Turkish Journal of Medical Sciences




Breast cancer is the most common malignancy in women worldwide. The Dickkopf1 (DKK1) gene product is a potent inhibitor of the Wnt pathway. DKK1 methylation status and its protein expression were examined in normal and cancer tissues of breast cancer patients. Materials and methods: We examined methylation changes in 83 tumor and adjacent normal tissues, and also in 9 normal breast tissues from unaffected women (no breast cancer history) as controls. DKK1 promoter methylation was assessed by methylation-specific polymerase chain reaction. Immunohistochemical staining was used to investigate DKK1 protein expression in the 9 controls and in 70 out of the 83 tumors as well as their adjacent normal tissues. Immunohistochemical results were categorized as positive or negative for DKK1. Results: DKK1 gene methylation was detected in 3 out of the 9 (33%) normal breast tissue samples of unaffected women. The DKK1 gene was hypermethylated in 58 out of the 83 (70%) tumor samples and 51 out of the 83 (61%) adjacent normal tissue samples. In immunohistochemistry, 33% of normal breast tissue from unaffected women, 31% of the tumors, and 17% of the adjacent normal tissues in the breast cancer patients were found to be DKK1-positive. DKK1 promoter methylation and protein expression were not associated with age, tumor size, lymph node status, histological grade, estrogen/progesterone receptor status, or HER2 positivity. Conclusion: Our results indicate that there is a concordant DKK1 methylation change between normal and cancerous breast tissue.


Breast cancer, Dickkopf1, DNA methylation

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