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

作者：Ozawa Tsuyoshi^*; Kazama Shinsuke; Akiyoshi Takashi; Murono Koji; Yoneyama Satomi; Tanaka Toshiaki; Tanaka Junichiro; Kiyomatsu Tomomichi; Kawai Kazushige; Nozawa Hiroaki; Kanazawa Takamitsu; Yamaguchi Hironori; Ishihara Soichiro; Sunami Eiji; Kitayama Joji; Morikawa Teppei; Fukayama Masashi; Watanabe Toshiaki

来源：Annals of Surgical Oncology, 2014, 21(8): 2650-2658.

DOI：10.1245/s10434-014-3659-9

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

• 出版日期2014-8
• 单位中国医学科学院肿瘤医院