title: Kras mutations and p53 overexpression in pseudomyxoma peritonei: association with phenotype and prognosis.
abstract: BACKGROUND
  Little information exists on Kras mutations and p53 overexpression in pseudomyxoma peritonei (PMP). These genetic alterations are associated with poorer prognoses in colorectal cancer. We postulated that these mutations might be more frequent in high-grade (HG) PMP (peritoneal mucinous carcinomatosis) versus low-grade (LG) PMP (disseminated peritoneal adenomucinosis/peritoneal mucinous carcinomatosis), for which survival differences are well documented.
  
  
  METHODS
  We collected data retrospectively on patients with PMP of appendiceal origin tested for Kras mutation (commercial assay) and p53 overexpression (immunohistochemistry). We used Fisher's exact test, chi-square test, and Kaplan-Meier survival curves for analysis.
  
  
  RESULTS
  Of 64 cases with Kras mutations, 25 were classified as LG and 39 as HG PMP. Median age at diagnosis was 53 ± 11.5 y. We detected Kras mutations in 37 of 64 patients (57.8%). In LG PMP, 15 of 25 (60%) were Kras mutant versus 22 of 39 (56.4%) in HG PMP (P=0.80). Nearly 89% of mutations were seen in codon 12. We noted overexpression of p53 in 44.3% (86 of 194) of patients overall, which was significantly different between LG PMP and HG PMP: 35.5% (37 of 104) versus 54.4% (49 of 90), respectively (P=0.009). Kras mutations did not affect prognosis. Overexpression of p53 was associated with a worse outcome.
  
  
  CONCLUSIONS
  Kras mutation and p53 overexpression rates are comparable to those of colorectal adenomas and mucinous colorectal cancer. Codon 12 mutations may be associated with mucin production. Kras mutation status is not prognostic for overall survival. Overexpression of p53 was significantly correlated with female sex, higher-grade disease, and worse survival.
authors.affiliation: Department of Surgery, Creighton University Medical Center, Omaha, NE, USA.
authors.forename: Shreya
authors.initials: S
authors.lastname: Shetty
authors.forename: Peter
authors.initials: P
authors.lastname: Thomas
authors.forename: Bala
authors.initials: B
authors.lastname: Ramanan
authors.forename: Poonam
authors.initials: P
authors.lastname: Sharma
authors.forename: Venkatesh
authors.initials: V
authors.lastname: Govindarajan
authors.forename: Brian
authors.initials: B
authors.lastname: Loggie
mesh_terms: D000328:Adult; D000368:Aged; D015179:Colorectal Neoplasms / Q000235:genetics; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010534:Peritoneal Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D010641:Phenotype; D011379:Prognosis; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D016283:Proto-Oncogene Proteins p21(ras); D011553:Pseudomyxoma Peritonei / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D012189:Retrospective Studies; D016159:Tumor Suppressor Protein p53 / Q000032:analysis* / Q000502:physiology; D018631:ras Proteins / Q000235:genetics*
chemical_list: 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