To better elucidate the role of genetic instability in the development of gastric cancer, microsatellite alterations were examined in a total of 30 gastric cancers that developed in 14 Japanese patients with multiple gastric cancers, which are considered to have possibly occurred under the same genetic background and in the same microenvironment of the stomach. Microsatellite instability (MSI) in multiple gastric cancers was recognized in 11 out of 14 cases (78.5%) and in 16 out of 30 cancers (53.3%). Eight out of 11 cases showing MSI exhibited a heterogeneity of microsatellite alterations. The incidence of microsatellite instability in the multiple gastric cancers cases was significantly higher than that in the solitary gastric cancer cases reported previously (20.8%: 5 out of 24 cases). These results suggested that (1) genetic instability plays a more important role in the development of multiple gastric cancers than in that of solitary gastric cancer and (2) the heterogeneity of MSI in multiple gastric cancers may not be a rare event, although the significance of the heterogeneity could not be clarified.

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Lymphokine-activated killer (LAK) cell activity of peripheral blood mononuclear cells (PBM), spleen cells (SPC), regional lymph node cells (LNC), and tumor-infiltrating lymphocytes (TIL), induced by activation with interleukin 2 (IL 2) for 4 days, was evaluated in patients with gastric carcinoma. TIL exhibited the lowest LAK activity and the cytotoxicity of LNC was significantly lower than that of either PBM or SPC. There was no difference between PBM and SPC. Then, there were significant correlations of LAK activity among PBM, SPC, and LNC, whereas poor correlations were observed in the cytotoxicity between TIL and PBM, SPC, or LNC. Phenotypic analysis of each cell population was performed before and after activation with IL 2. Before culture, the cells mediating natural killer (NK) activity such as CD16+, CD56+, and CD57+ cells were few in LNC and TIL. However, CD56+ and CD57+ cells in TIL were increased after culture. Then, CD4+Leu8+ and CD8+CD11+ cells, which identify suppressor cell function, were not elevated in LNC or TIL, as compared to that in PBM or SPC. Further, the proportions of OKIa1+ and CD25+ cells expressing T-cell activation and IL 2 receptor were uniformly increased in all cell populations after culture. These results indicate the differential reactivity of each lymphocyte population to IL 2 and fundamental dysfunction of LNC and, especially TIL, suggesting the specific influence of the local tumor environment on the lymphocyte function in the area in patients with gastric carcinoma.