Histone deacetylase 1, 2, 6 and acetylated histone H4 in diffuse large B-cell lymphomas
Abstract:Overexpression of histone deacetylases (HDACs) has previously been associated with malignancy, and HDAC inhibitors are currently being tested in clinical trials for the treatment of a variety of malignancies, including diffuse large B-cell lymphoma (DLBCL). However, the expression of HDACs in DLBCL has not been investigated.
Here, we present an immunohistochemical study on the expression of three HDACs (HDAC1, HDAC2, and HDAC6) together with acetylated histone H4 in pre-treatment, clinical samples from 31 primary nodal DLBCL patients. Expression was characterized as low, moderate, or high expression based on the number of positively stained malignant B-cells, and the staining intensity. The expression profiles were correlated with the DLBCL subtype, i.e. germinal center B-cell (GCB) (n=11) vs. non-GCB (n=20) and with overall survival.
The results showed moderate to high expression of HDAC1, HDAC2, HDAC6, and acetylated H4 in the malignant B-cells of 80.6%, 90.4%, 71.0%, and 74.2% of the samples, respectively. When looking at the entire cohort, HDAC2 was expressed more abundantly than HDAC6 (p=0.0006). The expression profiles of the remaining compounds were similar (p>0.05) and no differences were detected between DLBCL GCB vs. non-GCB subtype. In terms of survival, moderate to strong HDAC6 expression was significantly correlated with a favourable outcome (p=0.016) compared to low expression. Expression levels of HDAC1, HDAC2, and acetylated H4 did not correlate with survival (>0.05).
In conclusion, it is shown that HDAC1, HDAC2, HDAC6, and acetylated H4 are overexpressed in DLBCL, and that HDAC6 may be an important prognostic marker in this disease.
Document Type: Abstract
Affiliations: 1: Finsenlaboratoriet, Københavns Biocenter, Rigshospitalet, Ole Maaløes Vej 5, 2200 København N 2: Eksperimentel Patologienhed, Patologiafdelingen, Rigshospitalet, Ole Maaløes vej 5, 2200 København N
Publication date: 2008-05-01