title: Prognostic value of microsatellite instability and p53 expression in metastatic colorectal cancer treated with oxaliplatin and fluoropyrimidine-based chemotherapy.
abstract: OBJECTIVE
  The aim of this study was to evaluate the prognostic value of MSI-H and p53 overexpression in metastatic colorectal cancer (mCRC) treated with oxaliplatin and fluoropyrimidine-based first line chemotherapy.
  
  
  METHODS
  Tumour samples were retrospectively obtained from 229 patients from a prospective randomised phase III trial of the AIO colorectal study group, comparing CAPOX and FUFOX in mCRC. Immunohistochemistry of p53 and MMR proteins as well as microsatellite analysis were performed.
  
  
  RESULTS
  The incidence of MSI-H and p53 overexpression was 7.9 % and 65.4 %, respectively. MSI-H status was not correlated with ORR, PFS and OS. We observed a trend to lower DCR for MSI-H tumours (65 % vs. 85 %, p = 0.055). p53 overexpression was not correlated with DCR, ORR and PFS. The median OS of patients with tumors with p53 overexpression was significantly longer compared to tumors withhout p53 overexpression (19.6 vs. 15.8 months; p = 0.05). The post-progression survival (PPS) of p53-positive patients undergoing 2nd and/or 3rd line chemotherapy with irinotecan and/or cetuximab was significantly longer compared to p53-negative patients.
  
  
  CONCLUSIONS
  MSI-H tumours tend to have lower disease control rates when treated with an oxaliplatin/fluoropyrmidin combination. mCRC patients with p53 overexpression undergoing an irinotecan containing second- or third-line chemotherapy after oxaliplatin failure have a significantly longer post-progression survival compared to patients without p53 overexpression. To validate the clinical impact of p53 in patients with mCRC treated with irinotecan- and/or cetuximab further studies are needed.
authors.affiliation: Department of Internal Medicine, Ruhr-University of Bochum, Knappschaftskrankenhaus, Bochum.
authors.forename: S
authors.initials: S
authors.lastname: Nöpel-Dünnebacke
authors.affiliation: Departement of Oncology, Klinikum Arnsberg.
authors.forename: K
authors.initials: K
authors.lastname: Schulmann
authors.affiliation: Departement of Hematology and Oncology, Ruhr-University of Bochum, St. Josef Hospital, Bochum.
authors.forename: A
authors.initials: A
authors.lastname: Reinacher-Schick
authors.affiliation: Clinic of Internal Medicine, Hospital Bremen East, Bremen.
authors.forename: R
authors.initials: R
authors.lastname: Porschen
authors.affiliation: Department of Internal Medicine, Ruhr-University of Bochum, Knappschaftskrankenhaus, Bochum.
authors.forename: W
authors.initials: W
authors.lastname: Schmiegel
authors.affiliation: Institute of Pathology, Ruhr-University of Bochum.
authors.forename: A
authors.initials: A
authors.lastname: Tannapfel
authors.affiliation: Medizinische Klinik, Maria-Hilf-Krankenhaus, Mönchengladbach.
authors.forename: U
authors.initials: U
authors.lastname: Graeven
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D015415:Biomarkers / Q000378:metabolism; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D002277:Carcinoma / Q000175:diagnosis / Q000188:drug therapy / Q000556:secondary*; D015179:Colorectal Neoplasms / Q000175:diagnosis* / Q000188:drug therapy* / Q000235:genetics; D005260:Female; D005472:Fluorouracil / Q000627:therapeutic use; D006801:Humans; D008297:Male; D053842:Microsatellite Instability; D018895:Microsatellite Repeats; D008875:Middle Aged; D009944:Organoplatinum Compounds / Q000627:therapeutic use; D000077150:Oxaliplatin; D011379:Prognosis; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D016896:Treatment Outcome; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
chemical_list: D015415:Biomarkers; D014408:Biomarkers, Tumor; D009944:Organoplatinum Compounds; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D000077150:Oxaliplatin; D005472:Fluorouracil