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Expression of epidermal growth factor receptor (EGFR) and downstream-activated peptides in surgically excised
Toru Mukohara1, Shinzoh Kudoh, Setsuko Yamauchi
1First Department of Internal Medicine, Osaka City University School of Medicine, 1-4-3, Asahi-machi, Abeno-ku, Osaka 545-8585, Japan. toru_mukohara@dfci.harvard.edu
Abstract:
Extracellular signal-regulated kinases (ERKs), Akt, and signal transducer and activator of transcription 3 (STAT3) are on signal transduction pathways triggered by epidermal growth factor receptor (EGFR). The purpose of this study was to evaluate the expressions of these peptides and to correlate the level of EGFR expression with downstream-activated peptide expression in non-small-cell lung cancer (NSCLC). A total of 60 specimens were studied by immunohistochemistry. EGFR overexpression was detected in 78% of specimens, but no significant relationship was found between it and any clinicopathological factors investigated. Phosphorylated (p)-ERK, p-Akt, and p-STAT3 expressions were observed in 28, 53, and 58% of specimens, respectively, and p-Akt and p-STAT3 expressions were correlated with well-differentiated tumor (P=0.045 and 0.014, respectively). Half of the 60 specimens expressed two or three downstream-activated peptides. The level of EGFR expression was associated with expressions of p-ERK and p-Akt (P=0.045 and 0.020, respectively). In a preliminary analysis, no peptides examined had an impact on relapse-free survival. In summary, various signal transduction pathways appeared frequently to participate in NSCLC, and the level of EGFR expression appeared to correlate with those of activated ERK and Akt, suggesting some role of receptor overexpression in more potent downstream activation.
Insights
Epidermal growth factor receptor (EGFR) overexpression is common in non-small-cell lung cancer (NSCLC). EGFR levels correlate with activated ERK and Akt signaling pathways, suggesting a role in downstream activation.
Area of Science:
- Oncology
- Molecular Biology
- Signal Transduction
Background:
- Epidermal growth factor receptor (EGFR) signaling pathways, including extracellular signal-regulated kinases (ERKs), Akt, and signal transducer and activator of transcription 3 (STAT3), are crucial in cancer development.
- Aberrant EGFR signaling is implicated in non-small-cell lung cancer (NSCLC) pathogenesis.
Purpose of the Study:
- To evaluate the expression levels of EGFR, p-ERK, p-Akt, and p-STAT3 in NSCLC specimens.
- To correlate EGFR expression with the activation of downstream signaling peptides.
- To investigate the association between these signaling molecules and clinicopathological factors, including tumor differentiation and relapse-free survival.
Main Methods:
- Immunohistochemistry was performed on 60 NSCLC tissue specimens.
- Expression levels of EGFR, phosphorylated ERK (p-ERK), phosphorylated Akt (p-Akt), and phosphorylated STAT3 (p-STAT3) were quantified.
- Statistical analyses were used to determine correlations between peptide expressions and clinicopathological parameters.
Main Results:
- EGFR overexpression was detected in 78% of NSCLC specimens.
- p-ERK, p-Akt, and p-STAT3 were expressed in 28%, 53%, and 58% of specimens, respectively.
- EGFR expression levels were significantly associated with p-ERK and p-Akt expression (P=0.045 and 0.020, respectively).
- p-Akt and p-STAT3 expression correlated with well-differentiated tumors (P=0.045 and 0.014, respectively).
- No significant impact on relapse-free survival was observed for any of the examined peptides.
Conclusions:
- Various signal transduction pathways are frequently involved in NSCLC.
- EGFR overexpression is associated with increased activation of downstream ERK and Akt pathways.
- These findings suggest a potential role for EGFR overexpression in driving downstream signaling activation in NSCLC.
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