Molecular diagnostic algorithm for epidermal growth factor receptor mutation detection in Asian lung adenocarcinomas: Comprehensive analyses of 445 Taiwanese patients with immunohistochemistry, PCR-direct sequencing and Scorpion/ARMS methods


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Abstract

Background and objective:Therapeutic responses of lung adenocarcinoma patients to tyrosine kinase inhibitors (TKIs) of epidermal growth factor receptor (EGFR) are closely associated with activating mutations within the EGFR tyrosine kinase domain. Screening activating EGFR mutations prior to selection for therapeutic strategy has been considered extremely valuable for clinical management of lung adenocarcinoma patients in Asian countries including Taiwan, where the EGFR mutation rate is higher than in the rest of the world. Currently there is no consensus on the method of choice to assess EGFR mutations in tumour tissue.Methods:We enrolled 445 lung adenocarcinoma patients for analysis of tumour EGFR mutations using polymerase chain reaction (PCR)-direct sequencing, scorpion/amplified refractory mutation system (ARMS) technology and immunohistochemistry with mutation-specific antibodies.Results:Two hundred forty-five patients (245/445; 55%) were found to harbour activating EGFR mutations using PCR-direct sequencing method, with a majority of patients (233/245; 95%) carrying exon 19 deletion or p.L858R point mutations. One hundred three of 200 patients were negative for EGFR mutations from PCR-direct sequencing were further analysed using Scorpion/ARMS technology. Up to 30% of the PCR-direct sequencing negative patients turned out to be positive in the Scorpion/ARMS EGFR mutation tests. For immunohistochemistry analysis of EGFR mutations, the p.E746_A750del specific antibody showed a sensitivity of 57% and a specificity of 100% for exon 19 deletions while the p.L858R point mutation specific antibody showed a sensitivity of 68% and a specificity of 95%.Conclusions:Based on this study, we proposed an algorithm for comprehensive and efficient testing of EGFR mutations on lung adenocarcinoma patients in Asia.SUMMARY AT A GLANCEFour hundred forty-five lung adenocarcinoma patients were enrolled for analysis of tumour epidermal growth factor receptor (EGFR) mutation status using polymerase chain reaction/direct sequencing, immunohistochemistry and Scorpion/amplified refractory mutation system technology. An algorithm for comprehensive and efficient testing of EGFR mutations on lung adenocarcinoma patients in Asia is proposed.

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