Angiogenesis in normal tissue adjacent to colon cancer.

Abstract

Angiogenesis in malignant neoplasms, as measured by microvessel density, has been shown to correlate with survival or stage in some studies of breast, gastric, and colorectal cancer. We hypothesized that aggressive cancers promote angiogenesis in normal tissue adjacent to the invading neoplasm. To test this hypothesis, 36 specimens of colon adenocarcinoma curatively resected between 1986 and 1990 were sectioned and stained for factor VIII-related antigen, vascular endothelial growth factor (VEGF), and interleukin-8 (IL-8). Microvessel density was measured within the colon cancer and in adjacent, histologically normal tissue. Clinical/pathological variables were examined using multivariate analysis and Student t-test. Microvessel density was higher in the neoplasms (26.0+/-1.66/ 0.25 mm2) than in the surrounding normal tissue (22.3+/-1.88/0.25 mm2) (P=0.03). The difference was primarily due to smaller neoplasms (T1 and T2) which had vessel counts of 10.6+/-0.74/0.25 mm2 in the adjacent normal tissue compared to vessel counts of 18.9+/-3.02/0.25 mm2 within these tumors (P=0.02). T3 and T4 neoplasms had equivalent amounts of angiogenesis within the lesion (26.9+/-1.81/0.25 mm2) and in the histologically normal margin (24.2+/-1.98/0.25 mm2) (P=0.12). VEGF was present in the tumor microenvironment in 100% and IL-8 in 45% of specimens stained for these angiogenic cytokines. Microvessel density did not correlate with 5-year survival. Our data suggest that colon cancers that invade through the muscularis propria may have a greater ability to induce angiogenesis in adjacent normal tissue.