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BACKGROUND: Some patients with stage IV gastric cancer have a long survival. Host immune response and proteolytic activity in the primary tumor may be associated with outcome in these patients. The purpose of this study was to assess prognostic factors in patients with stage IV far advanced gastric cancer.METHODS: Findings in 26 patients who underwent resection of stage IV gastric cancer were retrospectively analyzed for clinicopathological variables, and for the immunohistochemical expression of human leukocyte antigen (HLA)-DR as an index of host immune response and for expression of urokinase type-plasminogen activator (u-PA) as an index of proteolytic activity in the tumor.RESULTS: Of the 13 clinicopathological and immunohistochemical variables tested by univariate analysis surgical curability, lymph node metastasis, HLA-DR expression, and u-PA expression had a significant influence on survival after surgery. Multivariate analysis showed that surgical curability, HLA-DR expression, and u-PA expression independently influenced survival. Patients positive for HLA-DR expression [HLA-DR (+)] and regative for u-PA expression [u-PA (-)] had the best survival: 25-month median survival and 25% 5-year survival rate. Patients who were HLA-DR (+) and u-PA (+), or HLA-DR (-) and u-PA (-) had a median survival of 10 months, a 1-year survival rate of 46.2%, and a 2-year survival rate of 7.7%. HLA-DR (-) and u-PA (+) patients had the worst survival: 4.5-month median survival and 0% 1-year survival.CONCLUSIONS: These findings suggest that host immune response and proteolytic activity in the primary tumor may determine malignant potential, and that the combination of positive-HLA-DR and negative-u-PA expression in cancer cells may be a predictor of prolonged survival in stage IV gastric cancer patients.

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Strain-2 guinea pigs, each with microscopic deposits of line 10 hepatocarcinoma in the liver, were treated by ID immunization with a mixture of irradiated tumor cells and an oil-in-water emulsion containing cell walls of Mycobacterium bovis strain Bacillus Calmette-Guérin (BCG CWE). Injection of line 10 hepatoma cells into the hepatic portal vein led to the development of tumor foci in the liver, metastasis in the hepatic lymph node, malignant ascites, and death. Active immunization using irradiated line 10 cells and BCG CWE was effective therapy when administered 1, 7, and 14 days after intraportal injection of line 10 cells. Effective immunization required both irradiated line 10 tumor cells and the BCG cell wall emulsion. Immunization with BCG CWE admixed with irradiated line 1 tumor cells, a hepatoma antigenically distinct from line 10, did not prevent outgrowth of line 10 deposits in the liver. Animals rendered free of disease could reject a challenge of line 10 tumor cells but not of line 1 tumor cells.