Angiogenic switch in earliest stages of human colonic tumorigenesis.
BACKGROUND
Angiogenesis is activated in numerous physiological and pathological conditions. We examined whether new vessel formation exists in the earliest stages of colonic tumorigenesis.


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.


CONCLUSIONS
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.
Department of Surgery, Sapir Medical Center, Meir General Hospital, Laboratory of Oncogenetics, Sapir Medical Center, Kfar Sava, Israel. shpitzca@post.tau.ac.il
Baruch
B
Shpitz
Semion
S
Gochberg
David
D
Neufeld
Mila
M
Grankin
Genadi
G
Buklan
Ehud
E
Klein
Joelle
J
Bernheim
D001241:Aspirin / Q000494:pharmacology; D003110:Colonic Neoplasms / Q000098:blood supply*; D006801:Humans; D007413:Intestinal Mucosa / Q000098:blood supply; D009389:Neovascularization, Pathologic / Q000188:drug therapy / Q000473:pathology*; D011230:Precancerous Conditions / Q000098:blood supply*
D001241:Aspirin