Increased microvascular blood content is an early event in colon carcinogenesis.
BACKGROUND
Increased premalignant epithelial microvascular blood content is a common theme in neoplastic transformation; however, demonstration of this phenomenon in colon carcinogenesis has been stymied by methodological limitations. Our group has recently developed a novel optics technology, four dimensional elastic light scattering fingerprinting (4D-ELF), which allows examination of the colonic mucosal architecture with unprecedented accuracy. In this study, we utilised 4D-ELF to probe the preneoplastic colonic microvasculature.


METHODS
Colonic mucosal blood content was assessed by 4D-ELF at serial preneoplastic time points from azoxymethane (AOM) treated Fisher 344 rats and age matched control animals. We also examined the pretumorigenic intestinal mucosa of the MIN mouse, and compared with wild-type mice. Finally, in a pilot study, we examined superficial blood content from the endoscopically normal mid transverse colon in 37 patients undergoing screening colonoscopy.


RESULTS
In the AOM treated rat model, augmentation of superficial mucosal and total mucosal/superficial submucosal blood supply preceded the appearance of aberrant crypt foci (ACF) and temporally and spatially correlated with future ACF occurrence. These findings were replicated in MIN mice. The 4D-ELF based results were corroborated with immunoblot analysis for haemoglobin on mucosal scrapings from AOM treated rats. Moreover, 4D-ELF analysis of normal human colonic mucosa indicated that there was a threefold increase in superficial blood in patients who harboured advanced adenomas.


CONCLUSIONS
We report, for the first time, that blood content is increased in the colonic microvasculature at the earliest stages of colon carcinogenesis. These findings may provide novel insights into early biological events in colorectal carcinogenesis and have potential applicability for screening.
Wali
R K
RK
Department of Internal Medicine, Evanston-Northwestern Healthcare, Evanston, IL 60201, USA.
Roy
H K
HK
Kim
Y L
YL
Liu
Y
Y
Koetsier
J L
JL
Kunte
D P
DP
Goldberg
M J
MJ
Turzhitsky
V
V
Backman
V
V
D000236:Adenoma / Q000098:blood supply; D000818:Animals; D001397:Azoxymethane; D002471:Cell Transformation, Neoplastic / Q000473:pathology*; D003106:Colon / Q000098:blood supply*; D003110:Colonic Neoplasms / Q000098:blood supply* / Q000139:chemically induced; D004195:Disease Models, Animal; D018450:Disease Progression; D006454:Hemoglobins / Q000378:metabolism; D006801:Humans; D007413:Intestinal Mucosa / Q000098:blood supply; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008833:Microcirculation; D055095:Optics and Photonics; D010865:Pilot Projects; D011230:Precancerous Conditions / Q000098:blood supply*; D051381:Rats; D011916:Rats, Inbred F344; D012542:Scattering, Radiation
D006454:Hemoglobins; D001397:Azoxymethane