Phil Gold

Absence of carcinoembryonic antigen‐like material in mesothelioma An immunohistochemical differentiation from other lung cancers

This study is to examine the potential usefulness of immunohistochemical staining for carcinoembryonic antigen (CEA)‐like material in the differential diagnosis of mesotheliomas (12 cases) from other lung cancers (14 cases) that had been previously diagnosed by transmission and scanning electron microscopy and conventional light microscopy. Indirect immunofluorescent staining for CEA was carried out on formalin‐fixed paraffin‐embedded sections, and the slides were examined under code. All 9 cases of diffuse mesothelioma were negative, and all 12 cases of adenocarcinoma and bronchioloalveolar carcinoma were positive for CEA‐like material. Three localized mesotheliomas and a carcinoid tumor were also negative. A squamous cell carcinoma was positive. A positive immunohistochemical result for CEA‐like material in lung cancers will raise the possibility of its being of bronchial epithelial origin.

Dietary Milk Proteins Inhibit the Development of Dimethylhydrazine-Induced Malignancy

This study investigated the influence of two formula diets containing 20 g/100 g diet of either whey protein concentrate or casein, or Purina mouse chow on 1,2-dimethylhydrazine (DMH)-induced colon carcinoma in A/J mice. Four weeks after the 24th DMH treatment the incidence of tumour and tumour area in the whey protein-fed mice was substantially less in comparison to either the casein or Purina groups. The Purina group exhibited the greatest tumour burden. At the end of the experiment all animals continuously fed the whey protein diet were found to be alive, whereas 33% of those on the casein or Purina diet had died. Animals fed Purina diet for 20 weeks and then switched to either milk protein diet for a further 8 weeks exhibited a decrease in tumour burden as compared to those animals fed the Purina diet continuously. Body weights were similar in all dietary groups. In conclusion, a whey protein diet appears to significantly influence the development of chemically induced colon tumours and the short-term survival of mice.

Opposite Functions for Two Classes of Genes of the Human Carcinoembryonic Antigen Family

The human carcinoembryonic antigen (CEA) family can be divided into two subgroups according to the means of anchorage of member glycoproteins to the cell membrane: glycophosphatidyl inositol (GPI) linkage and transmembrane linkage. The GPI-linked members tend to be up-regulated in human tumours, whereas the transmembrane-linked members tend to be down-regulated. Thus the question as to whether the GPI members could be formally considered to function as oncogenes and the transmembrane members as tumour suppressors deserves consideration. Members of both subgroups function in vitro as intercellular adhesion molecules, but the characteristics of this adhesion, including temperature and divalent-cation dependence, differ markedly between the groups. Even the mechanism of intermolecular adhesion appears to differ fundamentally in that GPI-linked CEA-CEA binding involves a double reciprocal bonding between two domains, whereas transmembrane-linked biliary glycoprotein (BGP)-BGP binding requires only one domain. Finally, the ectopic expression of CEA in myoblasts can block myogenic differentiation leaving the cells with the ability to divide, while expression of BGP does not affect or may even accelerate myogenic differentiation. These differences in phenotypic effects in vitro thus mirror the differences observed in expression in tumours and support the view that the GPI and transmembrane groups have opposite effects on cells in relation to the malignant phenotype.

β2-Microglobulin: Methods and Clinical Applications

beta 2-Microglobulin is a low molecular weight protein that is found in most biological fluids. It was originally isolated from urine of cadmium-poisoned patients. Its amino acid sequence was established and shown to be structurally related to immunoglobulin constant domains. With the aid of antibodies specific against beta 2-microglobulin, the protein was detected on the membranes of all nucleated cells, normal and neoplastic. Measuring the quantity of beta 2-microglobulin showed that high levels are present in patients with renal tubular deficiencies and several other pathological conditions including neoplastic diseases. Extremely high levels were detected in seminal fluid and colostrum. Despite the structural relationship to immunoglobulins, no immunological relationship was demonstrated with these proteins using antibodies specific for beta 2-microglobulin. However, such antibodies are cytotoxic to all cells carrying beta 2-microglobulin on their surfaces. The discovery that beta 2-microglobulin is an integral part of the histocompatibility antigens of human and murine origin stimulated further research and interest in this molecule. Several groups of investigators have shown that beta 2-microglobulin is the low molecular weight chain and is noncovalently bound to a high molecular weight chain which carries the histocompatibility antigens. The structure of the histocompatibility antigens of lymphocytes (HLA) was shown by immunochemical as well as biological methods, and it is now well accepted. The antibodies against beta 2-microglobulin are extremely useful in the isolation of the histocompatibility antigens for sequence studies. Furthermore, the antibody to beta 2-microglobulin revealed that other structures may be bound to beta 2-microglobulin such as phytohemoagglutimin (PHA) receptors, mixed lymphocyte culture (MLC) antigens, etc. Murine thymus leukemia (TL) antigen also contains beta 2-microglobulin as an integral part of its structure; other tumor antigens may have a similar structure. Through all these studies, beta 2-microglobulin emerged as the best known membrane protein that can serve as a model for study of the arrangement and the function of the cell membrane.

Immunohistopathologic study on carcinoembryonic antigen (CEA)-like material and immunoglobulin a in gastric malignancies

Immunofluorescent staining for carcinoembryonic antigen (CEA)‐like material and immunoglobulin A (IgA) was performed on 54 gastric specimens showing normal mucosa and various lesions including malignancy. Both CEA‐like material and IgA were demonstrated in normal mucosa and benign and malignant epithelial lesions. Abnormal findings in respect of CEA‐like material included staining of cell membranes with disordered pattern and increased cytoplasmic staining. Several staining characteristics for CEA‐like material were shown by various types of malignant epithelial tumors. This staining provides a means of distinguishing anaplastic carcinoma from histiocytic lymphoma, as the latter does not demonstrate CEA‐like material. IgA was consistently absent in anaplastic carcinomas, but was noted on the inner surface of tubular components in the differentiated adenocarcinomas, indicating functional preservation in the differentiated tumors. Immunohistochemical staining for CEA‐like material and IgA is considered to be useful in the structural and functional study of gastric malignancies.

A human colon tumour antigen associated with β2-Microglobulin and isolated from solid tumour, serum and urine, is unrelated to carcinoembryonic antigen

Abstract The antigen-induced leukocyte adherence inhibition response is directed to an organ-type specific neoantigen. Cancers of the colorectum, pancreas and stomach each expressed a unique organ-specific neoantigen. The relationship of the colon tumour antigen to the previously described carcinoembryonic antigen (CEA) of GIT cancers was examined by a tube blocking LAI assay and CEA radioimmunoassay. The colon tumour antigen was papain-solubilized from colon cancer membranes. An affinity column of horse anti-human β 2 -microglobulin bound the colon tumour antigen but did not bind CEA. In contrast, the colon tumour antigen failed to bind to an affinity column of antisera prepared to cell surface proteins that had failed to bind to the anti-human β 2 -microglobulin affinity column. Both the colon tumour antigen and CEA existed in the serum of patients with metastatic cancer. The colon tumour antigen co-isolated with the HDL fraction of serum by polyanion precipitation which suggested that the colon tumour antigen was lipoprotein in composition. By contrast, CEA was recovered in the non-lipoprotein fraction of serum. A proportion of the colon tumour antigen and CEA in the serum were eliminated into the urinary protein by filtration in the kidney. The results of the present study indicate that the colon tumour antigen epitope and the CEA epitope exist on separate molecules.

Theoretical and Practical Considerations of the Utility of the Radioimmunoassay for Carcinoembryonic Antigen (CEA) In Clinical Medicine

Carcinoembryonic antigen (CEA) was discovered in 1965 and defined as a tumor-specific antigen of the human digestive system (Gold and Freedman, 1965). The fact that CEA was absent from corresponding normal adult tissues, but was demonstrated in human embryonic and fetal digestive organs by the immunologic techniques employed in the initial observations, accounts for the designation given the molecule and the hypothesis that the reinitiation of its synthesis by bowel cancer cells in the adult is the result of a process variously termed derepressive dedifferentiation, retrodifferentiation, or antigenic reversion.