Epidermal growth factor receptor gene promoter methylation in primary colorectal tumors and corresponding metastatic sites: a new perspective for an "old" therapeutic target.
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.
Scartozzi
Mario
M
Clinic of Medical Oncology, Azienda Ospedaliera Ospedali Riuniti-Università Politecnica delle Marche, Ancona Italy. marioscartozzi@libero.it
Bearzi
Italo
I
Mandolesi
Alessandra
A
Galizia
Eva
E
Pierantoni
Chiara
C
Loupakis
Fotios
F
Berardi
Rossana
R
Zaniboni
Alberto
A
Quadri
Antonello
A
Zorzi
Fausto
F
Biagetti
Simona
S
Loretelli
Cristian
C
Biscotti
Tommasina
T
Labianca
Roberto
R
Masi
Gianluca
G
Falcone
Alfredo
A
Cascinu
Stefano
S
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
D014408:Biomarkers, Tumor; D066246:ErbB Receptors