title: Comparison of microsatellite instability and chromosomal instability in predicting survival of patients with T3N0 colorectal cancer.
abstract: BACKGROUND
  At least 2 apparently independent mechanisms, microsatellite instability (MSI) and chromosomal instability, are implicated in colorectal tumorigenesis. Their respective roles in predicting clinical outcomes of patients with T3N0 colorectal cancer remain unknown.
  
  
  METHODS
  Eighty-eight patients with a sporadic T3N0 colon or rectal adenocarcinoma were followed up for a median of 67 months. For chromosomal instability analysis, Ki-ras mutations were determined by single-strand polymerase chain reaction, and p53 protein staining was studied by immunohistochemistry. For MSI analysis, DNA was amplified by polymerase chain reaction at 7 microsatellite targets (BAT25, BAT26, D17S250, D2S123, D5S346, transforming growth factor receptor II, and BAX).
  
  
  RESULTS
  Overall 5-year survival rate was 72%. p53 protein nuclear staining was detected in 39 patients (44%), and MSI was detected in 21 patients (24%). MSI correlated with proximal location (P <.001) and mucinous content (P <.001). In a multivariate analysis, p53 protein expression carried a significant risk of death (relative risk = 4.0, 95% CI = 1.6 to 10.1, P =.004). By comparison, MSI was not a statistically significant prognostic factor for survival in this group (relative risk = 2.2, 95% CI = 0.6 to 7.3, P =.21).
  
  
  CONCLUSIONS
  p53 protein overexpression provides better prognostic discrimination than MSI in predicting survival of patients with T3N0 colorectal cancer. Although MSI is associated with specific clinicopathologic parameters, it did not predict overall survival in this group. Assessment of p53 protein expression by immunocytochemistry provides a simple means to identify a subset of T3N0 patients with a 4-times increased risk for death.
authors.affiliation: Department of Surgery, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland.
authors.forename: Pascal
authors.initials: P
authors.lastname: Gervaz
authors.forename: Jean-Philippe
authors.initials: JP
authors.lastname: Cerottini
authors.forename: Hanifa
authors.initials: H
authors.lastname: Bouzourene
authors.forename: Dieter
authors.initials: D
authors.lastname: Hahnloser
authors.forename: Christy L
authors.initials: CL
authors.lastname: Doan
authors.forename: Jean
authors.initials: J
authors.lastname: Benhattar
authors.forename: Pascal
authors.initials: P
authors.lastname: Chaubert
authors.forename: Michelle
authors.initials: M
authors.lastname: Secic
authors.forename: Michel
authors.initials: M
authors.lastname: Gillet
authors.forename: John M
authors.initials: JM
authors.lastname: Carethers
mesh_terms: D000328:Adult; D000368:Aged; D002869:Chromosome Aberrations; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000401:mortality; D005260:Female; D011905:Genes, ras; D006801:Humans; D008297:Male; D018895:Microsatellite Repeats; D008875:Middle Aged; D009154:Mutation; D015996:Survival Rate; D016159:Tumor Suppressor Protein p53 / Q000032:analysis
chemical_list: D016159:Tumor Suppressor Protein p53