Quantification of EGFR mutations in primary and metastatic tumors in non-small cell lung cancer

Bing Wei,Jiuzhou Zhao,Zihui Ma,Yuxi Chang,Ke Yang,Yongjun Guo,Jie Ma,Bing Dong

doi:10.1186/1756-9966-33-5

Abstract

BackgroundEGFR mutation detection has been widely applied in the prediction of TKIs therapy in Non-Small Cell Lung Cancer (NSCLC). Metastatic tumors rather than primary tumors were usually assayed for those patients in advanced stages. Although the difference of EGFR mutation status in primary and metastatic tumors has been reported, the quantitative difference (ratio of mutated EGFR among total EGFR) in primary and metastatic tumors as well as in different sites of primary tumors was not clear.MethodsGenomic DNA in Formalin Fixed-Paraffin Embedded samples of primary and metastatic tumors of 50 NSCLC patients was extracted. Real-time fluorescent PCR was performed to quantify the EGFR mutation ratios.ResultsThe EGFR mutation ratios detected in different sites of primary tumors were highly concordant, whereas the EGFR mutation ratios in metastatic tumors were lower than those in primary tumors.ConclusionsRandomly chosen sample may reliably represent the type and ratio of mutations of EGFR in primary tumors. EGFR mutation ratios in primary tumors and metastatic tumors are different. If metastatic tumors are used for the detection of EGFR mutation, the sensitivity of the detection assay must be considered.

Highlights

Epidermal growth factor receptor (EGFR) mutation detection has been widely applied in the prediction of tyrosine kinase inhibitors (TKIs) therapy in Non-Small Cell Lung Cancer (NSCLC)
It is worth noting that gefitinib has been reported to be beneficial for patients in which EGFR mutations were detected in metastases but not primary tumors [15]
EGFR mutations in primary tumors and metastases Of the 50 cases of NSCLC that had EGFR mutations in primary tumors, exon 19 mutations were present in 28 cases (56%), and exon (L858R point mutations only) mutations were detected in cases (44%)

Summary

Introduction

EGFR mutation detection has been widely applied in the prediction of TKIs therapy in Non-Small Cell Lung Cancer (NSCLC). Multiple studies showed that the efficacy of tyrosine kinase inhibitors (TKIs) in the treatment of Non-Small Cell Lung Cancer (NSCLC) is highly correlated with EGFR mutation status in exon 18–21 [1,2,3,4]. For some of the NSCLC patients, especially those with metastatic cancer, the primary tumor specimen may not be available; EGFR mutations in metastases are often analyzed. It is worth noting that gefitinib has been reported to be beneficial for patients in which EGFR mutations were detected in metastases but not primary tumors [15]. Since these studies used qualitative detection of EGFR mutations, it is impossible to quantitatively evaluate the abundance of EGFR mutations in the primary tumor and metastases

Methods

Results

Discussion

Conclusion