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

Authors

  • Masako Ochiai,

    1. Division of Cancer Development System, National Cancer Center Research Institute, Tokyo, Japan
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  • Yoshitaka Hippo,

    Corresponding author
    1. Division of Cancer Development System, National Cancer Center Research Institute, Tokyo, Japan
    • Correspondence

      Yoshitaka Hippo, Division of Cancer Development System, National Cancer Center Research Institute, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045, Japan.

      Tel: +81-3-3547-5201; Fax: +81-3-3542-2530;

      E-mail: yhippo@ncc.go.jp

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  • Masashi Izumiya,

    1. Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
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  • Masatoshi Watanabe,

    1. Division of Materials Science and Chemical Engineering, Graduate School of Engineering, Yokohama National University, Yokohama, Japan
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  • Hitoshi Nakagama

    1. Division of Cancer Development System, National Cancer Center Research Institute, Tokyo, Japan
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  • Funding Information

    Ministry of Health, Labor and Welfare of Japan; Japan Society for the Promotion of Science.

Abstract

Dysplasia represents a preneoplastic status in multistep colon carcinogenesis. Whereas laborious preparation of thin sections is required for its diagnosis, we here show that newly defined aberrant crypt foci (ACF) simply mark the majority of the dysplasia on the whole colon. 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. They were morphologically classified into three subtypes, of which two with compressed luminal openings proved highly correlated with dysplasia. Accordingly, we designated those foci harboring either of the two crypt subtypes as dysplasia-associated ACF (dACF). By serially applying different detection methods for known preneoplastic lesions to the same colon, we showed that most dACF had already been identified as cACF, and a few newly identified dACF contained an entire population of more advanced lesions, such as flat ACF and mucin-depleted foci. Consequently, integrative scoring of cACF and dACF enabled capture of all early lesions of the colon. Furthermore, 94% of the dACF showed dysplasia and 90% of the dysplastic lesions proved to be dACF. Thus, dACF is a promising marker for dysplasia, likely facilitating precise identification of the early stages of colon carcinogenesis.

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