Spectral markers in preneoplastic intestinal mucosa: an accurate predictor of tumor risk in the MIN mouse.
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.
Roy
Hemant K
HK
Feinberg School of Medicine at Northwestern University, Department of Internal Medicine, Evanston Northwestern Healthcare, 2650 Ridge Avenue, Evanston, IL 60201, USA. h-roy@northwestern.edu
Kim
Young L
YL
Wali
Ramesh K
RK
Liu
Yang
Y
Koetsier
Jennifer
J
Kunte
Dhananjay P
DP
Goldberg
Michael J
MJ
Backman
Vadim
V
D000818:Animals; D000068579:Celecoxib; D003110:Colonic Neoplasms / Q000175:diagnosis* / Q000517:prevention & control; D016861:Cyclooxygenase Inhibitors / Q000627:therapeutic use; D007413:Intestinal Mucosa / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D011237:Predictive Value of Tests; D011720:Pyrazoles / Q000627:therapeutic use; D013449:Sulfonamides / Q000627:therapeutic use
D016861:Cyclooxygenase Inhibitors; D011720:Pyrazoles; D013449:Sulfonamides; D000068579:Celecoxib