ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Endocrine Abstracts (2019) 63 S1.1 | DOI: 10.1530/endoabs.63.S1.1

What is the value of molecular markers in nodules?

Laura Fugazzola


Cytological evaluation establishes the diagnosis of a benign or malignant nodule in 70–80% of all cases, but the remaining cases lack the features needed for a definitive diagnosis. Molecular tests have been developed to assist in determining if a nodule with indeterminate cytology is benign or malignant. The first studies focused on the analysis of the most common thyroid cancer (TC) mutation, BRAFV600E. However, since many TCs are driven by other mutations, testing for BRAF alone does not provide sufficiently high negative predictive value (NPV) to avoid surgery for nodules lacking this gene mutation. The sensitivity of molecular testing was improved through the introduction of gene panels, which became available for clinical use in the late 2000s. In addition to BRAF, they tested for several other common genes mutated in TC, and these typically rule-in tests panels detected genetic alterations present in ~70% of cases. The next step in the evolution of molecular testing has involved the use of NGS. The ThyroSeq panels are NGS panels with a high sensitivity and are able to quantitatively assess the proportion of cells carrying a given mutation. In 2012 a ‘rule out’ test was introduced, namely the Afirma test, which does not rely on detecting gene mutations but is based on the analysis of expression changes in 167 genes. The Afirma test evaluates the gene expression profiles, reports the result as either ‘benign’ or ‘suspicious’, and has a high NPV. The main disadvantage of these tests is the high cost, which makes them rarely used in Europe. In order to generate a reliable but cheaper test, we set up a custom Mass Array platform (PTC-MA), which allows the simultaneous detection of the 13 hotspot mutations and seven fusion genes more frequently found in TC, in a time and cost-effective manner.

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