Field carcinogenesis is the initial stage of cancer progression. Understanding field carcinogenesis is valuable for both cancer biology and clinical medicine. Here, we used inverse spectroscopic optical coherence tomography to study colorectal cancer (CRC) and pancreatic cancer (PC) field carcinogenesis. Depth-resolved optical and ultrastructural properties of the mucosa were quantified from histologically normal rectal biopsies from patients with and without colon adenomas (n = 85) as well as from histologically normal peri-ampullary duodenal biopsies from patients with and without PC (n = 22). Changes in the epithelium and stroma in CRC field carcinogenesis were separately quantified. In both compartments, optical and ultra-structural alterations were consistent. Optical alterations included lower backscattering (μb) and reduced scattering (μsI) coefficients and higher anisotropy factor g. Ultrastructurally pronounced alterations were observed at length scales up to ∼450 nm, with the shape of the mass density correlation function having a higher shape factor D, thus implying a shift to larger length scales. Similar alterations were found in the PC field carcinogenesis despite the difference in genetic pathways and etiologies. We further verified that the chromatin clumping in epithelial cells and collagen cross-linking caused D to increase in vitro and could be among the mechanisms responsible for the observed changes in epithelium and stroma, respectively.
Bibliographical noteFunding Information:
The authors would like to acknowledge the grant support from both the National Institutes of Health (R01CA128641, R01CA165309, and R01CA156186) and the National Science Foundation (CBET-1240416). A. J. Radosevich is supported by a National Science Foundation Graduate Research Fellowship under Grant No. DGE-0824162. The author also would like to thank Benjamin Keane and Andrew Gomes for their help on the manuscript editing.
Copyright 2014 Elsevier B.V., All rights reserved.
- Field carcinogenesis
- Optical properties