High levels of DJ‐1 protein in nipple fluid of patients with breast cancer

Abstract

As we have previously demonstrated that some breast cancer cell lines secrete DJ-1 protein, we examined here whether breast cancer cells secrete DJ-1 protein in vivo. To this end, the levels of DJ-1 protein present in 136 specimens of nipple fluid was examined by enzyme-linked immunosorbent assay (ELISA). The average concentration of DJ-1 protein detected in diluted samples from 47 patients with invasive ductal carcinoma (IDC) was 22.4 ng/mL, while it was 18.6 ng/mL in 26 patients with ductal carcinoma in situ (DCIS). In contrast, the average DJ-1 concentration in samples from 63 women with benign lesions was 2.7 ng/mL, demonstrating that higher DJ-1 protein levels were detected in nipple fluid in the presence of cancer cells than in the presence of benign lesions (P < 0.0001). When a cut-off level of 3.0 ng/mL was applied, the higher level of DJ-1 was shown to be of significant clinical value for predicting the presence of breast cancer (85.9% specificity, 75% sensitivity; P < 0.0001). Multivariate logistic analysis that included established factors such as nipple discharge cytology, ductoscopic cytology, and carcinoembryonic antigen level further showed that the level of DJ-1 protein alone is of significant value for predicting the presence of breast cancer. Immunohistochemistry and in situ hybridization also showed that the low expression of DJ-1 protein, despite high mRNA expression, was significantly correlated with high DJ-1 protein levels in the nipple fluid. These data indicate that breast cancer cells secrete DJ-1 protein in vivo, and that its level is a potential indicator of breast cancer in patients with nipple discharge. (Cancer Sci 2012; 103: 1172-1176 N ipple discharge is a common complaint among women that is classified as normal or abnormal depending on features such as laterality, cyclic variation, quantity, or color.(1-3)Although the majority of cases of nipple discharge are due to benign conditions such as intraductal papilloma, ductal ectasia, or plasma cell mastitis, approximately 10-20% of cases are attributable to malignant conditions such as ductal carcinoma in situ (DCIS), or the early clinical stages of invasive ductal and/or lobular carcinoma. (4,5) While it has been proposed that patients with nipple discharge should undergo biopsy or subareolar exploration based on the presence or absence of a palpable mass, less invasive, non-surgical methods can also be applied in these cases. (6,7) The cytological evaluation of nipple discharge obtained directly from the nipple is widely used for clinical examination. In previous investigations of asymptomatic women with nipple discharge, a definitive diagnosis of malignancy was not possible in approximately 70% of cases (8,9) ; however, cytology has been improved by new techniques such as "duct lavage" and "duct endoscopy" (ductoscopy).(10-12) These newer techniques are designed to examine the abnormal cells that travel from the ducts to the nipple. Moreover, biological markers such as carcinoembryonic antigen (CEA) or human epidermal growth fac...

DJ-1-Dependent Regulation of Oxidative Stress in the Retinal Pigment Epithelium (RPE)

“…However, recently DJ-1 has emerged as a significant biomarker since its presence has been detected in the serum of gastric cancer [99], prostate carcinomas [100], pancreatic cancer [101], non-small cell lung cancer [102] and uveal melanoma [103] patients. Similarly, higher DJ-1 levels have been noted in nipple secretions from breast carcinoma patients [104]. Moreover, DJ-1 has been detected in cerebrospinal fluid from Parkinson’s Disease patients [105], [106], [107] and urine from hepatocellular carcinoma [108] patients.…”

Expression of novel tumor markers of pancreatic adenocarcinomas in intrahepatic cholangiocarcinomas

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High-expression of DJ-1 and Loss of PTEN Associated with Tumor Metastasis and Correlated with Poor Prognosis of Gastric Carcinoma

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