ABSTRACT
PURPOSE: This research aimed to establish a diagnostic technique for breast cancer using nipple discharge (ND), with the objective of preventive diagnosis. ND has been proposed as a source of secreted proteomes that reflect early pathological changes in the ductal-lobular epithelial microenvironment, and could thus provide breast-specific cancer biomarkers that could be accessed noninvasively as a new clinical diagnostic technique. EXPERIMENTAL DESIGN: Minute amounts of ND from patients with and without breast cancer (n = 19 and 12, respectively) were collected at the hospital and kept frozen until just before use. They were analyzed using high-pH RP peptide fractionations/low-pH RP 2D nano-LC/ESI-MS/MS. Biomarker candidates were also investigated using Western blot analysis and sandwich ELISA on ND and/or sera. RESULTS: We found distinct tendencies in protein expression and three candidate breast cancer biomarkers (carbonic anhydrase 2, catalase, and peroxiredoxin-2) whose levels differed significantly between ND specimens from patients with and without breast cancer. CONCLUSIONS AND CLINICAL RELEVANCE: These tendencies in protein expression and markers provide new ways to identify breast cancer patients. Therefore, RP/RP 2D LC/MS/MS analyses of ND and the above three markers are supported as a new breast cancer diagnostic technique.
Subject(s)
Biomarkers, Tumor/genetics , Breast Neoplasms/diagnosis , Carbonic Anhydrase II/genetics , Carcinoma, Intraductal, Noninfiltrating/diagnosis , Catalase/genetics , Peroxiredoxins/genetics , Adult , Aged , Biomarkers, Tumor/metabolism , Breast Neoplasms/genetics , Breast Neoplasms/metabolism , Carbonic Anhydrase II/metabolism , Carcinoma, Intraductal, Noninfiltrating/genetics , Carcinoma, Intraductal, Noninfiltrating/metabolism , Case-Control Studies , Catalase/metabolism , Chromatography, High Pressure Liquid/methods , Early Diagnosis , Female , Gene Expression , Gene Expression Profiling , Humans , Middle Aged , Neoplasm Grading , Neoplasm Staging , Nipple Discharge/chemistry , Peroxiredoxins/metabolism , Proteome/genetics , Proteome/metabolism , Spectrometry, Mass, Matrix-Assisted Laser Desorption-IonizationABSTRACT
RATIONALE AND OBJECTIVES: The aim of this study was to evaluate the breast cancer diagnostic capability of "dual-side readout" computed radiography-based mammography (DRCRM) with a 50-microm pixel size compared to that of conventional film-screen mammography (FSM). MATERIALS AND METHODS: Thirty patients who were scheduled for surgical treatment for breast cancer and 10 normal volunteers were enrolled. All 30 patients underwent surgical treatment, and breast cancer was proved histopathologically. Twenty-eight patients had 35 invasive carcinomas, and the remaining two had ductal carcinomas in situ. Each of the 40 women underwent both DRCRM and FSM (with double exposure and the same view, without removing compression). Three observers retrospectively interpreted the mammograms independently and evaluated and rated masses and class categories. The accuracy of the detection of masses was evaluated with alternative free-response receiver-operating characteristic analysis. Sensitivity for the detection of masses and of cancers was also evaluated. RESULTS: The mean areas under the alternative free-response receiver-operating characteristic curves in the detection of the masses were 0.88 for DRCRM and 0.91 for FSM (P = .08). The corresponding values for mean sensitivity for the detection of masses were 0.74 and 0.77 (P = .48) and those for the detection of cancers 0.79 and 0.84 (P = .20). CONCLUSION: No significant differences were observed between DRCRM and FSM for diagnosis of breast cancers.
