VEGF significance in peritoneal recurrence from gastric cancer

Abstract

Background. In gastric cancer, the management of peritoneal dissemination in the Peritoneal cavity is extremely important; however, peritoneal dissemination in the final stage of gastric cancer remains untreatable. Peritoneal dissemination involves several steps, including tumor-cell attachment, invasion, and growth in the peritoneum. Many cytokines, growth factors, matrix metalloproteinases (MMPs), and angiogenic factors play important roles in these steps. So far, few studies have investigated the correlation, if any, between peritoneal dissemination and the angiogenic factor, vascular endothelial growth factor (VEGF). Methods. Immunohistochemical staining, using the avidin-biotin peroxidase complex method, was performed on slides of surgical specimens from 40 patients with stage II gastric cancer with serosal invasion, who underwent surgery at our hospital between 1990 and 2000. Anti-human VEGF rabbit polyclonal IgG was used as the primary antibody. VEGF expression was classified in one of four categories depending on the percentage of tumor-cell staining (P). VEGF expression was also classified in one of three categories depending on the staining intensity (I). The VEGF expression score was calculated as P x I. Results. There were ten patients with peritoneal recurrence. Of these, seven had macroscopic type-4 scirrhous-type gastric carcinoma. In the immunohistochemical study, the VEGF score of patients with peritoneal recurrence was 9.40 ± 2.46; on the other hand, that of patients without peritoneal recurrence was 3.47 ± 2.36. The VEGF score of patients with peritoneal recurrence was significantly higher than that of patients without peritoneal recurrence. In patients with macroscopic type 4, the VEGF score of those with peritoneal recurrence was 9.14 ± 2.19, while on the other hand, that of the patients without peritoneal recurrence was 3.80 ± 3.03. The VEGF score of these patients with peritoneal recurrence was significantly higher than that of those without peritoneal recurrence. The survival rate in the VEGF low-expression group was significantly higher than that in the VEGF high-expression group. Multivariate analysis showed that the VEGF score was a significant parameter of peritoneal recurrence. Conclusion. These results suggested that VEGF was correlated with peritoneal metastasis from gastric cancer, and that VEGF was a useful indicator of peritoneal recurrence. © 2005 by International and Japanese Gastric Cancer Associations.