Figure 1.

Three manifestations of tissue alterations in colorectal field carcinogenesis: (A) Alterations in the extracellular matrix (ECM) include the abnormal cross-linking and alignment of collagen fibers. Both alterations are typical features found in the increasingly stiff matrix. Second-harmonic generation microscopy images of the collagen fiber network in the ECMs of a control rat (saline-treated, top panel) and an AOM-treated rat (bottom panel) illustrate the ECM alterations. (B): Increase in mucosal microvascular blood supply (EIBS). Paraffin embedded, hematoxylin and eosin (H and E) stained colon tissue sections from the pre-neoplastic AOM-treated rat (bottom panel; 14 weeks after second AOM injection) and the age-matched control rat (top panel) show increased microvessel density in the mucosa (pericryptal network) and the superficial submucosa. No histologically-detectable dysplastic alterations in tissue were noted. Necropsies confirmed lack of evidence of neoplasia. (C): Alterations in the intracellular nanoscale architture (nanoarchitecture) include changes in higher order chromatin structure (e.g., chromatin compaction) and in the cytoplasm. The top part of the panel shows the examples of representative PWS images of three rectal cells (cells (i-iii)) from a control patient with intracellular disorder strength, which is a measure of macromolecular compaction, shown in pseudocolor. The bottom part of the panel shows three examples of PWS images of histologically normal rectal cells (cells (iv-vi)) obtained from a patient with an advanced adenoma of the colon. In the latter case, the brushing was taken from a non-neoplastic, histologically normal rectal mucosa.