title: Epidermal growth factor receptor gene promoter methylation in primary colorectal tumors and corresponding metastatic sites: a new perspective for an "old" therapeutic target.
abstract: OBJECTIVE
  To clarify the role of epidermal growth factor receptor (EGFR) promoter methylation in primary colorectal cancers and corresponding metastases and its relationship to EGFR expression.
  
  
  METHODS
  Formalin-fixed tumor samples (primary site and metastasis)from colorectal cancer patients were analyzed for EGFR promoter methylation and EGFR immunohistochemistry expression.
  
  
  RESULTS
  Among the 63 assessable patients, 25 cases (39.7%) showed EGFR promoter methylation. Forty-two primary colorectal tumors and corresponding metastases were available for paired analysis of EGFR methylation status. EGFR methylation status of the primary tumor was in accordance with that of metastasis in 29 patients (69%). In contrast, 7 patients (50%) with EGFR promoter methylation in the primary tumor showed unmethylated EGFR in metastasis, and 6 metastases (46%) showed EGFR promoter hypermethylation derived from unmethylated EGFR primary tumors. Lack of EGFR protein expression was observed in 8 EGFR promoter methylated primary tumors (44%) and in 7 EGFR promoter methylated metastatic sites (44%).
  
  
  CONCLUSIONS
  EGFR promoter hypermethylation does not seem to represent a rare event in colorectal cancer and may be present differently in different tumor sites. These findings may be relevant to further studies investigating the role of EGFR in colorectal cancer patients.
authors.affiliation: Clinic of Medical Oncology, Azienda Ospedaliera Ospedali Riuniti-Università Politecnica delle Marche, Ancona Italy. marioscartozzi@libero.it
authors.forename: Mario
authors.initials: M
authors.lastname: Scartozzi
authors.forename: Italo
authors.initials: I
authors.lastname: Bearzi
authors.forename: Alessandra
authors.initials: A
authors.lastname: Mandolesi
authors.forename: Eva
authors.initials: E
authors.lastname: Galizia
authors.forename: Chiara
authors.initials: C
authors.lastname: Pierantoni
authors.forename: Fotios
authors.initials: F
authors.lastname: Loupakis
authors.forename: Rossana
authors.initials: R
authors.lastname: Berardi
authors.forename: Alberto
authors.initials: A
authors.lastname: Zaniboni
authors.forename: Antonello
authors.initials: A
authors.lastname: Quadri
authors.forename: Fausto
authors.initials: F
authors.lastname: Zorzi
authors.forename: Simona
authors.initials: S
authors.lastname: Biagetti
authors.forename: Cristian
authors.initials: C
authors.lastname: Loretelli
authors.forename: Tommasina
authors.initials: T
authors.lastname: Biscotti
authors.forename: Roberto
authors.initials: R
authors.lastname: Labianca
authors.forename: Gianluca
authors.initials: G
authors.lastname: Masi
authors.forename: Alfredo
authors.initials: A
authors.lastname: Falcone
authors.forename: Stefano
authors.initials: S
authors.lastname: Cascinu
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics* / Q000378:metabolism / Q000556:secondary; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D019175:DNA Methylation; D066246:ErbB Receptors / Q000235:genetics* / Q000378:metabolism; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D020868:Gene Silencing; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D011401:Promoter Regions, Genetic
chemical_list: D014408:Biomarkers, Tumor; D066246:ErbB Receptors