Chromatin remodeling and activation of transcription are important aspects of gene regulation, but these often go awry in
disease progression, including during
colon cancer development. We investigated the status of global
histone acetylation (by measuring H3, H4 acetylation of
lysine residues, which also occur over large regions of
chromatin including coding regions and non-promoter sequences) and expression of
histone deacetylase 2 (HDAC2) in
colorectal cancer (CRC) tissue microarrays using immunohistochemical staining. Specifically, HDAC2 and the acetylation of
histones H4K12 and H3K18 were evaluated in 134 colonic
adenomas, 55 moderate to well differentiated
carcinomas, and 4 poorly differentiated
carcinomas compared to matched normal tissue. In addition, the correlation between expression of these epigenetic
biomarkers and various clinicopathological factors including, age, location, and stage of the disease were analyzed. HDAC2 nuclear expression was detected at high levels in 81.9%, 62.1%, and 53.1% of CRC,
adenomas, and normal tissue, respectively (P = 0.002). The corresponding nuclear global expression levels in moderate to well differentiated
tumors for H4K12 and H3K18 acetylation were increased while these levels were decreased in poorly differentiated
tumors (P = 0.02). HDAC2 expression was correlated significantly with progression of
adenoma to
carcinoma (P = 0.002), with a discriminative power of 0.74, when comparing
cancer and non-
cancer cases. These results suggest HDAC2 expression is significantly associated with CRC progression.