Overexpression of tyrosine kinase B protein as a predictor for distant metastases and prognosis in gastric carcinoma

Objective: Tyrosine kinase B (TrkB) is associated with aggressive behavior and poor prognosis in various cancers. Here we examined the association between TrkB expression and distant metastases/prognosis in gastric carcinoma (GC). Patients and Methods: We analyzed TrkB expression in 161 GC patients by immunohistochemistry and Western blot analysis. The correlation of TrkB mRNA and protein expression levels was examined in 10 patients by RT-PCR assay. Results: TrkB expression was of level 1 in 97 (60.2%) and level 2 in 64 (39.8%) patients. Patients with level 2 expression had a significantly higher incidence of distant metastases (p < 0.0001), well-differentiated tumors (p < 0.005), deeper depth of invasion (p < 0.005) and poorer disease-free and overall survival (p < 0.0001 each) compared to patients with level 1. Multivariate analysis identified the level of TrkB expression as an independent prognostic factor for both disease-free and overall survival (p < 0.01 and p < 0.0001, respectively). Both lymph node metastasis (odds ratio = 10.7) and TrkB expression (odds ratio = 9.3) were independent predictors of distant metastases. Conclusion: A high level of TrkB expression was observed in well-differentiated GC subtypes and is a predictor for distant metastases and prognosis in GC. Copyright (C) 2008 S. Karger AG, Basel.