Evaluation of Dot-immunobinding Assay for Carcinoembryonic Antigen Determination in Nipple Discharge as an Adjunct in the Diagnosis of Early Breast Cancer

Abstract

We have previously reported carcinoembryonic antigen (CEA) measurement in nipple discharge to be a useful adjunct in the diagnosis of non-palpable breast cancer. As an extension, a dot-immunobinding assay was developed to screen a large number of patients with nipple discharge for non-palpable breast cancer. The principle is as follows. CEA bound to a solid phase monoclonal anti-CEA antibody is detected by a second monoclonal anti-CEA antibody conjugated with horseradish peroxidase. The use of tetramethylbenzidine as a chromogen results in a stable color reaction that can be semiquantitively analyzed by the naked eye. The CEA levels determined by this dot assay correlated well with CEA levels determined using the former Elmotec assay. To determine whether or not the method could also be feasible in the detection of non-palpable breast cancer, a collaborative study from 12 Japanese institutes was organized. The CEA levels in nipple discharges from 155 patients were assayed. Thirteen of 30 patients with palpable breast cancer and 22 of 30 patients with non-palpable breast cancer exhibited CEA values higher than 400 ng/ml, a cut-off value determined using 89 benign controls. The specificity (91%) and sensitivity (73%) of this test were higher than those of mammography or cytology. The incidence of elevated CEA levels in nipple discharge correlated significantly with the incidence of intratumoral antigen expression. Thus, the system could prove useful in screening for early breast cancer.