Overexpression of vascular endothelial growth factor is responsible for the hematogenous recurrence of early-stage gastric carcinoma

Abstract

Vascular endothelial growth factor (VEGF) is crucial for angiogenesis in various malignant tumors. However, it is still unclear whether VEGF is responsible for hematogenous metastasis after the curative resection of gastric carcinoma. In the present study, we evaluated the relevance of VEGF expression to the hematogenous recurrence of stage 1 or 2 primary gastric adenocarcinoma. Among 530 patients, 11 (2.1%) had hematogenous recurrence. Clinicopathological variables were compared between these 11 patients (group R) and 88 patients without intramucosal carcinoma who survived for more than 5 years (group S). Microvessel density (MVD) was assessed immunohistochemically along with VEGF protein expression in all patients from group R and 21 randomly selected patients from group S. There were significant differences in age, tumor size and VEGF expression in tumor tissue between the groups. Positive staining for VEGF protein was observed in all patients of group R, of whom 6 had strongly positive staining. On the other hand, 11 out of 21 patients in group S had positive staining and it was weak in all cases. Both the positive and strongly positive rate were significantly higher in group R than those in group S. There was no significant difference in MVD between the 2 groups (17.7 +/- 11.09/field in group R vs. 14.8 +/- 10. 27/field in group S) and no significant correlation between VEGF expression, MVD and venous invasion, though a weak correlation between the intensity of VEGF staining and MVD was observed (negative staining 12.1 +/- 10.51; weakly positive 16.67 +/- 10.41; strongly positive 19.7 +/- 9.97). Our results suggest that overexpression of VEGF, and not MVD or venous invasion, plays an important role in the hematogenous recurrence of curatively resected gastric carcinoma.