title: Tubulin, BRCA1, ERCC1, Abraxas, RAP80 mRNA expression, p53/p21 immunohistochemistry and clinical outcome in patients with advanced non small-cell lung cancer receiving first-line platinum-gemcitabine chemotherapy.
abstract: BACKGROUND
  The aim of this study was to assess the predictive value of tumor expression of nine genes on clinical outcome in patients with advanced NSCLC receiving platinum-gemcitabine chemotherapy.
  
  
  METHODS
  Quantitative PCR or immunohistochemistry were used to analyze the expression of β-tubuline IIA (TUBB2A), β-tubuline III (TUBB3), BRCA1, ERCC1, Abraxas (ABRX) and RAP80 in mRNA isolated from paraffin-embedded tumor biopsies of 45 NSCLC patients treated as part of a larger observational trial. All patients received first-line platinum-gemcitabine chemotherapy for stage IIIB or IV NSCLC.
  
  
  RESULTS
  Median progression-free survival (PFS) was 7 months, overall survival (OS) 12 months. A partial treatment response was found in 14 patients (33%). Patients with low ERCC1 or ABRX expression had a significantly better response to chemotherapy (R=-0.45, p<0.01 for ERCC1; R=-0.40, p=0.016 for ABRX). A significant correlation was found between the individual time for PFS and the expression of both ERCC1 (R=-0.36, p=0.015) and ABRX (R=-0.46, p=0.001). Patients with low ERCC1 expression had a longer OS as compared to patients with high ERCC1 expression (HR=0.26, log-rank p=0.02).
  
  
  CONCLUSIONS
  The study confirms tumor expression of ERCC1 as a predictor for clinical outcome in patients with advanced NSCLC receiving platinum-based chemotherapy, and found ABRX expression to be similarly predictive of clinical outcome. Prospective validation is warranted and - if confirmed - non platinum-containing chemotherapy should be explored as the preferred treatment in patients with high ERCC1 or ABRX expression and no activating mutations of EGFR.
authors.affiliation: Department of Pharmacy and Pharmacology, Slotervaart Hospital, The Netherlands Cancer Institute, Amsterdam, The Netherlands. markus.joerger@kssg.ch
authors.forename: M
authors.initials: M
authors.lastname: Joerger
authors.forename: D
authors.initials: D
authors.lastname: deJong
authors.forename: A
authors.initials: A
authors.lastname: Burylo
authors.forename: J A
authors.initials: JA
authors.lastname: Burgers
authors.forename: P
authors.initials: P
authors.lastname: Baas
authors.forename: A D R
authors.initials: AD
authors.lastname: Huitema
authors.forename: J H
authors.initials: JH
authors.lastname: Beijnen
authors.forename: J H M
authors.initials: JH
authors.lastname: Schellens
mesh_terms: D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D019313:BRCA1 Protein / Q000235:genetics / Q000378:metabolism; D054316:Biomarkers, Pharmacological / Q000378:metabolism*; D002289:Carcinoma, Non-Small-Cell Lung / Q000175:diagnosis* / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D018450:Disease Progression; D004720:Endonucleases / Q000235:genetics / Q000378:metabolism; D005260:Female; D056488:Histone Chaperones; D006801:Humans; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000175:diagnosis* / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D010984:Platinum / Q000008:administration & dosage; D011237:Predictive Value of Tests; D012333:RNA, Messenger / Q000032:analysis; D016896:Treatment Outcome; D014404:Tubulin / Q000235:genetics / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D000093542:Gemcitabine
chemical_list: C520310:ABRAXAS1 protein, human; D019313:BRCA1 Protein; D054316:Biomarkers, Pharmacological; C493956:CDKN1A protein, human; D002352:Carrier Proteins; D050759:Cyclin-Dependent Kinase Inhibitor p21; D004268:DNA-Binding Proteins; D056488:Histone Chaperones; D009687:Nuclear Proteins; D012333:RNA, Messenger; D014404:Tubulin; D016159:Tumor Suppressor Protein p53; C466234:UIMC1 protein, human; D003841:Deoxycytidine; D010984:Platinum; C071447:ERCC1 protein, human; D004720:Endonucleases; D000093542:Gemcitabine