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 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), a correlation which was not significant in multivariate analysis. Conclusion: These findings suggest a differential expression of HDAC-2, -4 and -5, providing evidence for a potential role in the pathobiology of EOC.