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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.

View Article: PubMed Central - PubMed

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

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Crypt-based characterization of azoxymethane-induced dysplasia-associated aberrant crypt foci (dACF). (a) Typical images of the three crypt subtypes (closed arrowheads) constituting dACF: c-type, enlarged crypt and broad opening; cd-type, enlarged crypt and narrow opening; and d-type, small crypt and narrow opening. Each arrowhead points to a single crypt. Note that normal crypts in surrounding mucosa (open arrowheads) could serve as a reference with a diameter of approximately 30 μm. (b) Schematic view of the crypt subtypes. A ring-shaped image represents the morphology of epithelial lining. Dashed lines indicate invisible status. (c) Classification of aberrant crypts by objective and subjective methods. Note that visual judgment and strict quantification gave completely concordant results for randomly selected crypts (n = 66). r, internal diameter of aberrant crypts; R, external diameter of aberrant crypts; RN, external diameter of normal crypts. (d) Venn diagram for classical ACF (cACF) and dACF. Dysplasia-associated ACF (shaded box) was divided into two subgroups, cACF+ve and cACF−ve, depending on the presence of overlap with cACF (open box). Composition of crypt subtype in stained foci is indicated in parenthesis. (e) Breakdown of crypt subtypes within stained foci. Each axis of the bar chart depicts the number of aberrant foci, c-type crypt and d- or cd-type crypt.
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fig01: Crypt-based characterization of azoxymethane-induced dysplasia-associated aberrant crypt foci (dACF). (a) Typical images of the three crypt subtypes (closed arrowheads) constituting dACF: c-type, enlarged crypt and broad opening; cd-type, enlarged crypt and narrow opening; and d-type, small crypt and narrow opening. Each arrowhead points to a single crypt. Note that normal crypts in surrounding mucosa (open arrowheads) could serve as a reference with a diameter of approximately 30 μm. (b) Schematic view of the crypt subtypes. A ring-shaped image represents the morphology of epithelial lining. Dashed lines indicate invisible status. (c) Classification of aberrant crypts by objective and subjective methods. Note that visual judgment and strict quantification gave completely concordant results for randomly selected crypts (n = 66). r, internal diameter of aberrant crypts; R, external diameter of aberrant crypts; RN, external diameter of normal crypts. (d) Venn diagram for classical ACF (cACF) and dACF. Dysplasia-associated ACF (shaded box) was divided into two subgroups, cACF+ve and cACF−ve, depending on the presence of overlap with cACF (open box). Composition of crypt subtype in stained foci is indicated in parenthesis. (e) Breakdown of crypt subtypes within stained foci. Each axis of the bar chart depicts the number of aberrant foci, c-type crypt and d- or cd-type crypt.

Mentions: We previously showed that more accurate detection of dysplasia might be achieved by destaining of cACF, although with laborious procedures, and found that the narrow opening might suggest the dysplastic nature of the foci.(29) We then hypothesized that stained foci harboring crypts with narrow opening, or dACF as tentatively designated, might be equivalent to dysplasia. To address this issue, we examined a rat colon treated with AOM. Starting with examining 161 induced cACF, we noted that decoloring gave rise to three morphologically distinct subtypes of stained crypts (Fig. 1a). We designated enlarged crypts with large openings, and small crypts with narrow openings as c-type and d-type, respectively, to emphasize specific features of cACF and dACF (Fig. 1B). Accordingly, enlarged crypts with narrow openings were designated as cd-type. Normal crypts and a subset of crypts within cACF turned invisible after decoloring. We designated the latter as h-type crypts (Fig. 1B), as such crypts constituted hyperplasia.(29) Thus, various types of crypts were differentially visualized through decoloring. We now redefined dACF as foci harboring at least single d- or cd-type crypt.


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)

Crypt-based characterization of azoxymethane-induced dysplasia-associated aberrant crypt foci (dACF). (a) Typical images of the three crypt subtypes (closed arrowheads) constituting dACF: c-type, enlarged crypt and broad opening; cd-type, enlarged crypt and narrow opening; and d-type, small crypt and narrow opening. Each arrowhead points to a single crypt. Note that normal crypts in surrounding mucosa (open arrowheads) could serve as a reference with a diameter of approximately 30 μm. (b) Schematic view of the crypt subtypes. A ring-shaped image represents the morphology of epithelial lining. Dashed lines indicate invisible status. (c) Classification of aberrant crypts by objective and subjective methods. Note that visual judgment and strict quantification gave completely concordant results for randomly selected crypts (n = 66). r, internal diameter of aberrant crypts; R, external diameter of aberrant crypts; RN, external diameter of normal crypts. (d) Venn diagram for classical ACF (cACF) and dACF. Dysplasia-associated ACF (shaded box) was divided into two subgroups, cACF+ve and cACF−ve, depending on the presence of overlap with cACF (open box). Composition of crypt subtype in stained foci is indicated in parenthesis. (e) Breakdown of crypt subtypes within stained foci. Each axis of the bar chart depicts the number of aberrant foci, c-type crypt and d- or cd-type crypt.
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Related In: Results  -  Collection

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fig01: Crypt-based characterization of azoxymethane-induced dysplasia-associated aberrant crypt foci (dACF). (a) Typical images of the three crypt subtypes (closed arrowheads) constituting dACF: c-type, enlarged crypt and broad opening; cd-type, enlarged crypt and narrow opening; and d-type, small crypt and narrow opening. Each arrowhead points to a single crypt. Note that normal crypts in surrounding mucosa (open arrowheads) could serve as a reference with a diameter of approximately 30 μm. (b) Schematic view of the crypt subtypes. A ring-shaped image represents the morphology of epithelial lining. Dashed lines indicate invisible status. (c) Classification of aberrant crypts by objective and subjective methods. Note that visual judgment and strict quantification gave completely concordant results for randomly selected crypts (n = 66). r, internal diameter of aberrant crypts; R, external diameter of aberrant crypts; RN, external diameter of normal crypts. (d) Venn diagram for classical ACF (cACF) and dACF. Dysplasia-associated ACF (shaded box) was divided into two subgroups, cACF+ve and cACF−ve, depending on the presence of overlap with cACF (open box). Composition of crypt subtype in stained foci is indicated in parenthesis. (e) Breakdown of crypt subtypes within stained foci. Each axis of the bar chart depicts the number of aberrant foci, c-type crypt and d- or cd-type crypt.
Mentions: We previously showed that more accurate detection of dysplasia might be achieved by destaining of cACF, although with laborious procedures, and found that the narrow opening might suggest the dysplastic nature of the foci.(29) We then hypothesized that stained foci harboring crypts with narrow opening, or dACF as tentatively designated, might be equivalent to dysplasia. To address this issue, we examined a rat colon treated with AOM. Starting with examining 161 induced cACF, we noted that decoloring gave rise to three morphologically distinct subtypes of stained crypts (Fig. 1a). We designated enlarged crypts with large openings, and small crypts with narrow openings as c-type and d-type, respectively, to emphasize specific features of cACF and dACF (Fig. 1B). Accordingly, enlarged crypts with narrow openings were designated as cd-type. Normal crypts and a subset of crypts within cACF turned invisible after decoloring. We designated the latter as h-type crypts (Fig. 1B), as such crypts constituted hyperplasia.(29) Thus, various types of crypts were differentially visualized through decoloring. We now redefined dACF as foci harboring at least single d- or cd-type crypt.

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