Histone Acetyl Transferase 1 Is Overexpressed in Poor Prognosis, High-grade Meningeal and Glial Brain Cancers: Immunohistochemical and Aptahistochemical Study

Abstract

Primary malignancies of the central nervous system account for 2% of all cancers in adults and almost 15% in children under 15 years of age. The prognosis of brain anaplastic cancers and glioblastomas remains extremely poor, with devastating survival expectative, and new molecular markers and therapeutic targets are essential. Epigenetic changes constitute an extensive field for the development of new diagnostic and therapeutic strategies. Histone acetyl transferase-1 (HAT1) has merged as a potential prognostic marker and therapy target for different malignancies. Data repository analysis showed HAT1 mRNA overexpression in gliomas and has been described its alternative splicing in glioblastomas. Using immunohistochemical and aptahistochemical methods, we analyzed the expression of HAT1 in meningiomas, oligodendrogliomas, and astroglial cancers. We observed that HAT1 overexpression is associated with the most aggressive tumor types and the worse prognosis, as well as with a higher probability of early relapse in meningiomas. Its cytosolic localization correlates with tumor progression and prognosis. Aptamers, synthetic oligonucleotides capable to bind and inhibit a wide variety of targets, are considered as promising diagnostic and therapeutic tools. Aptahistochemistry using the aptamer apHAT610 offered superior results in comparison with the antibody used, as a good example of the potential of aptamers as diagnostic tools for histopathology.