Serum levels and biochemical characteristics of cancer-associated antigen CA-549, a circulating breast cancer marker.
CA-549 is a circulating breast cancer-associated antigen that reacts with monoclonal antibody BC4E 549. Biochemical characterization of CA-549 revealed that it is an acidic (isoelectric point 5.2) glycoprotein that exhibits two bands by sodium dodecyl sulfate-polyacrylamide gel electrophoresis under reducing conditions of apparent molecular weights of 400,000 and 512,000. Immunohistochemical staining of unfixed frozen tissue sections of human breast tumors and a variety of benign tissues with BC4E 549 revealed no preferential staining of tumor over benign breast tissue and cross-reactivity with a wide range of other benign tissues including kidney, liver, lung, colon, pancreas, ovary, and spleen. Serum levels of CA-549 were initially tested by an enzyme-linked immunosorbent assay inhibition using BC4E 549. This assay showed that CA-549 concentrations were elevated in 19 of 27 sera from patients with advanced breast cancer compared to 0 of 22 and 0 of 129 sera from benign breast disease patients and healthy females, respectively. These preliminary data suggested that CA-549 was a useful breast tumor marker; thus BC4E 549 was adapted to a sandwich immunoradiometric assay format suitable for routine use in the clinical laboratory and its performance was evaluated on a panel of 668 serum samples. The test detected significant concentrations of CA-549 in the sera of 40 of 80 patients with advanced breast cancer, 1 of 30 with early breast cancer, 4 of 19 with advanced lung cancer, 2 of 40 with advanced colon cancer, and 5 of 29 with advanced prostate cancer. The test showed a high degree of specificity, producing false-positives in only 3 of 79 benign breast patients, 2 of 25 benign liver patients, 2 of 70 benign colon patients, 2 of 19 benign lung patients, 0 of 20 benign prostate patients, and 3 of 257 healthy individuals. These data represent an overall 50% sensitivity and 98% specificity as a test for advanced breast cancer. These data indicate that this immunoradiometric assay is a useful test for the detection of circulating CA-549 in advanced breast cancer patients and suggest that it may prove useful as a monitor in the management of that disease.
D000911:Antibodies, Monoclonal; D000936:Antigen-Antibody Complex; D000951:Antigens, Neoplasm / Q000032:analysis*; D015295:Antigens, Tumor-Associated, Carbohydrate; D014408:Biomarkers, Tumor / Q000032:analysis*; D001943:Breast Neoplasms / Q000175:diagnosis* / Q000276:immunology / Q000473:pathology; D004797:Enzyme-Linked Immunosorbent Assay; D000939:Epitopes / Q000032:analysis*; D005260:Female; D006801:Humans; D008297:Male; D008970:Molecular Weight; D009369:Neoplasms / Q000276:immunology*; D009439:Neuraminidase; D011863:Radioimmunoassay; D012016:Reference Values
D000911:Antibodies, Monoclonal; D000936:Antigen-Antibody Complex; D000951:Antigens, Neoplasm; D015295:Antigens, Tumor-Associated, Carbohydrate; D014408:Biomarkers, Tumor; D000939:Epitopes; D009439:Neuraminidase