title: Prognostic implications of netrin-1 expression and its receptors in patients with adenocarcinoma of the pancreas.
abstract: BACKGROUND
  To assess the interaction between the expression of netrin-1 or of its receptors to the prognosis of ductal adenocarcinoma of the pancreas.
  
  
  METHODS
  In 82 patients with resectable pancreatic adenocarcinoma who underwent curative operation, the expression patterns of netrin-1, deleted in colorectal carcinomas (DCC), UNC5H3, and neogenin were determined by immunohistochemical staining. Kaplan-Meier analysis was performed to assess the prognostic relevance of the examined expression patterns.
  
  
  RESULTS
  Median follow-up was 15 +/- 19.9 months (range, 4-108 months). Patients suffering from tumors with no or little expression of netrin-1 (n = 67) had a median recurrence-free survival of 10 months (95% CI, 7-13 months), while a middle to strong expression (n = 15) was associated with a significantly worse median recurrence-free survival of only four months (95% CI, three to five months, p = 0.0165). Overall and recurrence-free survival showed no significant differences between the different expression patterns of DCC, UNC5H3 or neogenin. Netrin-1 expression had significant impact (p = 0.001) on overall survival of patients suffering from poorly differentiated tumors. Stratification according to the nodal status revealed significant influence (p = 0.007) of UNC5H3 expression on the overall survival of patients with pN1 status.
  
  
  CONCLUSIONS
  Expression of netrin-1 has significant impact on time to tumor relapse in adenocarcinoma of the pancreas. Netrin-1 expression is associated with worse outcome in poorly differentiated pancreatic adenocarcinomas. Risk-stratification according to the UNC5H3 receptor expression pattern shows that node positive patients (pN1) with no to little UNC5H3 expression carry a significantly worse prognosis than those with middle to strong UNC5H3 expression.
authors.affiliation: Department of General, Visceral and Thoracic Surgery, University Medical Center of Hamburg-Eppendorf, Martinistr. 52, 20246, Hamburg, Germany. blink@uke.uni-hamburg.de
authors.forename: Björn-Christian
authors.initials: BC
authors.lastname: Link
authors.forename: Uta
authors.initials: U
authors.lastname: Reichelt
authors.forename: Matthias
authors.initials: M
authors.lastname: Schreiber
authors.forename: Jussuf T
authors.initials: JT
authors.lastname: Kaifi
authors.forename: Robin
authors.initials: R
authors.lastname: Wachowiak
authors.forename: Dean
authors.initials: D
authors.lastname: Bogoevski
authors.forename: Michael
authors.initials: M
authors.lastname: Bubenheim
authors.forename: Guel
authors.initials: G
authors.lastname: Cataldegirmen
authors.forename: Karim A
authors.initials: KA
authors.lastname: Gawad
authors.forename: Rana
authors.initials: R
authors.lastname: Issa
authors.forename: Susann
authors.initials: S
authors.lastname: Koops
authors.forename: Jakob R
authors.initials: JR
authors.lastname: Izbicki
authors.forename: Emre F
authors.initials: EF
authors.lastname: Yekebas
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism* / Q000601:surgery; D014408:Biomarkers, Tumor / Q000378:metabolism; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008197:Lymph Node Excision; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local; D009414:Nerve Growth Factors / Q000378:metabolism*; D000075386:Netrin Receptors; D000075388:Netrin-1; D010190:Pancreatic Neoplasms / Q000378:metabolism* / Q000601:surgery; D016577:Pancreaticoduodenectomy; D011379:Prognosis; D016016:Proportional Hazards Models; D011956:Receptors, Cell Surface / Q000378:metabolism; D018709:Statistics, Nonparametric; D015996:Survival Rate; D025521:Tumor Suppressor Proteins / Q000378:metabolism*
chemical_list: D014408:Biomarkers, Tumor; D008565:Membrane Proteins; C000617351:NTN1 protein, human; D009414:Nerve Growth Factors; D000075386:Netrin Receptors; D011956:Receptors, Cell Surface; D025521:Tumor Suppressor Proteins; C091279:neogenin; D000075388:Netrin-1; D017871:Calcium-Calmodulin-Dependent Protein Kinases