Angiogenic Switch in Earliest Stages of Human Colonic Tumorigenesis

Baruch Shpitz, Semion Gochberg, David Neufeld, Mila Grankin, Genadi Buklan, Ehud Klein, Joelle Bernheim

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)5153-5157
Number of pages5
JournalAnticancer Research
Volume23
Issue number6 D
StatePublished - Nov 2003

Keywords

  • Aberrant crypt foci
  • Angiogenesis
  • Colorectal carcinogenesis
  • Precursor

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