Epidermal growth factor receptor genotype in plasma DNA and outcome of chemotherapy in the Chinese patients with advanced non-small cell lung cancer.

BACKGROUND: The genotype of epidermal growth factor receptor (EGFR) is associated with tyrosine kinase inhibitor and effectiveness of therapy, but its role in cytotoxic chemotherapy is still unknown. Previous studies indicated that certain EGFR mutations were associated with response and progression free survival following platinum based chemotherapy. Our recent studies have identified that EGFR genotypes in the tumour tissues were not associated with response to the first-line chemotherapy in Chinese patients with advanced non-small cell lung cancer (NSCLC). In this study, we investigated associations of EGFR genotypes from plasma of patients with advanced NSCLC and response to first-line chemotherapy and prognosis. METHODS: We enrolled 145 advanced NSCLC patients who had received first-line chemotherapy in our department. We examined plasma EGFR genotypes for these patients and associations of EGFR mutations with response to chemotherapy and clinical outcomes. RESULTS: There were 54 patients with known EGFR mutations and 91 cases of wild types. No significant difference was detected in the response rate to first-line chemotherapy between mutation carriers and wild-type patients (37.0% vs. 31.9%). The median survival time and 1-, 2-year survival rates were higher in mutation carriers than wild-types (24 months vs. 18 months, 85.7% vs. 65.7% and 43.7% vs. 25.9%, P = 0.047). Clinical stage (IV vs. IIIb), response to the first-line chemotherapy (partial vs. no) and EGFR genotype were independent prognostic factors. CONCLUSION: Plasma EGFR mutations in the Chinese patients with advanced NSCLC is not a predictor for the response to first-line chemotherapy, but an independent prognostic factor indicating longer survival.

[The detection by denaturing high performance liquid chromatography of epidermal growth factor receptor mutation in tissue and peripheral blood from patients with advanced non-small cell lung cancer].

OBJECTIVE: To study the application of denaturing high performance liquid chromatography (DHPLC) as a screening tool in detecting plasma and matched tissue epidermal growth factor receptor (EGFR) mutations for advanced non-small-cell lung cancer (NSCLC). METHODS: Plasma DNA samples and matched tumors from 230 cases of NSCLC were analyzed for EGFR mutations in exons 19 and 21 using DHPLC. The mutations in the plasma samples and the matched tumors were compared, and the association between EGFR mutations and the clinicopathological features were evaluated. RESULTS: Mutation of EGFR was found by DHPLC to be 33.5% (77/230) in tissues and 34.3% (79/230) in matched peripheral blood samples. Consistency of EGFR mutation status between tissues and matched plasma DNA was confirmed (kappa is 0.74, P < 0.01). The sensitivity and specificity of DHPLC for detecting EGFR mutation were 96.9% and 91.9%, respectively (kappa is 0.88). EGFR mutations in both tissue and blood was correlated with histology type (OR = 3.38, 95% CI 1.81 - 6.36, P < 0.05) and smoking status (OR = 1.61, 95% CI 1.13 - 2.28, P < 0.05), but no association with age, sex and stage was found (P > 0.05). CONCLUSION: The detection of EGFR mutation is highly consistent in tissues and in plasma DNA samples. DHPLC may serve as a preliminary screening tool for detecting EGFR mutations.