Abstract

Aims: The histone-modifying enzymes histone deacetylase (HDAC) and histone acetyltransferase (HAT) control gene transcriptional activation and repression in human malignancies. The authors analyzed the expression of HDAC/HAT-associated molecules such as HDAC1, CREB-binding protein (CBP) and p300 in human colorectal carcinomas and investigated the relationship between their expression levels and clinicopathological parameters.

Methods: Expression levels of HDAC1, CBP, and p300 in human colorectal cancer were investigated by immunohistochemistry. In situ hybridization (ISH) and reverse transcription-polymerase chain reaction (RT-PCR) analyses were also carried out to confirm mRNA expression levels of these genes. Immunoreactivity was evaluated semi-quantitatively using a staining index (SI). The relationships between the SIs and clinicopathological findings were analyzed and survival curves were calculated using the Kaplan-Meier method and log-rank tests.

Results: The mean SIs for HDAC1, CBP, and p300 in this series of tumors were much higher than those in normal colonic mucosa. The presence of HDAC1 and CBP mRNAs on colorectal carcinoma cells as well as normal epithelial cells was confirmed by ISH analysis. A marked increase in p300 mRNA levels was detected in a majority of cases by RT-PCR. Interestingly, among our patients with colorectal cancer, overexpression of p300 (SI > 11.9) correlated with a poor prognosis, whereas high CBP expression levels (SI > 16.6) indicated long-term survival.

Conclusion: These data demonstrated the up-regulation of these three histone-modifying molecules in this series of colorectal cancers and suggested that monitoring of CBP and p300 may assist prediction of the prognosis in patients with colorectal adenocarcinoma.