Interview with Dr. Hunter

A monoclonal antibody, FBT3, was raised against Tn positive erythrocytes and, using immuno-histochemistry, fresh and fixed tissues from patients with cancer were studied to detect any expression of a Tn-like epitope. Expression was found in neoplastic cells, usually both in cytoplasm and on cell membranes, from 104 of 147 cases of carcinoma and 1 of 13 cases of lymphoma, but rarely in adjacent, morphologically normal cells. Tn expression was seen in some normal glandular cells but, unlike cancer cells, it was distributed as fine granules in a supranuclear position. Detection of a Tn-like epitope is of theoretical interest and may be of direct diagnostic value. Alpha sialoglycoprotein (synonym glycophorin A) is an important constituent of the membrane of erythroid cells and is responsible for the antigenic determinants of the erythrocyte MN blood group system (Issitt, 1981). The molecule consists of a polypeptide chain to which are attached a number of sugar residues and one or more terminal sialic acid molecules. Sialoglycoprotein bears two cryptic antigenic determinants termed T and Tn and all individuals have in their plasma anti-T and anti-Tn anti-bodies which are thought to develop in response to organisms of their intestinal flora which bear related antigens. Removal of the terminal sialic acid of sialoglycoprotein in erythrocytes leads to uncovering of the T antigen; this is not uncommon and is usually due to bacterial infection and the activity of bacterial neuraminidase. Lack of the penultimate residue, galactose (and the terminal sialic acid) leads to uncovering of the Tn antigen. Biochemically, Tn antigen expression corresponds to exposure of N-acetyl-D-galacto-samine residues 0-glycosidically linked to serine or threonine. Tn expression is thought to be rare and has been reported in a few cases of malignant or premalignant haemopoietic disorders in which its presence has been detected following observation of polyagglutination of the erythrocytes by all blood grouping antisera. In these conditions the appearance of Tn appears to be due to a deficiency of the enzyme, 3-,B-D-galactosyl transferase which appears to result from a somatic mutation at the gene locus for this enzyme (Cartron et al., 1978). As part of a study into the importance of somatic mutation in human cells, we investigated whether uncovering of Tn would be a useful marker for somatic mutation in a variety of cell types. To this end a number of monoclonal antibodies were produced against the Tn epitope and tested against a variety of normal and …