Clinical Significance of the Immunohistochemical Expression of Histone Deacetylases (HDACs)-2, -4, and -5 in Ovarian Adenocarcinomas.

ABSTRACT

BACKGROUND: Histone deacetylases (HDACs) are implicated in carcinogenesis, and HDAC inhibitors (HDACis) are explored as a therapeutic tool in several tumors. The aim of this study was to evaluate the clinical significance of HDAC-2, -4, and -5 expression in epithelial ovarian carcinoma (EOC). METHODS: HDAC-2, -4, and -5 immunohistochemical expression was examined in 92 EOC tissue specimens and was correlated with clinicopathological characteristics. RESULTS: HDAC-2 was the most frequently (94.4%) expressed isoform, being marginally higher in serous tumors compared with other types (p = 0.08). HDAC-5 was the less frequently expressed (28.1%), being positively associated with HDAC-4. HDAC-4 positivity was associated with lower FIGO-stage (p = 0.045) and T-category (p = 0.043) and the absence of lymph node (p = 0.05) or distant metastasis (p = 0.09) in serous carcinomas. HDAC-2 positivity was correlated with the absence of lymph node metastasis in serous tumors (p = 0.045). On the contrary, HDAC-5 nuclear positivity was correlated with lymph node metastasis in the entire cohort (p = 0.048). HDAC-4 positivity was marginally associated with favorable prognosis in serous carcinomas in univariate survival analysis (p = 0.086), but this correlation was not significant in multivariate analysis. CONCLUSIONS: These findings suggest a differential expression among HDAC-2, -4, and -5 in ovarian adenocarcinomas in terms of immunolocalization, positivity rate, and associations with clinicopathological parameters, providing evidence for a potential role in the pathobiology of EOC.