Expression of blood group-related antigens in normal and malignant pancreatic tissue correlated with genotype of the patient defined by saliva glycoprotein.

Abstract

Seven murine monoclonal antibodies (MoAb) detecting blood group antigens of the Lewis system and their sialylated derivatives were used to define their immunohistochemical distribution in normal and malignant pancreatic tissues. The specific blood group antigens studied included Lewis(a) (Le(a)), Lewisb (Leb), Lewisx (Le(x)), Lewis(y) (Le(y)), sialyl-Lewis(a) (s-Le(a)), sialyl-lacto-N-tetraose (s-LNT), and sialyl-Lewisx (s-Le(x)). The expression of these antigens was analyzed by immunoperoxidase technique in pancreatic tissue of patients with (n = 27) and without (n = 19) pancreatic cancer. The genetic background of their secretor status and their Lewis phenotypes were determined by the enzyme-linked immunosorbent assay using purified salivary glycoprotein and MoAb against eight different blood group-related antigens (Le(a), Leb, Le(x), Le(y), H1, H2, A, B2), and the putative genotypes of the patients were classified as follows: SeLe, Sele, seLe, and sele. The following results were obtained: (1) In normal pancreas, Le(a), s-Le(a), s-LNT, and s-Le(x) were expressed in ducts, but their expression was restricted to the luminal side of the cytoplasm (cytoplasmic type with positive polarity). Leb and Le(y) showed similar patterns of expression in ducts and some parts of the acinus. In contrast, Le(x) was absent in most cases. (2) Expression of Leb was observed in normal pancreatic ducts in all 46 patients, regardless of their genotypes. Le(a) and s-Le(a) were not expressed in specimens from patients with the seLe and sele saliva phenotypes. (3) In pancreatic cancer, the following antigens were expressed cytoplasmically in the proportion of cases indicated: Le(a) (78%), Leb (85%), Le(x) (33%), Le(y) (44%), s-Le(a) (78%), s-LNT (89%), and s-Le(x) (85%). They also were detected in the surrounding stroma. This pattern of expression is distinct from that found in normal pancreatic tissue. Patients with Sele and sele genotypes did not express Le(a) or s-Le(a), except in one case. (4) Serum levels of carbohydrate antigen 19-9 (CA 19-9) were not elevated in patients with pancreatic cancer with the Sele and sele genotypes but were elevated in most patients with SeLe and seLe genotypes. The overall findings indicate that Lewis-related antigens act as pancreatic tissue-related antigens, depending in part on salivary phenotypes of the patient. With proper antigen selection and the determination of secretor status, these anti-blood group MoAb may be of clinical utility in the diagnosis of pancreatic cancer.