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Immunohistochemical expression of 14-3-3 sigma protein in various histological subtypes of uterine cervical cancers

Authors

  • Takaaki Sano,

    Corresponding author
    1. Department of Tumor Pathology, Gunma University, Graduate School of Medicine, Faculty of Medicine, Gunma, Japan
      Takaaki Sano, MD, Department of Tumor Pathology, Gunma University, Graduate School of Medicine, Faculty of Medicine, 3-39-22 Showa-machi, Maebashi, Gunma 371-8511, Japan. Email: sanot@med.gunma-u.ac.jp
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  • Hanako Shimooka,

    1. Department of Tumor Pathology, Gunma University, Graduate School of Medicine, Faculty of Medicine, Gunma, Japan
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  • Peng Weixa,

    1. Department of Tumor Pathology, Gunma University, Graduate School of Medicine, Faculty of Medicine, Gunma, Japan
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  • Atsuki Segawa,

    1. Department of Tumor Pathology, Gunma University, Graduate School of Medicine, Faculty of Medicine, Gunma, Japan
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  • Zhang Jian,

    1. Department of Tumor Pathology, Gunma University, Graduate School of Medicine, Faculty of Medicine, Gunma, Japan
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  • Atsushi Motegi,

    1. Department of Tumor Pathology, Gunma University, Graduate School of Medicine, Faculty of Medicine, Gunma, Japan
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  • Hiroko Nakayama,

    1. Department of Tumor Pathology, Gunma University, Graduate School of Medicine, Faculty of Medicine, Gunma, Japan
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  • Tetsunari Oyama,

    1. Department of Tumor Pathology, Gunma University, Graduate School of Medicine, Faculty of Medicine, Gunma, Japan
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  • Takashi Nakajima

    1. Department of Tumor Pathology, Gunma University, Graduate School of Medicine, Faculty of Medicine, Gunma, Japan
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Takaaki Sano, MD, Department of Tumor Pathology, Gunma University, Graduate School of Medicine, Faculty of Medicine, 3-39-22 Showa-machi, Maebashi, Gunma 371-8511, Japan. Email: sanot@med.gunma-u.ac.jp

Abstract

14-3-3 sigma (σ) has been a major G2/M checkpoint control gene and has demonstrated that its inactivation in various cancers occurs mostly by epigenetic hypermethylation, not by genetic change. In order to confirm 14-3-3σ protein expression together with p16 and p53 in cervical cancers, immunohistochemistry was performed using various histological subtypes of cervical cancers and dysplasia. Strong and diffuse immunoreactivity for 14-3-3σ was uniformly observed in all the cervical dysplasia (17/17) and squamous cell carcinomas (29/29) including human papillomavirus (HPV)-negative cases. Even in adenosquamous carcinomas and adenocarcinomas of the cervix, immunohistochemical expression of 14-3-3σ was shown with relatively high frequency (13/15, 87% and 22/27, 81%). In the in situ hybridization study, mRNA of 14-3-3σ was expressed in six of eight immunohistochemical-negative cases. Therefore, the undetectable expression of 14-3-3σ protein in cervical cancers might, at least in part, be due to a proteolysis not epigenetic hypermethylation. It is of interest that cancers without 14-3-3σ expression were predominantly those lacking HPV DNA, and that there were no cases with concomitant inactivation of 14-3-3σ and p16 in the present study. These observations are consistent with the hypothesis that inactivation of either 14-3-3σ or p16 has an effect equivalent to the expression of E6 and E7 oncoproteins of HPV.

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