title: Prognostic value of RKIP and p-ERK in gastric cancer.
abstract: BACKGROUND
  The mitogen-activated protein kinase (MAPK) signaling pathway participates in several steps of tumour development and is considered a prominent therapeutic target for the design of chemotherapeutic agents. We evaluated the expressions of extracellular signal-regulated kinase (ERK), mitogen-activated protein kinase (MEK), an upstream regulator of ERK, and Raf kinase inhibitor protein (RKIP), and investigated correlations of these expressions with clinicopathological features and outcomes in gastric cancer.
  
  
  METHODS
  Tumour samples were obtained from 105 patients with gastric adenocarcinomas who underwent radical gastrectomy. The expressions of phosphorylated ERK (p-ERK), phosphorylated MEK (p-MEK), and RKIP were analysed by immunohistochemical staining.
  
  
  RESULTS
  Expression of RKIP, p-MEK, and p-ERK was found in 69 (66%), 54 (51%), and 64 (61%) of all tumours, respectively. RKIP expression negatively correlated with the depth of invasion (p < 0.001), lymph node involvement (p = 0.028), and Union for International Cancer Control (UICC) stage (p = 0.007). RKIP expression was associated with significantly longer relapse-free survival (RFS) (p = 0.0033), whereas p-MEK was not (p = 0.79). Patients with p-ERK expression had slightly, but not significantly shorter RFS than those without such expression (p = 0.054). Patients with positive p-ERK and negative RKIP expression had significantly shorter RFS than the other patients (p < 0.001). The combination of RKIP and p-ERK expression was an independent prognostic factor (hazard ratio, 2.4; 95% confidence interval, 1.3 - 4.6; p = 0.008).
  
  
  CONCLUSIONS
  Our results demonstrated that loss of RKIP was associated with tumour progression and poor survival. Negative RKIP expression combined with positive p-ERK expression was an independent predictor of poor outcomes in patients with gastric cancer.
authors.affiliation: Department of Surgical Oncology, Tokyo Medical and Dental University, 1-5-45, Yushima, Bunkyo-ku, Tokyo 113-8519, Japan.
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Fujimori
authors.forename: Mikito
authors.initials: M
authors.lastname: Inokuchi
authors.forename: Yoko
authors.initials: Y
authors.lastname: Takagi
authors.forename: Keiji
authors.initials: K
authors.lastname: Kato
authors.forename: Kazuyuki
authors.initials: K
authors.lastname: Kojima
authors.forename: Kenichi
authors.initials: K
authors.lastname: Sugihara
mesh_terms: D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D006801:Humans; D053208:Kaplan-Meier Estimate; D049488:Phosphatidylethanolamine Binding Protein / Q000378:metabolism*; D010766:Phosphorylation; D011379:Prognosis; D015398:Signal Transduction; D013274:Stomach Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology
chemical_list: C511482:PEBP1 protein, human; D049488:Phosphatidylethanolamine Binding Protein; D048049:Extracellular Signal-Regulated MAP Kinases