Relationships Between Local and Systemic Expression of Interleukin-12 and Plasma Levels of Vascular Endothelial Growth Factor in Patients with Gastric Cancer

Background: Interleukin 12 (IL-12) is a heterodimeric cytokine that exhibits potent anti-tumor and anti-metastatic activities. Very few studies have investigated the expression of IL-12 in patients with gastric cancer. The purpose of the present study was to evaluate the immunohistochemical expression and serum levels of IL-12, and plasma levels of vascular endothelial growth factor (VEGF) in patients with gastric cancer. Patients and Methods: IL-12 was immunohistochemically stained using monoclonal anti-human IL-12 antibody (1-1A4) in surgical specimens of 27 gastric cancer patients. IL-12-positive cells were counted and positive cell density was calculated. Blood was obtained before surgery. Serum levels of IL-12 and plasma levels of VEGF were assessed using the quantitative sandwich enzyme immunoassay technique. The relationships of IL-12-positive cell density, serum levels of IL-12, plasma levels of vascular endothelial growth factor (VEGF) and clinicopathological factors were evaluated. Results: Although IL-12-positive cell density was not associated with serum levels of IL-12, the IL-12-positive cell density tended to increase in patients with serum levels of IL-12 higher than the mean level (p=0.0518). IL-12-positive cell density significantly decreased in the patients with CEA positive or differentiated type. Moreover, IL-12-positive cell density tended to be inversely correlated with plasma levels of VEGF (p=0.0801, r=-0.343). Conclusion: These results suggest that the immune efficiency in patients with gastric cancer may be reflected by IL-12-positive cell density and serum levels of IL-12. Thus, patients with low IL-12-positive cell density or serum levels of IL-12 in gastric cancer may require additional immunochemotherapy after surgery.