title: 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.
abstract: 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).
  
  
  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.
  
  
  CONCLUSIONS
  Our observations indicate that MSI status and p53 expression may influence the impact of oxaliplatin on adjuvant treatment of stage III colon cancer patients.
authors.affiliation: INSERM, UMR_S 938, Saint-Antoine Research Centre; UPMC Univ Paris 06, UMR_S 938, Saint-Antoine Research Centre; Department of Medical Oncology.
authors.forename: A
authors.initials: A
authors.lastname: Zaanan
authors.affiliation: INSERM, UMR_S 938, Saint-Antoine Research Centre; UPMC Univ Paris 06, UMR_S 938, Saint-Antoine Research Centre; Department of Pathology.
authors.forename: P
authors.initials: P
authors.lastname: Cuilliere-Dartigues
authors.affiliation: INSERM, UMR_S 938, Saint-Antoine Research Centre; UPMC Univ Paris 06, UMR_S 938, Saint-Antoine Research Centre.
authors.forename: A
authors.initials: A
authors.lastname: Guilloux
authors.affiliation: INSERM, UMR_S 938, Saint-Antoine Research Centre; UPMC Univ Paris 06, UMR_S 938, Saint-Antoine Research Centre; Department of General and Digestive Surgery, Saint-Antoine Hospital, Assistance Publique Hôpitaux de Paris.
authors.forename: Y
authors.initials: Y
authors.lastname: Parc
authors.affiliation: INSERM, UMR_S 938, Saint-Antoine Research Centre; UPMC Univ Paris 06, UMR_S 938, Saint-Antoine Research Centre; Department of Medical Oncology.
authors.forename: C
authors.initials: C
authors.lastname: Louvet
authors.affiliation: INSERM, UMR_S 938, Saint-Antoine Research Centre; UPMC Univ Paris 06, UMR_S 938, Saint-Antoine Research Centre; Department of Medical Oncology.
authors.forename: A
authors.initials: A
authors.lastname: de Gramont
authors.affiliation: UPMC Univ Paris 06, UMR_S 938, Saint-Antoine Research Centre; Department of General and Digestive Surgery, Saint-Antoine Hospital, Assistance Publique Hôpitaux de Paris.
authors.forename: E
authors.initials: E
authors.lastname: Tiret
authors.affiliation: Institut Fédératif de Recherche65, UPMC Univ Paris 06.
authors.forename: S
authors.initials: S
authors.lastname: Dumont
authors.affiliation: Department of Digestive Disease Medical Surgery.
authors.forename: B
authors.initials: B
authors.lastname: Gayet
authors.affiliation: Department of Pathology, Institut Mutualiste Montsouris, University Paris Descartes, Paris, France.
authors.forename: P
authors.initials: P
authors.lastname: Validire
authors.affiliation: INSERM, UMR_S 938, Saint-Antoine Research Centre; UPMC Univ Paris 06, UMR_S 938, Saint-Antoine Research Centre; Department of Pathology.
authors.forename: J-F
authors.initials: JF
authors.lastname: Fléjou
authors.affiliation: INSERM, UMR_S 938, Saint-Antoine Research Centre; UPMC Univ Paris 06, UMR_S 938, Saint-Antoine Research Centre.
authors.forename: A
authors.initials: A
authors.lastname: Duval
authors.affiliation: INSERM, UMR_S 938, Saint-Antoine Research Centre; UPMC Univ Paris 06, UMR_S 938, Saint-Antoine Research Centre. Electronic address: francoise.praz@upmc.fr.
authors.forename: F
authors.initials: F
authors.lastname: Praz
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D018572:Disease-Free Survival; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D002955:Leucovorin / Q000008:administration & dosage; D008297:Male; D053842:Microsatellite Instability; D008875:Middle Aged; D009367:Neoplasm Staging; D009944:Organoplatinum Compounds / Q000008:administration & dosage; D000077150:Oxaliplatin; D012189:Retrospective Studies; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism* / Q000502:physiology
chemical_list: D009944:Organoplatinum Compounds; D016159:Tumor Suppressor Protein p53; D000077150:Oxaliplatin; D002955:Leucovorin; D005472:Fluorouracil