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Background Dendritic cells (DCs) are potent antigenpresenting cells that are central to the regulation, maturation, and maintenance of the cellular immune response against cancer. In contrast, CD4? CD25 ? regulatory T cells (Tregs) play a central role in self-tolerance and suppress antitumor immunity. In this study, we investigated the clinical significance of mature CD83? DCs and Foxp3 ?Tregs in the primary tumor and regional lymph nodes from the viewpoint of the two opposing players in the immune responses.Methods We investigated, immunohistochemically, the density of CD83 ? DCs and Foxp3 ? Tregs in primary lesions of gastric cancer (n = 123), as well as in regional lymph nodes with (n = 40) or without metastasis (n = 40). Results Decreased density of CD83? DCs and increased density of Foxp3? Tregs were observed in the primary tumor and metastatic lymph nodes. Density was significantly correlated with certain clinicopathological features. Poor prognosis was observed in patients with a low density of CD83? DCs and a high density of Foxp3 ? Tregs in primary lesions. For patients with metastatic lymph nodes, the density of CD83? DCs in negative lymph nodes was found to be an independent prognostic factor by multivariate analysis. Conclusion The density of CD83? DCs and Foxp3 ?Tregs was inversely correlated with tumor progression and reflected the prognosis of gastric cancer.

The incidence of disseminated cancer cells in bone marrow in our study appears low, unlike that in previous reports. The significance of disseminated cancer cells in bone marrow may also be quite low in gastric cancer.

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Immunosuppressive acidic protein (IAP) suppresses several immune responses in vivo and in vitro , and high preoperative IAP levels could predict the impairment of the host's immunity. In this study prognostic significance of preoperative IAP levels was investigated in 68 esophageal cancer patients with curative resection and eight with non-curative resection. The curative group had significantly lower levels than the non-curative group (432 +/- 183 mg/mL vs. 739 +/- 235 mg/mL, P < 0.0001). The IAP levels were associated with T-status (P < 0.0001), lymphatic invasion (P < 0.05), and p-stages (P < 0.0001). When 5-year survival rate of patients with curative resection was compared by setting various cutoff values of IAP between high and low IAP groups, several cutoff points (400-580 mg/mL) were revealed to be significantly associated with survival. Setting cutoff value of IAP to 560 mg/mL resulted in a most significant difference of 5-year survival rate of patients between the high and low IAP groups (13.9% and 61.5%, P < 0.0001). These data indicate that pre-operative IAP level is a useful parameter to predict the prognosis of esophageal cancer patients after curative resection.

15000 Background: A tight junction is one of components of intercellular junctional complexes and play an important role in maintaining barrier function and cellular porlarity. Claudin, occluding, and ZO-1 are known as trans-membrane proteins which compose tight junction. Roles of these tight junction-associated proteins of gastric cancer is not yet determined. In this study, we investigated expression levels of these proteins in gastric cancer immunohistochemically and compared the results with clinicopathological features of the tumors and patient prognosis. Methods: One hundred and twenty-four gastric cancer patients underwent gastrectomy between 2000 and 2004 were included in this study. Formalin fixed and parafine embedded tissues were sliced into 4-μm sections and immunohistchemistry was performed using anti-claudin-4, anti-occluding and anti-ZO-1 antibodies. Stained slides were investigated and the incidence of positive cells was graded as: 0, negative; 1, < 20 %; 2, 20–80 %; 3, >80 %. Results: The expression of claudin-4, occludin, and ZO-1 was observed at the membrane, and the positivity rates in cancer tissues were 87.1%, 95.2% and 100%, respectively. In concerning with correlation between protein expression and clinicopathologic features, claudin-4 expression was significantly decreased in tumors with undifferentiated type adenocarcinoma (p<0.001), advanced T stage (p=0.0022), lymph node metastasis (p<0.001), and peritoneal metastasis (p<0.001). However, there was no significant correlation between the expression of occluding and ZO-1 and clinicopathological features. Survival time was significantly shorter in patients with reduced claudin-4 expression (p=0.0018). Cox’s multivariate analysis revealed that claudin-4 was selected as an independent prognostic factor as well as histological type and peritoneal metastasis. Conclusions: Tight junction associated proteins, especially claudin-4, appears to play an important role on tumor progression, invasion, and metastasis and correlate with poor prognosis in patients with gastric cancer. No significant financial relationships to disclose.

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13034 Background: We have previously reported that tumors with high orotate phosphoribosil transferase (OPRT) and low dihydropyrimidine dehydrogenase (DPD) mRNA expression levels showed remarkable sensitivity to 5-fluorouracil (5-FU) by real-time RT-PCR using fresh frozen (FF) tumor samples. However, the use of fresh frozen samples has some limitations. The use of formalin fixed parafine embedded (FFPE) samples has great advantage to apply these technologies for clinical settings. In order to investigate the feasibility of real-time RT-PCR from FFPE samples to predict sensitivitiy to 5-fluorouracil (5-FU), we investigated the gene expression levels of 5-FU metabolism-relating enzymes by real-time RT-PCR from FFPE samples and compared the results from FF samples in gastric and colorectal cancer. Methods: FFPE samples and FF samples were obtained from 46 patients with gastric cancer and 29 patients with colorectal cancer. Gene expression levels of tymidylate synthase (TS), OPRT, thymidine phosphorylase (TP) and DPD were determined by quantitative real-time RT-PCR. In FFPE samples tumor tissue was obtained using laser captured microdissection (LCM). Tumor sensitivity to 5-FU was evaluated by in vitro ATP assay. Results: Gene expression levels of TS, TP, DPD determined from FFPE samples significantly correlated with those from FF samples. Although respective gene expression levels alone failed to show signifcianct correlation with the in vitro 5-FU sensitivity, statistically significant correlation was noted either from the samples of FF or FFPE in both gastric (FF: r = 0.660, FFPE: r = 0.780) and colorectal cancer (FF: r = 0.780, FFPE: r = 0.660), when OPRT/DPD mRNA ratio was applied for comparison with the results of 5-FU sensitivity. Thus, high OPRT/DPD ratio determined from FFPE samples resulted in high sensitivity to 5-FU. Conclusions: From these results, it is suggested that sensitivity to 5-FU is predictable by quantitative RT-PCR using FFPE samples. Measurement of 5-FU metabolism-relating enzyme gene expression level from FFPE samples appeared to be feasible for predicting 5-FU sensitivity and to have great advantage to apply the molecular predicting assay in clinical settings. [Table: see text]