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The surface epithelium of normal gastric mucosa from patients with gastric adenocarcinoma expressed the type 1 blood group precursor only in Lewis (Le) non-secretor individuals, Le a+b- (se/se, Le/-) and Le a-b- (se/se, le/le). In secretors, the superficial mucosa was negative. Deep areas of the mucosa showed no type 1 precursor regardless of secretor status. Expression of type 1 precursor was anomalously found in neoplastic cells in 14 of 16 Le a-b+ (secretors) patients and in 4 of 5 Le a-b- (secretors) patients. The 1 Le a-b- non-secretor carcinoma expressed type 1 precursor strongly. 6 of 8 Le a+b- non-secretor carcinomas showed positivity for the monoclonal antibody K-21. Thus the type 1 precursor reacted with the non-neoplastic gastric surface of non-secretors but not with those of secretors, and also with most gastric adenocarcinoma regardless of secretor status and Lewis phenotype.

Alterations in the expression of type 1 blood group-related antigens (Lewis a and b) were examined immunohistochemically in 371 consecutives gastric biopsy and 80 surgical specimens from patients of gastric carcinoma. The ABH and Lewis phenotype and secretor status of the patients were correlated with histologic findings. An anomalous expression of Lewis a antigen was found in 88 of 249 gastric biopsy specimens of Lewis (a-b+) phenotype patients. The prevalence of this anomaly increased with the evolution of the premalignant process, in agreement with the commonly accepted model of gastric carcinogenesis. Thus, anomalous Lewis a antigen appeared in 66.6% of gastric dysplasia cases, in 64.6% of intestinal metaplasia, in 15.4% of atrophic gastritis, and in 7.4% of superficial gastritis. No alterations were found in subjects with normal gastric mucosa. Forty-seven of the 49 Lewis (a-b+) phenotype gastric carcinoma patients showed antigenic alterations in tumor cells (anomalous Lewis a antigen in 36 and loss of Lewis antigens in 11). In 26 of these gastric specimens an anomalous Lewis a antigen was present in areas of intestinal metaplasia and/or dysplasia away from the area of neoplastic transformation. The expression of Lewis a antigen in Lewis (a-b+) phenotype patients is a frequent phenomenon in gastric neoplastic cells and could result from the blocked synthesis of Lewis b antigen with accumulation of its precursors. These findings suggest that, during gastric carcinogenesis, antigenic alterations may precede neoplastic transformation. An anomalous Lewis a antigen could constitute a significant index of severity of the histologic lesion and contribute to identifying high-risk individuals.

Ten monoclonal antibodies and one lectin were used to study the localization and distribution of Blood Group ABH, type 1 chain (Lewis a, Lewis b) and type 2 chain (H-2, Y) antigens in 22 cases of normal uterine cervix, with known ABO and Lewis phenotype and secretor status. The results showed that ABH isoantigen expression is clearly related to the secretor status. It is positive in the endo- and exocervical epithelium of secretor individuals and negative in non-secretors. Lewis antigen expression in both endocervical and exocervical epithelium is related to the patient's Lewis phenotype and is clearly controlled by the secretor gene. Indeed, the expression of the Lewis a antigen is limited to the tissue of people of Lewis (a + b-) phenotype (non-secretors), and the expression of Lewis b antigen is limited to the tissue of people of Lewis a-b+) phenotype (secretors). The Y antigen showed a focal expression in endocervical mucosa in all the cases, independently of secretor status or Lewis phenotype. The same pattern was observed for H-type 2 antigen, though only in secretor individuals.

Expression of type 1 and type 2 chain Lewis antigens was studied in 32 rectal adenocarcinoma specimens; the results were correlated with the patients' Lewis phenotype and secretor status. In addition, the pattern of expression of these antigens was analyzed in adjacent and distant normal mucosa. We used an indirect immunofluorescence technique with p-phenylenediamine counterstaining (Oriol technique) and a panel of monoclonal antibodies directed against the different antigenic specificities. Normal distal colonic mucosa only expresses monofucosylated structures (Lea and X) arising from activity of the alpha 1-3,4-fucosyltransferase coded by the Le gene. Rectal adenocarcinomas also show Lea and X, but also reexpress blood group antigens ABH and exhibit difucosylated determinants (Leb and Y). The accumulation of mono- and difucosylated type 2 chain in neoplastic processes, independently of the Le and Se genes, could be due to the enzymes coded by reactivation of the H and X genes. Blood group antigens form a complex signal code, genetically regulated, which intervenes in differentiation, growth and cellular recognition processes, and which may undergo important modifications during malignant transformation. These alterations could be useful in the diagnosis and prognosis of some types of carcinoma.