The carcinoembryonic antigen (CEA) family: structures, suggested functions and expression in normal and malignant tissues.

To determine whether tumors containing carcinoembryonic antigen could be detected by administration of a Radio-labeled, affinity-purified, goat IgG having 70 per cent immunoreactivity against carcinoembryonic antigen, 18 patients with a history of cancer of diverse histopathology received an average total dose of 1.0 mCi of 131l-labeled IgG. Total-body photoscans were performed with a gamma scintillation camera at various intervals after administration of the radioactive antibody. Ordinary photoscans proved difficult to interpret because of blood-pool background radioactivity, thus necessitating the computer subtraction of radioactive blood-pool agents from the antibody's 131I activity. Tumor location could be demonstrated at 48 hours after injection in almost all cases studied. The scans were negative in patients without demonstrable tumors or with tumors apparently devoid of carcinoembryonic antigen. Circulating antigen levels of up to 350 ng per milliliter did not prevent successful tumor imag...

Use of Radiolabeled Antibodies to Carcinoembryonic Antigen for the Detection and Localization of Diverse Cancers by External Photoscanning

The carcinoembryonic antigen (CEA) gene family belongs to the immunoglobulin supergene family and can be divided into two main subgroups based on sequence comparisons In humans it is clustered on the long arm of chromosome 19 and consists of approximately 20 genes The CEA subgroup genes code for CEA and its classical crossreacting antigens, which are mainly membrane-bound, whereas the other subgroup genes encode the pregnancy-specific glycoproteins (PSG), which are secreted Splice variants of individual genes and differential post-translational modifications of the resulting proteins, eg, by glycosylation, indicate a high complexity in the number of putative CEA-related molecules So far, only a limited number of CEA-related antigens in humans have been unequivocally assigned to a specific gene Rodent CEA-related genes reveal a high sequence divergence and, in part, a completely different domain organization than the human CEA gene family, making it difficult to determine individual gene counterparts However, rodent CEA-related genes can be assigned to human subgroups based on similarity of expression patterns, which is characteristic for the subgroups Various functions have been determined for members of the CEA subgroup in vitro, including cell adhesion, bacterial binding, an accessory role for collagen binding or ecto-ATPases activity Based on all that is known so far on its biology, the clinical outlook for the CEA family has been reassessed

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Carcinoembryonic antigen gene family: molecular biology and clinical perspectives.

An antiserum raised against human milk fat globule membranes has been used to stain a wide variety of human tissues by the indirect immunoperoxidase method. The antigen detected has been designated Epithelial Membrane Antigen and was confined to the luminal and surface membranes (and to a lesser extent the cytoplasm) of epithelial tissues in the normal state. Increased staining was observed in a variety of nonneoplastic disease states as well as in many neoplasms. The staining of tumors is related both to their histogenesis and degree of differentiation, being found only in lesions of surface epithelial or mesothelial origin and being more consistently present in well and moderately differentiated neoplasms. However, strong staining was also present in many anaplastic tumors and this together with the resistance of the antigen to formol fixation and paraffin embedding suggest that the antiserum has a valuable role to play in diagnostic tumor histopathology as an indicator of epithelial differentiation. The distinction of anaplastic carcinomas from malignant lymphomas and the recognition of spindle-cell epithelial malignancies are especially useful applications. The identification of minute metastatic deposits of carcinoma in organs such as the liver and bone marrow is also greatly facilitated. Malignant neoplasms often exhibit patterns of staining different from those of the normal tissues. The possible significance of these patterns is discussed.

Distribution of epithelial membrane antigen in normal and neoplastic tissues and its value in diagnostic tumor pathology

The discovery of the carcinoembryonic antigen (CEA) as a tumor marker for colorectal cancer some 50 years ago became the first step in the identification of a much larger family of 12 carcinoembryonic antigen-related cell adhesion molecules (CEACAMs) with surprisingly diverse functions in cell adhesion, in intracellular and intercellular signaling, and during complex biological processes such as cancer progression, inflammation, angiogenesis, and metastasis. The development of proper molecular and biochemical tools and mouse models has enabled bidirectional translation of the CEACAM network biology. Indeed, CEACAM1, CEACAM5, and CEACAM6 are now considered valid clinical biomarkers and promising therapeutic targets in melanoma, lung, colorectal, and pancreatic cancers. These fascinating proteins illustrate how a better understanding of the CEACAM family of cell adhesion molecules reveals their functional link to the underlying disease and lead to new monitoring and targeting opportunities.

Carcinoembryonic antigen-related cell adhesion molecules (CEACAMs) in cancer progression and metastasis

A glycoprotein present in normal human tissue is characterized that is neither organ- nor tumor-specific (nonspecific crossreacting antigen) and that crossreacts (by the Ouchterlony double-diffusion technique) with the carcinoembryonic antigen. This immunological relationship indicates common determinants on the molecules of both antigens. We demonstrate that the nonspecific crossreacting antigen is not a fragment of the carcinoembryonic antigen molecule.

https://www.pnas.org/content/pnas/69/9/2492.full.pdf

G. Chavanel

Papers

Identification of an Antigen from Normal Human Tissue That Crossreacts with the Carcinoembryonic Antigen

Brief communication: demonstration in normal human plasma of an antigen that cross-reacts with the carcinoembryonic antigen of digestive tract tumors.