Impact of p53 expression and microsatellite instability on stage III colon cancer disease-free survival in patients treated by 5-fluorouracil and leucovorin with or without oxaliplatin

Ann Oncol. 2010 Apr;21(4):772-780. doi: 10.1093/annonc/mdp383. Epub 2009 Oct 15.


Background: The aim was to determine the values of p53 tumour expression and microsatellite instability (MSI) phenotype to predict benefit from adjuvant chemotherapy of colon cancer by 5-fluorouracil and leucovorin (FL) alone or with oxaliplatin (FOLFOX).

Patients and methods: This retrospective study included 233 unselected patients with stage III colon cancer treated by FL (n = 124) or FOLFOX (n = 109). The impact of p53 expression and MSI on disease-free survival (DFS) was defined using univariate and multivariate analyses. A Cox proportional hazards model was specifically designed to evaluate the interaction between chemotherapy and these genetic alterations.

Results: In univariate analyses, addition of oxaliplatin significantly improved DFS provided that tumour overexpressed p53 [hazard ratio (HR) 0.39; 95% confidence interval (CI) 0.19-0.82; P = 0.01] or displayed MSI phenotype (HR 0.17; 95% CI 0.04-0.68; P = 0.01). In multivariate analyses, p53 was confirmed as an independent factor predictive of benefit from FOLFOX (P = 0.03), while the interaction of MSI with chemotherapy could not be determined in the absence of relapse in the MSI group treated with FOLFOX.

Conclusion: Our observations indicate that MSI status and p53 expression may influence the impact of oxaliplatin on adjuvant treatment of stage III colon cancer patients.

Publication types

  • Evaluation Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / drug therapy*
  • Adenocarcinoma / genetics
  • Adenocarcinoma / metabolism
  • Adenocarcinoma / pathology
  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Colonic Neoplasms / drug therapy*
  • Colonic Neoplasms / genetics
  • Colonic Neoplasms / metabolism
  • Colonic Neoplasms / pathology
  • Disease-Free Survival
  • Female
  • Fluorouracil / administration & dosage
  • Humans
  • Leucovorin / administration & dosage
  • Male
  • Microsatellite Instability*
  • Middle Aged
  • Neoplasm Staging
  • Organoplatinum Compounds / administration & dosage
  • Oxaliplatin
  • Retrospective Studies
  • Tumor Suppressor Protein p53 / metabolism*
  • Tumor Suppressor Protein p53 / physiology


  • Organoplatinum Compounds
  • Tumor Suppressor Protein p53
  • Oxaliplatin
  • Leucovorin
  • Fluorouracil