Major disagreements between immunoassays of carcinoembryonic antigen may be caused by nonspecific cross-reacting antigen 2 (NCA-2)

Abstract

Abstract Four "sandwich"-type immunoassays of carcinoembryonic antigen (CEA) based on the use of monoclonal antibodies (Abbott CEA-RIA Monoclonal, Pharmacia/Wallac Delfia CEA kit, Roche CEA EIA Duomab 60, and our in-house immunoradiometric assay) were tested for cross-reaction with nonspecific cross-reacting antigen 2 (NCA-2) in meconium. The Roche assay did not react with NCA-2, but the other three assays cross-reacted strongly and to about the same extent with this antigen. NCA-2 is the CEA gene family member that is structurally most similar to CEA, and other authors have found by indirect evidence that this antigen also is increased in the serum of many cancer patients. In a previous study we found that the Roche assay yielded lower mean values than the other assays for CEA in serum from colorectal cancer patients. Furthermore, the correlation between the Roche CEA values and those of each of the other three assays was weaker than the correlation between these NCA-2 cross-reactive assays. We conclude that these results can be explained by the different cross-reactivity with NCA-2 of the antibodies used by the various assays, as described here. Our findings raise interesting questions regarding the possible role of NCA-2 as a tumor marker.