45 Diagnostic utility of molecular and imaging biomarkers 2 Bethesda III and IV FNAC specimens [61]. Prospective clinical validation of the ThyraMIR™ could affirm the diagnostic value of microRNA expression profiling in indeterminate thyroid nodules in the pre-operative setting. Immunocytochemistry Tissue characterization through selective staining of expressed proteins, i.e. immunohistochemistry (IHC), is a technique that combines histopathology and biochemistry. Exploiting basic antigenantibody interactions, IHC is able to visualize the distribution and localization of specific cellular components within the cell and in the proper tissue context. This includes tissue biomarkers specific for e.g. infection or malignancy. IHC has been fully incorporated in the histopathological routine and is crucial to morphological and molecular tissue characterization. When immunocytochemistry (ICC) – the application of this immunology-based technique in cytology – became available, the possibilities were extended to the preoperative setting, too. Specific immunomarkers have been developed to differentiate between benign and malignant thyroid nodules. The 2015 ATA guidelines acknowledge ICC as a technique under development with limited prospective validation studies in indeterminate cytology [17]. In unselected thyroid cytology, the much-used immunomarkers galectin-3, Hector Battifora mesothelial-1 (HBME-1) and cytokeratin 19 (CK-19) demonstrated 85%, 83% and 80% sensitivity, and 90%, 79% and 79% specificity, respectively [201]. Galectin-3 Galectin-3 is a β-galactosyl-binding protein from the lectin group. It is involved in cell-cycle regulation, including cell migration and adhesion. Its exact function is still to be unravelled, but a role in the pathogenesis and progression of PTC is presumed [82, 201-203]. It is related to inhibition of apoptosis, induced by abnormal p53 expression [203]. Galectin-3 can be present both in the intracellular as well as the extracellular matrix [204]. Normal thyrocytes do not express galectin-3, but the physiological expression of galectin-3 in macrophages, neutrophils, mast cells and Langerhans cells provides an internal positive control of the investigated FNAC samples [205, 206]. Positive cytoplasmic staining – as opposed to nuclear staining – for galectin-3 is suspicious for malignancy and mainly associated with PTC [155, 207, 208]. Galectin-3 expression has also been associated with the malignant transformation of follicular neoplasms, as it was present in follicular adenoma as well as FTC [204, 209, 210]. Encapsulated FVPTC and minimally invasive FTC showed less frequent and weaker staining [210, 211]. In 2001, Bartolazzi et al. argued that galectin-3 staining could accurately diagnose thyroid carcinoma in unselected thyroid cytology [155]. Subsequent studies in indeterminate thyroid cytology mostly could not reproduce these promising results. With a positive stain in approximately a third of all nodules, sensitivity and specificity of galectin-3 ranged from 0% to 92% and from 68% to 100%, respectively [82, 212-215]. Merely Saggiorato et al. demonstrated that galectin-3
RkJQdWJsaXNoZXIy MTk4NDMw