title: Prognostic value of tropomyosin-related kinases A, B, and C in gastric cancer.
abstract: OBJECTIVE
  Tropomyosin-related kinase (Trk) receptors play critical roles in tumor development and are considered attractive targets for cancer therapy. We investigated correlations of the expression of TrkA, TrkB, and TrkC with clinicopathological features and outcomes in gastric cancer.
  
  
  METHODS
  Tumor samples were obtained from 221 patients with gastric cancer who underwent gastrectomy between 2003 and 2007. The expression of TrkA, TrkB, and TrkC was analyzed using immunohistochemical staining. The relationship of their expression to clinicopathological factors and outcomes was assessed.
  
  
  RESULTS
  High expression of TrkA, TrkB, or TrkC was significantly associated with histopathology (p = 0.022, p < 0.001, and p < 0.001). High expression of TrkA was significantly correlated with variables related to tumor progression, including lymph node metastasis (p = 0.024) and distant metastasis or recurrence (p < 0.001). Distant metastasis or recurrence was found in a significantly higher proportion of patients with high expression of TrkC than in those with low expression (p = 0.036). High expression of TrkA was significantly associated with poorer relapse-free survival (RFS) in univariate analysis (p = 0.001). High expression of TrkA or TrkC was significantly associated with poorer disease-specific survival (DSS) in univariate analysis (p < 0.001 and p = 0.008). In multivariate analysis, TrkA was an independent predictor of RFS [hazard ratio (HR), 2.294; 95 % confidence interval (CI), 1.309-4.032; p = 0.004] and DSS (HR, 2.146; 95 % CI, 1.195-3.861; p = 0.011). Expression of TrkB was not associated with RFS or DSS in univariate analysis.
  
  
  CONCLUSIONS
  Our results demonstrated that TrkA expression was associated with tumor progression and poor survival, and was an independent predictor of poor outcomes in gastric cancer patients.
authors.affiliation: Department of Surgical Oncology, Tokyo Medical and Dental University Graduate School, 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8519, Japan. vc_ayako_vc@yahoo.co.jp.
authors.forename: A
authors.initials: A
authors.lastname: Kamiya
authors.affiliation: Department of Surgical Oncology, Tokyo Medical and Dental University Graduate School, 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8519, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Inokuchi
authors.affiliation: Department of Surgical Oncology, Tokyo Medical and Dental University Graduate School, 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8519, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Otsuki
authors.affiliation: Department of Surgical Oncology, Tokyo Medical and Dental University Graduate School, 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8519, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Sugita
authors.affiliation: Department of Surgical Oncology, Tokyo Medical and Dental University Graduate School, 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8519, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Kato
authors.affiliation: Department of Surgical Oncology, Tokyo Medical and Dental University Graduate School, 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8519, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Uetake
authors.affiliation: Department of Surgical Oncology, Tokyo Medical and Dental University Graduate School, 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8519, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Sugihara
authors.affiliation: Department of Translational Oncology, Tokyo Medical and Dental University Graduate School, Tokyo, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Takagi
authors.affiliation: Center for Minimally Invasive Surgery, Tokyo Medical and Dental University Graduate School, Tokyo, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Kojima
mesh_terms: D000328:Adult; D000368:Aged; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008297:Male; D008562:Membrane Glycoproteins / Q000032:analysis / Q000096:biosynthesis*; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D011379:Prognosis; D016016:Proportional Hazards Models; D011505:Protein-Tyrosine Kinases / Q000032:analysis / Q000096:biosynthesis*; D020917:Receptor, trkA / Q000032:analysis / Q000096:biosynthesis*; D020813:Receptor, trkB; D020812:Receptor, trkC / Q000032:analysis / Q000096:biosynthesis*; D013274:Stomach Neoplasms / Q000201:enzymology* / Q000401:mortality
chemical_list: D008562:Membrane Glycoproteins; C000611485:NTRK1 protein, human; D011505:Protein-Tyrosine Kinases; D020917:Receptor, trkA; D020813:Receptor, trkB; D020812:Receptor, trkC; C000591259:tropomyosin-related kinase-B, human
keywords: Gastric cancer; TrkA; TrkB; TrkC