Histone Acetylation Patterns of Typical and Atypical Pituitary Adenomas Indicate Epigenetic Shift of these Tumours

Abstract

Pituitary adenomas are benign endocrine tumours of the anterior pituitary that are subclassified as typical (conventional) or atypical adenomas, with uncertain prognosis based on histopathological features. Clarifying epigenetic alterations of pituitary tumours, as well as the mechanisms underlying them, will hopefully open new windows to treatment and the classification of these tumours and maybe even prediction of patient survival. In the present study, using immunohistochemistry, we investigated the acetylation pattern of histone 3 lysine 9 (H3K9), an epigenetic marker of active chromatin state and gene transcription, in typical and atypical pituitary adenomas and the normal pituitary. We observed a significant increase in H3K9 acetylation from the normal pituitary to typical and atypical pituitary adenomas, which was associated with significant hyperacetylation of H3K9 in atypical adenomas (P < 0.0001). MIB-1 (Ki-67) overexpression was also highly associated with increased acetylation of H3K9, correlating prositively with tumour severity (P < 0.0001). p53 overexpression had a contributing effect on altered global H3K9 acetylation of atypical pituitary adenomas (P < 0.05). These data suggests that H3K9 acetylation status might serve as a relevant additional biomarker of tumour severity in pituitary adenomas, and also as a proper target for epigenetic-based therapies.