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Review
. 2020 Mar;13(3):229-240.
doi: 10.1158/1940-6207.CAPR-19-0316.

Dysplastic Aberrant Crypt Foci: Biomarkers of Early Colorectal Neoplasia and Response to Preventive Intervention

Affiliations
Review

Dysplastic Aberrant Crypt Foci: Biomarkers of Early Colorectal Neoplasia and Response to Preventive Intervention

Margie L Clapper et al. Cancer Prev Res (Phila). 2020 Mar.

Abstract

The discovery of aberrant crypt foci (ACF) more than three decades ago not only enhanced our understanding of how colorectal tumors form, but provided new opportunities to detect lesions prior to adenoma development and intervene in the colorectal carcinogenesis process even earlier. Because not all ACF progress to neoplasia, it is important to stratify these lesions based on the presence of dysplasia and establish early detection methods and interventions that specifically target dysplastic ACF (microadenomas). Significant progress has been made in characterizing the morphology and genetics of dysplastic ACF in both preclinical models and humans. Image-based methods have been established and new techniques that utilize bioactivatable probes and capture histologic abnormalities in vivo are emerging for lesion detection. Successful identification of agents that target dysplastic ACF holds great promise for intervening even earlier in the carcinogenesis process to maximize tumor inhibition. Future preclinical and clinical prevention studies should give significant attention to assessing the utility of dysplastic ACF as the earliest identifiable biomarker of colorectal neoplasia and response to therapy.See all articles in this Special Collection Honoring Paul F. Engstrom, MD, Champion of Cancer Prevention.

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Figures

Figure 1.
Figure 1.
Dysplastic ACF (microadenoma) within the colonic mucosa of Apc+/Min - FCCC mice. Panels show a representative single crypt (A) and a three-crypt (C) microadenoma (100X). Panels B and D include a high-power view (400X) of the same microadenoma, respectively.
Figure 2.
Figure 2.
Fluorescent image of a colon excised from an Apc+/Min-FCCC mouse, generated using the IVIS Spectrum. The upper colon lesion (purple arrow) was not visible grossly, while the lower lesion (green arrow) was detected at the time of necropsy.
Figure 3.
Figure 3.
Immunohistochemical staining of MMP-7 of a colonic microadenoma in an Apc+/Min-FCCC mouse. The microadenoma (arrows) exhibits expression of MMP-7, while the non-neoplastic crypts are negative for MMP-7 (400X).

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