title: ERCC1/BRCA1 expression and gene polymorphisms as prognostic and predictive factors in advanced NSCLC treated with or without cisplatin.
abstract: BACKGROUND
  The FAST was a factorial trial in first-line treatment of advanced non-small-cell lung cancer (NSCLC), addressing the role of replacing cisplatin with a non-platinum agent. The prognostic and predictive effect of ERCC1/BRCA1 expression and ERCC1/XPD/XRCC1-3 gene polymorphisms on outcomes of patients was examined.
  
  
  METHODS
  Patients were randomised to receive treatment with or without cisplatin. ERCC1/BRCA1 expression was determined by immunohistochemistry. ERCC1 (C8092A, C118T), XPD (Lys751Gln), XRCC1 (Arg399Gln) and XRCC3 (Thr241Met) gene polymorphisms were evaluated on tumour DNA by TaqMan allelic discrimination assay.
  
  
  RESULTS
  Tumour samples were available from 110 of 433 patients enrolled: 54.7% were ERCC1 positive and 51.4% were BRCA1 positive. Overall, ERCC1-negative patients had better response rate (P=0.004), progression-free survival (P=0.023) and overall survival (P=0.012) compared with positive ones, with no statistically significant treatment interaction. The BRCA1-positive patients showed numerically better outcomes, although not statistically significant, with no treatment interaction. Among DNA repair gene polymorphisms, only XRCC1 Gln/Gln genotype evidenced a potential prognostic role (P=0.036).
  
  
  CONCLUSIONS
  This study confirms the prognostic role of ERCC1 expression and XRCC1 (Arg399Gln) polymorphism in advanced NSCLC treated with first-line chemotherapy. None of these biomarkers was shown to be a specific predictive factor of cisplatin efficacy.
authors.affiliation: Oncology Unit, University Hospital, Via Gramsci 14, 43126 Parma, Italy. mtiseo@ao.pr.it
authors.forename: M
authors.initials: M
authors.lastname: Tiseo
authors.forename: P
authors.initials: P
authors.lastname: Bordi
authors.forename: B
authors.initials: B
authors.lastname: Bortesi
authors.forename: L
authors.initials: L
authors.lastname: Boni
authors.forename: C
authors.initials: C
authors.lastname: Boni
authors.forename: E
authors.initials: E
authors.lastname: Baldini
authors.forename: F
authors.initials: F
authors.lastname: Grossi
authors.forename: F
authors.initials: F
authors.lastname: Recchia
authors.forename: F
authors.initials: F
authors.lastname: Zanelli
authors.forename: G
authors.initials: G
authors.lastname: Fontanini
authors.forename: N
authors.initials: N
authors.lastname: Naldi
authors.forename: N
authors.initials: N
authors.lastname: Campanini
authors.forename: C
authors.initials: C
authors.lastname: Azzoni
authors.forename: C
authors.initials: C
authors.lastname: Bordi
authors.forename: A
authors.initials: A
authors.lastname: Ardizzoni
mesh_terms: D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D019313:BRCA1 Protein / Q000096:biosynthesis / Q000235:genetics*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D002945:Cisplatin / Q000008:administration & dosage; D004260:DNA Repair; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000235:genetics*; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D004720:Endonucleases / Q000096:biosynthesis / Q000235:genetics*; D005260:Female; D006801:Humans; D007069:Ifosfamide / Q000008:administration & dosage; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011237:Predictive Value of Tests; D011379:Prognosis; D014747:Vinblastine / Q000008:administration & dosage / Q000031:analogs & derivatives; D000077235:Vinorelbine; D000093542:Gemcitabine
chemical_list: D019313:BRCA1 Protein; D004268:DNA-Binding Proteins; D003841:Deoxycytidine; D014747:Vinblastine; C071447:ERCC1 protein, human; D004720:Endonucleases; D002945:Cisplatin; D000077235:Vinorelbine; D007069:Ifosfamide; D000093542:Gemcitabine
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