Lewis system alterations in gastric carcinogenesis

Abstract

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. Fortyseven 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.

Pathogenesis of the transformation from gastritis to malignancy

“…This is demonstrated, for example, by the occurrence of abnormal synthesis of mucus glycoproteins [Lewis blood groups, Ca 19-9, sialyl Le(x)], and unexpected expression of abnormal gene products (K-ras) in gastritic stomach or intestinal metaplasia without any evidence of coexist, overt precancerous lesions, such as dysplasia or adenoma. [5][6][7][8][9][10][11] It seems plausible that an array of various genotoxic affections are triggered by the H. pylori gastritis, and that the resulting gene errors may play a role as effector mechanisms modulating the further course and outcomes of the H. pylori acquisition. Correspondingly, it is possible that even atrophic gastritis may result from unknown mutations in epithelial cell genes and may, thereby, stem from an imbalance between abnormal proliferation and death (apoptosis) of the epithelial cells.…”

Terminal α1,4-linked N-acetylglucosamine in Helicobacter pylori-associated Intestinal Metaplasia of the Human Stomach and Gastric Carcinoma Cell Lines

“…Development of IM in the stomach is characterized by extensive modifications in the profile of mucins ) and mucin-glycosylation (Torrado et al 1990;Mullen et al 1995;Silva et al 2002;Bodger et al 2003). In the present study we characterized the expression of mucins MUC1, MUC2, MUC5AC, MUC5B, and MUC6 using specific MAbs.…”

Type III intestinal metaplasia and carcinoma express an identical carbohydrate‐epitope revealed by a novel monoclonal antibody (2D11)

“…3c); however, there was no such relation in the carcinomas and fetal intestine examined, indicating that carbohydrate antigen defined by 2D11 is not carried on sulfomucin. Aberrant expression of various carbohydrate antigens, Thomsen-Friedenreich antigen, 10,11 Lewis antigens 12,13 and sulfo-Lewis antigens 14,15 in intestinal metaplastic mucosa have been reported. None of them, however, were specific for the Type III intestinal metaplastic mucosa.…”