RT Journal Article
SR Electronic
T1 Loss of SIRT1 histone deacetylase expression associates with tumour progression in colorectal adenocarcinoma
JF Journal of Clinical Pathology
JO J Clin Pathol
FD BMJ Publishing Group Ltd and Association of Clinical Pathologists
SP 735
OP 739
DO 10.1136/jclinpath-2012-200685
VO 65
IS 8
A1 Si-Hyong Jang
A1 Kyeung-Whan Min
A1 Seung Sam Paik
A1 Ki-Seok Jang
YR 2012
UL http://jcp.bmj.com/content/65/8/735.abstract
AB Background The class III histone deacetylase SIRT1 is a nicotinamide adenine dinucleotide (NAD+)-dependent deacetylase, and has been reported to serve diverse roles in various biological processes, such as caloric restriction, apoptosis, neuronal protection, cell growth, differentiation and tumourigenesis. With respect to tumourigenesis, there have been conflicting data supporting whether SIRT1 act as a tumour promoter or as a tumour suppressor. Methods SIRT1 protein expression, determined by immunohistochemistry, was investigated in human normal colonic mucosa, adenoma, adenocarcinoma and metastatic tissue samples. Results All normal colonic mucosa showed SIRT1 expression with no exception, and 42 (80.8%) of 52 adenomatous polyps were positive for SIRT1. However, only 208 (41.9%) of 497 colorectal adenocarcinomas were positive. Moreover, 45 (35.7%) of 126 metastatic tissues were positive. Collectively, the SIRT1 expression was gradually decreased during carcinogenesis and tumour progression. The associations between SIRT1 expression and clinicopathological parameters revealed that loss of SIRT1 expression was associated with proximal tumour location, mucinous histology and defective mismatch repair protein expression. This suggests that loss of SIRT1 expression is associated with the microsatellite instability phenotype of colorectal adenocarcinoma. In survival analyses, the loss of SIRT1 expression was significantly associated with overall survival (p=0.027, log-rank test) in univariable analysis, but multivariable analysis failed to achieve significance. Conclusions SIRT1 expression was gradually decreased during the normal–adenoma–adenocarcinoma–metastasis sequence, suggesting a possible role of SIRT1 in tumour suppression in the colorectum, and a probable link to the microsatellite instability pathway.