Recent studies of glycolipid and glycoprotein profiles and characterization of the major glycolipid antigen in gastric cancer of a patient of blood group genotype pp (Tja-) first studied in 1951.

Abstract

Abstract The lyophilized gastric tumor tissue (20 mg) of the patient (D. J.) studied serologically in 1951 absorbed 16 to 32 agglutinating units of her own stimulated antibody (1:512) induced by a test injection of 25 ml of incompatible blood from an initial 1:4 to 1:8 titer. When in 1975 the lyophilized tissue (about 3.5 g) was located, it was mailed to Seattle for biochemical analysis of the antigens involved, and these investigations were not completed until 1982. This paper describes the glycolipids and glycoproteins in the gastric cancer tissue of a patient whose erythrocytes contained the first example of a very rare variant of the P system, identified as genotype pp (initially referred to as Tj a- ) and later shown to contain anti-P 1 PP k (anti-Tj a ) in her serum. Sodium dodecyl sulfate:polyacrylamide gel electrophoresis of the immunoprecipitates with anti-globoside, anti-P 1 , and anti-P 1 PP k of [ 3 H]galactose-labeled tissue extract demonstrated the major component in glycolipids and a few minor components in glycoproteins. The purified glycolipid fraction (upper neutral glycolipid) showed complement fixation with anti-P 1 PP k ; nevertheless, the glycolipid fraction contained neither globoside nor ceramide trihexoside. The major glycolipid had the same thin-layer chromatography mobility and antigenic reactivity as a new “x 2 glycolipid” of human erythrocytes which cross-reacts with anti-globoside antibodies, the pentasaccharide structure of which was identified as GalNAcβ1 → 3Galβ1 → 4GlcNAcβ1 → 3Galβ1 → 4Glcβ1 → 1Cer. The latter is a glycolipid with the same terminal structure as globoside and with an internal structure identical to paragloboside. Although the purified glycolipid fractions display a clear inhibition of anti-P 1 agglutinins, only a minor component had the same thin-layer chromatography mobility as P 1 glycolipid, which is a ceramide pentasaccharide susceptible to hydrolysis with fig α-galactosidase. It is possible that some other glycolipid having a more complex structure may also have P 1 activity. The results indicate that the tumor activated the synthesis of P 1 antigen but not the synthesis of the globo series glycolipid; it also showed an enhanced synthesis in the lacto series glycolipid with the same terminal structure as globoside. There are indications that this patient survived for 22 years, until 1973, when she died at 88 years from old age without developing any metastasis, while her younger compatible sib, also of genotype pp (Tj a- ), died of cancer of the uterus and metastasis at the age of 63.