Title: Activated EGFR as a prognostic marker in human colon cancer
Abstract: 22119 Background: The Epidermal Growth Factor Receptor (EGFR, ErbB-1) is a cellular transmembrane receptor that regulates cell growth and survival, and is a therapeutic target. We determined whether EGFR activation, as indicated by EGFR phosphorylation (p-EGFR), is a more clinically important prognostic marker than is EGFR expression. Methods: Archival TNM stage II and III primary colon carcinomas (n=303) from patients treated in 5-fluorouracil-based adjuvant therapy trials conducted by the Mayo Clinic/North Central Cancer Treatment Group were studied. Immunohistochemical analysis of p-EGFR (Tyr-1173) and EGFR (Dako phramDx kit) were performed using tissue microarrays. Staining for Ki-67 and caspase-3 proteins was also performed. Protein expression was correlated with clinicopathological variables and patient survival rates. Results: Membranous EGFR was detected in 214 (70.6%) colon cancers and of these, p-EGFR expression was found in 44 of 139 (31.7%) tumors examined. Increased p-EGFR and EGFR intensity were associated with higher proliferation as indicted by a higher median number of Ki-67-positive tumor cells (p= 0.0058 and p< 0.001, respectively). p-EGFR correlated with proximal tumor site (p=0.0331), but not with other clinicopathological variables. Increased EGFR intensity was correlated with apoptosis, analyzed by caspase-3 (p=0.02), and with poor tumor differentiation (p=0.02). In a univariate analysis, tumor stage and number of involved lymph nodes were significantly associated with disease-free and overall survival (OS). Histologic grade was also associated with OS. Neither p-EGFR nor EGFR expression was prognostic by univariate or multivariate analysis. Conclusions: Activated EGFR (p-EGFR) was detected in nearly one-third of primary colon cancers and was associated with increased tumor cell proliferation. However, neither p- EGFR nor EGFR confered prognostic information. No significant financial relationships to disclose.
Publication Year: 2008
Publication Date: 2008-05-20
Language: en
Type: article
Indexed In: ['crossref']
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