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A significant imbalance in mitosis versus apoptosis accelerates the growth rate of sessile serrated adenoma/polyps

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Abstract

Sessile serrated adenoma/polyps (SSA/Ps) of the colon are thought to be precursors of sporadic carcinomas. Although it is suggested that SSA/P may grow rapidly from the early stage, its cell kinetics remains obscure. To solve this problem, we analyzed the mitotic and apoptotic activity of normal crypts, microvesicular hyperplastic polyps (MVHPs), and tubular adenomas (TAs), using phospho-histone H3 and cleaved caspase 3 immunohistochemistry. The mitotic index for SSA/Ps (mean, 5.63) and TAs (6.98) was significantly higher than those for normal crypts (2.72) and MVHPs (2.86). Of all tested lesions, the apoptotic index was lowest for SSA/Ps (0.96; normal, 2.71; MVHPs, 2.62; TAs, 6.01) with statistically significant differences. The net growth ratio was close to 1.0 in normal crypts (1.07) while remaining low in MVHPs (1.06) and TAs (1.38), but was markedly elevated in SSA/Ps (7.32, P < 0.01) due to the large imbalance between mitosis and apoptosis. As to apoptosis regulatory proteins, expression of anti-apoptotic Bcl-2 was significantly reduced or undetectable in MVHPs and SSA/Ps, while TAs showed stronger staining than normal crypts. Expression of pro-apoptotic Bax and its activators, Bim and Bad, was significantly reduced in MVHPs and SSA/Ps. We suggest that other complex mechanisms may act synergistically with Bax, Bim, or Bad deficiency to regulate apoptosis suppression in SSA/Ps.

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The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Department of Pathology, St. Marianna University School of Medicine, Kawasaki, Japan

    Akira Endo, Hirotaka Koizumi, Makiko Takahashi, Tomohiro Tamura & Masayuki Takagi

  2. Unit of Medical Statistics, Faculty of Education and Culture, St. Marianna University School of Medicine, Kawasaki, Japan

    Shinobu Tatsunami

  3. Division of Gastroenterology and Hepatology, Department of Internal Medicine, St. Marianna University School of Medicine, Kawasaki, Japan

    Yoshiyuki Watanabe

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  1. Akira Endo
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  2. Hirotaka Koizumi
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Correspondence to Hirotaka Koizumi.

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Akira Endo and Hirotaka Koizumi contributed equally to this work.

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Endo, A., Koizumi, H., Takahashi, M. et al. A significant imbalance in mitosis versus apoptosis accelerates the growth rate of sessile serrated adenoma/polyps. Virchows Arch 462, 131–139 (2013). https://doi.org/10.1007/s00428-012-1365-1

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  • DOI: https://doi.org/10.1007/s00428-012-1365-1

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