Similar to findings in
colorectal cancers, it has been suggested that disruption of the
adenomatous polyposis coli (APC)/
beta-catenin pathway may be involved in breast
carcinogenesis. However, somatic mutations of APC and
beta- catenin are infrequently reported in breast
cancers, in contrast to findings in
colorectal cancers. To further explore the role of the APC/
beta-catenin pathway in breast
carcinogenesis, we investigated the status of APC gene promoter methylation in primary breast
cancers and in their non-cancerous breast tissue counterparts, as well as mutations of the APC and
beta- catenin genes. Hypermethylation of the APC promoter CpG island was detected in 18 of 50 (36%) primary breast
cancers and in none of 21 non-cancerous breast tissue samples, although no mutations of the APC and
beta- catenin were found. No significant associations between APC promoter hypermethylation and patient age,
lymph node metastasis, oestrogen and
progesterone receptor status, size, stage or histological type of tumour were observed. These results indicate that APC promoter CpG island hypermethylation is a
cancer-specific change and may be a more common mechanism of inactivation of this tumour suppressor gene in primary breast
cancers than previously suspected.