Expanded T cell clones and cytokines expression in human gastric carcinomas of different histological types.

OBJECTIVE: To study the characteristics of host immune response against human gastric carcinoma of different histological types. METHODS: The expression of 24 families of T cell receptor beta chain variable region (TCRVbeta) and cytokine profiles in isolated CD4(+) and CD8(+) subsets, as well as the cytokine profiles in purified epithelial cells from the tumor tissue and the residual benign tissue of patients with gastric carcinoma, was detected by a highly sensitive radioactivity labeled semi-quantitative RT-PCR technique. RESULTS: The number of expanded T cell clones in CD8(+) subset from tumor tissue of the intestinal-type carcinoma was larger than that of diffuse-type (P = 0.046). The mRNA levels of IL-6, IL-8 in CD8(+) T subset, as well as the level of TNF-alpha in CD4(+) T subset from the tumor tissue of the diffuse type (0.61 +/- 0.29, 0.56 +/- 0.22, 0.09 +/- 0.03) were significantly higher than that from the residual benign tissue (0.14 +/- 0.05, 0.27 +/- 0.09, 0.04 +/- 0.02; P = 0.028, P = 0.043, P = 0.046). However, the mRNA level of IL-8 in CD8(+) subset and epithelial tumor cells of the intestinal-type (0.57 +/- 0.25, 0.27 +/- 0.07) was significantly higher than that from the residual benign tissue (0.21 +/- 0.07, 0.14 +/- 0.06; P = 0.028, P = 0.028). CONCLUSIONS: The characteristics of host immune response against tumor are different between intestinal-type and diffuse-type gastric carcinoma. Both fewer expanded T cell clones and more suppressive cytokines suggest a more suppressive immune status in the local tumor lesion of diffuse-type than in the intestinal-type of the gastric carcinoma.

Recurrent genomic aberrations in gastric carcinomas associated with Helicobacter pylori and Epstein-Barr virus.

Helicobacter pylori and Epstein-Barr virus (EBV) both have been associated with gastric carcinoma. No specific genomic aberrations have been reported in association with these agents. We studied 20 cases of primary gastric carcinoma (including 11 positive for and 6 for EBV) by comparative genomic hybridization with validation of results by fluorescence in situ hybridization, loss of heterozygosity analysis, and immunohistochemistry. The results were analyzed in respect to presence or absence of and EBV. The tumors were also compared in terms of histologic type, tumor location, and lymph node metastases. The most frequently observed aberrations in the gastric carcinomas were gains of chromosome 19, 17, 1p, 11, 20q, and 22. The more common losses were found in 4q, 6q, 13q, and 15q. Gains in chromosome 19 and losses in 9p23-pter were found more commonly in cases with (P < 0.05). Gains in centromeric region of chromosome 19 were more common in the EBV-negative cases (P < 0.05). Immunohistochemical expression of and correlated with gains in the regions containing these genes. Gains in chromosome 11 and losses in 15q15 were more common in cases with EBV (P < 0.01 and P < 0.001, respectively). There was no significant association between any genomic aberration and histologic type, tumor location, or nodal metastases. and EBV are associated with different genomic imbalances, suggesting that these infectious agents exert different influences in the development of gastric carcinoma.

Changes of interleukin expression correlate with Helicobacter pylori infection and lymph node metastases in gastric carcinoma.

Helicobacter pylori (HP) infection induces expression of IL-8 and IL-10 in benign gastric epithelium. This study compared the expression of cytokines in CD4+ and CD8+ lymphocyte subsets of peripheral blood lymphocytes (PBL), benign mucosal lymphocytes (ML), and tumor infiltrative lymphocytes (TIL) as well as in the benign and malignant epithelial cells of the same patient, with respect to the presence of HP infection, lymph node metastases, and tumor histologic type. The mRNA of the cytokines was measured by a semiquantitative RT-PCR method. The levels were ranked and compared using the Wilcoxon sign-ranked test. Compared with CD8+ ML, the CD8+ TIL expresses higher levels of IL-6 and IL-8 but lower level of IL-4 in patients with lymph node metastases. In patients with HP infection, expression of IL-8 and IL-10 was higher in the gastric carcinoma cells than in the benign epithelial cells while expression of IL-6 and IL-8 were higher in CD8+ TIL than CD8+ ML. Overexpression of IL-8 in HP associated gastric carcinomas suggested that they might have arisen from HP-infected epithelial cells.