Abstract 1167: Aberrant expression of trefoil factor 3 (TFF3) is associated with tumor progression and an unfavorable prognosis in patients with colorectal cancer .
Authors: Kondo Satoru , Tanaka Koji , Saigusa Susumu , Kitajima Takahito , Shimura Tadanobu , Toiyama Yuji , Okugawa Yoshinaga , Inoue Yasuhiro , Araki Toshimitsu , Uchida Keiichi , Mohri Yasuhiko , Ishii Kenichiro , Kusunoki Masato 
Published: August 2014

Background. Trefoil factor 3 (TFF3) is predominantly expressed by goblet cells of the small intestine and colon and its expression is maintained throughout the colon adenoma-carcinoma sequence. Aberrant TFF3 expression in tumor cells has been reported to be involved in tumor progression and unfavorable prognosis of certain human malignancies. In colorectal cancer (CRC), the association between TFF3 expression and tumor progression remains uncertain.

Aim. We aimed to investigate the expression of TFF3 in tumor cells using immunohistochemistry and to evaluate its clinical and prognostic values in patients with colorectal cancer (CRC).

Materials and methods. Three hundred (n=300) samples of CRC patients were investigated for the expression of TFF3 in tumor cells using standard immunohistochemistry (IHC). The IHC score of TFF3 in tumor cells was determined on the basis of both staining intensity and the percentage of positive cells. The IHC score was dichotomized at the cutoff value predictive of overall survival using a non-parametric receiver operating characteristic analysis. The association between the expression of TFF3 in tumor cells and clinicopathological features was analyzed. Impact of TFF3 expression in tumor cells on overall survival (OS) was also analyzed using univariate and multivariate analyses

Results. TFF3 was expressed in all goblet cells of adjacent normal tissue. In adjacent normal colonic crypt, immunoreactive TFF3 protein was localized mainly in the cytoplasm or supranuclear cytoplasm of epithelial cells. Colorectal cancer cells showed an aberrant cytoplasmic TFF3 staining. By use of our dichotomous scoring system, 110 tumors (66%) were low and 190 (34%) were high for TFF3 immunostaining. Decreased expression of TFF3 was significantly associated with larger tumor size (&lt;0.05), poorly differentiated histology (&lt;0.01), advanced T stage (T4) (p=0.02), synchronous liver metastasis (p=0.03), and advanced UICC stage (stage 4) (p=0.02). In univariate analysis, decreased tumoral TFF3 was significantly associated with poor prognosis [p=0.02, hazard ratio (HR)=2.13, 95 % CI, 1.15-3.97]. In multivariate analysis, decreased tumoral TFF3 showed a trend toward being an independent prognostic factor for CRC patients [p=0.09, hazard ratio (HR)=1.76, 95 % CI, 0.92-3.37].

Conclusions. Decreased TFF3 expression was associated with colorectal tumor progression. Decreased or lack of TFF3 expression in tumor cells may have a potential prognostic value in CRC patients.

Citation Format: Satoru Kondo, Koji Tanaka, Susumu Saigusa, Takahito Kitajima, Tadanobu Shimura, Yuji Toiyama, Yoshinaga Okugawa, Yasuhiro Inoue, Toshimitsu Araki, Keiichi Uchida, Yasuhiko Mohri, Kenichiro Ishii, Masato Kusunoki. Aberrant expression of trefoil factor 3 (TFF3) is associated with tumor progression and an unfavorable prognosis in patients with colorectal cancer . [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1167. doi:10.1158/1538-7445.AM2013-1167