期刊
ONCOLOGIST
卷 17, 期 7, 页码 978-985出版社
ALPHAMED PRESS
DOI: 10.1634/theoncologist.2011-0385
关键词
Lung neoplasm; Epidermal growth factor receptor; Metastasis; Heterogeneity
类别
资金
- National Natural Science Foundation of China [81001031, 30772531]
- Foundation of Guangdong Science and Technology Department [2006B60101010, 2007A032000002]
- Natural Science Foundation of Guangdong [8151008004000015]
- Medical Research and Science Technology Foundation of Guangdong Province [A20100011]
- Chinese Lung Cancer Research Foundation
Background. Non-small cell lung cancer patients with epidermal growth factor receptor (EGFR) mutations have mixed responses to tyrosine kinase inhibitors (TKIs). Intertumor heterogeneity in EGFR mutations is one potential explanation for this phenomenon. Methods. We performed direct sequencing to identify EGFR mutations in 180 pairs of lung adenocarcinoma samples (from 3,071 patients). The high-resolution melting method was used in discordant cases to confirm EGFR mutation status. Matching samples were divided into four groups: primary lesions detected at different times, primary tumors with matched metastatic lymph nodes, multiple pulmonary nodules, and primary tumors with matched distant metastases. Multivariate analyses were performed to evaluate correlations between heterogeneity and patient characteristics. Results. In the study population, the discordance rate was 13.9% (25 of 180). The multiple pulmonary nodules group had the highest discordance rate of 24.4% (10 of 41; odds ratio for heterogeneity in primary lesions detected at different times, 6.37; 95% confidence interval, 1.71-23.72; p = .006). Discordance rates in the metachronous and synchronous settings were 15.7% (22 of 140) and 7.5% (three of 40), respectively. In the 34 patients who developed EGFR TKI resistance, 10 (29.4%) cases exhibited heterogeneity and five (14.7%) patients exhibited a mixed response to the drug. Three (8.8%) of the patients with a mixed response also exhibited discordant EGFR mutations. Conclusions. The overall discordance rate of EGFR mutation heterogeneity in Asian patients with pulmonary adenocarcinoma is relatively low, but the rate in patients with multiple pulmonary nodules is significantly higher. This observation may explain the mixed tumor response to EGFR TKIs. The Oncologist 2012;17:978-985
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