title: EGFR and KRAS mutational analysis and their correlation to survival in pancreatic and periampullary cancer.
abstract: OBJECTIVE
  Pancreatic and periampullary cancers have a high incidence of activating KRAS mutations. The aim of this study was to determine the incidence of KRAS and EGFR mutations in pancreatic and periampullary cancers and their relationship with survival.
  
  
  METHODS
  One hundred patients undergoing pancreaticoduodenectomy or pancreatic biopsy for cancer were recruited. Samples of formalin-fixed paraffin-embedded or fresh pancreatic tissue were obtained. EGFR was analyzed by DNA sequencing of exons 18 to 21. KRAS was analyzed by pyrosequencing of codons 12, 13, and 61.
  
  
  RESULTS
  EGFR mutations were found in 2 (2.3%) of 88 assessable cases. One in exon 18 (c.1966C>T, p.Q710X) and 1 in exon 19 (c.2066A>G, p.E734G). A synonymous single-nucleotide polymorphism in exon 20 (c.2361G>A, p.Q787) was identified in 57 (67.8%) of 84 patients studied. Twenty-eight (41.2%) of 68 cases harbored a point mutation in KRAS codon 12 (26 cases) and codon 61 (2 cases). The overall median survival was 308 days (range, 7-2623 days). The presence of KRAS point mutations did not significantly alter median survival time (22.8 vs 28.1 months, P = 0.88).
  
  
  CONCLUSIONS
  EGFR somatic mutations are rare in pancreatobiliary malignancies. KRAS mutations are less common than previous reports and do not correlate with survival.
authors.affiliation: Hepatobiliary Surgery Unit, University of Manchester and Central Manchester University Hospitals NHS Foundation Trust, Manchester, UK. melissacunha@doctors.org.uk
authors.forename: Melissa
authors.initials: M
authors.lastname: Oliveira-Cunha
authors.forename: Kristen D
authors.initials: KD
authors.lastname: Hadfield
authors.forename: Ajith K
authors.initials: AK
authors.lastname: Siriwardena
authors.forename: William
authors.initials: W
authors.lastname: Newman
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001706:Biopsy; D003062:Codon; D004252:DNA Mutational Analysis; D004067:Digestive System Neoplasms / Q000235:genetics* / Q000401:mortality* / Q000473:pathology / Q000601:surgery; D004739:England / Q000453:epidemiology; D066246:ErbB Receptors / Q000235:genetics*; D005091:Exons; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000235:genetics* / Q000401:mortality* / Q000473:pathology / Q000601:surgery; D016577:Pancreaticoduodenectomy; D010641:Phenotype; D017354:Point Mutation; D020641:Polymorphism, Single Nucleotide; D011446:Prospective Studies; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D016283:Proto-Oncogene Proteins p21(ras); D012189:Retrospective Studies; D013997:Time Factors; D016896:Treatment Outcome; D018631:ras Proteins / Q000235:genetics*
chemical_list: D003062:Codon; C117307:KRAS protein, human; D011518:Proto-Oncogene Proteins; C512478:EGFR protein, human; D066246:ErbB Receptors; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins