hypermethylation is an independent prognostic biomarker in breast cancer.

BACKGROUND

Cadherin-like protein 22 (CDH22) is a transmembrane glycoprotein involved in cell-cell adhesion and metastasis. Its role in cancer is controversial because it has been described as being upregulated in colorectal cancer, whereas it is downregulated in metastatic melanoma. However, its status in breast cancer (BC) is unknown. The purpose of our study was to determine the molecular status and clinical value of in BC.

RESULTS

We observed by immunohistochemistry that the level of CDH22 expression was lower in BC tissues than in their matched adjacent-to-tumour and non-neoplastic tissues from reduction mammoplasties. Since epigenetic alteration is one of the main causes of gene silencing, we analysed the hypermethylation of 3 CpG sites in the promoter by pyrosequencing in a series of 142 infiltrating duct BC cases. was found to be hypermethylated in tumoral tissues relative to non-neoplastic mammary tissues. Importantly, this epigenetic alteration was already present in adjacent-to-tumour tissues, although to a lesser extent than in tumoral samples. Furthermore, gene regulation was dynamically modulated in vitro by epigenetic drugs. Interestingly, hypermethylation in all 3 CpG sites simultaneously, but not expression, was significantly associated with shorter progression-free survival ( 0.015) and overall survival ( = 0.021) in our patient series. Importantly, hypermethylation was an independent factor that predicts poor progression-free survival regardless of age and stage ( = 0.006).

CONCLUSIONS

Our results are the first evidence that is hypermethylated in BC and that this alteration is an independent prognostic factor in BC. Thus, hypermethylation could be a potential biomarker of poor prognosis in BC.