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Spectral Markers in Preneoplastic Intestinal Mucosa: An Accurate Predictor of Tumor Risk in the MIN Mouse

¹ Department of Internal Medicine, Evanston-Northwestern Healthcare; ² Biomedical Engineering Department, Northwestern University, Evanston, Illinois

Requests for reprints: Hemant K. Roy, Feinberg School of Medicine at Northwestern University, Department of Internal Medicine, Evanston Northwestern Healthcare, 2650 Ridge Avenue, Evanston, IL 60201. Phone: 847-570-2339; Fax: 847-657-1961. E-mail: h-roy{at}northwestern.edu

Background: We have reported recently that microarchitectural analysis of the histologically normal mucosa using a novel optics technology, four-dimensional elastic light scattering fingerprinting (ELF), provided unprecedented sensitivity for early detection of colon carcinogenesis. In the present study, we explored the ability of four-dimensional ELF to identify an inherited predisposition to colorectal cancer, an issue of considerable importance for optimizing population screening strategies.

Methods: We used the MIN mouse, a model whose germ line adenomatous polyposis coli truncation leads to spontaneous intestinal tumorigenesis, thus replicating the human syndrome, familial adenomatous polyposis. Spectral markers were assessed by four-dimensional ELF analysis in MIN mice at preneoplastic time points and compared with age-matched controls (C57BL6 mice with wild-type adenomatous polyposis coli). To assess the responsiveness of spectral markers to chemopreventive agents, a subset of MIN mice was supplemented with celecoxib 1,500 ppm.

Results: Spectral slope, fractal dimension, and principal component 3 were dramatically altered in the uninvolved MIN mouse mucosa at the earliest time points. Furthermore, alteration in spectral variables increased over time, consonant with the microarchitectural underpinnings of subsequent tumorigenesis. Additionally, these markers spatially correlated with future adenoma development (small intestine > colon). Short-term treatment with the potent chemopreventive agent, celecoxib, resulted in near normalization of fractal dimension and principal component 3.

Conclusions: We report, for the first time, that spectral markers, assayed by four-dimensional ELF, were able to sensitively identify a genetic predisposition for intestinal tumorigenesis before the occurrence of phenotypic manifestations. Moreover, the reversal of spectral markers by celecoxib treatment supports the neoplastic relevance.

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