ORIGINAL ARTICLES

Expression of HDAC1 and CBP/p300 in human colorectal carcinomas

Katsuyoshi Ishihama¹, Mitsunori Yamakawa¹, Shuho Semba¹, Hiroaki Takeda², Sumio Kawata², Seishi Kimura³ and Wataru Kimura³

¹ Department of Pathology, Yamagata University School of Medicine, Yamagata, Japan
² Second Department of Internal Medicine, Yamagata University School of Medicine, Yamagata, Japan
³ First Department of Surgery, Yamagata University School of Medicine, Yamagata, Japan

Correspondence to:
Professor M Yamakawa, Department of Pathology, Yamagata University School of Medicine, 2-2-2 Iida-Nishi, Yamagata 990-9585, Japan; myamakaw{at}med.id.yamagata-u.ac.jp

Background: The histone-modifying enzymes histone deacetylase (HDAC) and histone acetyltransferase (HAT) control gene transcriptional activation and repression in human malignancies.

Aims: To analyse the expression of HDAC/HAT-associated molecules such as HDAC1, CREB-binding protein (CBP) and p300 in human colorectal carcinomas, and investigate 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 hybridisation (ISH) and reverse transcription (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 analysed 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 tumours 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. Among the 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: Results showed 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.

Abbreviations: CBP, CREB-binding protein; HAT, histone acetyltransferase; HDAC, histone deacetylase; ISH, in situ hybridisation; SI, staining index

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