Abstract
BACKGROUND & AIMS: The acquisition of metastatic potential is accompanied by phenotypic changes. The aim of this study was to identify those changes that may lead to the development of new antimetastatic strategies in gastric cancer. METHODS: A new murine monoclonal antibody showing differential reactivity with benign and malignant gastric tissues was isolated. The expression pattern of the recognized 2B4 antigen was determined with immunohistochemistry, and the antigen was analyzed by immunoprecipitation and enzyme digestion. Its prognostic impact in gastric cancer was tested in univariate and multivariate analyses. RESULTS: In gastric mucosa, 2B4 expression was significantly reduced on mucosal glands in the presence of an inflammatory infiltrate and could be modulated in vitro by exposure to interferon alfa and gamma and phorbol esters. Twenty-eight percent of the primary gastric carcinomas showed high levels of 2B4. This correlated significantly with clinicopathological parameters of advanced disease (tumor size of > 50 mm, M1 stage, and UICC stage IIIB/IV). In multivariate analysis, high 2B4 expression was found to be a new, independent parameter of poor prognosis. The 2B4 monoclonal antibody was shown to react with the trisaccharide Gal beta 1→4(Fuc alpha 1→3)GlcNAc, i.e., Lewis(x). CONCLUSIONS: High levels of the Lewis(x)-related epitope defined by MAb 2B4 in primary gastric carcinomas is an independent parameter of poor survival. (Gastroenterology 1996 Dec;111(6):1433-46)
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