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High Expression of Atypical Protein Kinase C λ/ι in Gastric Cancer as a Prognostic Factor for Recurrence

  • Gastrointestinal Oncology
  • Published:
Annals of Surgical Oncology Aims and scope Submit manuscript

Abstract

Background

The atypical protein kinase C lambda/iota (aPKCλ/ι) is involved in several signal transduction pathways that influence cell growth, apoptosis, and the establishment and maintenance of epithelial cell polarity. Overexpression of aPKCλ/ι has been reported in several cancers and been shown to be associated with oncogenesis. However, the expression and role of aPKCλ/ι in gastric cancer, one of the commonest cancers in Asia, have not so far been investigated. This study aimed to clarify the relationship between aPKCλ/ι expression and the clinicopathological features of gastric cancer.

Patients and Methods

Gastric adenocarcinoma samples were obtained from 177 patients who underwent gastrectomy at the Yokohama City University Hospital between 1999 and 2004. Expression of aPKCλ/ι and E-cadherin was examined immunohistochemically and compared with clinicopathological features of the tumors. Univariate and multivariate analyses were performed for both disease-specific and relapse-free survival.

Results

Overexpression of aPKCλ/ι protein was detected in 126 of the 177 (71.2%) gastric cancers. Immunohistological staining for aPKCλ/ι was stronger in gastric adenocarcinoma of intestinal type than diffuse type (p = 0.036), but was not correlated with E-cadherin expression. A multivariate analysis suggested that nodal metastasis and aPKCλ/ι overexpression were prognostic factors for disease recurrence.

Conclusions

Our results suggested that aPKCλ/ι overexpression was a strong prognostic factor for gastric adenocarcinoma recurrence. As well as being a new prognostic indicator, aPKCλ/ι is also likely to be a novel therapeutic target for gastric cancer.

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Acknowledgment

The authors wish to thank Ms. Harumi Sakurada, Tamiyo Taniguchi, Shizuko Kobayashi, and Sayuri Kanaya for their technical and secretarial assistance. This research was supported by Grants-in-Aid from the Japanese Ministry of Education, Culture, Sports, Science and Techonology for Fundamental Research (C2) (to Y.N., #20590368; to K.A., #20570138; to Y. Ichikawa, #205914076) and for Scientific Research on Priority Area (to S.O., #17014076), and from the Yokohama Academic Foundation, Yokohama, Japan (to R.T.).

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Authors and Affiliations

  1. Department of Gastroenterological Surgery, Yokohama City University Graduate School of Medicine, Yokohama, Japan

    Ryo Takagawa MD, Hirotoshi Akiyama MD, PhD, Yasuyuki Kojima MD & Itaru Endo MD, PhD

  2. Department of Molecular Biology, Yokohama City University Graduate School of Medicine, Yokohama, Japan

    Kazunori Akimoto PhD & Shigeo Ohno PhD

  3. Department of Clinical Oncology, Yokohama City University Graduate School of Medicine, Yokohama, Japan

    Yasushi Ichikawa MD, PhD

  4. Department of Urology, Yokohama City University Graduate School of Medicine, Yokohama, Japan

    Hitoshi Ishiguro PhD

  5. Photocatalyst Group, Kanagawa Academy of Science and Technology, Kawasaki, Japan

    Hitoshi Ishiguro PhD

  6. Division of Anatomical and Surgical Pathology, Yokohama City University Hospital, Yokohama, Japan

    Yoshiaki Inayama MD, PhD

  7. Department of Molecular Pathology, Yokohama City University Graduate School of Medicine, Yokohama, Japan

    Ichiro Aoki MD, PhD & Yoji Nagashima MD, PhD

  8. Advanced Medical Research Center, Yokohama City University, Yokohama, Japan

    Ichiro Aoki MD, PhD, Yoji Nagashima MD, PhD & Shigeo Ohno PhD

  9. Department of Gastroenterological Surgery, Yokohama City University Medical Center, Yokohama, Japan

    Chikara Kunisaki MD, PhD

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  1. Ryo Takagawa MD
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  2. Kazunori Akimoto PhD
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  5. Yasuyuki Kojima MD
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  7. Yoshiaki Inayama MD, PhD
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  8. Ichiro Aoki MD, PhD
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  12. Shigeo Ohno PhD
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Corresponding author

Correspondence to Yoji Nagashima MD, PhD.

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Takagawa, R., Akimoto, K., Ichikawa, Y. et al. High Expression of Atypical Protein Kinase C λ/ι in Gastric Cancer as a Prognostic Factor for Recurrence. Ann Surg Oncol 17, 81–88 (2010). https://doi.org/10.1245/s10434-009-0708-x

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  • DOI: https://doi.org/10.1245/s10434-009-0708-x

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