title: TP53 mutations in advanced colorectal cancer: the dark side of the moon.
abstract: BACKGROUND
  Evidence for TP53 mutations as biomarker in colorectal cancer (CRC) is conflicting.
  
  
  METHODS
  We assessed TP53 mutations in 51 patients with advanced CRC enrolled into a phase II, randomised trial of first-line tegafur-uracil (UFT)/leucovorin (LV) plus irinotecan (n = 23) versus UFT/LV plus oxaliplatin (n = 28).
  
  
  RESULTS
  Non-functional TP53 mutations were found in 35% of patients. The response rate was not significantly different according to TP53 status. Progression-free and overall survival were longer in patients with TP53 mutations compared to those with wild-type TP53 (9 vs. 6.5 months, p = 0.0504, and 39.2 vs. 19.6 months, p = 0.0055, respectively). On multivariable analysis, TP53 mutation was independently associated with a decreased risk of death (hazard ratio 0.329, 95% CI 0.159-0.679; p = 0.0026). Treatment arm did not interact with TP53 in influencing outcomes.
  
  
  CONCLUSIONS
  TP53 was not predictive of benefit from first-line irinotecan- or oxaliplatin-based chemotherapy. TP53 mutations may possibly be associated with a more indolent course of CRC after the diagnosis of metastatic disease.
authors.affiliation: Medical Oncology Department, Fondazione IRCCS Istituto Nazionale dei Tumori (National Cancer Institute), Milan, Italy.
authors.forename: Filippo
authors.initials: F
authors.lastname: Pietrantonio
authors.forename: Pamela
authors.initials: P
authors.lastname: Biondani
authors.forename: Federica
authors.initials: F
authors.lastname: Perrone
authors.forename: Maria
authors.initials: M
authors.lastname: Di Bartolomeo
authors.forename: Monica
authors.initials: M
authors.lastname: Pacifici
authors.forename: Massimo
authors.initials: M
authors.lastname: Milione
authors.forename: Flavia
authors.initials: F
authors.lastname: Melotti
authors.forename: Claudia
authors.initials: C
authors.lastname: Maggi
authors.forename: Gabriella
authors.initials: G
authors.lastname: Montemurro
authors.forename: Ilaria
authors.initials: I
authors.lastname: Bossi
authors.forename: Luigi
authors.initials: L
authors.lastname: Mariani
authors.forename: Filippo
authors.initials: F
authors.lastname: de Braud
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D017322:Clinical Trials, Phase II as Topic; D015179:Colorectal Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D004252:DNA Mutational Analysis; D018572:Disease-Free Survival; D005260:Female; D056726:Genetic Association Studies; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009367:Neoplasm Staging; D016016:Proportional Hazards Models; D016032:Randomized Controlled Trials as Topic; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*
chemical_list: C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53