title: Integral analysis of p53 and its value as prognostic factor in sporadic colon cancer.
abstract: BACKGROUND
  p53 (encoded by TP53) is involved in DNA damage repair, cell cycle regulation, apoptosis, aging and cellular senescence. TP53 is mutated in around 50% of human cancers. Nevertheless, the consequences of p53 inactivation in colon cancer outcome remain unclear. Recently, a new role of p53 together with CSNK1A1 in colon cancer invasiveness has been described in mice.
  
  
  METHODS
  By combining data on different levels of p53 inactivation, we aimed to predict p53 functionality and to determine its effects on colon cancer outcome. Moreover, survival effects of CSNK1A1 together with p53 were also studied.Eighty-three formalin fixed paraffin embedded colon tumors were enriched for tumor cells using flow sorting, the extracted DNA was used in a custom SNP array to determine chr17p13-11 allelic state; p53 immunostaining, TP53 exons 5, 6, 7 and 8 mutations were determined in combination with mRNA expression analysis on frozen tissue.
  
  
  RESULTS
  Patients with a predicted functional p53 had a better prognosis than patients with non functional p53 (Log Rank p=0.009). Expression of CSNK1A1 modified p53 survival effects. Patients with low CSNK1A1 expression and non-functional p53 had a very poor survival both in the univariate (Log Rank p<0.001) and in the multivariate survival analysis (HR=4.74 95% CI 1.45 - 15.3 p=0.009).
  
  
  CONCLUSIONS
  The combination of mutational, genomic, protein and downstream transcriptional activity data predicted p53 functionality which is shown to have a prognostic effect on colon cancer patients. This effect was specifically modified by CSKN1A1 expression.
authors.affiliation: Department of Pathology, Leiden University Medical Centre, Leiden, the Netherlands.
authors.forename: Arantza Fariña
authors.initials: AF
authors.lastname: Sarasqueta
authors.forename: Giusi
authors.initials: G
authors.lastname: Forte
authors.forename: Wim E
authors.initials: WE
authors.lastname: Corver
authors.forename: Noel F
authors.initials: NF
authors.lastname: de Miranda
authors.forename: Dina
authors.initials: D
authors.lastname: Ruano
authors.forename: Ronald
authors.initials: R
authors.lastname: van Eijk
authors.forename: Jan
authors.initials: J
authors.lastname: Oosting
authors.forename: Rob A E M
authors.initials: RA
authors.lastname: Tollenaar
authors.forename: Tom
authors.initials: T
authors.lastname: van Wezel
authors.forename: Hans
authors.initials: H
authors.lastname: Morreau
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics* / Q000378:metabolism / Q000401:mortality; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis / Q000235:genetics*; D003110:Colonic Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000401:mortality; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011379:Prognosis; D046888:Tissue Array Analysis; D016159:Tumor Suppressor Protein p53 / Q000032:analysis / Q000235:genetics* / Q000378:metabolism
chemical_list: D014408:Biomarkers, Tumor; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53