HDAC and HLA Class I expression in uveal melanoma

Abstract

PurposeHistone deacytylases (HDACs) can be a target for therapy in oncology. We determined the expression of four families of HDACs in Uveal Melanoma (UM) to see whether expression differed between low‐ and high‐risk tumors and whether their expression is related to survival.MethodsThe expression of nine HDAC’s was determined using an Illumina HT12V4 array in 64 primary UM. Tumors were divided into BAP1‐positive or ‐negative based on immune‐histochemical nuclear staining. Survival status was determined using Kaplan‐Meier analyses, using the time period between enucleation and death (mean 83 months).ResultsHigh‐risk BAP1‐negative UM (n = 30) showed a higher expression of HDAC4 (p = 0.003), HDAC7 (p = 0.02), and HDAC8 (p ≤ 0.001), and a decreased expression of HDAC11 (p ≤ 0.001) compared to BAP1‐positive UM (n = 25). When analyzing survival, we found that a high HDAC8 (p = 0.002) and low HDAC11 (p = 0.002) expression were associated with a lower overall survival.ConclusionsAs HDAC’s are being used as targets for cancer therapy, we studied the expression of a range of them in UM and identified upregulated expression of two of these epigenetic regulators in high‐risk BAP1‐negative tumors, and a down‐regulated expression of one (HDAC11). Our findings indicate that pan‐HDAC inhibitors differentially affect different HDACs and may specifically be useful for those with BAP1‐negative tumors.