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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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Serial scoring of multiple preneoplastic lesions on the same colon. (a) A schematic diagram of the serial detection of multiple preneoplastic lesions. The images of mucosal surfaces were captured at the end of each step (arrows) for comparison at a later time point. (b) Colons were cut open longitudinally and separated into four segments (I–IV). (c) Bar chart showing the number of preneoplastic lesions per segment. #1–3 corresponds to the colons of three individual F344 male rats. Note that dysplasia-associated aberrant crypt foci (dACF), flat ACF (fACF), and mucin-depleted foci (MDF) are more enriched in segments III and IV compared to classical ACF (cACF). (d) Venn diagram for the number of cACF, dACF, and fACF/MDF for each rat.
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fig03: Serial scoring of multiple preneoplastic lesions on the same colon. (a) A schematic diagram of the serial detection of multiple preneoplastic lesions. The images of mucosal surfaces were captured at the end of each step (arrows) for comparison at a later time point. (b) Colons were cut open longitudinally and separated into four segments (I–IV). (c) Bar chart showing the number of preneoplastic lesions per segment. #1–3 corresponds to the colons of three individual F344 male rats. Note that dysplasia-associated aberrant crypt foci (dACF), flat ACF (fACF), and mucin-depleted foci (MDF) are more enriched in segments III and IV compared to classical ACF (cACF). (d) Venn diagram for the number of cACF, dACF, and fACF/MDF for each rat.

Mentions: To relate dACF to other known preneoplastic lesions, the colons from three AOM-treated rats were serially stained to detect these lesions, and images of the same foci were directly compared (Fig. 3a). Staining with AB visualized four to five MDF per rat exclusively in the distal colon (Fig. 3b), as previously reported.(9,21) Subsequent brief exposure to MB visualized fACF, which completely coincided with MDF in a total of 14 lesions from three rats (Fig. 3c). By longer exposure to MB and subsequent destaining, 200–300/rat cACF and ˜120/rat dACF were visualized (Fig. 3c). Dysplasia-associated ACF tended to be in the more distal colon than cACF, in line with the dysplastic nature of dACF. Approximately 100 and 20 dACF were diagnosed as cACF+ve and cACF−ve, respectively (Fig. 3d), consistent with our pilot experiment. Taken together, dACF had a significant overlap with cACF and contained an entire population of MDF and fACF. Representative cases are shown in Figure 4; dACF-1 is cACF+ve (Fig. 4a–e) and dACF-2,3,4 are cACF−ve (Fig. 4f–q). Unlike dACF, all the other lesions were not constantly positive for these four foci. Of note, dACF-2 could be detected only as dACF, strongly suggesting higher sensitivity of dACF for dysplasia.


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)

Serial scoring of multiple preneoplastic lesions on the same colon. (a) A schematic diagram of the serial detection of multiple preneoplastic lesions. The images of mucosal surfaces were captured at the end of each step (arrows) for comparison at a later time point. (b) Colons were cut open longitudinally and separated into four segments (I–IV). (c) Bar chart showing the number of preneoplastic lesions per segment. #1–3 corresponds to the colons of three individual F344 male rats. Note that dysplasia-associated aberrant crypt foci (dACF), flat ACF (fACF), and mucin-depleted foci (MDF) are more enriched in segments III and IV compared to classical ACF (cACF). (d) Venn diagram for the number of cACF, dACF, and fACF/MDF for each rat.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4317850&req=5

fig03: Serial scoring of multiple preneoplastic lesions on the same colon. (a) A schematic diagram of the serial detection of multiple preneoplastic lesions. The images of mucosal surfaces were captured at the end of each step (arrows) for comparison at a later time point. (b) Colons were cut open longitudinally and separated into four segments (I–IV). (c) Bar chart showing the number of preneoplastic lesions per segment. #1–3 corresponds to the colons of three individual F344 male rats. Note that dysplasia-associated aberrant crypt foci (dACF), flat ACF (fACF), and mucin-depleted foci (MDF) are more enriched in segments III and IV compared to classical ACF (cACF). (d) Venn diagram for the number of cACF, dACF, and fACF/MDF for each rat.
Mentions: To relate dACF to other known preneoplastic lesions, the colons from three AOM-treated rats were serially stained to detect these lesions, and images of the same foci were directly compared (Fig. 3a). Staining with AB visualized four to five MDF per rat exclusively in the distal colon (Fig. 3b), as previously reported.(9,21) Subsequent brief exposure to MB visualized fACF, which completely coincided with MDF in a total of 14 lesions from three rats (Fig. 3c). By longer exposure to MB and subsequent destaining, 200–300/rat cACF and ˜120/rat dACF were visualized (Fig. 3c). Dysplasia-associated ACF tended to be in the more distal colon than cACF, in line with the dysplastic nature of dACF. Approximately 100 and 20 dACF were diagnosed as cACF+ve and cACF−ve, respectively (Fig. 3d), consistent with our pilot experiment. Taken together, dACF had a significant overlap with cACF and contained an entire population of MDF and fACF. Representative cases are shown in Figure 4; dACF-1 is cACF+ve (Fig. 4a–e) and dACF-2,3,4 are cACF−ve (Fig. 4f–q). Unlike dACF, all the other lesions were not constantly positive for these four foci. Of note, dACF-2 could be detected only as dACF, strongly suggesting higher sensitivity of dACF for dysplasia.

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