Histone deacetylases (HDACs) have a critical role in epigenetic gene silencing, rendering a compact
chromatin structure by removing acetyl groups from
lysine residues within the tails of core
histones, thereby repressing gene expression. Epigenetic transcriptional dysregulation is an important oncogenic mechanism in some
sarcomas associated with translocations, for which antitumor activity by
HDAC inhibitors has been shown in preclinical studies. Nevertheless, the expression of the
protein targets of these drugs has not yet been broadly surveyed in this
neoplasia. In this study, we assess the expression of HDAC1 and 2 by immunohistochemistry in a tissue microarray series of 1332 cases, representing 44 categories of malignant and borderline mesenchymal
tumors. HDAC2 was the more highly expressed
isoform, and was more strongly expressed in translocation-associated
sarcomas than in other mesenchymal
tumors or normal tissues. HDAC1, in contrast, displayed lower expression in translocation-associated
sarcomas than in other mesenchymal
tumors or in normal tissues. These results indicate that HDAC1 and HDAC2 are differentially expressed in mesenchymal
neoplasms, and suggest that HDAC2 is the
isoform more likely contributing to the pathogenesis of many translocation-associated
sarcomas and to their response to
HDAC inhibitors.