COLORECTAL CANCER

Increased microvascular blood content is an early event in colon carcinogenesis

R K Wali^1,*, H K Roy^1,*, Y L Kim², Y Liu², J L Koetsier¹, D P Kunte¹, M J Goldberg¹, V Turzhitsky², V Backman²

¹ Department of Internal Medicine, Evanston-Northwestern Healthcare, Evanston IL 60201, USA
² Biomedical Engineering Department, Northwestern University, Evanston IL 60208, USA

Correspondence to:
Correspondence to:
Dr H K Roy
Feinberg School of Medicine at Northwestern University, Evanston Northwestern Healthcare Research Institute, 1001 University Place, Evanston IL 60201, USA; h-roy{at}northwestern.edu

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.

Conclusion: 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.

Abbreviations: ACF, aberrant crypt foci; EIBS, early increase in blood supply; 4D-ELF, four dimensional elastic light scattering fingerprinting; AOM, azoxymethane; VEGF, vascular endothelial growth factor; CRC, colorectal cancer; APC, adenomatous polyposis coli; MIN, multiple intestinal neoplasias; RBC, red blood cells

Keywords: mucosal blood; biomarker; colon carcinogenesis; four dimensional elastic light scattering fingerprinting; aberrant crypt foci

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