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

Georgia Levidou; Pawel Gajdzis; Nathalie Cassoux; Piotr Donizy; Christos Masaoutis; Malgorzata Gajdzis; Sophie Gardrat; Alexandros Pergaris; Eougken Danas; Jerzy Klijanienko; Stamatios Theocharis

doi:10.3390/cancers13194763

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

Cancers (Basel). 2021 Sep 23;13(19):4763. doi: 10.3390/cancers13194763.

Authors

Affiliations

¹ First Department of Pathology, National and Kapodistrian University of Athens, 15772 Athens, Greece.
² Department of Pathology, Paracelsus Medical University, 90419 Nuremberg, Germany.
³ Department of Pathology, Curie Institute, 75005 Paris, France.
⁴ Department of Clinical and Experimental Pathology, Wroclaw Medical University, Borowska 213, 50-556 Wroclaw, Poland.
⁵ Department of Ophthalmology, Institut Curie, 75005 Paris, France.
⁶ Department of Ophthalmology, Wroclaw Medical University, 50-556 Wroclaw, Poland.
⁷ Department of Biopathology, Institut Curie, PSL Research University, 75005 Paris, France.

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.

Keywords: HDAC; immunohistochemistry; prognosis; uveal melanoma.