 89% sensitivity and 85% speciﬁcity.
Here, we demonstrate the equivalency between FNA smears and FNA in protective buﬀer as sample types for molecular testing. We also report on the clinical performance of ThyGenX and ThyraMIR molecular testing using cytology smear slides from a multi‐center double-blinded prospective study.