Newly defined aberrant crypt foci as a marker for dysplasia in the rat colon.
Bottom Line: Specifically, decoloring of the azoxymethane-treated rat colon after scoring classical ACF (cACF) resulted in visualization of a subset of aberrant crypts that remained densely stained.Accordingly, we designated those foci harboring either of the two crypt subtypes as dysplasia-associated ACF (dACF).Consequently, integrative scoring of cACF and dACF enabled capture of all early lesions of the colon.
Affiliation: Division of Cancer Development System, National Cancer Center Research Institute, Tokyo, Japan.Show MeSH
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Mentions: The three crypt subtypes were morphologically so distinct that the right diagnosis could be made even by visual judgment. In fact, rigorous quantification of the size of both the crypt and its luminal openings for 66 randomly selected crypts gave completely concordant results (Fig. 1c). Direct comparison of the images of 71 dACF before and after decolorization revealed that 62 and 9 had been diagnosed as cACF+ve and cACF−ve, respectively (Fig. 1d). Nine newly identified cACF−ve consisted solely of d-type crypts, whereas 62 cACF+ve had various compositions of crypt subtypes. Most foci contained both cd- and c-type crypts (51/62), but some foci consisted of cd-type crypts alone (2/62), or with both c- and d-type crypts (9/62) (Figs 1d and 2a). Interestingly, cd- and d-type crypts never coexisted in the same foci, and the foci with more than two d-type crypts tended not to coexist with c-type crypts, which was not the case with c-type crypts (Fig. 1e). These observations strongly suggested that cd- and d-type crypts might have evolved independently. The SIR of the foci(29) was in fact more than 1.0 for all the stained lesions and tended to be higher in dACF than in cACF, but failed to completely distinguish between the two (Fig. S1), consistent with our previous study.(29) These observations confirmed the relevance of the size of the luminal opening, but not SIR of the foci, for the right diagnosis of dACF.
Affiliation: Division of Cancer Development System, National Cancer Center Research Institute, Tokyo, Japan.