Histone Deacetylases (HDACs): Promising Biomarkers and Potential Therapeutic Targets in Thymic Epithelial Tumors

Histone deacetylases (HDACs) are core epigenetic factors, with pivotal roles in the regulation of various cellular procedures, and their deregulation is a major trait in the acquisition of malignancy properties. In this study we attempt the first comprehensive evaluation of six class I (HDAC1, HDAC2, HDAC3) and II HDACs (HDAC4, HDAC5, HDAC6) expression patterns in thymic epithelial tumors (TETs), with the aim of identifying their possible association with a number of clinicopathological parameters. Our study revealed higher positivity rates and expression levels of class I enzymes compared to class II. Sub-cellular localization and level of staining varied among the six isoforms. HDAC1 was almost exclusively restricted to the nucleus, while HDAC3 demonstrated both nuclear and cytoplasmic reactivity in the majority of examined specimens. HDAC2 expression was higher in more advanced Masaoka-Koga stages, and displayed a positive correlation with dismal prognoses. The three class II HDACs (HDAC4, HDAC5, HDAC6) exhibited similar expression patterns, with predominantly cytoplasmic staining, that was higher in epithelial rich TETs (B3, C) and more advanced tumor stages, while it was also associated with disease recurrence. Our findings could provide useful insights for the effective implementation of HDACs as biomarkers and therapeutic targets for TETs, in the setting of precision medicine.