title: EGFR CA repeat polymorphism predict clinical outcome in EGFR mutation positive NSCLC patients treated with erlotinib.
abstract: OBJECTIVE
  Somatic mutations in the epidermal growth factor receptor (EGFR) are predictors of efficacy for treatment with the EGFR tyrosine kinase inhibitor erlotinib in non-small cell lung cancer (NSCLC). A CA repeat polymorphism in intron 1 of the EGFR gene influences the transcription of the EGFR gene. This study evaluates the association between the CA repeat polymorphism and outcome in NSCLC patients treated with erlotinib.
  
  
  METHODS
  Number of CA repeats in the EGFR gene was evaluated with PCR-fragment length analysis by capillary electrophoresis in 432 advanced NSCLC patients treated with erlotinib irrespective of EGFR mutation status. Patients were dichotomized into harboring short allele (CA≤16 in any allele) or long alleles (CA>16 in both alleles). Number of repeats was correlated with clinical characteristic and outcome. A subgroup analysis was performed based on the somatic EGFR mutation status.
  
  
  RESULTS
  In EGFR mutation positive patients (N=62) we demonstrate a significantly higher median progression free survival (HR=0.39 (0.22-0.70); p=0.002) and overall survival (HR=0.43 (0.23-0.78); p=0.006) in patients also harboring a short CA repeat length vs. a long (median follow-up time of 52.2 months). The result remained highly significant in a multivariate Cox proportional hazards model. This correlation was not seen in EGFR mutation negative patients.
  
  
  CONCLUSIONS
  Our study demonstrate that in EGFR mutation positive NSCLC patients treated with erlotinib a low number of CA repeats in intron 1 of the EGFR gene is a predictor for both longer progression free survival and overall survival.
authors.affiliation: Department of Clinical Biochemistry, Aarhus University Hospital, Aarhus, Denmark; Department of Oncology, Aarhus University Hospital, Aarhus, Denmark. Electronic address: anlarsen@rm.dk.
authors.forename: Anne
authors.initials: A
authors.lastname: Winther Larsen
authors.affiliation: Department of Clinical Biochemistry, Aarhus University Hospital, Aarhus, Denmark.
authors.forename: Peter Henrik
authors.initials: PH
authors.lastname: Nissen
authors.affiliation: Department of Oncology, Aarhus University Hospital, Aarhus, Denmark.
authors.forename: Peter
authors.initials: P
authors.lastname: Meldgaard
authors.affiliation: Department of Oncology, Aarhus University Hospital, Aarhus, Denmark.
authors.forename: Britta
authors.initials: B
authors.lastname: Weber
authors.affiliation: Department of Clinical Biochemistry, Aarhus University Hospital, Aarhus, Denmark.
authors.forename: Boe Sandahl
authors.initials: BS
authors.lastname: Sorensen
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D018450:Disease Progression; D066246:ErbB Receptors / Q000235:genetics*; D000069347:Erlotinib Hydrochloride; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009154:Mutation; D011110:Polymorphism, Genetic; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use; D011799:Quinazolines / Q000627:therapeutic use*; D012091:Repetitive Sequences, Nucleic Acid; D012307:Risk Factors; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; D011799:Quinazolines; D000069347:Erlotinib Hydrochloride; D066246:ErbB Receptors
keywords: CA repeat; EGFR somatic mutations; Epidermal growth factor receptor; Erlotinib; Non-small cell lung cancer; Polymorphism