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APC(adenomatous polyposis coli) promoter methylation has been linked to the early development of colorectal cancers. However, the role ofAPCmethylation and its effect on protein expression in colon cancer metastasis is largely unknown. In this study, we investigatedAPCpromoter methylation by Methylight analysis and analysed the APC protein levels by immunohistochemistry and western blot analysis in 24 liver metastasis and 39 primary colorectal cancers. Promoter methylation of theAPCgene was found to be a frequent event in liver metastasis (10/24) and significantly more frequent compared with primary colorectal cancer (7/39,P= 0.047).APCmethylation was not found in 14 matched normal colon tissues. APC protein was detected in the cytoplasm of primary and metastatic cancer cells and non-tumorous colon epithelium. By western blot analysis, APC protein levels were found to be decreased in primary tumour tissues compared with the normal colon mucosa. In contrast, APC protein levels were not decreased in the cancer cells that had metastasized to the liver. APC protein levels were independent of the presence ofAPCpromoter methylation or gene mutations. In summary,APCpromoter methylation is a frequent epigenetic alteration in colorectal cancer metastasis. However, we observed no significant association betweenAPCpromoter methylation or gene mutation and APC protein expression in colorectal metastasis. Therefore, metastatic cancer cells seem to harbour a heterogenous genetic and epigenetic background, in which cancer cells may exhibitAPCpromoter methylation that is independent of APC expression.

Molecular analysis of APC promoter methylation and protein expression in colorectal cancer metastasis