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Nuclear Notch3 Expression is Associated with Tumor Recurrence in Patients with Stage II and III Colorectal Cancer

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

Abstract

Background

The importance of Notch signaling in colorectal cancer (CRC) tumorigenesis has been recently recognized. However, the significance of Notch3 expression and its association with Notch1 expression in CRC is unclear. In the present study, we investigated Notch1 and Notch3 expression in Stage II and III CRC to assess their association with clinicopathological characteristics.

Methods

The protein expression of Notch1 and Notch3 was examined using immunohistochemistry in 305 CRC specimens. Nuclear expression of Notch1 and Notch3 and their associations with clinicopathological characteristics and distant relapse-free survival (dRFS) were evaluated.

Results

Nuclear Notch1 was overexpressed in 37 % of specimen, and nuclear Notch3 in 38 %. Nuclear Notch3 expression correlated with tumor differentiation status (P = 0.0099). Nuclear expression of Notch1 and Notch3 was associated with tumor recurrence (P = 0.0311 and P = 0.0053, respectively). In multivariate analysis, nuclear Notch3 expression [hazard ratio (HR) = 1.71; 95 % confidence interval (CI), 1.06–2.78; P = 0.0271), lymph node metastasis, and venous involvement were independently correlated with dRFS. In subgroup analysis, nuclear Notch3 expression was strongly associated with dRFS in Stage II CRC (HR = 3.47; 95 % CI 1.44–9.22; P = 0.0055). Both nuclear Notch1 and Notch3 were positive in 67 specimens (22 %) and both were negative in 144 specimens (47 %). Coexpression of nuclear Notch1 and Notch3 had an additive effect toward poorer dRFS compared with a negative subtype (HR = 2.48; 95 % CI, 1.41–4.40; P = 0.0019).

Conclusions

Nuclear Notch3 expression might be a novel predictive marker for recurrence in Stage II and III CRC.

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Acknowledgment

This work was supported by Kaoru Amitani, Department of Surgical Oncology, The Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.

Conflicts of interest

All of the authors declare no conflicts of interest or financial ties to disclose.

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Authors and Affiliations

  1. Department of Surgical Oncology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan

    Tsuyoshi Ozawa MD, Shinsuke Kazama MD, PhD, Koji Murono MD, Satomi Yoneyama MD, PhD, Toshiaki Tanaka MD, PhD, Junichiro Tanaka MD, PhD, Tomomichi Kiyomatsu MD, PhD, Kazushige Kawai MD, PhD, Hiroaki Nozawa MD, PhD, Takamitsu Kanazawa MD, PhD, Hironori Yamaguchi MD, PhD, Soichiro Ishihara MD, PhD, Eiji Sunami MD, PhD, Joji Kitayama MD, PhD & Toshiaki Watanabe MD, PhD

  2. Department of Gastroenterological Surgery, Cancer Institute Hospital, Tokyo, Japan

    Takashi Akiyoshi MD, PhD

  3. Department of Pathology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan

    Teppei Morikawa MD, PhD & Masashi Fukayama MD, PhD

Authors
  1. Tsuyoshi Ozawa MD
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  2. Shinsuke Kazama MD, PhD
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  9. Kazushige Kawai MD, PhD
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  12. Hironori Yamaguchi MD, PhD
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  13. Soichiro Ishihara MD, PhD
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  16. Teppei Morikawa MD, PhD
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  17. Masashi Fukayama MD, PhD
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  18. Toshiaki Watanabe MD, PhD
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Corresponding author

Correspondence to Tsuyoshi Ozawa MD.

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Ozawa, T., Kazama, S., Akiyoshi, T. et al. Nuclear Notch3 Expression is Associated with Tumor Recurrence in Patients with Stage II and III Colorectal Cancer. Ann Surg Oncol 21, 2650–2658 (2014). https://doi.org/10.1245/s10434-014-3659-9

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  • DOI: https://doi.org/10.1245/s10434-014-3659-9

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