Clinical significance of DJ-1 as a secretory molecule: retrospective study of DJ-1 expression at mRNA and protein levels in ductal carcinoma of the breast.

AIMS: DJ-1 is a molecule secreted into serum by some breast cancer cells. However, little is known about the clinical significance of the DJ-1 expression. METHODS AND RESULTS: Expression of DJ-1 protein was examined by immunohistochemistry, and expression of DJ-1 mRNA was detected using in-situ hybridization in 273 invasive ductal carcinomas (IDCs) and 41 ductal carcinomas in situ (DCISs) of the breast, and also in breast cancer cell lines. Breast cancer cells were examined for their secretion of DJ-1 using immunoblot analysis. By immunohistochemistry DJ-1 protein expression was lower than adjacent non-cancerous epithelium in 6 (14.6%) of the 41 DCISs and 146 (53%) of the 273 IDCs, even although all 314 carcinomas retained expression of DJ-1 mRNA, which was higher than that in adjacent non-cancerous epithelium in 220 cases (70%). Patients with IDC whose cancer cells showed low expression of DJ-1 protein had significantly shorter disease-free survival (P = 0.0152) and overall survival (P = 0.0196) than those whose cancer cells retained DJ-1 expression. MDA-MB-231 cells, which secreted DJ-1, showed low expression of DJ-1 protein. CONCLUSIONS: Low expression of DJ-1 protein with high expression of its mRNA, which may reflect a secretory expression pattern, is predictive of poor outcome in patients with IDC.