Detection and Characterization of Flat Aberrant Crypt Foci (Flat ACF) in the Novel A/J Min/ plus Mouse

Background/Aim: Flat aberrant crypt foci (flat ACF) and mucin-depleted foci (MDF) have previously been described as preneoplastic colonic lesions. We used the novel A/J Min/+ mouse model, that demonstrates extensive spontaneous colon carcinogenesis to refine the method of detection of flat ACF and further characterize and define them as early lesions by histological examination and comparison with MDF. Materials and Methods: Colons were stained with methylene blue (MB) for flat ACF detection and restained with high-iron diamine-alcian blue (HID-AB) for MDF detection. Results: Optimal flat ACF recognition required at least 24 h of storage post-MB staining and adherence to a set of characteristics. The fraction of flat ACF corresponding with MDF was 93%. Flat ACF/MDF displayed the same picture of severe dysplasia, lack of mucus and goblet cells and accumulation of cytoplasmic beta-catenin. Conclusion: The easily detectable flat ACF are reliable surface biomarkers of Apc-driven colon carcinogenesis.