title: 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.
authors.affiliation: Department of Basic Pathology, National Defense Medical College, Saitama, Japan.
authors.forename: Miki
authors.initials: M
authors.lastname: Oda
authors.forename: Masujiro
authors.initials: M
authors.lastname: Makita
authors.forename: Keiichi
authors.initials: K
authors.lastname: Iwaya
authors.forename: Futoshi
authors.initials: F
authors.lastname: Akiyama
authors.forename: Norio
authors.initials: N
authors.lastname: Kohno
authors.forename: Benio
authors.initials: B
authors.lastname: Tsuchiya
authors.forename: Takuji
authors.initials: T
authors.lastname: Iwase
authors.forename: Osamu
authors.initials: O
authors.lastname: Matsubara
mesh_terms: D014408:Biomarkers, Tumor / Q000032:analysis; D001943:Breast Neoplasms / Q000175:diagnosis* / Q000378:metabolism* / Q000473:pathology; D002272:Carcinoembryonic Antigen / Q000032:analysis; D018270:Carcinoma, Ductal, Breast / Q000175:diagnosis / Q000378:metabolism / Q000473:pathology; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000032:analysis* / Q000378:metabolism*; D008875:Middle Aged; D055966:Nipple Aspirate Fluid / Q000737:chemistry*; D009558:Nipples / Q000473:pathology; D015513:Oncogene Proteins / Q000032:analysis* / Q000378:metabolism*; D000071617:Protein Deglycase DJ-1
chemical_list: D014408:Biomarkers, Tumor; D002272:Carcinoembryonic Antigen; D047908:Intracellular Signaling Peptides and Proteins; D015513:Oncogene Proteins; C105131:PARK7 protein, human; D000071617:Protein Deglycase DJ-1