Angiogenic switch in earliest stages of human colonic tumorigenesis

Abstract

Background: Angiogenesis is activated in numerous physiological and pathological conditions. We examined whether new vessel formation exists in the earliest stages of colonic tumorigenesis.

Materials and methods: Microvascular density (MVD) was examined in 176 formalin-fixed and paraffin-embedded aberrant crypt foci (ACF) dissected from macroscopically-normal mucosa obtained from patients with colorectal cancer. ACF were classified as non-hyperplastic, non-dysplastic (NH-ACF, n = 80), hyperplastic (H-ACF, n = 72) and dysplastic (D-ACF, n = 24). Mucosal strips were stained with methylene blue solution and screened under x 40 magnification for ACF. The identified ACF were microdissected and stained with an anti-CD-34 monoclonal antibody. MVD in ACF were compared to that of normal corresponding mucosa.

Results: The mean MVD for normal mucosa and ACF were 13.7 +/- 7.7 and 23 +/- 13, respectively. Microvessel counts increased in NH-ACF versus normal mucosa (18.7 +/- 10 vs. 13.7 +/- 7.7, p = 0.05), in H-ACF versus NH-ACF (24.8 +/- 14 vs. 18.7 +/- 10, p = 0.002) and in D-ACF versus H-ACF (31.7 +/- 10 vs. 24.8 +/- 14, p = 0.014). We further evaluated the effect of low-dose aspirin on MVD in ACF. No effect of aspirin on microvessel counts could be detected.

Conclusion: Our data suggest that angiogenesis occurs in ACF which are the earliest morphologically identifiable preneoplastic and early neoplastic lesions in colonic mucosa. With progression from NH-ACF to D-ACF there is a progressive, statistically significant increase in MVD, suggesting active angiogenesis during the earliest steps of colorectal tumorigenesis.