Expression of phosphorylated epidermal growth factor receptor (p-EGFR) in early stage non-small cell lung cancer: its relationship with overexpression of EGFR and cyclooxygenase-2 (COX-2), and survival.
9614 Background: Epidermal growth factor receptor (EGFR) is widely overexpressed in various cancers, and reported to relate with growth and invasion of cancer cells. However, clinical significance of EGFR overexpression is still controversial because its correlation with prognosis is not universal. Thus, activated form of EGFR (phosphorylated EGFR, p-EGFR) may better predict prognosis. We determined the association of p-EGFR and prognosis, and its relationship with EGFR and COX-2, and other biomarkers. METHODS: We immunohistochemically examined the expression of p-EGFR, EGFR, and COX-2 in 77 resected stage I/II non-small cell lung cancers (NSCLCs). Their correlation with prognosis and other biomarkers was also assessed including Ki-67, vascular endothelial growth factor (VEGF), and microvessel density (MVD). RESULTS: EGFR overexpression, defined as membranous staining in more than 10% of cancer cells, was found in 37 patients (48.1%). 45 patients (58.4%) showed COX-2 overexpression, cytoplasmic granular staining in more than 10%. 28.6% of patients were positive expression of p-EGFR, cytoplasmic staining in more than 5% of cells (22/77). Expression of p-EGFR was significantly associated with COX-2 overexpression (p = 0.047), and showed a modest relationship with EGFR overexpression and high Ki-67 (p = 0.087, and 0.092, respectively). COX-2 overexpression also had a clear correlation with high Ki-67 expression (p = 0.011). However, no correlation was found between EGFR and COX-2 overexpression. VEGF expression and MVD showed no association with p-EGFR, EGFR, and COX-2 overexpression. Positive expression of p-EGFR was significantly related with a short disease free survival (p = 0.045), but not with overall survival. However, neither EGFR nor COX-2 overexpression were associated with prognosis (p > 0.05). CONCLUSIONS: Expression of p-EGFR may better predict increased malignant potential and worse prognosis of early stage NSCLC than EGFR overexpression itself and this may be related with COX-2 overexpression and high proliferative activity of cancer cells No significant financial relationships to disclose.
Kim, SJ; Rabbani, ZN; Vollmer, RT; Schreiber, EG; Dewhirst, MW; Vujaskovic, Z; Kelley, MJ
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