Histone Deacetylase (HDAC)-1, -2, -4, and -6 in Uveal Melanomas: Associations with Clinicopathological Parameters and Patients' Survival.

Abstract

BACKGROUND:

Uveal melanoma (UM) represents the most common primary intraocular malignancy in adults, exerting high metastatic potential and poor prognosis. Histone deacetylases (HDACs) play a key role in carcinogenesis, and HDAC inhibitors (HDACIs) are currently being explored as anti-cancer agents in clinical settings. The aim of this study was to evaluate the clinical significance of HDAC-1, -2, -4, and -6 expression in UM.

METHODS:

HDAC-1, -2, -4, and -6 expression was examined immunohistochemically in 75 UM tissue specimens and was correlated with tumors' clinicopathological characteristics, the presence of tumor-infiltrating lymphocytes (TILS), as well as with our patients' overall survival (OS).

RESULTS:

HDAC-2 was the most frequently expressed isoform (66%), whereas we confirmed in addition to the expected nuclear expression the presence of cytoplasmic expression of class I HDAC isoforms, namely HDAC-1 (33%) and HDAC-2 (9.5%). HDAC-4 and -6 expression was cytoplasmic. HDAC-1 nuclear expression was associated with increased tumor size (p = 0.03), HDAC-6 with higher mitotic index (p = 0.03), and nuclear HDAC-2 with epithelioid cell morphology (p = 0.03) and presence of tumor-infiltrating lymphocytes (p = 0.04). The association with the remaining parameters including Monosomy 3 was not significant. Moreover, the presence as well as the nuclear expression pattern of HDAC-2 were correlated with patients' improved OS and remained significant in multivariate survival analysis.

CONCLUSIONS:

These findings provide evidence for a potential role of HDACs and especially HDAC-2 in the biological mechanisms governing UM evolution and progression.

• Authors: Georgia Levidou, Pawel Gajdzis, Nathalie Cassoux, Piotr Donizy, Christos Masaoutis, Malgorzata Gajdzis, Sophie Gardrat, Alexandros Pergaris, Eougken Danas, Jerzy Klijanienko, Stamatios Theocharis
• Journal: Cancers (Cancers (Basel)) Vol. 13 Issue 19 (Sep 23 2021) ISSN: 2072-6694 [Print] Switzerland
• PMID: 34638249 (Publication Type: Journal Article)