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Newly defined aberrant crypt foci as a marker for dysplasia in the rat colon.

Ochiai M, Hippo Y, Izumiya M, Watanabe M, Nakagama H - Cancer Sci. (2014)

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.

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Affiliation: Division of Cancer Development System, National Cancer Center Research Institute, Tokyo, Japan.

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Histological features of dysplasia-associated aberrant crypt foci (dACF). (a) Representative images of dACF (left panel) and corresponding histological features with H&E (middle panel) and Alcian blue–periodic acid–Schiff (AB-PAS) (right panel) staining. A single crypt of c-type (enlarged crypt and broad opening; open arrowheads), cd-type (enlarged crypt and narrow opening; arrow), and d-type (small crypt and narrow opening; closed arrowheads) is individually indicated for classical ACF (cACF)+ve (#1–3). Classical ACF−ve consisted solely of d-type crypts (#4–6). Mucin expression was decreased in cd-type crypts (arrow) and completely depleted in d-type crypts (closed arrowheads). Accumulation of red granules indicative of Paneth cell differentiation (#4 and #5), consistent with severe dysplasia. (b–e) Comparison of cACF+ve and cACF–ve. The number of lesions with hyperplasia and dysplasia (b), and proportion of dysplastic lesions with each histological grade (c), with mucin depletion (d), and with β-catenin accumulation (e) are shown in the bar charts.
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fig02: Histological features of dysplasia-associated aberrant crypt foci (dACF). (a) Representative images of dACF (left panel) and corresponding histological features with H&E (middle panel) and Alcian blue–periodic acid–Schiff (AB-PAS) (right panel) staining. A single crypt of c-type (enlarged crypt and broad opening; open arrowheads), cd-type (enlarged crypt and narrow opening; arrow), and d-type (small crypt and narrow opening; closed arrowheads) is individually indicated for classical ACF (cACF)+ve (#1–3). Classical ACF−ve consisted solely of d-type crypts (#4–6). Mucin expression was decreased in cd-type crypts (arrow) and completely depleted in d-type crypts (closed arrowheads). Accumulation of red granules indicative of Paneth cell differentiation (#4 and #5), consistent with severe dysplasia. (b–e) Comparison of cACF+ve and cACF–ve. The number of lesions with hyperplasia and dysplasia (b), and proportion of dysplastic lesions with each histological grade (c), with mucin depletion (d), and with β-catenin accumulation (e) are shown in the bar charts.

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.


Newly defined aberrant crypt foci as a marker for dysplasia in the rat colon.

Ochiai M, Hippo Y, Izumiya M, Watanabe M, Nakagama H - Cancer Sci. (2014)

Histological features of dysplasia-associated aberrant crypt foci (dACF). (a) Representative images of dACF (left panel) and corresponding histological features with H&E (middle panel) and Alcian blue–periodic acid–Schiff (AB-PAS) (right panel) staining. A single crypt of c-type (enlarged crypt and broad opening; open arrowheads), cd-type (enlarged crypt and narrow opening; arrow), and d-type (small crypt and narrow opening; closed arrowheads) is individually indicated for classical ACF (cACF)+ve (#1–3). Classical ACF−ve consisted solely of d-type crypts (#4–6). Mucin expression was decreased in cd-type crypts (arrow) and completely depleted in d-type crypts (closed arrowheads). Accumulation of red granules indicative of Paneth cell differentiation (#4 and #5), consistent with severe dysplasia. (b–e) Comparison of cACF+ve and cACF–ve. The number of lesions with hyperplasia and dysplasia (b), and proportion of dysplastic lesions with each histological grade (c), with mucin depletion (d), and with β-catenin accumulation (e) are shown in the bar charts.
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Related In: Results  -  Collection

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fig02: Histological features of dysplasia-associated aberrant crypt foci (dACF). (a) Representative images of dACF (left panel) and corresponding histological features with H&E (middle panel) and Alcian blue–periodic acid–Schiff (AB-PAS) (right panel) staining. A single crypt of c-type (enlarged crypt and broad opening; open arrowheads), cd-type (enlarged crypt and narrow opening; arrow), and d-type (small crypt and narrow opening; closed arrowheads) is individually indicated for classical ACF (cACF)+ve (#1–3). Classical ACF−ve consisted solely of d-type crypts (#4–6). Mucin expression was decreased in cd-type crypts (arrow) and completely depleted in d-type crypts (closed arrowheads). Accumulation of red granules indicative of Paneth cell differentiation (#4 and #5), consistent with severe dysplasia. (b–e) Comparison of cACF+ve and cACF–ve. The number of lesions with hyperplasia and dysplasia (b), and proportion of dysplastic lesions with each histological grade (c), with mucin depletion (d), and with β-catenin accumulation (e) are shown in the bar charts.
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.

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.

View Article: PubMed Central - PubMed

Affiliation: Division of Cancer Development System, National Cancer Center Research Institute, Tokyo, Japan.

Show MeSH
Related in: MedlinePlus