The relation of serum anti-(GalNAc beta) and -para-Forssman disaccharide IgG levels to the progression and histological grading of gastrointestinal cancer.

UNLABELLED: Earlier we found two unusual IgG-antibody specificities to GalNAc beta and GalNAc beta1-3GalNAc beta (para-Forssman disaccharide, PFdi) carbohydrate ligands in human serum. The aim of the study was to evaluate whether elevated antibody levels are related to the progression of gastrointestinal cancer and the histopathological grading. METHODS: Specific IgG levels were tested in 159 patients with gastric cancer, 88 patients with colorectal cancer and 96 blood donors by the ELISA using synthetic polyacrylaamide (PAA) conjugates, GalNAc beta-PAA and PFdi-PAA. Biochemical and haematological analyses were performed using automatic equipment. RESULTS: The anti-PFdi IgG levels were significantly higher in patients with gastric and colorectal cancer than in donors: in stages II-IV, P = 0.0002 - 0.04 (U-test). The elevated anti-PFdi IgG level was associated with the advanced gastric cancer: in stages II, III, IV vs stage I (P = 0.004 - 0.06) and in case of the tumor size T2 + T3 vs T1 (stages I, II; P = 0.03). Differences in anti-GalNAc beta IgG level were insignificant. No relation between antibody levels and the regional and distant metastases of gastric or colorectal cancer was found. The lower anti-GalNAc beta IgG level was associated with lower-differentiated carcinomas (P = 0.01 - 0.04). Prolonged postoperative changes in the levels of both antibodies during the follow-up were established. An elevation of both antibody levels in patients with gastrointestinal cancer was revealed after a surgical removal of G3-tumors (P = 0.003 - 0.01). The anti-PFdi IgG levels correlated with the levels of the C-reactive protein: r = 0.50, P = 0.003. The anti-GalNAc beta IgG levels correlated with the percentage of peripheral blood monocytes: r = 0.42, P = 0.002. CONCLUSION: The association of the anti-PFdi IgG level with cancer progression suggests the implication of antibodies in the pathogenesis of gastrointestinal cancer. Further studies are required to identify natural targets of antibodies, their relation to other diseases, prognostic significance in cancer.

Humoral immune response to MUC1 and to the Thomsen-Friedenreich (TF) glycotope in patients with gastric cancer: relation to survival.

Humoral immune responses to the MUC1 peptide and to MUC1-related Thomsen-Friedenreich (TF) glycotope was investigated in patients with gastric cancer (n = 247), chronic gastroduodenal diseases (n = 199) and in healthy blood donors (n = 100). Data were correlated with disease type, stage of cancer, tumor morphology and survival. MUC1 IgG antibody levels were higher in patients with gastric cancer (p < 0.0001) than in healthy controls. Higher levels of anti-MUC1 IgG were also detected in patients with ulcer of the stomach (p = 0.015) and in atrophic gastritis (p = 0.027). Compared to blood donors, significantly lower levels of anti-TF IgG were found both in the cancer (p = 0.002) and in the benign group (p < 0.0001). At early stages of cancer a positive correlation (p < 0.0001) was found between MUC1 IgG and TF IgG antibody levels. High levels of TF IgG antibodies were significantly associated with a benefit in survival of gastric cancer patients (p = 0.003). A similar though weaker association was observed for patients with high levels of MUC1 IgG antibodies and locoregional disease (stage I-III) (p = 0.037). Thus IgG immune responses to MUC1 are increased in patients with gastric cancer. High levels of either TF IgG or MUC1 IgG antibodies may predict better outcome in surgically treated patients with gastric cancer.

Natural IgM and IgG antibodies to Thomsen-Friedenreich (T) antigen in serum of patients with gastric cancer and blood donors--relation to Lewis (a,b) histo-blood group phenotype.

A possible association of serum anti-T IgM and IgG antibody levels with Lewis blood-group phenotype was investigated in 168 blood donors and 132 gastric cancer patients using ELISA with synthetic T-disaccharide-polyacrylamide conjugate as antigen. The donors of Le(a-b+) phenotype showed the highest anti-T IgM level irrespective of ABO(H) blood group. A significant decrease in anti-T IgM in serum was observed among cancer patients of Le(a-b+) phenotype: 95% of weak responders versus 17.5% for related groups of donors (p < 10(-6)). In contrast, no significant difference between patients and donors was found for Le(b-) individuals. Thus, a level of natural anti-T antibodies in serum of blood donors and its decrease in patients with gastric cancer are related to Le(a,b) phenotype. This should be taken into account where anti-T antibody level in the serum is used as a tumour marker or for monitoring patients during cancer immunotherapy with mucin-type vaccines.