title: Biological and prognostic relevance of mitogen-activated protein kinases in pancreatic adenocarcinoma.
abstract: OBJECTIVE
  The aims of this study were to study the biological and clinical significance of 3 main proteins of the mitogen-activated protein kinase (MAPK) signaling pathway, ERK1/2, P38, and MKK4, in a series of patients having pancreatic adenocarcinomas treated by surgery.
  
  
  METHODS
  We examined the immunohistochemical expression of 3 MAPK proteins, ERK1/2, P38, and MKK4 in 99 surgically resected pancreatic ductal adenocarcinomas. Tumor protein expression was studied with regard to pathological characteristics and to postsurgical recurrence-free and overall survivals.
  
  
  RESULTS
  MKK4 expression was related to tumor cell proliferation, evaluated by the Ki67 index (P < 0.01). ERK1/2 expression was related to a shorter recurrence-free survival on both univariate and multivariate analysis (P < 0.01; odds ratio, 8.39; 95% confidence interval, 2.68-26.26) independently of lymph node metastases and tumor size, and to a shorter overall survival (P = 0.01) on univariate analysis. In patients without postsurgical treatment, both ERK1/2 and P38 tumor expression correlated with a shorter recurrence-free survival (P < 0.01 and P = 0.02, respectively).
  
  
  CONCLUSIONS
  The results of our study suggest that in pancreatic ductal adenocarcinomas, the MKK4 protein was directly related to high cell proliferation, and that tumor ERK1/2 and P38 expression correlated to shorter postsurgical recurrence-free and overall survivals.
authors.affiliation: Service d'Anatomie Pathologique, APHP Groupe Hospitalier Universitaire Nord, Bobigny, France. adriana.handra-luca@avc.aphp.fr
authors.forename: Adriana
authors.initials: A
authors.lastname: Handra-Luca
authors.forename: Claude
authors.initials: C
authors.lastname: Lesty
authors.forename: Pascal
authors.initials: P
authors.lastname: Hammel
authors.forename: Alain
authors.initials: A
authors.lastname: Sauvanet
authors.forename: Vinciane
authors.initials: V
authors.lastname: Rebours
authors.forename: Antoine
authors.initials: A
authors.lastname: Martin
authors.forename: Remi
authors.initials: R
authors.lastname: Fagard
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Fléjou
authors.forename: Sandrine
authors.initials: S
authors.lastname: Faivre
authors.forename: Pierre
authors.initials: P
authors.lastname: Bédossa
authors.forename: Philippe
authors.initials: P
authors.lastname: Ruszniewski
authors.forename: Anne
authors.initials: A
authors.lastname: Couvelard
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis*; D021441:Carcinoma, Pancreatic Ductal / Q000201:enzymology* / Q000401:mortality / Q000556:secondary / Q000601:surgery; D049109:Cell Proliferation; D016009:Chi-Square Distribution; D018572:Disease-Free Survival; D005260:Female; D005602:France; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D019394:Ki-67 Antigen / Q000032:analysis; D048670:MAP Kinase Kinase 4 / Q000032:analysis; D008297:Male; D008875:Middle Aged; D019950:Mitogen-Activated Protein Kinase 1 / Q000032:analysis; D048052:Mitogen-Activated Protein Kinase 3 / Q000032:analysis; D020928:Mitogen-Activated Protein Kinases / Q000032:analysis*; D015999:Multivariate Analysis; D009364:Neoplasm Recurrence, Local; D010180:Pancreatectomy; D010190:Pancreatic Neoplasms / Q000201:enzymology* / Q000401:mortality / Q000473:pathology / Q000601:surgery; D012189:Retrospective Studies; D018570:Risk Assessment; D012307:Risk Factors; D013997:Time Factors; D016896:Treatment Outcome; D048051:p38 Mitogen-Activated Protein Kinases / Q000032:analysis
chemical_list: D014408:Biomarkers, Tumor; D019394:Ki-67 Antigen; C535150:MAPK1 protein, human; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D048670:MAP Kinase Kinase 4; C482559:MAP2K4 protein, human