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

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• 作者：Tsuyoshi Ozawa MD (1)
  Shinsuke Kazama MD ; PhD (1)
  Takashi Akiyoshi MD ; PhD (2)
  Koji Murono MD (1)
  Satomi Yoneyama MD ; PhD (1)
  Toshiaki Tanaka MD ; PhD (1)
  Junichiro Tanaka MD ; PhD (1)
  Tomomichi Kiyomatsu MD ; PhD (1)
  Kazushige Kawai MD ; PhD (1)
  Hiroaki Nozawa MD ; PhD (1)
  Takamitsu Kanazawa MD ; PhD (1)
  Hironori Yamaguchi MD ; PhD (1)
  Soichiro Ishihara MD ; PhD (1)
  Eiji Sunami MD ; PhD (1)
  Joji Kitayama MD ; PhD (1)
  Teppei Morikawa MD ; PhD (3)
  Masashi Fukayama MD ; PhD (3)
  Toshiaki Watanabe MD ; PhD (1)
  
• 刊名：Annals of Surgical Oncology
• 出版年：2014
• 出版时间：August 2014
• 年：2014
• 卷：21
• 期：8
• 页码：2650-2658
• 全文大小：3,705 KB
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• 作者单位：Tsuyoshi Ozawa MD (1)
  Shinsuke Kazama MD, PhD (1)
  Takashi Akiyoshi MD, PhD (2)
  Koji Murono MD (1)
  Satomi Yoneyama MD, PhD (1)
  Toshiaki Tanaka MD, PhD (1)
  Junichiro Tanaka MD, PhD (1)
  Tomomichi Kiyomatsu MD, PhD (1)
  Kazushige Kawai MD, PhD (1)
  Hiroaki Nozawa MD, PhD (1)
  Takamitsu Kanazawa MD, PhD (1)
  Hironori Yamaguchi MD, PhD (1)
  Soichiro Ishihara MD, PhD (1)
  Eiji Sunami MD, PhD (1)
  Joji Kitayama MD, PhD (1)
  Teppei Morikawa MD, PhD (3)
  Masashi Fukayama MD, PhD (3)
  Toshiaki Watanabe MD, PhD (1)
  
  1. Department of Surgical Oncology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
  2. Department of Gastroenterological Surgery, Cancer Institute Hospital, Tokyo, Japan
  3. Department of Pathology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
  
• ISSN：1534-4681

文摘

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-.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-.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-.40; P?=?0.0019). Conclusions Nuclear Notch3 expression might be a novel predictive marker for recurrence in Stage II and III CRC.