title: EGFR gene copy number assessment from areas with highest EGFR expression predicts response to anti-EGFR therapy in colorectal cancer.
abstract: BACKGROUND
  Only 40-70% of metastatic colorectal cancers (mCRCs) with wild-type (WT) KRAS oncogene respond to anti-epidermal growth factor receptor (anti-EGFR) antibody treatment. EGFR amplification has been suggested as an additional marker to predict the response. However, improved methods for bringing the EGFR analysis into routine laboratory are needed.
  
  
  METHODS
  The material consisted of 80 patients with mCRC, 54 of them receiving anti-EGFR therapy. EGFR gene copy number (GCN) was analysed by automated silver in situ hybridisation (SISH). Immunohistochemical EGFR protein analysis was used to guide SISH assessment.
  
  
  RESULTS
  Clinical benefit was seen in 73% of high (≥ 4.0) EGFR GCN patients, in comparison with 59% of KRAS WT patients. Only 20% of low EGFR GCN patients responded to therapy. A high EGFR GCN number associated with longer progression-free survival (P<0.0001) and overall survival (P=0.004). Together with KRAS analysis, EGFR GCN identified the responsive patients to anti-EGFR therapy more accurately than either test alone. The clinical benefit rate of KRAS WT/high EGFR GCN tumours was 82%.
  
  
  CONCLUSIONS
  Our results show that automated EGFR SISH, in combination with KRAS mutation analysis, can be a useful and easily applicable technique in routine diagnostic practise for selecting patients for anti-EGFR therapy.
authors.affiliation: Department of Oncology and Radiotherapy, Turku University Hospital, Hämeentie 11, PO Box 52, Turku FIN-20521, Finland. annika.algars@utu.fi
authors.forename: A
authors.initials: A
authors.lastname: Ålgars
authors.forename: M
authors.initials: M
authors.lastname: Lintunen
authors.forename: O
authors.initials: O
authors.lastname: Carpén
authors.forename: R
authors.initials: R
authors.lastname: Ristamäki
authors.forename: J
authors.initials: J
authors.lastname: Sundström
mesh_terms: D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000627:therapeutic use; D054316:Biomarkers, Pharmacological / Q000032:analysis; D002277:Carcinoma / Q000175:diagnosis* / Q000235:genetics / Q000628:therapy; D015179:Colorectal Neoplasms / Q000175:diagnosis* / Q000235:genetics / Q000628:therapy; D004252:DNA Mutational Analysis; D066246:ErbB Receptors / Q000037:antagonists & inhibitors / Q000276:immunology*; D005260:Female; D018628:Gene Dosage; D015972:Gene Expression Regulation, Neoplastic; D018773:Genes, erbB-1 / Q000235:genetics*; D011905:Genes, ras; D006801:Humans; D007167:Immunotherapy; D017403:In Situ Hybridization / Q000379:methods; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D012189:Retrospective Studies; D016896:Treatment Outcome
chemical_list: D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D054316:Biomarkers, Pharmacological; C512478:EGFR protein, human; D066246:ErbB Receptors