Background and Objectives: 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.
Methods: To test this hypothesis, 36 specimens of colon adenocarcinoma cura
tively resected between 1986 and 1990 were sectioned and stained for factor
VIII-related antigen, vascular endothelial growth factor (VEGF;), and inte
rleukin-8 (IL-8). Microvessel density was measured within the colon cancer
and in adjacent, histologically normal tissue. Clinical/pathological variab
les were examined using multivariate analysis and Student t-test.
Results: Microvessel density was higher in the neoplasms (26.0 +/- 1.66/ 0.
25 mm(2)) than in the surrounding normal tissue (22.3 +/- 1.88/0.25 mm(2))
(P = 0.03). The difference was primarily due to smaller neoplasms (T1 and T
2) which had vessel counts of 10.6 +/- 0.74/0.25 mm(2) in the adjacent norm
al tissue compared to vessel counts of 18.9 +/- 3.02/0.25 mm(2) within thes
e tumors (P = 0.02). T3 and T3 neoplasms had equivalent amounts of angiogen
esis within the lesion (26.9 +/- 1.81/0.25 mm(2)) and in the histologically
normal margin (24.2 +/- 1.98/0.25 mm(2)) (P = 0.12). VEGF was present in t
he tumor microenvironment in 100% and IL-8 in 45% of specimens stained for
these angiogenic cytokines. Microvessel density did not correlate with 5-ye
ar survival.
Conclusions: Our data suggest that colon cancers that invade through the mu
scularis propria may have a greater ability to induce angiogenesis in adjac
ent normal tissue. (C) 1998 Wiley-Liss, Inc.