title: Functional TP53 mutations have no impact on response to cytotoxic agents in metastatic colon cancer.
abstract: BACKGROUND
  Survival of metastatic colon cancer (mCC) patients has considerably improved with optimization of new drugs regimen. Inactivation of TP53 pathway by TP53 mutations is observed in nearly half of colorectal tumors. The impact of such mutations has been poorly studied in the metastatic setting.
  
  
  METHODS
  The files of 254 mCC treated in a single institution at Saint-Louis hospital between January 1999 and April 2011 were retrospectively reviewed. Tissue samples for analysis of TP53 mutations were available for 68 patients, performed using FASAY. The prognostic value of TP53 status was evaluated by comparing progression free survival (PFS) and overall survival (OS) in the group of TP53-mutated and wild type patients.
  
  
  RESULTS
  PFS was 6.9 months and OS 21.7 months in the whole population. There was no statistical difference in TP53-mutated and wild type groups in term of PFS (HR=1.04; IC 95%=0.6-1.79) and OS (HR=0.99; IC 95%=0.53-1.55) whatever the chemotherapy regimen (oxaliplatin- or irinotecan-based). Only BRAF V600 mutation was demonstrated to be a poor prognostic factor for PFS and OS, and CEA level for OS.
  
  
  CONCLUSIONS
  Routine determination of TP53 mutations, even with a highly sensitive method, cannot be recommended to predict chemotherapy response in mCC.
authors.affiliation: AP-HP, Saint-Louis Hospital, Department of Gastroenterology, 75010 Paris, France.
authors.forename: Jeanne
authors.initials: J
authors.lastname: Netter
authors.affiliation: AP-HP, Saint-Louis Hospital, Department of Biochemistry, 75010 Paris, France; Inserm/CNRS UMR 944/7212, 75010 Paris, France.
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Lehmann-Che
authors.affiliation: AP-HP, Saint-Louis Hospital, Department of Biostatistics, 75010 Paris, France; Inserm UMR 717, 75010 Paris, France.
authors.forename: Jerome
authors.initials: J
authors.lastname: Lambert
authors.affiliation: AP-HP, Saint-Louis Hospital, Department of Biochemistry, 75010 Paris, France.
authors.forename: Anne
authors.initials: A
authors.lastname: Tallet
authors.affiliation: AP-HP, Saint-Louis Hospital, Department of Gastroenterology, 75010 Paris, France.
authors.forename: Nelson
authors.initials: N
authors.lastname: Lourenco
authors.affiliation: AP-HP, Saint-Louis Hospital, Department of Biochemistry, 75010 Paris, France; Inserm/CNRS UMR 944/7212, 75010 Paris, France.
authors.forename: Hany
authors.initials: H
authors.lastname: Soliman
authors.affiliation: AP-HP, Saint-Louis Hospital, Department of Pathology, 75010 Paris, France; University Paris Diderot, UMR-S-728 Inserm, 75013 Paris, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Bertheau
authors.affiliation: AP-HP, Saint-Louis Hospital, Department of Gastroenterology, 75010 Paris, France; Équipe Avenir Inserm U940, 75010 Paris, France.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Pariente
authors.affiliation: AP-HP, Saint-Louis Hospital, Department of General, Endocrine and Digestive Surgery, 75010 Paris, France.
authors.forename: Mircea
authors.initials: M
authors.lastname: Chirica
authors.affiliation: Surgical Oncologic and Digestive Unit, Lariboisière Hospital, AP-HP, 75010 Paris, France.
authors.forename: Marc
authors.initials: M
authors.lastname: Pocard
authors.affiliation: AP-HP, Saint-Louis Hospital, Department of Gastroenterology, 75010 Paris, France; Équipe Avenir Inserm U940, 75010 Paris, France.
authors.forename: Matthieu
authors.initials: M
authors.lastname: Allez
authors.affiliation: AP-HP, Saint-Louis Hospital, Department of Biochemistry, 75010 Paris, France; Inserm/CNRS UMR 944/7212, 75010 Paris, France.
authors.forename: Hugues
authors.initials: H
authors.lastname: De The
authors.affiliation: AP-HP, Saint-Louis Hospital, Department of Gastroenterology, 75010 Paris, France. Electronic address: jean-marc.gornet@sls.aphp.fr.
authors.forename: Jean-Marc
authors.initials: JM
authors.lastname: Gornet
mesh_terms: D000368:Aged; D000483:Alleles; D000704:Analysis of Variance; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002277:Carcinoma / Q000235:genetics / Q000473:pathology / Q000556:secondary; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D004252:DNA Mutational Analysis / Q000379:methods; D018572:Disease-Free Survival; D020868:Gene Silencing; D016158:Genes, p53 / Q000235:genetics*; D005819:Genetic Markers; D005820:Genetic Testing / Q000379:methods; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics / Q000473:pathology / Q000556:secondary; D008175:Lung Neoplasms / Q000235:genetics / Q000473:pathology / Q000556:secondary; D008297:Male; D053842:Microsatellite Instability; D008875:Middle Aged; D009154:Mutation; D010858:Pigmentation / Q000235:genetics; D011518:Proto-Oncogene Proteins / Q000235:genetics; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics; D016283:Proto-Oncogene Proteins p21(ras); D012189:Retrospective Studies; D015003:Yeasts / Q000235:genetics; D018631:ras Proteins / Q000235:genetics
chemical_list: D000970:Antineoplastic Agents; D005819:Genetic Markers; C117307:KRAS protein, human; D011518:Proto-Oncogene Proteins; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins
keywords: Cancer colique metastatique; Chemotherapy response; Metastatic colon cancer; Mutations TP53; Réponse à la chimiothérapie; TP53 mutation