Hypermethylation status of APC inversely correlates with the presence of submucosal invasion in laterally spreading colorectal tumors

Authors

  • Kazuo Hashimoto,

    1. Department of Molecular Science and Applied Medicine (Gastroenterology and Hepatology), Yamaguchi University Graduate School of Medicine, 1-1-1 Minami Kogushi, Ube, Yamaguchi, Japan
    2. Department of Laboratory Medicine, Yamaguchi University Graduate School of Medicine, 1-1-1 Minami Kogushi, Ube, Yamaguchi, Japan
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    • Kazuo Hashimoto and Yoshihisa Shimizu are the first authors, with equal contributions.

  • Yoshihisa Shimizu,

    1. Department of Laboratory Medicine, Yamaguchi University Graduate School of Medicine, 1-1-1 Minami Kogushi, Ube, Yamaguchi, Japan
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    • Kazuo Hashimoto and Yoshihisa Shimizu are the first authors, with equal contributions.

  • Yutaka Suehiro,

    Corresponding author
    1. Department of Laboratory Medicine, Yamaguchi University Graduate School of Medicine, 1-1-1 Minami Kogushi, Ube, Yamaguchi, Japan
    • Department of Laboratory Medicine, Yamaguchi University Graduate School of Medicine, 1-1-1 Minami Kogushi, Ube, Yamaguchi 755-8505, Japan.
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  • Naoko Okayama,

    1. Division of Laboratory, Yamaguchi University Hospital, 1-1-1 Minami Kogushi, Ube, Yamaguchi, Japan
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  • Shinichi Hashimoto,

    1. Department of Molecular Science and Applied Medicine (Gastroenterology and Hepatology), Yamaguchi University Graduate School of Medicine, 1-1-1 Minami Kogushi, Ube, Yamaguchi, Japan
    2. Department of Laboratory Medicine, Yamaguchi University Graduate School of Medicine, 1-1-1 Minami Kogushi, Ube, Yamaguchi, Japan
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  • Toshiyuki Okada,

    1. Department of Laboratory Medicine, Yamaguchi University Graduate School of Medicine, 1-1-1 Minami Kogushi, Ube, Yamaguchi, Japan
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  • Mikako Hiura,

    1. Department of Laboratory Medicine, Yamaguchi University Graduate School of Medicine, 1-1-1 Minami Kogushi, Ube, Yamaguchi, Japan
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  • Koji Ueno,

    1. Department of Laboratory Medicine, Yamaguchi University Graduate School of Medicine, 1-1-1 Minami Kogushi, Ube, Yamaguchi, Japan
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  • Shoichi Hazama,

    1. Department of Digestive Surgery and Surgical Oncology (Surgery II), Yamaguchi University Graduate School of Medicine, 1-1-1 Minami Kogushi, Ube, Yamaguchi, Japan
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  • Shingo Higaki,

    1. Department of Molecular Science and Applied Medicine (Gastroenterology and Hepatology), Yamaguchi University Graduate School of Medicine, 1-1-1 Minami Kogushi, Ube, Yamaguchi, Japan
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  • Yuichiro Hamanaka,

    1. Department of Laboratory Medicine, Yamaguchi University Graduate School of Medicine, 1-1-1 Minami Kogushi, Ube, Yamaguchi, Japan
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  • Masaaki Oka,

    1. Division of Laboratory, Yamaguchi University Hospital, 1-1-1 Minami Kogushi, Ube, Yamaguchi, Japan
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  • Isao Sakaida,

    1. Department of Molecular Science and Applied Medicine (Gastroenterology and Hepatology), Yamaguchi University Graduate School of Medicine, 1-1-1 Minami Kogushi, Ube, Yamaguchi, Japan
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  • Yuji Hinoda

    1. Department of Laboratory Medicine, Yamaguchi University Graduate School of Medicine, 1-1-1 Minami Kogushi, Ube, Yamaguchi, Japan
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Abstract

Little is known about epigenetic alterations in laterally spreading colorectal tumors (LSTs). The goal of the present study was to elucidate the epigenetic background of LSTs and compare the methylation status of DNA CpG islands (CGIs) with clinicopathologic features. Methylation of MINT1, MINT2, MINT31, p16, O6-methylguanine-DNA methyltransferase (MGMT), adenomatous polyposis coli (APC), and human MutL homologue 1 (hMLH1) in 42 LSTs was assessed by methylation-specific polymerase chain reaction (MSP) and compared with clinicopathologic parameters. The frequency of hypermethylation was 12.5% (4/32) for MINT1, 40.0% (16/40) for MINT2, 25.0% (10/40) for MINT31, 25.7% (9/35) for p16, 7.7% (3/39) for hMLH1, 26.5% (9/34) for MGMT, and 35.9% (14/39) for APC. APC methylation was inversely associated with submucosal invasion (P = 0.034), which was not found in any of 14 LST cases with APC methylation, whereas submucosal invasion was present in 8 of 25 (32.0%) cases without APC methylation. These data suggest that hypermethylation of APC could be a predictive marker for the absence of submucosal invasion of LSTs. © 2007 Wiley-Liss, Inc.

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