Abstract 1144: Expression of tropomyosin-related kinase B (TrkB) at the tumor invasive front as an independent prognostic factor in gastric cancer.
Authors: Tanaka Koji , Shimura Tadanobu , Saigusa Susumu , Kondo Satoru , Kitajima Takahito , Toiyama Yuji , Okugawa Yoshinaga , Inoue Yasuhiro , Ohi Masaki , Araki Toshimitsu , Uchida Keiichi , Mohri Yasuhiko , Kusunoki Masato 
Published: August 2014

Background. Previously, we have reported the association between the expression of tropomyosin-related kinase B (TrkB) in tumor cells and gastric tumor progression, chemoresistance of esophageal cancer, and epithelial-mesenchymal transition in colorectal cancer. In gastric cancer, high tumoral TrkB mRNA level demonstrated to be an independent prognostic factor.

Aim. In this study, we investigated the TrkB protein expression in tumor cells using immunohistochemistry, and evaluated its clinical and prognostic significance in patients with human gastric cancer (GC).

Materials and methods. Three hundred and twenty (n=320) samples of GC patients were investigated for the TrkB protein expression in tumor cells using a standard immunohistochemistry (IHC). The IHC score of TrkB 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 median value as a cutoff value. The association between the TrkB protein expression in tumor cells and clinicopathological features was analyzed. Impact of TrkB protein expression in tumor cells on overall survival (OS) was also analyzed using univariate and multivariate analyses.

Results. Immunoreactive TrkB protein was localized in both cytoplasm and nucleus of gastric cancer cells. High cytoplasmic TrkB expression was significantly associated with larger tumor size (p &lt;0.01), well differentiated histology (&lt;0.01), advanced T stage (p &lt;0.01), lymphovascular invasion (p &lt;0.01), lymph node involvement (p &lt;0.01), synchronous distant metastasis (p &lt;0.01), and advanced UICC stage (p &lt;0.01). Fifty patients (16%) showed a higher TrkB expression in either cytoplasm or nucleus of tumor cells at the tumor invasive front, as compared with the tumor center. In univariate analysis, higher TrkB expression at the tumor invasive front was significantly associated with poor prognosis [hazard ratio (95%): 4.50 (2.78-7.18), p&lt;0.01]. High cytoplasmic TrkB expression did not reach statistical significance. In multivariate analysis, higher TrkB expression at the tumor invasive front retained an independent prognostic factor for GC patients [hazard ratio (95%): 1.77 (1.07-2.88), p=0.03].

Conclusions. Tumoral TrkB expression was associated with tumor progression in human gastric cancer. Increased TrkB at the tumor invasive front was an independent prognostic factor in patients with gastric cancer.

Citation Format: Koji Tanaka, Tadanobu Shimura, Susumu Saigusa, Satoru Kondo, Takahito Kitajima, Yuji Toiyama, Yoshinaga Okugawa, Yasuhiro Inoue, Masaki Ohi, Toshimitsu Araki, Keiichi Uchida, Yasuhiko Mohri, Masato Kusunoki. Expression of tropomyosin-related kinase B (TrkB) at the tumor invasive front as an independent prognostic factor in gastric 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 1144. doi:10.1158/1538-7445.AM2013-1144