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.
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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