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. STUDY DESIGN: 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%). CONCLUSION: 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. (Anal Quant Cytol Histol 2009;31:417-423)