Abstract
Purpose: It has been shown that the R497K polymorphism of the epidermal growth factor receptor (EGFR) has attenuated functions in ligand binding, tyrosine kinase activation, and growth stimulation. Because the activation of EGFR results in an unfavorable prognosis of patients with colorectal carcinoma, a pilot study was conducted to assess the influence of this polymorphism on colorectal carcinoma patients.
Experimental Design: We retrospectively analyzed the effect of the R497K polymorphism of EGFR on clinicopathologic features in 209 colorectal carcinoma patients, including 100 with stage II/III colorectal carcinoma receiving curative surgery and the other 109 with metastatic diseases.
Results: An excellent correlation in codon 497 statuses examined by patients' WBCs and tumor tissues was found but no significant between-group difference in patients with or without colorectal carcinoma (P = 0.97). A marked decrease on EGFR phosphorylation (P < 0.01) and c-Myc activation (P = 0.02) was observed in patients with R497K polymorphism, which is associated with decreased invasion (P = 0.01), lower nodal involvement (P = 0.02), reduced subsequent metastasis (P < 0.01), and longer disease-free (P < 0.01) as well as overall (P < 0.01) survival in stage II/III colorectal carcinoma patients who had received curative surgery. For patients with metastatic colorectal carcinoma, this polymorphism was associated with a higher response to 5-fluorouracil/oxaliplatin treatment (P = 0.02) and a longer survival (P < 0.01). By multivariate analysis, this polymorphism was also identified as an independent prognostic factor (P = 0.03).
Conclusions: These data suggest that the R497K polymorphism of the EGFR, by reducing its activation and a consequential down-regulation of its target genes, could be a key determinant for reduced tumor recurrence of stage II/III colorectal carcinoma patients receiving curative surgery and a longer survival of patients with stage II/III as well as metastatic colorectal carcinoma.
- EGFR
- R497K
- polymorphism
- colorectal carcinoma
- prognosis
Footnotes
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Grant support: Taipei Veterans General Hospital grant V95S5-005 and National Science Council of the Republic of China grant NSC 94-2320-B-010-050.
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The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
- Received October 27, 2006.
- Revision received March 18, 2007.
- Accepted March 30, 2007.
Volume 13, Issue 12
