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Ji et al. BMC Cancer 2013, 13:606 http://biomedcentral/1471-2407/13/RESEARCH ARTICLEOpen AccessMechanisms of acquired resistance to EGFR-tyrosine kinase inhibitor in Korean patients with lung cancerWonjun Ji1, Chang-Min Choi1,two, Jin Kyung Rho1, Se Jin Jang3, Young Soo Park3, Sung-Min Chun3, Woo Sung Kim1, Jung-Shin Lee2, Sang-We Kim2, Dae Ho Lee2 and Jae Cheol Lee2AbstractBackground: Despite an initial excellent response to epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI), resistance to remedy sooner or later develops. Even though numerous resistance mechanisms have already been discovered, small data exist relating to Asian patient populations. Methods: Among patients at a tertiary referral hospital in Korea who initially responded properly to gefitinib and later acquired resistance to remedy, we selected those with sufficient tissues obtained prior to EGFR-TKI therapy and soon after the onset of resistance to examine mutations by mass spectrometric genotyping technologies (Asan-Panel), MET amplification by fluorescence in situ hybridization (FISH), and evaluation of AXL status, epithelial-to-mesenchymal transition (EMT) and neuroendocrine markers by immunohistochemistry. Results: Twenty-six patients had been enrolled, all of whom had been diagnosed with adenocarcinoma with EGFR mutations (19del: 16, L858R: ten) except one (squamous cell carcinoma with 19del). Secondary T790M mutation was detected in 11 COX-2 Modulator Gene ID subjects (42.three ) and four of those patients had other co-existing resistance mechanisms; elevated AXL HDAC8 Inhibitor Purity & Documentation expression was observed in 5/26 sufferers (19.two ), MET gene amplification was noted in 3/26 (11.five ), and 1 patient acquired a mutation in the phosphatidylinositol-4, 5-bisphosphate 3-kinase catalytic subunit alpha isoform (PIK3CA) gene. None from the patients exhibited EMT; nonetheless, increased CD56 expression suggesting neuroendocrine differentiation was observed in two sufferers. Interestingly, conversion from L858R-mutant to wild-type EGFR occurred in one patient. Seven individuals (26.9 ) did not exhibit any identified resistance mechanisms. Patients with a T790M mutation showed a much more favorable prognosis. Conclusion: The mechanisms and frequency of acquired EGFR-TKI resistance in Koreans are comparable to those observed in Western populations; even so, much more information concerning the mechanisms that drive EGFR-TKI resistance are required. Keywords: Non-small cell lung carcinoma, Epidermal development aspect receptor mutation, EGFR tyrosine kinase inhibitor, Acquired resistance, Resistant mechanism, Mass spectrometric genotyping Correspondence: [email protected] 2 Department of Oncology, Asan Health-related Center, University of Ulsan College of Medicine, 88, Olympic-ro 43-gil, Seoul, Songpa-gu, Korea Full list of author info is available in the end with the article2013 Ji et al.; licensee BioMed Central Ltd. This is an open access post distributed beneath the terms from the Inventive Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original perform is correctly cited.Ji et al. BMC Cancer 2013, 13:606 http://biomedcentral/1471-2407/13/Page 2 ofBackground Lung cancer will be the top result in of cancer deaths [1]. 3 out of four sufferers present with advanced-stage illness, plus the prognosis is generally poor. However, recent advances with targeted therapies, for instance epidermal development factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs), have resulted in mar.