Sulphoglycoprotein antigens in the human alimentary canal and gastric cancer. An immunohistological study

Abstract

Biochemical studies on glycoproteins secreted by the epithelium of the alimentary canal have been hampered to some extent because the mucosubstances in secretions are products of various cell types. The histochemical stainability of mucins within the same cell type also varies. Considerable differences can be seen when superficial and deep glandular epithelium are compared (Spicer and Sun, 1967). lmmunological techniques offer another way of identifying gastrointestinal glycoproteins. Using specific anti-A, -B or -H sera and the immunofluorescence technique, Glynn and Holborow (1 959), Szulman (1 960, 1962) and Davidsohn et al. (1966) studied the site of production of blood-group substances in gastrointestinal epithelium. The sequential order of sugars which determine the serological specificity of these macromolecules is we1 1 established (Watk ins, 1966). On the other hand, macromolecules having the same serological specificity can be structurally quite different. Examples of this are membrane glycolipids and water-soluble glycoproteins. Differences in molecular structure can also be postulated for water-soluble glycoproteins. Evidence for this comes from immunization experiments with an isolated gastric sulphoglycoprotein fraction possessing blood-group specificity (Hakkinen, 1966Hakkinen and Virtanen, 1967). The immunized rabbits apparently formed antibodies directed not against blood-group antigens, but against some other specific sites in these macromolecules. Molecular configuration in gastric sulphoglycoproteins may be altered in certain pathological conditions such as intestinalization of the gastric epithelium or gastric cancer. A preliminary attempt t o locate the sulphoglycoproteins possessing these antigenic configurations was made by the immunofluorescence technique using specific rabbit antisera . In the present study the same technique has been used to study also the

Monoclonal antibody 91.9H raised against sulfated mucins is specific for the 3'-sulfated Lewisa tetrasaccharide sequence

“…Gastric mucosae showing intestinal metaplasia and gastric carcinomas, particularly those with a poor prognosis, acquire a colonic-type "phenotype" and become rich in the 3′-sulfated Le a tetrasaccharide and longer structures (Ohe et al, 1994). Our findings also provide an explanation for the observations of Hakkinen and colleagues on the accumulation of sulfated antigens in precancerous and cancerous gastric mucosae (Hakkinen et al, 1968).…”

Sulfated Muco-Substances and Gastric Diseases

“…Indeed when gastric secretions are obtained at gastrostomy after an extensive esophagectomy for cancer, sulfated muco-substances disappear from the juice collected [14]. The normal gastric antigen isolated by Häkki nen from the gastric juice is localized in immunofluorescence on the apical pole of surface gastric cells [9] but its assimilation to a sulfoglycoprotein is uncertain. The immunizing material was obtained by cetylpyridinium precipitation at pH 6.5 without proteolysis; in such conditions the precipi tation is not specific of sulfated polyanions and a number of antigens remain associated to these molecules.…”

“…The antipeptic activity of these sulfated glycoproteins has been demonstrated [2], Owing to pathophysiological implications they have been explored in the diseased stomach. A qualitative study of sulfated mucosubstances in the gastric juice was reported by Häkkinen [7,9,10], Three distinct antigens were obtained after immunization of rabbits against a fraction of gastric juice containing the polyanions: a normal gastric antigen in young healthy people; an intestinal antigen in older patients with atrophic gastritis; a cancer antigen in patients with gastric carcinoma, common to the fetal gastric mucosa (carcino-embryonar antigen). Sulfated muco-substances being detected in the saliva as well as in gastric secretions [21] a contamination remains possible.…”

Foetal antigens and their role in the diagnosis and clinical management of human neoplasms: a review

“…One of them, located in the cells of the superficial epithelium of the foetal stomach, disappears from this site 9 months after birth and is called foetal sulphoglycoprotein antigen (FSA). Hakkinen and Viikari (1969) (Hakkinen, Jarvi and Gironroos, 1968 (Leese, 1969). While these observations have important basic connotations in the field of differentiation, of great clinical importance are qualitative isozymic alterations which are also reflected in the body fluids.…”