title: KRAS mutations in codon 12 or 13 are associated with worse prognosis in pancreatic ductal adenocarcinoma.
abstract: OBJECTIVE
  Mutations in the KRAS and P53 genes belong to the most frequently observed genetic alterations in pancreatic ductal adenocarcinoma. The aim of this study was to examine the frequency and prognostic impact of KRAS mutations. In addition, we attempted to define molecular subgroups with distinct biologic behavior by combination of KRAS sequencing data with p53 protein expression data.
  
  
  METHODS
  KRAS mutational analyses were performed in a study group of 153 patients by Sanger sequencing. Immunohistochemistry for p53 was performed on tissue microarrays.
  
  
  RESULTS
  KRAS mutations in codon 12 or 13 were found in 68% of cases. Nuclear staining for p53 was detectable in 110 (68%) of 162 evaluable cases. We found no correlation between KRAS mutational status and p53 expression. KRAS mutational status but not p53 immunohistochemistry was an independent prognostic factor in the study group (P = 0.02). In a stratified analysis according to KRAS mutational status, p53 expression failed to define prognostic groups beyond the impact of KRAS mutational status.
  
  
  CONCLUSIONS
  Our results support the crucial role of KRAS mutational status in pancreatic cancer biology. KRAS mutational status may serve as a prognostic marker. However, its predictive role for targeted therapies remains to be evaluated.
authors.affiliation: From the Departments of *Pathology, †Hematology, Oncology and Tumor Immunology, and ‡General, Visceral, and Transplantation Surgery, Charité - Universitätsmedizin Berlin, Berlin; and §Department of Pathology, University Hospital Heidelberg, Heidelberg, Germany.
authors.forename: Bruno V
authors.initials: BV
authors.lastname: Sinn
authors.forename: Jana K
authors.initials: JK
authors.lastname: Striefler
authors.forename: Marc A
authors.initials: MA
authors.lastname: Rudl
authors.forename: Annika
authors.initials: A
authors.lastname: Lehmann
authors.forename: Marcus
authors.initials: M
authors.lastname: Bahra
authors.forename: Carsten
authors.initials: C
authors.lastname: Denkert
authors.forename: Marianne
authors.initials: M
authors.lastname: Sinn
authors.forename: Jens
authors.initials: J
authors.lastname: Stieler
authors.forename: Frederick
authors.initials: F
authors.lastname: Klauschen
authors.forename: Jan
authors.initials: J
authors.lastname: Budczies
authors.forename: Wilko
authors.initials: W
authors.lastname: Weichert
authors.forename: Albrecht
authors.initials: A
authors.lastname: Stenzinger
authors.forename: Carsten
authors.initials: C
authors.lastname: Kamphues
authors.forename: Manfred
authors.initials: M
authors.lastname: Dietel
authors.forename: Hanno
authors.initials: H
authors.lastname: Riess
mesh_terms: D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis / Q000235:genetics*; D021441:Carcinoma, Pancreatic Ductal / Q000737:chemistry / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D003062:Codon; D004252:DNA Mutational Analysis; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010190:Pancreatic Neoplasms / Q000737:chemistry / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D010641:Phenotype; D011237:Predictive Value of Tests; D011379:Prognosis; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D016283:Proto-Oncogene Proteins p21(ras); D012307:Risk Factors; D016159:Tumor Suppressor Protein p53 / Q000032:analysis; D018631:ras Proteins / Q000235:genetics*
chemical_list: D014408:Biomarkers, Tumor; D003062:Codon; C117307:KRAS protein, human; D011518:Proto-Oncogene Proteins; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins