Deutscher et al. BMC Cancer 2010, 10:519 http://www.biomedcentral.com/1471-2407/10/519 R E S E A R C H A R T I C L E Open Access Carbohydrate antigens in nipple aspirate fluid predict the presence of atypia and cancer in women requiring diagnostic breast biopsy Susan L Deutscher1,3, Marie Dickerson1,3, Gerald Gui4, Jessica Newton1,3, Jeffrey E Holm5, Nancy Vogeltanz-Holm5, Beth Kliethermes6, John E Hewett2, Senthil R Kumar1,3, Thomas P Quinn1,3, Edward R Sauter6* Abstract Background: The goal of this prospective study was to determine (a) concentrations of the carbohydrate biomarkers Thomsen Friedenreich (TF) antigen and its precursor, Tn antigen, in nipple discharge (ND) collected from women requiring biopsy because of a suspicious breast lesion; and (b) if concentration levels predicted pathologic diagnosis. Methods: Adult women requiring biopsy to exclude breast cancer were enrolled and ND obtained. The samples from 124 women were analyzed using an anti-TF and anti-Tn monoclonal antibodies in direct immunoassay. Results: The highest median concentration in ND for TF and Tn was in women with ductal carcinoma in situ (DCIS). TF was higher in women with 1) cancer (DCIS or invasive) vs. either no cancer (atypia or benign pathology, p = .048), or benign pathology (p = .018); and 2) abnormal (atypia or cancer) versus benign pathology (p = .016); and was more predictive of atypia or cancer in post- compared to premenopausal women. Tn was not predictive of disease. High TF concentration and age were independent predictors of disease, correctly classifying either cancer or abnormal vs. benign pathology 83% of the time in postmenopausal women. Conclusions: TF concentrations in ND were higher in women with precancer and cancer compared to women with benign disease, and TF was an independent predictor of breast atypia and cancer. TF may prove useful in early breast cancer detection. Background The Thomsen-Friedenreich (TF; Galactose-b-(1®3)-N- acetyl-D-galactosamine) antigen and its biosynthetic pre- cursor, Tn (N-acetyl-D-galactosamine), are displayed on cell-surface proteins and lipids in 70% to 90% of adeno- carcinomas including those of the breast, prostate, and ovary [1]. Antibodies to TF and Tn have been used clinically as indicators of cancer and have been detected in primary breast cancer, lymph node, and metastatic tissue samples [2,3]. Obtaining tissue samples requires invasive biopsy procedures, which result in expense and considerable discomfort to the patient. An attractive alternative would be to screen a body fluid sample * Correspondence: esauter@medicine.nodak.edu 6University of North Dakota, Department of Surgery, 501 N. Columbia Rd., Grand Forks, ND 58202, USA Full list of author information is available at the end of the article obtained non-invasively to determine if the organ con- tains cancer, thereby minimizing invasive diagnostic pro- cedures. Nipple discharge (ND) includes both nipple aspirate fluid (NAF), which is collected using a modified breast pump, and pathologic (P)ND, which comes forth spontaneously from one but not the other breast nipple and generally harbors a benign or malignant tumor [4]. Both types of ND can be obtained non-invasively and contain concentrated secreted proteins and lipids from the breast ductal epithelium, the cells that give rise to cancer. We hypothesized that TF and Tn antigen, displaced on proteins and lipids that arise from cancer cells and cancer cell turnover, would be present in ND. To test this hypothesis, an initial blinded screening of 50 banked NAF samples from women with breast cancer and from asymptomatic women without cancer were screened for © 2010 Deutscher et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.