DIFFERENTIAL EXPRESSION OF APOPTOSIS RECEPTORS ON DIFFUSE AND INTESTINAL-TYPE STOMACH CARCINOMA

BACKGROUND. Intestinal and diffuse adenocarcinomas of the stomach diff er in phenotypic properties, morphology, and growth behavior. Apoptosi s (programmed cell death) is induced via specific cell-surface recepto rs (SC-1, Fas/APO-1/CD95) and coregulated by intracellular molecules ( bcl-2, p53, etc.); the success of apoptotic processes is dependent on the expression of these signals. Differences in tile expression of spe cific apoptosis receptors and intracellular-related signals might help to explain the molecular pathogenesis of these two types of stomach a denocarcinoma. METHODS, Immunohistochemical studies were performed on frozen sections of tumor tissue using human monoclonal antibody SC-1 a nd murine monoclonal antibodies Fas and p53, followed by peroxidase-co upled second antibodies. To determine binding of SC-1 and Fas antibodi es to stomach carcinoma cells on the molecular level, Western blot ana lysis was performed with cell extract preparations from stomach carcin oma cells. To investigate functional apoptotic activity, MTT assays we re performed with SC-1 and Fas antibodies on stomach carcinoma cells. RESULTS, On frozen sections intestinal type stomach carcinoma cells de monstrate little or no expression of SC-1 and Fas receptors (4 of 17 a nd 1 of 17, respectively). Diffuse type stomach carcinoma cells show j ust the opposite: greater than 50% express SC-1 and Fas at a high leve l (15 of 30 and 22 of 30, respectively). Normal stomach mucosa is nega tive with both antibodies. Expression of p53 is positively correlated with intestinal type carcinomas (11 of 17) but not with diffuse type ( 5 of 30). In functional studies (MTT assay) the SC-1 and Fas antibodie s react with stomach carcinoma by inducing apoptosis and inhibiting gr owth. On Western blot analysis of extracts from stomach carcinoma cell s, SC-1 detects a protein of 50 kilodalton (kD) and Fas proteins of ap proximately 30, 45, and 60 kD. CONCLUSIONS, These data indicate that g astric carcinoma cells of the intestinal and diffuse type differ in th eir expression of the apoptotic receptors SC-1 and Fas and the tumor s uppressor gene product p53. These new data on phenotypic differences s upport the hypothesis that these two types of stomach carcinoma do not only differ in morphology, growth pattern, and risk factors but also in genetic pathways. (C) 1997 American Cancer Society.