Histone 3 and Histone 4 acetylation pattern in Well-differentiated thyroid lesions and normal thyroid tissue with their potential in diagnostic implication

Abstract

This study estimated the histone modification (hypoacetylation or hyperacetylation) in thyroid lesions, using immunohistochemistry compared with their normal counterpart. FFPE sections of surgically removed PTC, FA, FTC, and nodular goiter samples were collected from the archives of the Department of Pathology, Faculty of Medicine, Chulalongkorn University from 2016-2018 and stained with anti-acetyl histone 3 antibody (H3K9/K14ac) and anti-acetyl histone 4 antibody (H4K5,8,12 and 16ac). The intensity and proportion of immunostaining of the lesions and their normal thyroid tissue counterparts were automatically scored by Aperio ImageScope software. A total of 147 benign and malignant thyroid lesions cases, including 28 FA, 50 PTC, 19 FTC, and 50 nodular goiters, were studied. Deacetylation of both anti-acetyl histone 3 antibody (H3K9/K14ac) and anti-acetyl histone 4 antibody (H4K5,8,12 and 16ac) was detected in nodular goiter (p=0.0016 and p= <0.0001 respectively) compared to their normal counterpart. However, the difference in acetylation status for FTC, PTC, and FA were not statistically significant compared to that of their normal counterpart (p=>0.05 in all cases). For the first time, this study demonstrates that nodular goiters have H3 and H4 deacetylation compared with their normal tissue counterpart. In contrast, these epigenetic events are not found in well-differentiated thyroid neoplasms (FA, FTC, and PTC).