title: Epidermal growth factor receptor (EGFR) gene promoter methylation and cetuximab treatment in colorectal cancer patients.
abstract: BACKGROUND
  Epidermal growth factor receptor (EGFR) promoter methylation may be responsible for the loss of EGFR expression in neoplastic cells. The primary aim of our study was to verify a possible correlation between EGFR gene promoter methylation and clinical outcome in metastatic colorectal cancer patients receiving chemotherapy with irinotecan and cetuximab.
  
  
  METHODS
  Colorectal samples from patients treated with irinotecan-cetuximab were analysed for EGFR promoter methylation and EGFR immunohistochemistry.
  
  
  RESULTS
  Fifty-two patients were analysed. Thirty patients (58%) showed EGFR promoter hypermethylation. In EGFR promoter methylated and EGFR promoter unmethylated patients, we observed a partial response in 3 (10%) and 13 (59%) patients, respectively (P=0.03), progressive disease was obtained in 19 (63%) and 2 (9%) patients, respectively, with EGFR promoter methylated and EGFR promoter unmethylated tumours (P=0.0001). Median progression-free survival was 2.4 months in patients showing EGFR promoter methylated tumours and 7.4 months for those who had EGFR promoter unmethylated tumours (P<0.0001; Figure 1). Median overall survival was 6.1 months in patients showing EGFR promoter methylated tumours and 17.8 months for those who had EGFR promoter unmethylated tumours (P<0.0001; Figure 2).
  
  
  CONCLUSIONS
  EGFR promoter hypermethylation, after confirmation in larger data set, may represent a valuable asset in further studies investigating EGFR as a therapeutic target in colorectal cancer.
authors.affiliation: Department of Clinica di Oncologia Medica, AO Ospedali Riuniti-Università Politecnica delle Marche, Via Conca, 60020 Ancona, Italy. marioscartozzi@libero.it
authors.forename: M
authors.initials: M
authors.lastname: Scartozzi
authors.forename: I
authors.initials: I
authors.lastname: Bearzi
authors.forename: A
authors.initials: A
authors.lastname: Mandolesi
authors.forename: R
authors.initials: R
authors.lastname: Giampieri
authors.forename: L
authors.initials: L
authors.lastname: Faloppi
authors.forename: E
authors.initials: E
authors.lastname: Galizia
authors.forename: F
authors.initials: F
authors.lastname: Loupakis
authors.forename: A
authors.initials: A
authors.lastname: Zaniboni
authors.forename: F
authors.initials: F
authors.lastname: Zorzi
authors.forename: T
authors.initials: T
authors.lastname: Biscotti
authors.forename: R
authors.initials: R
authors.lastname: Labianca
authors.forename: A
authors.initials: A
authors.lastname: Falcone
authors.forename: S
authors.initials: S
authors.lastname: Cascinu
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000008:administration & dosage*; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives; D000068818:Cetuximab; D015179:Colorectal Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality; D019175:DNA Methylation; D018450:Disease Progression; D005260:Female; D018773:Genes, erbB-1; D006801:Humans; D000077146:Irinotecan; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D011401:Promoter Regions, Genetic; D016896:Treatment Outcome
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D000077146:Irinotecan; D000068818:Cetuximab; D002166:Camptothecin