Fine needle aspiration cytology, a diagnostic test central to thyroid nodule management, may yield indeterminate results in up to 30% of cases. A high proportion of these patients are subjected to diagnostic surgery, but only a minority of resected indeterminate thyroid nodules are histologically diagnosed as malignant.
In this clinical setting, molecular markers may be useful as diagnostic tools, complementing and integrating the information provided by cytology and improving preoperative risk stratification for indeterminate nodules.
We recently developed a dual-component assay that involves NGS-based detection of mutations and dPCR evaluation of the expression levels of an microRNA strongly associated with thyroid cancer. This assay offered some advantages over the currently available tests, including a relatively low number of molecular markers, which translates into lower overall testing costs, the employment of high-sensitivity methods. And finally, it offers higher performance in term of sensitivity and NPV. Despite the high performance, much effort should be done specially to increase positive predictive value in some tumor subtypes (i.e., in RAS-mutated cases, which encompass both benign and tumor cases).
Here we plan to further improve clinical performance of the assay by including a third molecular component based on the Raman spectroscopy (RS). RS spectra provide fingerprint information on biological structures of the analyzed samples and were already used to integrate the traditional tools used for cancer diagnosis. We demonstrated that RS technique is effective in discriminating benign from malignant thyroid tissues and it can be applied also to thyroid aspirates.
The integration of data from the three molecular assays with clinical, sonographic and morphological data has great potential to improve the diagnostic accuracy of cytology and personalize management of thyroid cancer patients thus reducing unnecessary surgery and health care costs.