Immunological Heterogeneity of Carcinoembryonic Antigen: Immunohistochemical Detection of Carcinoembryonic Antigen Determinants in Colonic Tumors with Monoclonal Antibodies

The immunoperoxidase localization of carcinoembryonic antigen (CEA) determinants was studied in colonic adenocarcinomas using four murine monoclonal antibodies to CEA in a bridged avidin:biotin technique. One of the monoclonal antibodies, NP-1, recognizes a CEA epitope shared with the nonspecific cross-reacting antigen and meconium antigen. Two others, NP-2 and NP-3, discriminate two separate CEA epitopes shared with meconium antigen only, whereas NP-4 reacts with a unique determinant expressed on a subpopulation of CEA molecules. The monoclonal antibodies and polyclonal goat antisera against CEA and nonspecific cross-reacting antigen stained columnar epithelial cells in morphologically normal mucosa. Neutrophils were stained by only the NP-1 monoclonal antibody and goat anti-nonspecific cross-reacting antigen antiserum. All moderately differentiated colorectal adenocarcinomas and most of their nodal and liver metastases reacted with the goat antisera and cross-reactive monoclonal antibodies. Thirty % of these primary tumors and most of the nodal and/or liver metastases from six patients with NP-4-positive primary tumors failed to stain with NP-4. These results suggest heterogeneity in the expression of a CEA variant and/or determinant recognized by the NP-4 monoclonal antibody that perhaps identifies a subgroup of colonic cancers which differ in their functional differentiation.